The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion 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 = 5000 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 1 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.

The safety of oral anticoagulants registry (SOAR): A national, ED-based study of the evaluation and management of bleeding and bleeding concerns due to the use of oral anticoagulants.

OBJECTIVE: The Safety of Oral Anticoagulants Registry (SOAR) was designed to describe the evaluation and management of patients with oral anticoagulant (OAC)-related major bleeding or bleeding concerns who present to the emergency department (ED) with acute illness or injury. Patients in the ED are increasingly taking anticoagulants, which can cause bleeding-related complications as well as impact the acute management of related or unrelated clinical issues that prompt presentation. Modifications of emergency evaluation and management due to anticoagulation have not previously been studied. METHODS: This was a multicenter observational in-hospital study of patients who were judged to be experiencing an active OAC effect and had (a) an obvious bleeding event or (b) were deemed at risk for serious bleeding spontaneously, after injury, or during an indicated invasive procedure. Diagnostic testing, therapies employed, and clinical outcomes were collected. RESULTS: Thirty-one US hospitals contributed data to SOAR. Of 1513 subjects, acute hemorrhage (AH) qualified 78%, while 22% had a bleeding concern (BC). Warfarin was the index OAC in 37.3%, dabigatran in 13.3%, and an anti-Factor Xa in 49.4%. The most common sites of AH were gastrointestinal (51.0%) and intracranial (26.8%). In warfarin-treated patients, the mean (IQR) presenting INR was 3.1 (2.2, 4.8) in AH patients and 3.9 (2.4, 7.2) in BC patients. Three-fifths of SOAR patients were treated with factor repletion or specific reversal agents, and those patients had a longer length of stay. In addition, seven (0.76%) of the treated patients experienced an in-hospital thrombotic complication; two of these seven died on the index admission, both of fatal pulmonary embolism. Vitamin K was used and dosed inconsistently in both warfarin and NOAC cohorts. CONCLUSION: Care of anticoagulated patients in the acute care setting is inconsistent, reflecting the diversity of presentation. As the prevalence of OAC use increases with the aging of the US population, further study and targeted educational efforts are needed to drive more evidence-based care of these patients.

The value of sPESI for risk stratification in patients with pulmonary embolism.

INTRODUCTION: Various risk stratification methods exist for patients with pulmonary embolism (PE). We used the simplified Pulmonary Embolism Severity Index (sPESI) as a risk-stratification method to understand the Veterans Health Administration (VHA) PE population. MATERIALS AND METHODS: Adult patients with ≥ 1 inpatient PE diagnosis (index date = discharge date) from October 2011-June 2015 as well as continuous enrollment for ≥ 12 months pre- and 3 months post-index date were included. We defined a sPESI score of 0 as low-risk (LRPE) and all others as high-risk (HRPE). Hospital-acquired complications (HACs) during the index hospitalization, 90-day follow-up PE-related outcomes, and health care utilization and costs were compared between HRPE and LRPE patients. RESULTS: Of 6746 PE patients, 95.4% were men, 67.7% were white, and 22.0% were African American; LRPE occurred in 28.4% and HRPE in 71.6%. Relative to HRPE patients, LRPE patients had lower Charlson Comorbidity Index scores (1.0 vs. 3.4, p < 0.0001) and other baseline comorbidities, fewer HACs (11.4% vs. 20.0%, p < 0.0001), less bacterial pneumonia (10.6% vs. 22.3%, p < 0.0001), and shorter average inpatient lengths of stay (8.8 vs. 11.2 days, p < 0.0001) during the index hospitalization. During follow-up, LRPE patients had fewer PE-related outcomes of recurrent venous thromboembolism (4.4% vs. 6.0%, p = 0.0077), major bleeding (1.2% vs. 1.9%, p = 0.0382), and death (3.7% vs. 16.2%, p < 0.0001). LRPE patients had fewer inpatient but higher outpatient visits per patient, and lower total health care costs ($12,021 vs. $16,911, p < 0.0001) than HRPE patients. CONCLUSIONS: Using the sPESI score identifies a PE cohort with a lower clinical and economic burden.

D-dimer levels in VTE patients with distal and proximal clots.

OBJECTIVES: There is growing evidence that venous thromboembolism (VTE) patients with distal clots (distal calf deep vein thrombosis [DVT] and sub-segmental pulmonary embolism [PE]) may not routinely benefit from anticoagulation. We compared the D-dimer levels in VTE patients with distal and proximal clots. METHODS: We conducted a multinational, prospective observational study of low-to-intermediate risk adult patients presenting to the emergency department (ED) with suspected VTE. Patients were classified as distal (calf DVT or sub-segmental PE) or proximal (proximal DVT or non-sub-segmental PE) clot groups and compared with univariate and multivariate analyses. RESULTS: Of 1752 patients with suspected DVT, 1561 (89.1%) had no DVT, 78 (4.4%) had a distal calf DVT, and 113 (6.4%) had a proximal DVT. DVT patients with proximal clots had higher D-dimer levels (3760 vs. 1670 mg/dL) than with distal clots. Sensitivity and negative predictive value (NPV) for proximal DVT at an optimal D-dimer cutoff of 5770 mg/dL were 40.7% and 52.1% respectively. Of 1834 patients with suspected PE, 1726 (94.1%) had no PE, 7 (0.4%) had isolated sub-segmental PE, and 101 (5.5%) had non-sub-segmental PE. PE patients with proximal clots had higher D-dimer levels (4170 vs. 2520 mg/dL) than those with distal clots. Sensitivity and NPV for proximal PE at an optimal D-dimer cutoff of 3499 mg/dL were 57.4% and 10.4% respectively. CONCLUSIONS: VTE patients with proximal clots had higher D-dimer levels than patients with distal clots. However, D-dimer levels cannot be used alone to discriminate between VTE patients with distal or proximal clots.

Management of Factor Xa inhibitor-associated life-threatening major hemorrhage: A retrospective multi-center analysis.

BACKGROUND: Factor Xa (FXa) inhibitors, used for stroke prevention in atrial fibrillation and venous thromboembolism treatment and prevention, are the dominant non-Vitamin K oral anticoagulants on the market. While major bleeding may be less common with these agents compared to warfarin, it is always a risk, and little has been published on the most serious bleeding scenarios. This study describes a cohort of patients with FXa inhibitor-associated life-threatening bleeding events, their clinical characteristics, interventions and outcomes. METHODS: We performed a retrospective, 5-center review of FXa inhibitor-treated major bleeding patients. Investigators identified potential cases by cross-referencing ICD-9/10 codes for hemorrhage with medication lists. Investigators selected cases they deemed to require immediate reversal of coagulopathy, and reviewed charts for characteristics, reversal strategies and other interventions, and outcomes. RESULTS: A total of 56 charts met the inclusion criteria for the retrospective cohort, including 29 (52%) gastrointestinal bleeds (GIB), 19 (34%) intracranial hemorrhages (ICH) and 8 (14%) others. Twenty-four (43%) patients received various factor or plasma products, and the remainder received supportive care. Thirty-day mortality was 21% (n=12). Re-anticoagulation within 30-days occurred in 23 (41%) patients. Thromboembolic events (TEEs) occurred in 6 (11%) patients. No differences were observed in outcomes by treatment strategy. CONCLUSIONS: This cohort of FXa inhibitor-associated major bleeding scenarios deemed appropriate for acute anticoagulant reversal illustrates the variable approaches in the absence of a specific reversal agent.

Developing a standardized measurement of alcohol intoxication.

INTRODUCTION: We assessed multiple examinations and assessment tools to develop a standardized measurement of alcohol intoxication to aid medical decision making in the Emergency Department. METHODS: Volunteers underwent an alcohol challenge. Pre- and post-alcohol challenge, subjects were videotaped performing three standardized clinical examinations: (1) Standardized Field Sobriety Test (SFST) examination, (2) Hack's Impairment Index (HII) examination, and (3) Cincinnati Intoxication Examination (CIE). Emergency clinicians evaluated the level of intoxication using five standardized assessment tools in a blinded and randomized fashion: (1) SFST assessment tool (range 0-18), (2) HII assessment tool (range 0-1), (3) St. Elizabeth Alcohol Intoxication Scale (STE, range 0-17), (4) a Visual Analog Scale (VAS, range 0-100), and (5) a Binary Intoxication Question (BIQ). Construct validity was assessed along with inter- and intra-rater reliability. RESULTS: Median scores pre- and post-alcohol challenge were: SFST 6 (interquartile range 5) and 11 (3), respectively; HII 0 (0.05), 0.1 (0.1); STE 0 (1), 1 (2); VAS 10 (22), 33 (31). For BIQ, 59% and 91% indicated intoxication, respectively. Inter-rater reliability scores were: SFST 0.71 (95% confidence interval 0.48-0.86) to 0.93 (0.88-0.97) depending on examination component; HII 0.90 (0.82-0.95); STE 0.86 (0.75-0.93); VAS 0.92 (0.88-0.94); BIQ 0.3. Intra-rater reliability scores were: SFST 0.74 (0.64-0.82) to 0.87 (0.81-0.91); HII 0.85 (0.79-0.90); STE 0.78 (0.68-0.85); VAS 0.82 (0.74-0.87); BIQ 0.71. VAS reliability was best when paired with the HII and SFST examinations. CONCLUSIONS: HII examination, paired with either a VAS or HII assessment tool, yielded valid and reliable measurements of alcohol intoxication.

Shortened hospital length of stay and lower costs associated with rivaroxaban in patients with pulmonary embolism managed as observation status.

BACKGROUND: Unlike rivaroxaban, treatment of patients with pulmonary embolism (PE) with warfarin requires parenteral bridging and coagulation monitoring that may prolong length-of-stay (LOS) and increase hospital costs. AIMS: The aim of this study was to compare LOS, hospital costs and readmissions in PE patients managed through observation stays treated with rivaroxaban or parenterally bridged warfarin. METHODS: Premier Hospital claims data from November 2012 to March 2015 were used to identify patients with a primary diagnosis code for PE managed through an observation stay and with ≥1 claim for a PE-related diagnostic test on day 0-2. Rivaroxaban users, allowing ≤2 days of prior parenteral therapy, were 1:1 propensity-score matched to patients receiving parenterally bridged warfarin. LOS, the proportion of encounters lasting >2 midnights, total hospital costs of the index visit and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between matched cohorts using multivariable regression. RESULTS: A total of 312 rivaroxaban users were matched to 312 patients receiving parenterally bridged warfarin. Rivaroxaban was associated with an average of 0.27-day shorter LOS, a 52% decreased odds of an encounter lasting >2 midnights and a $403 mean reduction in costs vs parenterally bridged warfarin (P≤.002 for all). The readmission rate for VTE during the same or subsequent 2 months following the index PE was similar between cohorts (P=.75). No patient in either cohort was readmitted for major bleeding. CONCLUSION: Rivaroxaban was associated with shortened LOS and lowered cost vs parenterally bridged warfarin in PE observation stay patients, without increases in the short-term rate of complications or readmission.

Observation management of pulmonary embolism and agreement with claims-based and clinical risk stratification criteria in United States patients: a retrospective analysis.

BACKGROUND: Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. METHODS: Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). RESULTS: We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each <4.5%), but 7.8% were >80 years-of-age and 19.4% had chronic lung disease. CONCLUSION: Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society of Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group.

Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF.

External validation of prognostic rules for early post-pulmonary embolism mortality: assessment of a claims-based and three clinical-based approaches.

BACKGROUND: Studies show the In-hospital Mortality for Pulmonary embolism using Claims daTa (IMPACT) rule can accurately identify pulmonary embolism (PE) patients at low-risk of early mortality in a retrospective setting using only claims for the index admission. We sought to externally validate IMPACT, Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI) and Hestia for predicting early mortality. METHODS: We identified consecutive adults admitted for objectively-confirmed PE between 10/21/2010 and 5/12/2015. Patients undergoing thrombolysis/embolectomy within 48 h were excluded. All-cause in-hospital and 30 day mortality (using available Social Security Death Index data through January 2014) were assessed and prognostic accuracies of IMPACT, PESI, sPESI and Hestia were determined. RESULTS: Twenty-one (2.6 %) of the 807 PE patients died before discharge. All rules classified 26.1-38.3 % of patients as low-risk for early mortality. Fatality among low-risk patients was 0 % (sPESI and Hestia), 0.4 % (IMPACT) and 0.6 % (PESI). IMPACT's sensitivity was 95.2 % (95 % confidence interval [CI] = 74.1-99.8 %), and the sensitivities of clinical rules ranged from 91 (PESI)-100 % (sPESI and Hestia). Specificities of all rules ranged between 26.8 and 39.1 %. Of 573 consecutive patients in the 30 day mortality analysis, 33 (5.8 %) died. All rules classified 27.9-38.0 % of patients as low-risk, and fatality occurred in 0 (Hestia)-1.4 % (PESI) of low-risk patients. IMPACT's sensitivity was 97.0 % (95%CI = 82.5-99.8 %), while sensitivities for clinical rules ranged from 91 (PESI)-100 % (Hestia). Specificities of rules ranged between 29.6 and 39.8 %. CONCLUSION: In this analysis, IMPACT identified low-risk PE patients with similar accuracy as clinical rules. While not intended for prospective clinical decision-making, IMPACT appears useful for identification of low-risk PE patient in retrospective claims-based studies.

Outcomes associated with observation stays versus inpatient admissions for pulmonary embolism.

Changes in reimbursement policies have led to an increased use of observation stays in the United States (US). We sought to compare outcomes among pulmonary embolism (PE) patients managed through observation stays or inpatient admissions.The Premier Perspective Comparative Hospital Database was used to identify patients with a primary International Classification of Diseases, ninth-edition diagnosis of PE (415.1×) from 11/2012-3/2015. Patients were required to have claims for ≥1 diagnostic tests for PE on days 0-2 and evidence of PE treatment. Patients managed through observation stays were 1:1 propensity score matched to those undergoing inpatient admissions. We compared length-of-stay (LOS), hospital costs (2015US$) and rates of hospital-acquired conditions and readmission between the cohorts. A total of 1105 PE observation stays were matched to 1105 inpatient admissions. The baseline characteristics of the cohorts were well-balanced (no standardized differences >10 %). Mean ± standard deviation LOS and hospital costs were 3.6 ± 2.6 days and $5423 ± $5770, respectively. LOS was shorter for observation stays 2.3 ± 1.3 days) vs. inpatient admissions (4.9 ± 3.0 days, p < 0.001). This corresponded to a mean $4390 lower treatment costs for observation stays (p < 0.001). Hospital-acquired conditions were less common among observation stay patients vs. inpatients (p < 0.001); driven predominantly by reductions in bacterial pneumonia and Clostridium difficile infection. Readmission for venous thromboembolism or major bleeding in the same or subsequent 2-months did not differ between the cohorts (p ≥ 0.16 for both).Compared with inpatient admissions, observation stays were associated with reduced LOS, costs and hospital-acquired conditions, without increased risk of readmission.

Plasma bioactive adrenomedullin as a prognostic biomarker in acute heart failure.

OBJECTIVE: The objective was to evaluate the prognostic performance of a new biomarker, plasma bioactive adrenomedullin (bio-ADM), for short-term clinical outcomes in acute heart failure. METHODS: A multicenter prospective cohort study of adult emergency department (ED) patients suspected of having acute heart failure was conducted to evaluate the association between plasma bio-ADM concentration and clinical outcomes. The primary outcome was a composite of the following within 30 days: death, cardiac arrest with resuscitation, respiratory failure, emergency dialysis, acute coronary syndrome, hospitalization >5 days, and repeat ED visit or hospitalization. Prognostic accuracy was evaluated with a nonparametric receiver operating characteristic curve. In addition, a multivariable logistic regression model was constructed to assess the additive prognostic performance of bio-ADM while adjusting for other biomarkers routinely used clinically, including B-type natriuretic peptide, cardiac troponin I, creatinine, and sodium concentration. RESULTS: Two hundred forty-six patients were enrolled, including 85 (34.6%) patients with the primary outcome. Plasma bio-ADM concentrations were higher among patients who experienced the primary outcome (median, 80.5 pg/mL; interquartile range [IQR], 53.7-151.5 pg/mL) compared with those who did not (median, 54.4 pg/mL; IQR, 43.4-78.4 pg/mL) (P < .01). Area under the receiver operating characteristic curve was 0.70 (95% confidence interval, 0.63-0.75). After adjusting for the other biomarkers, plasma bio-ADM remained a strong predictor of the primary outcome (adjusted odds ratio per IQR change, 2.68; 95% confidence interval, 1.60-4.51). CONCLUSIONS: Bioactive adrenomedullin concentrations at the time of ED evaluation for acute heart failure were predictive of clinically important 30-day outcomes, suggesting that bio-ADM is a promising prognostic marker for further study.

External validation of a multivariable claims-based rule for predicting in-hospital mortality and 30-day post-pulmonary embolism complications.

BACKGROUND: Low-risk pulmonary embolism (PE) patients may be candidates for outpatient treatment or abbreviated hospital stay. There is a need for a claims-based prediction rule that payers/hospitals can use to risk stratify PE patients. We sought to validate the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) prediction rule for in-hospital and 30-day outcomes. METHODS: We used the Optum Research Database from 1/2008-3/2015 and included adults hospitalized for PE (415.1x in the primary position or secondary position when accompanied by a primary code for a PE complication) and having continuous medical and prescription coverage for ≥6-months prior and 3-months post-inclusion or until death. In-hospital and 30-day mortality and 30-day complications (recurrent venous thromboembolism, rehospitalization or death) were assessed and prognostic accuracies of IMPACT with 95 % confidence intervals (CIs) were calculated. RESULTS: In total, 47,531 PE patients were included. In-hospital and 30-day mortality occurred in 7.9 and 9.4 % of patients and 20.8 % experienced any complication within 30-days. Of the 19.5 % of patients classified as low-risk by IMPACT, 2.0 % died in-hospital, resulting in a sensitivity and specificity of 95.2 % (95 % CI, 94.4-95.8) and 20.7 % (95 % CI, 20.4-21.1). Only 1 additional low-risk patient died within 30-days of admission and 12.2 % experienced a complication, translating into a sensitivity and specificity of 95.9 % (95 % CI, 95.3-96.5) and 21.1 % (95 % CI, 20.7-21.5) for mortality and 88.5 % (95 % CI, 87.9-89.2) and 21.6 % (95 % CI, 21.2-22.0) for any complication. CONCLUSION: IMPACT had acceptable sensitivity for predicting in-hospital and 30-day mortality or complications and may be valuable for retrospective risk stratification of PE patients.

Early management of patients with acute heart failure: state of the art and future directions. A consensus document from the society for academic emergency medicine/heart failure society of America acute heart failure working group.

Heart failure (HF) afflicts nearly 6 million Americans, resulting in one million emergency department (ED) visits and over one million annual hospital discharges. An aging population and improved survival from cardiovascular diseases is expected to further increase HF prevalence. Emergency providers play a significant role in the management of patients with acute heart failure (AHF). It is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics and alternatives to hospitalization. Further, clinical trials must be conducted in the ED in order to improve the evidence base and drive optimal initial therapy for AHF. Should ongoing and future studies suggest early phenotype-driven therapy improves in-hospital and post-discharge outcomes, ED treatment decisions will need to evolve accordingly. The potential impact of future studies which incorporate risk-stratification into ED disposition decisions cannot be underestimated. Predictive instruments that identify a cohort of patients safe for ED discharge, while simultaneously addressing barriers to successful outpatient management, have the potential to significantly impact quality of life and resource expenditures.

Estimating the size and scope of the academic emergency physician workforce.

BACKGROUND: Academic emergency medicine (EM) is foundational to the EM specialty through the development of new knowledge and clinical training of resident physicians. Despite recent increased attention to the future of the EM workforce, no evaluations have specifically characterized the U.S. academic EM workforce. We sought to estimate the national proportion of emergency physicians (EPs) identified as academic and the proportion of emergency department (ED) visits that take place at academic sites. METHODS: We performed a cross-sectional analysis of EPs and EDs using data from the American Hospital Association, the Centers for Medicare & Medicaid Services, and Doximity's Residency Navigator. EPs were identified as "academic" if they were affiliated with at least one facility determined to be academic, defined as EDs officially designated by the Accreditation Council for Graduate Medical Education (ACGME) as clinical training sites at accredited EM residency programs. Our primary outcomes were to estimate the national proportion of EPs identified as academic and the proportion of ED visits performed at academic sites. RESULTS: Our analytic sample included 26,937 EPs practicing clinically across 4920 EDs and providing care during 130,471,386 ED visits. Among EPs, 11,720 (43.5%) were identified as academic, and among EDs, 635 (12.9%) were identified as academic sites, including 585 adult/general sites, 45 pediatric-specific sites, and 10 sites affiliated with the Department of Veterans Affairs. In 2021, academic EDs provided care for 42,794,106 ED visits or 32.8% of all ED visits nationally. CONCLUSIONS: Approximately four in 10 EPs practice in at least one clinical training site affiliated with an ACGME-accredited EM residency program, and approximately one in three ED visits nationally occur in these academic EDs. We encourage further work using alternative definitions of an academic EPs and EDs, along with longitudinal research to identify trends in the workforce's composition.

Nitrates for acute heart failure syndromes.

BACKGROUND: Current drug therapy for acute heart failure syndromes (AHFS) consists mainly of diuretics supplemented by vasodilators or inotropes. Nitrates have been used as vasodilators in AHFS for many years and have been shown to improve some aspects of AHFS in some small studies. The aim of this review was to determine the clinical efficacy and safety of nitrate vasodilators in AHFS. OBJECTIVES: To quantify the effect of different nitrate preparations (isosorbide dinitrate and nitroglycerin) and the effect of route of administration of nitrates on clinical outcome, and to evaluate the safety and tolerability of nitrates in the management of AHFS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (1950 to July week 2 2011) and EMBASE (1980 to week 28 2011). We searched the Current Controlled Trials MetaRegister of Clinical Trials (compiled by Current Science) (July 2011). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. SELECTION CRITERIA: Randomised controlled trials comparing nitrates (isosorbide dinitrate and nitroglycerin) with alternative interventions (frusemide and morphine, frusemide alone, hydralazine, prenalterol, intravenous nesiritide and placebo) in the management of AHFS in adults aged 18 and over. DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using the Cochrane Collaboration tool for assessing risk of bias. MAIN RESULTS: Four studies (634 participants) met the inclusion criteria. Two of the included studies included only patients with AHFS following acute myocardial infarction (AMI); one study excluded patients with overt AMI; and one study included participants with AHFS with and without acute coronary syndromes.Based on a single study, there was no significant difference in the rapidity of symptom relief between intravenous nitroglycerin/N-acetylcysteine and intravenous frusemide/morphine after 30 minutes (fixed-effect MD -0.30, 95% CI -0.65 to 0.05), 60 minutes (fixed-effect MD -0.20, 95% CI -0.65 to 0.25), three hours (fixed-effect MD 0.20, 95% CI -0.27 to 0.67) and 24 hours (fixed-effect MD 0.00, 95% CI -0.31 to 0.31). There is no evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following outcome measures: requirement for mechanical ventilation, systolic blood pressure (SBP) change after three hours and 24 hours, diastolic blood pressure (DBP) change after 30, 60 and 90 minutes, heart rate change at 30 minutes, 60 minutes, three hours and 24 hours, pulmonary artery occlusion pressure (PAOP) change after three hours and 18 hours, cardiac output (CO) change at 90 minutes and three hours and progression to myocardial infarction. There is a significantly higher incidence of adverse events after three hours with nitroglycerin compared with placebo (odds ratio 2.29, 95% CI 1.26 to 4.16) based on a single study. There was no consistent evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following secondary outcome measures: SBP change after 30 and 60 minutes, heart rate change after 90 minutes, and PAOP change after 90 minutes. None of the included studies reported healthcare costs as an outcome measure. There were no data reported by any of the studies relating to the acceptability of the treatment to the patients (patient satisfaction scores).Overall there was a paucity of relevant quality data in the included studies. Assessment of overall risk of bias in these studies was limited as three of the studies did not give sufficient detail to allow assessment of potential risk of bias. AUTHORS' CONCLUSIONS: There appears to be no significant difference between nitrate vasodilator therapy and alternative interventions in the treatment of AHFS, with regard to symptom relief and haemodynamic variables. Nitrates may be associated with a lower incidence of adverse effects after three hours compared with placebo. However, there is a lack of data to draw any firm conclusions concerning the use of nitrates in AHFS because current evidence is based on few low-quality studies.

Initial management of patients with acute heart failure.

Pressure exists to manage patients with acute decompensated heart failure (ADHF) efficiently in the acute-care environment. Although most patients present with worsening of chronic heart failure, some may present with undifferentiated dyspnea and new-onset heart failure. Others have significant comorbidities that complicate both the diagnosis and treatment. The treatment of patients with ADHF is prioritized based on vital signs and presenting phenotype. The risk stratification of patients is the subject of ongoing evaluation. The disposition of patients to areas other than a monitored inpatient bed, such as an emergency department-based observation unit, may prove effective.

Definition of factor Xa inhibitor-related, life-threatening gastrointestinal bleeding and guidance on when to use reversal therapy: A Delphi panel.

Objective: To define and contextualize life-threatening gastrointestinal (GI) bleeding in the setting of factor Xa (FXa) inhibitor therapy and to derive a consensus-based, clinically oriented approach to the administration of FXa inhibitor reversal therapy. Methods: We convened an expert panel of clinicians representing specialties in emergency medicine, gastroenterology, vascular medicine, and trauma surgery. Consensus was reached among the clinician panelists using the Delphi technique, which consisted of 2 survey questionnaires followed by virtual, real-time consensus-building exercises. Results: Hypovolemia and hemodynamic instability were considered the most important clinical signs of FXa inhibitor-related, life-threatening GI bleeds. Clinician panelists agreed that potentially life-threatening GI bleeding should be determined on the basis of hemodynamic instability, signs of shock, individual patient characteristics, and clinical judgment. Last, the panel agreed that all patients with life-threatening, FXa inhibitor-associated GI bleeding should be considered for FXa inhibitor reversal therapy; the decision to reverse FXa inhibition should be individualized, weighing the risks and benefits of reversal; and when reversal is elected, therapy should be administered within 1 h after initial emergency department evaluation, when possible. Conclusions: Consensus-based definitions of life-threatening GI bleeding and approaches to FXa inhibitor reversal centered on hemodynamic instability, signs of shock, individual patient characteristics, and clinical judgment. The results from this Delphi panel may inform clinical decision-making for the treatment of patients experiencing GI bleeding associated with FXa inhibitor use in the emergency department setting.

Lower mortality with andexanet alfa vs 4-factor prothrombin complex concentrate for factor Xa inhibitor-related major bleeding in a U.S. hospital-based observational study.

Background: Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate clinical outcomes are limited. Objectives: To compare in-hospital mortality in patients hospitalized with rivaroxaban- or apixaban-related major bleeding who were treated with andexanet alfa or 4F-PCC. Methods: An observational cohort study (ClinicalTrials.gov identifier: NCT05548777) was conducted using electronic health records between May 2018 and September 2022 from 354 U.S. hospitals. Inclusion criteria were age ≥18 years, inpatient admission with diagnosis code D68.32 (bleeding due to extrinsic anticoagulation), a record of use of the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa or 4F-PCC treatment during index hospitalization, and a documented discharge disposition. Multivariable logistic regression on in-hospital mortality with andexanet alfa vs 4F-PCC was performed. The robustness of the results was assessed via a supportive propensity score-weighted logistic regression. Results: The analysis included 4395 patients (andexanet alfa, n = 2122; 4F-PCC, n = 2273). There were 1328 patients with intracranial hemorrhage (ICH), 2567 with gastrointestinal (GI) bleeds, and 500 with critical compartment or other bleed types. In the multivariable analysis, odds of in-hospital mortality were 50% lower for andexanet alfa vs 4F-PCC (odds ratio [OR], 0.50; 95% CI, 0.39-0.65; P < .01) and were consistent for both ICH (OR, 0.55; [0.39-0.76]; P < .01) and GI bleeds (OR, 0.49 [0.29-0.81]; P = .01). Similar results were obtained from the supporting propensity score-weighted logistic regression analyses. Conclusion: In this large observational study, treatment with andexanet alfa in patients hospitalized with rivaroxaban- or apixaban-related major bleeds was associated with 50% lower odds of in-hospital mortality than 4F-PCC. The magnitude of the risk reduction was similar in ICH and GI bleeds.