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Sex-differences in high sensitivity troponin (hs-Tn) concentrations are well established. There is, however, limited data to guide interpretation of hs-Tn in transgender patients, particularly those receiving gender-affirming hormone therapy. Our purpose was to evaluate troponin testing in transgender patients.Transgender adults attending a routine clinic visit provided demographic data, medical history, and venous blood samples. Patients with congestive heart failure or chronic kidney disease were excluded. hs-Tn was measured using the Architect Stat High Sensitivity Troponin-I (Abbott), Access 2 hsTnI (Beckman Coulter), and Elecsys Troponin T Gen 5 STAT (Roche) assays. hs-Tn below the limit of detection (LOD) is reported as the lower limit of detection (LLOD) RESULTS: Of 63 subjects, 76 % were transgender women. We found no significant difference in median hs-Tn concentrations or proportions of hs-Tn LOD.In this cohort of stable transgender patients without CHF or CKD, we did not observe differences in hs-Tn concentrations between transgender women and transgender men. Meaningful conclusions are limited owing to inadequate sample size and population differences. Further research on hs-troponin concentrations in this underrepresented, vulnerable population is needed.

Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope.The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies.The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE).Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines.ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements.

Background Most symptoms of coronavirus 2019 (COVID-19) are mild; however, some patients experience cardiovascular complications, including thromboembolic events and death. Data are needed to better inform prevention and treatment of these events. This analysis was designed to describe patient characteristics, medication use, thromboembolic events, and all-cause mortality in hospitalized COVID-19 patients in the United States. Methods This retrospective, observational cohort study identified adults hospitalized with COVID-19 (January 21, 2020–January 07, 2021) in the deidentified Optum COVID-19 Electronic Health Records dataset. Thromboembolic events and all-cause mortality were collected at any time during the variable follow-up period (up to 50 weeks). Results Of 181,995 COVID-19 patients who met eligibility criteria, 40,524 (22.3%) were hospitalized with COVID-19. Hospitalized patients had a mean age of 63 years and a Quan–Charlson comorbidity index of 1.3. Anticoagulants were used in 89.2% of patients during hospitalization and in 18.7% of postdischarge patients. Of hospitalized patients, 17.6% had a thromboembolic event during the entire follow-up period (mean time to the first event of 15 days), of whom 13.4% had an event during hospitalization; of discharged patients, 4.3% had a thromboembolic event (mean time from discharge to event of 43 days). Death during the follow-up period was reported in 15.0% of patients. Conclusions In this large, observational cohort study, patients hospitalized with COVID-19 had high rates of thromboembolic events during hospitalization and in the postdischarge period; mortality was also high in this population. Anticoagulant use was common during hospitalization. These findings support further studies to optimize in-hospital and extended prophylaxis for hospitalized COVID-19 patients.

Dyspnea is a common Emergency Department (ED) complaint of which acute pulmonary edema (APE) is a potentially life-threatening etiology. Remote Dielectric Sensing (ReDS™) is a novel, non-invasive, radar based, rapid, point of care vest testing system used to objectively quantify lung fluid content and may be useful in the early diagnosis of APE.To determine the accuracy of ReDS to detect pathologic lung fluid in ED undifferentiated dyspneic patients.We performed a prospective convenience sample observation pilot study enrolling adult ED patients with a chief complaint of "shortness of breath." After informed consent, patients were fitted with the ReDS vest and a reading, blinded to the care team, was recorded. A gold standard diagnosis of pulmonary edema, determined by 2 physicians performing a chart review and blinded to ReDs data, was compared to the ReDS reading.Overall, 123 patients were included; 59% (n = 73) were male, mean (SD) age 57.2 (±12) years, 46.3% (n = 57) Hispanic, 34.1%(n = 42) African American, 13.0% (n = 16) Caucasian and 5.7% (n = 7) Asian. The gold standard diagnosis showed pulmonary edema in 38 (30.9%) patients, of which 30 were detected by ReDS. At an optimal cutoff (≥ 37%), ReDS had a Sn of 79.5% (CI 63.5% - 90.5%), Sp of 72.6% (CI 61.8% - 81.8%), a PPV of 57.4% and a NPV of 88.4%.ReDS is moderately sensitive and specific with an accuracy of 74.8% for pulmonary edema.

Opioid-induced constipation (OIC) prescription medications (OIC-Rx) like methylnaltrexone subcutaneous (SC) have shown efficacy in treating OIC in the emergency department (ED). This study aimed to describe and compare healthcare resource utilization (HRU) and healthcare costs in ED patients with OIC receiving OIC-Rx versus those not receiving OIC-Rx.Adult patients with OIC during an ED encounter were identified from a hospital-based ED encounters database (2016-2019) and classified on the basis of receipt of OIC-Rx (OIC-Rx versus No OIC-Rx cohorts). Entropy balancing was used to reweight characteristics of the two cohorts. HRU and healthcare costs were measured and compared during the ED encounter and 30-day post-discharge period.Among 11,135 patients in the OIC-Rx cohort (21,474 in the No OIC-Rx cohort), 93% received methylnaltrexone SC. Patients in the OIC-Rx cohort had 0.7 fewer inpatient days per OIC ED encounter and 64% decreased odds of being hospitalized versus the No OIC-Rx cohort (both p 0.001). During the post-discharge period, the OIC-Rx cohort had 35% decreased odds of any re-encounter (p 0.001). The OIC-Rx cohort had a $732 reduction in costs per OIC ED encounter versus the No OIC-Rx cohort (p 0.001), driven by larger hospitals and patients with Medicare or Commercial insurance. During the post-discharge period, the OIC-Rx cohort had a $421 reduction in costs associated with any re-encounter versus the No OIC-Rx cohort (p = 0.004).Patients receiving OIC-Rx in the ED had decreased odds of being hospitalized and fewer re-encounters in the 30-day post-discharge period versus patients who did not receive OIC-Rx, resulting in cost savings for insurance agencies and healthcare providers.

Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations.We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up.Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction0.001 for MACE).In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients.

Although some emergency department risk stratification tools consider non-specific ECG findings as an aid in disposition decisions, their clinical value in patients with an initially low high-sensitivity cardiac troponin I (hsTnI) is unclear.Our purpose was to determine if non-specific ECG (ns-ECG) findings are associated with 30-day major adverse cardiac events (MACE) in ED patients presenting with suspected acute coronary syndromes (ACS) who have a low initial hsTnI.Using the prospective Siemens Atellica hsTnI Food and Drug Administration submission observational database, we conducted a retrospective cohort study of the association between ns-ECG findings (defined as left bundle branch block [LBBB], ST depression [STD], or T-wave inversions [TWI]) and 30-day MACE (death, myocardial infarction, heart failure hospitalization, or coronary revascularization). Eligible patients presented with suspected ACS to one of 29 US EDs from April 2015 to April 2016, had stable vital signs, a blood sample for hsTnI (Siemen's Atellica, Siemens Healthineers, Inc, Malvern, PA) obtained at 1, 3, and 6 hours after ED presentation, and were followed for 30 days. The relationship between 30-day outcome, initial hsTnI, and ns-ECG was evaluated using chi-square testing.Of 2676 enrolled, 1313 patients met the inclusion criteria and are included in the analysis. Median (interquartile range) age was 62 years (54, 72), 54% were male, with 56% white, and 39% African American. Median (interquartile range) times from symptom onset to presentation and presentation to specimen collection were 92 (0, 216) and 146 (117, 177) minutes, respectively. The most common presenting symptoms were chest pain (84%), followed by dyspnea (9%). ECG findings were categorized as T-wave inversion or non-specific T wave changes (42%), ST depression ns-ECG ST changes (16%), or LBBB (2%). Thirty-day MACE occurred in 72 (5.5%) patients, with coronary revascularization (35 patients, 2.7%) and heart failure (25 patients, 1.9%) being the most frequent outcomes. In patients with an initial hsTnI below the limit of quantitation (LOQ) of 2.5 ng/L (n = 449), there was no association between ns-ECG changes and 30-day MACE (In ED suspected ACS patients without unstable vital signs, and an initial hsTnI less than the LOQ (2.5 ng/L), ns-ECG findings are not associated with 30-day major adverse cardiac events. The use of ns-ECG findings in ACS disposition should be considered in the context of hsTnI levels.

BACKGROUND Whether American College of Cardiology (ACC) Chest Pain Center (CPC) accreditation alters guidelines adherence rates is unclear. METHODS We analyzed patient-level, hospital-reported, quality metrics for myocardial infarction (MI) patients from 644 hospitals collected in the ACC's Chest Pain-MI Registry from January 1, 2019, to December 31, 2020, stratified by CPC accreditation for >1 year. RESULTS Of 192,374 MI patients, 67,462 (35.1%) received care at an accredited hospital. In general, differences in guideline adherence rates between accredited and nonaccredited hospitals were numerically small, although frequently significant. Patients at accredited hospitals were more likely to undergo coronary angiography (98.6% vs. 97.9%, P < 0.0001), percutaneous coronary intervention for NSTEMI (55.4% vs. 52.3%, P < 0.0001), have overall revascularization for NSTEMI (63.5% vs. 61.0%, P < 0.0001), and receive P2Y12 inhibitor on arrival (63.5% vs. 60.2%, P < 0.0001). Nonaccredited hospitals more ECG within 10 minutes (62.3% vs. 60.4%, P < 0.0001) and first medical contact to device activation ≤90 minutes (66.8% vs. 64.8%, P < 0.0001). Accredited hospitals had uniformly higher discharge medication guideline adherence, with patients more likely receiving aspirin (97.8% vs. 97.4%, P < 0.0001), angiotensin-converting enzyme inhibitor (46.7% vs. 45.3%, P < 0.0001), beta blocker (96.6% vs. 96.2%, P < 0.0001), P2Y12 inhibitor (90.3% vs. 89.2%, P < 0.0001), and statin (97.8% vs. 97.5%, P < 0.0001). Interaction by accredited status was significant only for length of stay, which was slightly shorter at accredited facilities for specific subgroups. CONCLUSIONS ACC CPC accreditation was associated with small consistent improvement in adherence to guideline-based treatment recommendations of catheter-based care (catheterization and PCI) for NSTEMI and discharge medications, and shorter hospital stays.

Despite significant advances in drug‐based and device‐based therapies, heart failure remains a major and growing public health problem associated with substantial disability, frequent hospitalizations, and high economic costs. Keeping patients well and out of the hospital has become a major focus of heart failure disease management. Achieving and maintaining such stability in heart failure patients requires a holistic approach, which includes at least the management of the underlying heart disease, the management of comorbidities and the social and psychological aspects of the disease, and the management of haemodynamic/fluid status. In this regard, accurate assessment of elevated ventricular filling pressures or volume overload, that is, haemodynamic or pulmonary congestion, respectively, before the onset of worsening heart failure symptoms represents an important management strategy. Unfortunately, conventional methods for assessing congestion, such as physical examination and monitoring of symptoms and daily weights, are insensitive markers of worsening heart failure. Assessment tools that directly measure congestion, accurately and in absolute terms, provide more actionable information that enables the application of treatment algorithms designed to restore patient stability, in a variety of clinical settings. Two such assessment tools, implantable haemodynamic monitors and remote dielectric sensing (ReDS), meet the prerequisites for useful heart failure management tools, by providing accurate, absolute, and actionable measures of congestion, to guide patient management. This review focuses on the use of such technologies, across the spectrum of heart failure treatment settings. Clinical data are presented that support the broad use of pulmonary artery pressure‐guided and/or ReDS‐guided heart failure management in heart failure patients with reduced and preserved left ventricular ejection fraction.

Limited data are available on thromboembolic events (TEEs) and mortality in outpatients with coronavirus disease 2019 (COVID-19). This retrospective, observational cohort study identified non-hospitalized COVID-19 outpatients (01/21/2020-01/07/2021) using de-identified Optum® COVID-19 Electronic Health Records data. Patient characteristics, occurrence of TEEs, all-cause mortality, and anticoagulant or thrombolytic medication use were evaluated. Of 1,246,067 patients with COVID-19 diagnosis, 141 471 met entry criteria. Mean (standard deviation [SD]) age was 46.1 (17.2) years, 56.8% were female, 72.9% Caucasian, 11.2% African American, and 11.1% Hispanic. Comorbidity burden was low (mean [SD] Quan-Charlson comorbidity index score of 0.43 [1.10]); however, of those with body mass index data, half were obese. During the follow-up period, a TEE occurred in 1.4%, with the proportion of patients with ischemic stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism being similar (approximately 0.4% each). All-cause mortality was 0.7%. Medications included corticosteroids (13.7%), anticoagulants (4.9%), and antiplatelets (2.9%). Overall, in this large cohort analysis, certain demographic and clinical characteristics of patients who experienced TEEs were identified and may help guide management decisions and future clinical trials for COVID-19 outpatients.

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and β-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones—a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A−β+ KPD is marked by chronic but varying dysregulation of BCAA metabolism.

Background and Purpose: Early detection of large vessel occlusion (LVO) stroke optimizes endovascular therapy and improves outcomes. Clinical stroke severity scales used for LVO identification have variable accuracy. We investigated a portable LVO-detection device (PLD), using electroencephalography and somatosensory-evoked potentials, to identify LVO stroke. Methods: We obtained PLD data in suspected patients with stroke enrolled prospectively via a convenience sample in 8 emergency departments within 24 hours of symptom onset. LVO discriminative signals were integrated into a binary classifier. The National Institutes of Health Stroke Scale was documented, and 4 prehospital stroke scales were retrospectively calculated. We compared PLD and scale performance to diagnostic neuroimaging. Results: Of 109 patients, there were 25 LVO (23%), 38 non-LVO ischemic (35%), 14 hemorrhages (13%), and 32 stroke mimics (29%). The PLD had higher sensitivity (80% [95% CI, 74–85]) and similar specificity (80% [95% CI, 77–83]) to all prehospital scales at their predetermined high probability LVO thresholds. The PLD had high discrimination for LVO ( C -statistic=0.88). Conclusions: The PLD identifies LVO with superior accuracy compared with prehospital stroke scales in emergency department suspected stroke. Future studies need to validate the PLD’s potential as an LVO triage aid in prehospital undifferentiated stroke populations.

Objective To evaluate whether Clostridioides (formerly Clostridium) difficile–contaminated stethoscope diaphragms remained aseptic by the placement of an aseptic diaphragm barrier. Methods On November 1, 2019, fresh cultures of C difficile were diluted to 107 colony-forming units (CFU)/mL and used to inoculate 16 stethoscope diaphragms; 8 had an aseptic diaphragm barrier applied and 8 served as nonbarrier controls. Contaminated stethoscopes were anaerobically incubated, then swabbed at 15 and 30 minutes, 2 and 4 hours, and 1, 2, 3, and 7 days after inoculation and subsequently plated onto blood, chocolate, and cycloserine-cefoxitin fructose agar. Plates were incubated for 48 hours and on November 9, 2019, the resulting colonies were manually counted. Statistical analyses (RStudio, version 1.0.153) used analysis of variance with post hoc Tukey honestly significant difference. Results Overall, mean colony count was 33 CFU on stethoscopes without barriers vs zero on those with barriers (P≤.05). Growth was greatest at 48 hours, with colony counts as high as 160 CFU. The presence of the barrier resulted in no growth in 100% of stethoscope diaphragms for up to 1 week. Conclusion We found that stethoscope diaphragm barriers provide an aseptic patient contact point, thus reducing the potential for transmission of C difficile during the physical examination. In critical care environments, in which many hospitals use acoustically inferior disposable stethoscopes, the option of a disposable aseptic stethoscope barrier may allow high-quality auscultation while reducing the potential for pathogen transmission.

Background Inadequate decongestion is common in hospitalized heart failure (HF) patients and may contribute to readmissions. Our purpose was to use remote dielectric sensing (ReDS) technology to measure lung congestion at discharge in patients admitted with acute HF and to see if a device-targeted intervention could reduce HF readmission rates. Methods We conducted a prospective pilot study of patients admitted with acute decompensated HF randomized to receive standard therapy or ReDS-guided therapy to determine the timing of hospital discharge based on the amount of lung congestion present after diuresis. ReDS measurement was performed for all patients once they were deemed ready for discharge. Patients in the treatment arm with residual lung congestion defined by ReDS ≥39% had HF consultation and further diuresis. Results Of 108 HF patients (50% male, age 73.6 ± 12.6 years, BMI 29.3 ± 4.3 kg/m2, EF 38.5 ± 15.1%, BNP 1138 ± 987 pg/mL), 32% demonstrated residual lung congestion at the time of proposed hospital discharge. ReDS guided therapy triggered additional diuresis in 30% (18/60) of the patients in the treatment arm (average weight loss 5.6 pounds, p = 0.02). 30-day HF readmission rates were similar in the treatment and the control arms (1.7% vs 4.2%; p = 0.44). Patients discharged as planned with residual lung congestion with ReDS ≥39% had higher 30-day readmission rate compared to patients who were adequately decongested at discharge with ReDS Conclusion In our single-center cohort, ReDS testing demonstrated that 32% of HF patients deemed ready for discharge have clinically significant residual lung congestion which was associated with a higher risk of readmission. ReDS-guided management was associated with significant decongestion but not a reduction in HF readmissions in this sample.

Background In the United States, nosocomial infections are estimated to cause 72,000 annual deaths. The stethoscope, commonly used, is rarely reported as a potential vector. Our study aims to describe stethoscope contamination and the effect of self-reported cleaning practices among health care providers in a community hospital setting. Methods Stethoscopes were collected at random times from health care providers and cultured per standard techniques. Providers answered a structured questionnaire related to their cleaning practices. Differences in bacterial growth rates and the impact of profession, cleaning frequency, and prior sanitization were evaluated. Results Of 104 cultured stethoscopes, 44% were from residents and medical students, from which 76% had bacterial growth, and 56% were from attendings, nurses, and respiratory therapists who had 91.4% growth (95% = confidence interval 0.62-0.86 and 0.81-0.96, respectively). Overall, 86.5% of providers claimed disinfection frequency compliant with Center for Disease Control and Prevention guidelines but there were no statistical differences between self-reported cleaning frequency or methods, and the presence of bacteria. Conclusions Most stethoscopes are contaminated with bacteria, the presence of which was not affected by reported cleaning strategies.

Background Hyperkalemia (HK) is common and associated with mortality. Our purpose was to determine if the rapid correction of elevated serum potassium level (K+) was associated with reduced mortality in emergency department (ED) patients. Methods Design: We reviewed the electronic medical records (EMR) of ED patients with HK (K+ ≥ 5.5 mEq/L) from 10/2016–10/2017. Setting: Large, academic ED. Participants: Adult ED patients presenting with hyperkalemia. Main outcomes and measures: The main outcome was in-hospital mortality. We compared outcomes of patients whose K+ normalized (dropped below 5.5 mEq/L) with those whose K+ did not normalize using chi-square and multivariate analyses to determine the associations between predictor variables and outcomes. Results From 114,977 ED visits, 1033 patients (0.9%, 95%CI 0.85–0.95%) had HK. Their mean (SD) age was 60 (26) years and 58% were male. Of these, 884 had a second K+ measured within a median (IQR) of 5 (3–8) hours. Mortality and admission rates were higher in patients with HK vs. those with normal K+ (8.5% vs. 0.8%, P Conclusions Normalization of K+ during the ED stay in patients with HK is associated with a 50% mortality reduction. Efforts to rapidly identify and treat HK in the ED are needed.

Cardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and clinical diagnostic characteristics of the ACCESS hsTnI assay in a United States (US) population.All measurements and studies were conducted using a lithium heparin matrix. Sex-specific 99th percentile upper reference limits (URLs) were determined for 1089 healthy women (54.6%) and men using non-parametric statistics. High-sensitivity (hs) performance was assessed to determine if the total CV was ≤10% at sex-specific URLs, and if ≥50% of cTnI values for each sex exceeded the assay's limit of detection (LoD). Precision, analytical measurement range, high-dose hook effect, and endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization included serial sampling of 1854 suspected AMI subjects presenting to 14 US Emergency Departments. AMI was adjudicated by a panel of expert cardiologists. The study's only exclusion was end stage renal disease.99th percentile URLs were 11.6-, 19.8- and 17.5-ng/L for respective female, male and all-subject populations. Total %CV was8% from 6.8 to 19,000 ng/L, and6% at sex-specific 99th percentiles; ≥99% of ACCESS hsTnI values for each sex exceeded the LoD. No high-dose hook effect or endogenous/exogenous interferences were identified. A comparison of Baseline samples collected at ≤1 h and any-time after presentation, found 4% lower sensitivity for AMI than with earlier sampling. For 1-9 h post presentation, the sensitivity was90%, specificity85%; and negative and positive predictive value were ≥99% and60%, respectively.Analytical and clinical performance of the ACCESS hsTnI assay meets the definition of a hs cTn method. The ACCESS hsTnI assay has good precision over a wide range, no significant interferences, and sensitivity90% and NPV ≥99%. Performance is appropriate for aiding in AMI diagnosis.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients. The authors acknowledge the Heart Failure Association of the European Society of Cardiology for organizing the meeting during which this topic was discussed. The authors acknowledge T.J. for her expert review of the manuscript, and W.G. S., PharmD (Campbell University College of Pharmacy and Health Sciences), supported by the Heart Failure Association of the European Society of Cardiology for contributions to content development, writing, and editing the manuscript. J.M., C.M. and F.P. performed their expert review of the paper on behalf of Acute Cardiovascular Care Association of the European Society of Cardiology. J.B. and T.T. were supported by the Deutsche Forschungsgemeinschaft, Clinical Research Group 311 (KFO 311) '(Pre-)terminal heart and lung failure: unloading and repair' (DFG; TP1 and TP11). Harjola, VP (corresponding author), Helsinki Univ Hosp, Dept Emergency Med & Serv, Div Emergency Med, PL 340, Helsinki 00029, Finland. veli-pekka.harjola@hus.fi

Background and Purpose: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source. Methods: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily. Results: During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7–4.3]), East Asia region (HR, 2.5 [95% CI, 1.6–3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2–3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m 2 decrease, [95% CI, 1.0–1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2–18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin. Conclusions: Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.

Aims Concentrations of insulin‐like growth factor binding protein‐7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. Methods and results In this pre‐specified subgroup analysis of the International Collaborative of N‐terminal pro‐B‐type Natriuretic Peptide Re‐evaluation of Acute Diagnostic Cut‐Offs in the Emergency Department (ICON‐RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P

Background Determining diagnostic thresholds for cardiac troponin assays is key to interpreting their clinical performance. We describe the calculation of 99th percentile upper reference limits (URLs) for the Elecsys® Troponin T Gen 5 (TnT Gen 5) assay. Methods Plasma and serum samples from healthy US participants were prospectively evaluated using TnT Gen 5 Short Turn Around Time and 18-min assays on cobas e 411 and cobas e 601 analyzers (Roche Diagnostics); with, up to 8 TnT Gen 5 results per participant. Results A total of 10,402 TnT Gen 5 results from 1301 participants were included (50.4% female). Across 9 calculation methods, overall 99th percentile URL was 19.2 ng/l (females, 13.5–13.6 ng/l; males, 21.4–22.2 ng/l). Across different sample/assay/analyzer combinations, overall 99th percentile URLs ranged from 18.4–20.2 ng/l. Median TnT Gen 5 results increased with age, were higher in males, and ranged from 3.0–3.7 ng/l across races/ethnicities and from 3.0–3.6 ng/l across body mass index (BMI) classes. Applying additional exclusion criteria (N-terminal pro-brain natriuretic peptide, BMI and estimated glomerular filtration rate) resulted in lower 99th percentile URLs (overall, 16.9 ng/l; females, 11.8 ng/l; males, 18.5 ng/l). Conclusion Our findings facilitate the interpretation of TnT Gen 5 results in US clinical practice.

Objective To determine the utility of a highly sensitive troponin assay when utilized in the emergency department.Methods The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician’s clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible.Trial registration ClinicalTrials.gov Identifier NCT00880802

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 >2 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.

Despite an estimated 2.8 million annual ED visits, traumatic brain injury (TBI) is a syndromic diagnosis largely based on report of loss of consciousness, post-traumatic amnesia, and/or confusion, without readily available objective diagnostic tests at the time of presentation, nor an ability to identify a patient's prognosis at the time of injury. The recognition that “mild” forms of TBI and even sub-clinical impacts can result in persistent neuropsychiatric consequences, particularly when repetitive, highlights the need for objective assessments that can complement the clinical diagnosis and provide prognostic information about long-term outcomes. Biomarkers and neurocognitive testing can identify brain injured patients and those likely to have post-concussive symptoms, regardless of imaging testing results, thus providing a physiologic basis for a diagnosis of acute traumatic encephalopathy (ATE). The goal of the HeadSMART II (HEAD injury Serum markers and Multi-modalities for Assessing Response to Trauma) clinical study is to develop an in-vitro diagnostic test for ATE. The BRAINBox TBI Test will be developed in the current clinical study to serve as an aid in evaluation of patients with ATE by incorporating blood protein biomarkers, clinical assessments, and tools to measure, identify, and define associated pathologic evidence and neurocognitive impairments. This protocol proposes to collect data on TBI subjects by a multi-modality approach that includes serum biomarkers, clinical assessments, neurocognitive performance, and neuropsychological characteristics, to determine the accuracy of the BRAINBox TBI test as an aid to the diagnosis of ATE, defined herein, and to objectively determine a patient's risk of developing post-concussive symptoms.

ObjectiveTo develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.MethodsIn a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.ResultsIn the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.ConclusionIn patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.Trial registration numberNCT01548352 (BASEL IX), NCT01802398 (SRS study).

Background: We conducted a secondary analysis of changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 over 30 days in a randomized trial of self-care coaching versus structured usual care in patients with acute heart failure who were discharged from the emergency department. Methods: Patients in 15 emergency departments completed the KCCQ-12 at emergency department discharge and at 30 days. We compared change in KCCQ-12 scores between the intervention and usual care arms, adjusted for enrollment KCCQ-12 and demographic characteristics. We used linear regression to describe changes in KCCQ-12 summary scores and logistic regression to characterize clinically meaningful KCCQ-12 subdomain changes at 30 days. Results: There were 350 patients with both enrollment and 30-day KCCQ summary scores available; 166 allocated to usual care and 184 to the intervention arm. Median age was 64 years (interquartile range, 55–70), 37% were female participants, 63% were Black, median KCCQ-12 summary score at enrollment was 47 (interquartile range, 33–64). Self-care coaching resulted in significantly greater improvement in health status compared with structured usual care (5.4-point greater improvement, 95% CI, 1.12–9.68; P =0.01). Improvements in health status in the intervention arm were driven by improvements within the symptom frequency (adjusted odds ratio, 1.62 [95% CI, 1.01–2.59]) and quality of life (adjusted odds ratio, 2.39 [95% CI, 1.46–3.90]) subdomains. Conclusions: In this secondary analysis, patients with acute heart failure who received a tailored, self-care intervention after emergency department discharge had clinically significant improvements in health status at 30 days compared with structured usual care largely due to improvements within the symptom frequency and quality of life subdomains of the KCCQ-12. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02519283.

Whether American College of Cardiology (ACC) Chest Pain Center (CPC) accreditation alters guidelines adherence rates is unclear.We analyzed patient-level, hospital-reported, quality metrics for myocardial infarction (MI) patients from 644 hospitals collected in the ACC's Chest Pain-MI Registry from January 1, 2019, to December 31, 2020, stratified by CPC accreditation for1 year.Of 192,374 MI patients, 67,462 (35.1%) received care at an accredited hospital. In general, differences in guideline adherence rates between accredited and nonaccredited hospitals were numerically small, although frequently significant. Patients at accredited hospitals were more likely to undergo coronary angiography (98.6% vs. 97.9%, P0.0001), percutaneous coronary intervention for NSTEMI (55.4% vs. 52.3%, P0.0001), have overall revascularization for NSTEMI (63.5% vs. 61.0%, P0.0001), and receive P2Y12 inhibitor on arrival (63.5% vs. 60.2%, P0.0001). Nonaccredited hospitals more ECG within 10 minutes (62.3% vs. 60.4%, P0.0001) and first medical contact to device activation ≤90 minutes (66.8% vs. 64.8%, P0.0001). Accredited hospitals had uniformly higher discharge medication guideline adherence, with patients more likely receiving aspirin (97.8% vs. 97.4%, P0.0001), angiotensin-converting enzyme inhibitor (46.7% vs. 45.3%, P0.0001), beta blocker (96.6% vs. 96.2%, P0.0001), P2Y12 inhibitor (90.3% vs. 89.2%, P0.0001), and statin (97.8% vs. 97.5%, P0.0001). Interaction by accredited status was significant only for length of stay, which was slightly shorter at accredited facilities for specific subgroups.ACC CPC accreditation was associated with small consistent improvement in adherence to guideline-based treatment recommendations of catheter-based care (catheterization and PCI) for NSTEMI and discharge medications, and shorter hospital stays.

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic exposed and exacerbated health disparities between socioeconomic groups. Our purpose was to determine which disparities are most prevalent and their impact on length of stay (LoS) and in hospital mortality in patients diagnosed with Covid-19.MethodsDe-Identified data for patients who tested positive for COVID-19 was abstracted from the HCA enterprise database. Data was binned into summary tables. A negative binomial regression with LoS as the dependent variable and a logistic regression of in-hospital mortality data, using age, insurance status, sex, comorbidities as the dependent variables, were performed.ResultsFrom March 1, 2020 to August 23, 2020, of 111,849 covid testing patient records, excluding those with missing data (n=7), without confirmed COVID-19 (n=27,225), and those from a carceral environment (n=1,861), left 84,624 eligible patients. Compared to the US population, the covid cohort had more black patients (23.17% vs 13.4%). Compared to the white cohort, the black cohort had higher private insurance rates (28.52% vs. 23.68%), shorter LoS (IRR=0.97 CI=0.95-0.99, PConclusionConclusions We found that when blacks have higher rates of private insurance, they have shorter hospitalizations and lower mortality than whites, when diagnosed with Covid-19. Some other psychiatric and medical conditions also significantly impacted outcomes in patients with Covid-19.Key PointsQuestionWhich social determinants of health and comorbidities are most prevalent and their impact on length of stay and in-hospital mortality in patients diagnosed with Covid-19?FindingsIn this retrospective cohort of 84,624 with the black cohort having higher private insurance rates (28.52% vs. 23.68%), there was shorter LoS (IRR=0.97 CI=0.95-0.99, PMeaningThe genetics of race is not important in predicting mortality and length of stay in COVID-19 patients, but age, comorbidities, and insurance status appear to have a significant difference in mortality and length of stay.

Author(s): Schwab, Kim; Nguyen, Dacloc; Ungab, GilAnthony; Feld, Gregory; Maisel, Alan S; Than, Martin; Joyce, Laura; Peacock, W Frank | Abstract: ObjectiveAdvanced machine learning technology provides an opportunity to improve clinical electrocardiogram (ECG) interpretation, allowing non-cardiology clinicians to initiate care for atrial fibrillation (AF). The Lucia Atrial Fibrillation Application (Lucia App) photographs the ECG to determine rhythm detection, calculates CHA2DS2-VASc and HAS-BLED scores, and then provides guideline-recommended anticoagulation. Our purpose was to determine the rate of accurate AF identification and appropriate anticoagulation recommendations in emergency department (ED) patients ultimately diagnosed with AF.MethodsWe performed a single-center, observational retrospective chart review in an urban California ED, with an annual census of 70,000 patients. A convenience sample of hospitalized patients with AF as a primary or secondary discharge diagnosis were evaluated for accurate ED AF diagnosis and ED anticoagulation rates. This was done by comparing the Lucia App against a gold standard board-certified cardiologist diagnosis and using the American College of Emergency Physicians AF anticoagulation guidelines.ResultsTwo hundred and ninety seven patients were enrolled from January 2016 until December 2019. The median age was 79 years and 44.1% were female. Compared to the gold standard diagnosis, the Lucia App detected AF in 98.3% of the cases. Physicians recommended guideline-consistent anticoagulation therapy in 78.5%nversus 98.3% for the Lucia App. Of the patients with indications for anticoagulation and discharged from the ED, only 25.0% were started at discharge.ConclusionUse of a cloud-based ECG identification tool can allow non-cardiologists to achieve similar rates of AF identification as board-certified cardiologists and achieve higher rates of guideline-recommended anticoagulation therapy in the ED.

Objective: To describe from a noninterventional registry (Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Acute Coronary Syndrome), the short-term ischemic and hemorrhagic outcomes in patients with non-ST elevation myocardial infarction (MI) are managed with a loading dose (LD) of a P2Y12 inhibitor (P2Y12i) given at least 4 hours before diagnostic angiography and delineation of coronary anatomy. Prior data on the effects of such “upstream loading” have been inconsistent. Methods: In 53 US hospitals, we evaluated the in-hospital care and outcomes of patients with confirmed non-ST elevation MI managed with an interventional strategy and loaded upstream (at least 4 h before diagnostic angiography) with oral P2Y12i therapy. Patients entered into the database were grouped into 1 of 4 cohorts for analysis: (1) overall cohort, (2) thienopyridine (clopidogrel or prasugrel) load, (3) ticagrelor load, and (4) ticagrelor-consistent. The fourth cohort is a subset of cohort 3 that received ticagrelor throughout the index hospital stay and at discharge. We evaluated in-hospital clinical course and ischemic and bleeding outcomes in all patients and also 30-day outcomes in the ticagrelor-consistent cohort. Results: A total of 3355 patients were enrolled, of whom 1087 had 30-day follow-up. The mean (±SD) age was 63.3 ± 12.5 years, and 62.6% were male. Thrombolysis in MI and Global Registry of Acute Coronary Events scores placed these patients in the intermediate risk range, and CRUSADE scores were in the moderate risk range. The LD in Utilization of Ticagrelor in the Upstream Setting for Non-ST-Segment Elevation Acute Coronary Syndrome was clopidogrel in 45.6%, ticagrelor in 53.6%, and prasugrel in 0.8%. The median upstream interval (LD to angiography) was 17:27 hours and did not change appreciably over the course of the data collection period (2/15–10/19). Access was radial in 48.6% and femoral in 51.4%. Postangiography management was medical only in 32.3%, percutaneous coronary intervention in 59.4%, and coronary artery bypass grafting in 8.3%. Median length of stay was 2.7 days, and median time from angiography to coronary artery bypass grafting was 3.6 days. In-hospital mortality was 0.51%, and major bleeding (thrombolysis in MI) was 0.24%; the in-hospital major adverse cardiovascular events rate was 0.7%, and stent thrombosis occurred in 0.18%. No significant differences were seen between the ticagrelor and clopidogrel cohorts in hospital, but 16% received more than 1 P2Y12i in-hospital. On follow-up (93.2% response), 86.7% of patients reported taking ticagrelor as directed. Conclusions: Upstream loading of P2Y12i was associated with very low rates of bleeding and short length of stay in a large cohort of non-ST elevation MI (NSTEMI) patients managed invasively.

Background Idarucizumab is a humanized, monoclonal antibody fragment used specifically to reverse the anticoagulant effects of dabigatran. Case Reports We discuss 4 cases of patients who were treated with idarucizumab to reverse dabigatran before early/emergency surgery. Two of the patients had subdural hematomas, 1 had a splenic laceration, and 1 had Fournier gangrene. All patients received 5 g of idarucizumab before surgery. Intraoperative blood loss in all patients was normal, no adverse events were reported, and the patients recovered normally. Why Should an Emergency Physician be Aware of This? The case reports presented provide detailed, practical, real-world experience beyond that reported in other case reports and the Reversal Effects of Idarucizumab on Active Dabigatran study. This can help guide clinicians on how idarucizumab can reverse the anticoagulant effect of dabigatran in emergency situations, including patients with subdural hematoma. Our experience suggests that idarucizumab may be a safe and effective antidote to the effects of dabigatran in real-life bleeding situations involving early or emergency surgeries.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, post-concussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging, because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large scale (n = 5,000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for one year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.