Reducing duplicate genetic testing in inpatient and outpatient settings across a large safety-net system.

OBJECTIVES: To develop a system-wide electronic health record (EHR) intervention at a large safety-net hospital system to reduce wasteful duplicate genetic testing. METHODS: This project was initiated at a large urban public health care system. An EHR alert was designed to be triggered when a clinician attempted to order any of 16 specified genetic tests for which a previous result existed within the EHR system. Measurements included the proportion of completed genetic tests that were duplicates and alerts per 1,000 tests. Data were stratified by clinician type, specialty, and inpatient vs ambulatory setting. RESULTS: Across all settings, the rate of duplicate genetic testing decreased from 2.35% (1,050 of 44,592 tests) to 0.09% (21 of 22,323 tests) (96% relative reduction, P < .001). The alert rate per 1,000 tests was 277 for inpatient orders and 64 for ambulatory orders. Among clinician types, residents had the highest alert rate per 1,000 tests at 166 and midwives the lowest at 51 (P < .01). Among clinician specialties, internal medicine had the highest alert rate per 1,000 tests at 245 and obstetrics and gynecology the lowest at 56 (P < .01). CONCLUSIONS: The EHR intervention successfully reduced duplicate genetic testing by 96% across a large safety-net setting.

Characteristics and outcomes of COVID-19 patients in New York City's public hospital system.

BACKGROUND: New York City (NYC) bore the greatest burden of COVID-19 in the United States early in the pandemic. In this case series, we describe characteristics and outcomes of racially and ethnically diverse patients tested for and hospitalized with COVID-19 in New York City's public hospital system. METHODS: We reviewed the electronic health records of all patients who received a SARS-CoV-2 test between March 5 and April 9, 2020, with follow up through April 16, 2020. The primary outcomes were a positive test, hospitalization, and death. Demographics and comorbidities were also assessed. RESULTS: 22254 patients were tested for SARS-CoV-2. 13442 (61%) were positive; among those, the median age was 52.7 years (interquartile range [IQR] 39.5-64.5), 7481 (56%) were male, 3518 (26%) were Black, and 4593 (34%) were Hispanic. Nearly half (4669, 46%) had at least one chronic disease (27% diabetes, 30% hypertension, and 21% cardiovascular disease). Of those testing positive, 6248 (46%) were hospitalized. The median age was 61.6 years (IQR 49.7-72.9); 3851 (62%) were male, 1950 (31%) were Black, and 2102 (34%) were Hispanic. More than half (3269, 53%) had at least one chronic disease (33% diabetes, 37% hypertension, 24% cardiovascular disease, 11% chronic kidney disease). 1724 (28%) hospitalized patients died. The median age was 71.0 years (IQR 60.0, 80.9); 1087 (63%) were male, 506 (29%) were Black, and 528 (31%) were Hispanic. Chronic diseases were common (35% diabetes, 37% hypertension, 28% cardiovascular disease, 15% chronic kidney disease). Male sex, older age, diabetes, cardiac history, and chronic kidney disease were significantly associated with testing positive, hospitalization, and death. Racial/ethnic disparities were observed across all outcomes. CONCLUSIONS AND RELEVANCE: This is the largest and most racially/ethnically diverse case series of patients tested and hospitalized for COVID-19 in New York City to date. Our findings highlight disparities in outcomes that can inform prevention and testing recommendations.

Rapid and novel prenatal molecular assay for detecting aneuploidies and microdeletion syndromes.

OBJECTIVES: To develop a targeted aneuploidy and microdeletion detection platform for use in the prenatal setting, to assess the integrity of the platform with a robust validation system, and to prospectively determine the performance of the platform under routine clinical conditions. METHODS: To generate proxies for the various disorders assessed by the assay for analytical validation purposes, cells from ten microdeletion syndromes as well as from common aneuploidies were spiked into cleared amniotic fluid. Genomic DNA was isolated, labeled, and hybridized to microbeads that have been coupled to DNA derived from Bacterial Artificial Chromosome (BAC) from the relevant regions targeted by the array. Beads were read using a flow cytometric multiplex bead array detection system. In the prospective part of the study, 104 amniotic fluid samples were collected and analyzed. RESULTS: All microdeletion syndromes and aneuploidies were validated in a blinded fashion. In the prospective study, the total number of readable samples was 101 of 104 (97%). All sample results were confirmed independently. CONCLUSION: The bead array approach is a rapid and reliable test for detecting aneuploidies and microdeletions. This assay has the potential to provide the benefit of expanded molecular cytogenetic testing to pregnant women undergoing invasive prenatal diagnosis. This approach may be especially useful in parts of the world where cytogenetic personnel and facilities may be limited.

Population-based Tay-Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase A enzyme assay is essential for accurate testing.

Tay-Sachs disease (TSD) carrier screening, initiated in the 1970s, has reduced the birth-rate of Ashkenazi Jews with TSD worldwide by 90%. Recently, several nationwide programs have been established that provide carrier screening for the updated panel of Jewish genetic diseases on college campuses and in Jewish community settings. The goals of this study were to determine the performance characteristics of clinical TSD testing in college- and community-based screening programs and to determine if molecular testing alone is adequate in those settings. Clinical data for TSD testing were retrospectively anonymized and subsequently analyzed for 1,036 individuals who participated in these programs. The performance characteristics of the serum and the platelet Hexosaminidase assays were compared, and also correlated with the results of targeted DNA analysis. The serum assay identified 29 carriers and the platelet assay identified 35 carriers for carrier rates of 1/36 and 1/29, respectively. One hundred sixty-nine samples (16.3%) were inconclusive by serum assay in marked contrast to four inconclusive samples (0.4%) by the platelet assay. Molecular analysis alone would have missed four of the 35 carriers detected by the platelet assay, yielding a false negative rate of 11.4% with a sensitivity of 88.6%. Based on the results of this study, platelet assay was superior to serum with a minimal inconclusive rate. Due to changing demographics of the Ashkenazi Jewish population, molecular testing alone in the setting of broad-based population screening programs is not sufficient, and biochemical analysis should be the assay of choice.