Electronic Health Record-Based Surveillance for Community Transmitted COVID-19 in the Emergency Department

Introduction: SARS-CoV-2, a novel coronavirus, manifests as a respiratory syndrome (COVID-19) and is the cause of an ongoing pandemic. The response to COVID-19 in the United States has been hampered by an overall lack of diagnostic testing capacity. To address uncertainty about ongoing levels of SARS-CoV-2 community transmission early in the pandemic, we aimed to develop a surveillance tool using readily available emergency department (ED) operations data extracted from the electronic health record (EHR). This involved optimizing the identification of acute respiratory infection (ARI)-related encounters and then comparing metrics for these encounters before and after the confirmation of SARS-CoV-2 community transmission.Methods: We performed an observational study using operational EHR data from two Midwest EDs with a combined annual census of over 80,000. Data were collected three weeks before and after the first confirmed case of local SARS-CoV-2 community transmission. To optimize capture of ARI cases, we compared various metrics including chief complaint, discharge diagnoses, and ARI-related orders. Operational metrics for ARI cases, including volume, pathogen identification, and illness severity, were compared between the pre- and post-community transmission timeframes using chi-square tests of independence.Results: Compared to our combined definition of ARI, chief complaint, discharge diagnoses, and isolation orders individually identified less than half of the cases. Respiratory pathogen testing was the top performing individual ARI definition but still only identified 72.2% of cases. From the pre to post periods, we observed significant increases in ED volumes due to ARI and ARI cases without identified pathogen.Conclusion: Certain methods for identifying ARI cases in the ED may be inadequate and multiple criteria should be used to optimize capture. In the absence of widely available SARS-CoV-2 testing, operational metrics for ARI-related encounters, especially the proportion of cases involving negative pathogen testing, are useful indicators for active surveillance of potential COVID-19 related ED visits

Development and validation of a pragmatic natural language processing approach to identifying falls in older adults in the emergency department

BACKGROUND: Falls among older adults are both a common reason for presentation to the emergency department, and a major source of morbidity and mortality. It is critical to identify fall patients quickly and reliably during, and immediately after, emergency department encounters in order to deliver appropriate care and referrals. Unfortunately, falls are difficult to identify without manual chart review, a time intensive process infeasible for many applications including surveillance and quality reporting. Here we describe a pragmatic NLP approach to automating fall identification. METHODS: In this single center retrospective review, 500 emergency department provider notes from older adult patients (age 65 and older) were randomly selected for analysis. A simple, rules-based NLP algorithm for fall identification was developed and evaluated on a development set of 1084 notes, then compared with identification by consensus of trained abstractors blinded to NLP results. RESULTS: The NLP pipeline demonstrated a recall (sensitivity) of 95.8%, specificity of 97.4%, precision of 92.0%, and F1 score of 0.939 for identifying fall events within emergency physician visit notes, as compared to gold standard manual abstraction by human coders. CONCLUSIONS: Our pragmatic NLP algorithm was able to identify falls in ED notes with excellent precision and recall, comparable to that of more labor-intensive manual abstraction. This finding offers promise not just for improving research methods, but as a potential for identifying patients for targeted interventions, quality measure development and epidemiologic surveillance

Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction

BACKGROUND AND AIMS: We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate diet or a low-carbohydrate diet on hepatic and skeletal muscle insulin sensitivity. METHODS: Twenty-two obese subjects (body-mass index, 36.5±0.8kg/m(2)) were randomized to a high-carbohydrate (>180g/d) or low-carbohydrate (<60g/d) energy-deficit diet. A euglycemic–hyperinsulinemic clamp, muscle biopsies, and magnetic resonance spectroscopy were used to determine insulin action, cellular insulin signaling and intrahepatic triglyceride content before, after 48 h, and after ~11 wks (7% weight loss) of diet therapy. RESULTS: At 48 h, intrahepatic triglyceride content decreased more in the low-carbohydrate than the high-carbohydrate diet group (29.6±4.8% vs. 8.9±1.4%; P<0.05), but was similar in both groups after 7% weight loss (low-carbohydrate diet, 38.0±4.5% vs. high-carbohydrate diet, 44.5±13.5%). Basal glucose production rate decreased more in the low-carbohydrate than the high-carbohydrate diet group at 48 h (23.4±2.2% vs. 7.2±1.4%, P<0.05) and after 7% weight loss (20.0±2.4% vs. 7.9±1.2%, P<0.05). Insulin-mediated glucose uptake did not change at 48 h, but increased similarly in both groups after 7% weight loss (48.4±14.3%, P<0.05). In both groups, insulin-stimulated phosphorylation of Jun N-terminal kinase decreased by 29±13% and phosphorylation of Akt and insulin receptor substrate -1 increased by 35±9% and 36±9%, respectively, after 7% weight loss (all p<0.05). CONCLUSION: Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 h of calorie restriction affects the liver (intrahepatic triglyceride content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling)

Simultaneous Determination of 3-mercaptopyruvate and Cobinamide in Plasma by Liquid Chromatography–tandem Mass Spectrometry

The current suite of Food and Drug Administration (FDA) approved antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide antidotes. Therefore, a liquid chromatography–tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard (13C3-3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN)2). The limits of detection for 3-MP and Cbi were 0.5 μM and 0.2 μM, respectively. The linear ranges were 2–500 μM for 3-MP and 0.5–50 μM for Cbi. The accuracy and precision for 3-MP were 100 ± 9% and \u3c8.3% relative standard deviation (RSD), respectively. For Cbi(CN)2, the accuracy was 100 ± 13% and the precision was \u3c9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these antidotes for treatment of cyanide poisoning

The Catalytic Mechanism of Electron-Bifurcating Electron Transfer Flavoproteins (ETFs) Involves an Intermediary Complex with NAD\u3csup\u3e+\u3c/sup\u3e

Electron bifurcation plays a key role in anaerobic energy metabolism, but it is a relatively new discovery, and only limited mechanistic information is available on the diverse enzymes that employ it. Herein, we focused on the bifurcating electron transfer flavoprotein (ETF) from the hyperthermophilic archaeon Pyrobaculum aerophilum. The EtfABCX enzyme complex couples NADH oxidation to the endergonic reduction of ferredoxin and exergonic reduction of menaquinone. We developed a model for the enzyme structure by using nondenaturing MS, cross-linking, and homology modeling in which EtfA, -B, and -C each contained FAD, whereas EtfX contained two [4Fe-4S] clusters. On the basis of analyses using transient absorption, EPR, and optical titrations with NADH or inorganic reductants with and without NAD+, we propose a catalytic cycle involving formation of an intermediary NAD+-bound complex. A charge transfer signal revealed an intriguing interplay of flavin semiquinones and a protein conformational change that gated electron transfer between the low- and high-potential pathways. We found that despite a common bifurcating flavin site, the proposed EtfABCX catalytic cycle is distinct from that of the genetically unrelated bifurcating NADH-dependent ferredoxin NADP+ oxidoreductase (NfnI). The two enzymes particularly differed in the role of NAD+, the resting and bifurcating-ready states of the enzymes, how electron flow is gated, and the two two-electron cycles constituting the overall four-electron reaction. We conclude that P. aerophilum EtfABCX provides a model catalytic mechanism that builds on and extends previous studies of related bifurcating ETFs and can be applied to the large bifurcating ETF family

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

BACKGROUND: Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. METHODS: Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. RESULTS: After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. CONCLUSION: Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy

Comparison of nonculture blood-based tests for diagnosing invasive Aspergillosis in an animal model

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The Helium-Rich Cataclysmic Variable ES Ceti

We report photometry of the helium-rich cataclysmic variable ES Ceti during 2001-2004. The star is roughly stable at V ~ 17.0 and has a light curve dominated by a single period of 620 s, which remains measurably constant over the 3 year baseline. The weight of evidence suggests that this is the true orbital period of the underlying binary, not a "superhump" as initially assumed. We report GALEX ultraviolet magnitudes, which establish a very blue flux distribution (F_nu ~ nu^1.3), and therefore a large bolometric correction. Other evidence (the very strong He II 4686 emission, and a ROSAT detection in soft X-rays) also indicates a strong EUV source, and comparison to helium-atmosphere models suggests a temperature of 130+-10 kK. For a distance of 350 pc, we estimate a luminosity of (0.8-1.7)x10^34 erg/s, yielding a mass accretion rate of (2-4)x10^-9 M_sol/yr onto an assumed 0.7 M_sol white dwarf. This appears to be about as expected for white dwarfs orbiting each other in a 10 minute binary, assuming that mass transfer is powered by gravitational radiation losses. We estimate mean accretion rates for other helium-rich cataclysmic variables, and find that they also follow the expected M-dot ~ P_o^-5 relation. There is some evidence (the lack of superhumps, and the small apparent size of the luminous region) that the mass transfer stream in ES Cet directly strikes the white dwarf, rather than circularizing to form an accretion disk.Comment: PDF, 26 pages, 3 tables, 9 figures; accepted, in press, to appear February 2005, PASP; more info at http://cba.phys.columbia.edu

Utility of COVID-19 antigen testing in the emergency department

Background: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis. Methods: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. Results: From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID-19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms \u3e2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. Conclusions: The BinaxNOW point-of-care test has good sensitivity and excellent specificity for the detection of COVID-19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks