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These Annals of Internal Medicine results only contain recent articles.

Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak

Background: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. Objective: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. Design: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. Setting: A nursing home with an ongoing SARS-CoV-2 outbreak. Participants: 532 paired specimens collected from 234 available residents and staff. Measurements: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. Results: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). Limitation: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. Conclusion: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. Primary Funding Source: None.

Medical Schools as Racialized Organizations: A Primer

The year 2020 saw the largest social movement in response to the police killings of Black people and anti-Black racism in U.S. history. As a result, medical schools and professional societies such as the American Medical Association and the Association of American Medical Colleges are reckoning with their role in perpetuating racial inequality and the impact of structural racism on medical training. Whether these efforts will translate into meaningful change has yet to be determined. Success depends on a deep understanding of the fundamental role racism plays in how medical schools function and an acknowledgment that current organizational structures and processes often serve to entrench, not dismantle, racial inequities. Drawing on racialized organizations theory from the field of sociology, this article gives an overview of scholarship on race and racism in medical training to demonstrate how seemingly race-neutral processes and structures within medical education, in conjunction with individuals’ biases and interpersonal discrimination, serve to reproduce and sustain racial inequality. From entrance into medical school through the residency application process, organizational factors such as reliance on standardized tests to predict future success, a hostile learning climate, and racially biased performance metrics ultimately stunt the careers of trainees of color, particularly those from backgrounds underrepresented in medicine (URM). These compounding disadvantages contribute to URM trainees’ lower matching odds, steering into less competitive and lucrative specialties, and burnout and attrition from academic careers. In their commitment against structural racism in medical training and academic medicine, medical schools and larger organizations like the Association of American Medical Colleges should prioritize interventions targeted at these structural barriers to achieve equity.

Optimizing SARS-CoV-2 Surveillance in the United States: Insights From the National Football League Occupational Health Program

Background: Evidence to understand effective strategies for surveillance and early detection of SARS-CoV-2 is limited. Objective: To describe the results of a rigorous, large-scale COVID-19 testing and monitoring program. Design: The U.S. National Football League (NFL) and the NFL Players Association (NFLPA) instituted a large-scale COVID-19 monitoring program involving daily testing using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms (Roche cobas and Thermo Fisher QuantStudio), a transcription-mediated amplification platform (Hologic Panther), and an antigen point-of-care (aPOC) test (Quidel Sofia). Setting: 32 NFL clubs in 24 states during the 2020 NFL season. Participants: NFL players and staff. Measurements: SARS-CoV-2 test results were described in the context of medically adjudicated status. Cycle threshold (Ct) values are reported when available. Results: A total of 632 370 tests administered across 11 668 persons identified 270 (2.4%) COVID-19 cases from 1 August to 14 November 2020. Positive predictive values ranged from 73.0% to 82.0% across the RT-PCR platforms. High Ct values (33 to 37) often indicated early infection. For the first positive result, the median Ct value was 32.77 (interquartile range, 30.02 to 34.72) and 22% of Ct values were above 35. Among adjudicated COVID-19 cases tested with aPOC, 42.3% had a negative result. Positive concordance between aPOC test result and adjudicated case status increased as viral load increased. Limitations: Platforms varied by laboratory, and test variability may reflect procedural differences. Conclusion: Routine RT-PCR testing allowed early detection of infection. Cycle threshold values provided a useful guidepost for understanding results, with high values often indicating early infection. Antigen POC testing was unable to reliably rule out COVID-19 early in infection. Primary Funding Source: The NFL and the NFLPA.

Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening: A Diagnostic Test Accuracy Study: Annals of Internal Medicine: Vol 174, No 9

Background: The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement. Objective: To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT. Design: Diagnostic test accuracy study. Setting: Colonoscopy-controlled series. Participants: Persons (n = 1284) from a screening (n = 1038) and referral (n = 246) population were classified by their most advanced lesion (CRC [n = 47], advanced adenoma [n = 135], advanced serrated polyp [n = 30], nonadvanced adenoma [n = 250], and nonadvanced serrated polyp [n = 53]), along with control participants (n = 769). Measurements: Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity. Results: The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2—the mtFIT—to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT (P = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) (P = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT. Limitation: Study population is enriched with persons from a referral population. Conclusion: Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for population-based CRC screening. A prospective screening trial is in preparation. Primary Funding Source: Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.

A SARS-CoV-2 Cluster in an Acute Care Hospital

Background: Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals. Objective: To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies. Design: Descriptive study. Setting: Brigham and Women's Hospital, Boston, Massachusetts. Participants: Patients and staff with cluster-related SARS-CoV-2 infections. Intervention: Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing. A case–control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2–positive versus negative staff. Measurements: Description of the cluster, mitigation activities, and risk factor analysis. Results: Fourteen patients and 38 staff members were included in the cluster per whole-genome sequencing and epidemiologic associations. The index case was a symptomatic patient in whom isolation was discontinued after 2 negative results on nasopharyngeal polymerase chain reaction testing. The patient subsequently infected multiple roommates and staff, who then infected others. Seven of 52 (13%) secondary infections were detected only on second or subsequent tests. Eight of 9 (89%) patients who shared rooms with potentially contagious patients became infected. Potential contributing factors included high viral loads, nebulization, and positive pressure in the index patient's room. Risk factors for transmission to staff included presence during nebulization, caring for patients with dyspnea or cough, lack of eye protection, at least 15 minutes of exposure to case patients, and interactions with SARS-CoV-2–positive staff in clinical areas. Whole-genome sequencing confirmed that 2 staff members were infected despite wearing surgical masks and eye protection. Limitation: Findings may not be generalizable. Conclusion: SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies. Insights from this cluster may inform additional measures to protect patients and staff. Primary Funding Source: None.