The Chief Wellness Officer: A long overdue catalyst for systemic change in Emergency Medicine.

GOALS: The American healthcare system is amid a burnout epidemic, worsened by COVID, that must be addressed expeditiously and with high priority. The burden Emergency Physicians encountered before and during the pandemic is well known, with countless healthcare workers exiting the work force. A Chief Wellness Officer (CWO) is a senior leader who works primarily to cultivate organisational wellness and to foster and promote a culture of well-being throughout an institution. Specifically, the CWO assists the health system leadership promote clinician engagement and address clinician burnout. This paper explores the status of existing CWOs, and cites the benefits, impacts, and barriers to implementation of a CWO, with focus on the field of Emergency Medicine (EM). METHODS: A steering committee of wellness experts was formed from a national EM organisation. A purposive search and literature review using search terms relating to CWOs was completed. Publications were examined for relevance and recency. The committee created an online questionnaire surveying current US CWOs, conducted personal interviews, and met through regular focused meetings. A framework delineating the role of a CWO as an organisation evolves from instituting novice wellness interventions to expert organisational innovations was created. PRINCIPLE FINDINGS: Despite their title, CWOs are not regularly included in c-suite decisions. Barriers to instituting a CWO include perceived financial cost, the medical system itself, and physician resistance. Defining and measuring objective return on investment may be a solution to overcoming barriers. CWOs who create comprehensive institutional wellness innovations bring organisations to the highest proficient and expert levels of wellness practices, positively affecting physician engagement and deflecting burnout. CWOs instituting novice and beginner levels of wellness interventions, especially in EM, only modestly impact individual wellness practices. PRACTICAL APPLICATIONS: A CWO and team with an organisational voice and a C-suite stakeholder's seat are essential to centralising and leading effective wellness efforts and innovations in EM and other specialities. This team will improve the work environment and culture and begin to fix our broken healthcare system and providers.

SARS-CoV-2 Positivity in Ambulatory Symptomatic Patients Is Not Associated With Increased Venous or Arterial Thrombotic Events in the Subsequent 30 Days.

BACKGROUND: COVID-19 has been associated with increased risk of thromboembolism in critically ill patients. OBJECTIVE: We sought to examine the association of SARS-CoV-2 test positivity and subsequent acute vascular thrombosis, including venous thromboembolism (VTE) or arterial thrombosis (AT), in a large nationwide registry of emergency department (ED) patients tested with a nucleic acid test for suspected SARS-CoV-2. METHODS: The RECOVER (Registry of Potential COVID-19 in Emergency Care) registry includes 155 EDs across the United States. We performed a retrospective cohort study to produce odds ratios (ORs) for COVID-19-positive vs. COVID-19-negative status as a predictor of 30-day VTE or AT, adjusting for age, sex, active cancer, intubation, hospital length of stay, and intensive care unit (ICU) care. RESULTS: Comparing 14,056 COVID-19-positive patients with 12,995 COVID-19-negative patients, the overall 30-day prevalence of VTE events was 1.4% vs. 1.3%, respectively (p = 0.44, χ2). Multivariable analysis identified that testing positive for SARS-CoV-2 status was negatively associated with both VTE (OR 0.76; 95% confidence interval [CI] 0.61-0.94) and AT (OR 0.51; 95% CI 0.32-0.80), whereas intubation, ICU care, and age 50 years or older were positively associated with both VTE and AT. CONCLUSIONS: In contrast to other reports, results from this large, hetereogenous national sample of ED patients tested for SARS-CoV-2, showed no association between vascular thrombosis and COVID-19 test positivity.

Test Characteristics of Emergency Physician-Performed Limited Compression Ultrasound for Lower-Extremity Deep Vein Thrombosis.

BACKGROUND: The current literature suggests that emergency physician (EP)-performed limited compression ultrasound (LCUS) is a rapid and accurate test for deep vein thrombosis (DVT). OBJECTIVE: Our primary objective was to determine the sensitivity and specificity of LCUS for the diagnosis of DVT when performed by a large heterogeneous group of EPs. METHODS: This was a prospective diagnostic test assessment of LCUS conducted at two urban academic emergency departments. The scanning protocol involved compression at the common femoral, superficial femoral, and popliteal veins. Patients were eligible if undergoing radiology department ultrasound of the lower extremity with moderate or high pretest probability for DVT, or low pretest probability for DVT with a positive d-dimer. The enrolling EP performed LCUS before radiology department ultrasound of the same lower extremity. Sensitivity, specificity, and associated 95% confidence intervals (CIs) were calculated with the radiologist interpretation of the radiology department ultrasound as the criterion standard. RESULTS: A total of 56 EPs enrolled 296 patients for LCUS, with a median age of 50 years and 50% female. Fifty (17%) DVTs were identified by radiology department ultrasound, and another five (2%) cases were deemed indeterminate. The sensitivity and specificity of EP-performed LCUS was 86% (95% CI 73-94%) and 93% (95% CI 89-96%), respectively. CONCLUSIONS: A large heterogeneous group of EPs with limited training can perform LCUS with intermediate diagnostic accuracy. Unfortunately, LCUS performed by EPs with limited ultrasound training is not sufficiently sensitive or specific to rule out or diagnose DVT as a single testing modality.

Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism.

Acute pulmonary embolism (PE) can diminish patient quality of life (QoL). The objective was to test whether treatment with tenecteplase has an independent effect on a measurement that reflects QoL in patients with submassive PE. This was a secondary analysis of an 8-center, prospective randomized controlled trial, utilizing multivariate regression to control for predefined predictors of worsened QoL including: age, active malignancy, history of PE or deep venous thrombosis (DVT), recurrent PE or DVT, chronic obstructive pulmonary disease and heart failure. QoL was measured with the physical component summary (PCS) of the SF-36. Analysis included 76 patients (37 randomized to tenecteplase, 39 to placebo). Multivariate regression yielded an equation f(8, 67), P < 0.001, with R(2) = 0.303. Obesity had the largest effect on PCS (ß = -8.6, P < 0.001), with tenecteplase second (ß = 4.73, P = 0.056). After controlling for all interactions, tenecteplase increased the PCS by +5.37 points (P = 0.027). In patients without any of the defined comorbidities, the coefficient on the tenecteplase variable was not significant (-0.835, P = 0.777). In patients with submassive PE, obesity had the greatest influence on QoL, followed by use of fibrinolysis. Fibrinolysis had a marginal independent effect on patient QoL after controlling for comorbidities, but was not significant in patients without comorbid conditions.

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath.

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes.

Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases.

Increased Body Mass Index and Metabolic Syndrome Are Associated with Poor Outcomes in SARS-CoV-2-Positive Emergency Department Patients.

Background: Increased body mass index (BMI) and metabolic syndrome (MetS) have been associated with adverse outcomes in viral syndromes. We sought to examine associations of increased BMI and MetS on several clinical outcomes in patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: The registry of suspected COVID-19 in emergency care (RECOVER) is an observational study of SARS-CoV-2-tested patients (n=27,051) across 155 United States emergency departments (EDs). We used multivariable logistic regression to test for associations of several predictor variables with various clinical outcomes. Results: We found that a BMI ≥30 kg/m2 increased odds of SARS-CoV-2 test positivity (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.23-1.38), while MetS reduced odds of testing positive for SARS-CoV-2 (OR, 0.76; 95% CI, 0.71-0.82). Adjusted multivariable analysis found that MetS was significantly associated with the need for admission (OR, 2.11; 95% CI, 1.89-2.37), intensive care unit (ICU) care (OR, 1.58; 95% CI, 1.40-1.78), intubation (OR, 1.46; 95% CI, 1.28-1.66), mortality (OR, 1.29; 95% CI, 1.13-1.48), and venous thromboembolism (OR, 1.51; 95% CI, 1.07-2.13) in SARS-CoV-2-positive patients. Similarly, BMI ≥40 kg/m2 was significantly associated with ICU care (OR, 1.97; 95% CI, 1.65-2.35), intubation (OR, 2.69; 95% CI, 2.22-3.26), and mortality (OR, 1.50; 95% CI, 1.22-1.84). Conclusion: In this large nationwide sample of ED patients, we report a significant association of both high BMI and composite MetS with poor outcomes in SARS-CoV-2-positive patients. Findings suggest that composite MetS profile may be a more universal predictor of adverse disease outcomes, while the impact of BMI is more heavily modulated by SARS-CoV-2 status.

Drivers of professional fulfillment and burnout among emergency medicine faculty: A national wellness survey by the Society for Academic Emergency Medicine.

BACKGROUND: Professional fulfillment and the mitigation of burnout can enhance clinician well-being and the resiliency of the health care organization. This study examined the extent to which specific individual and workplace factors are associated with professional fulfillment and burnout among a national sample of academic emergency physicians. METHODS: This was a cross-sectional survey of faculty members of the Society for Academic Emergency Medicine. Primary outcomes were professional fulfillment and burnout. The survey also examined individual and workplace factors as well as faculty's thoughts of attrition from academic and clinical medicine. Logistic regression was performed to determine the relationships between each outcome and each factor, respectively. RESULTS: A total of 771 of 3130 faculty completed the survey (response rate 24.6%). A total of 38.7% reported professional fulfillment and 39.1% reported burnout. Meaningfulness of work (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.9-2.5), perceived appreciation (OR 1.9, 95% CI 1.7-2.1), and the academic work environment (OR 1.7, 95% CI 1.5-1.9) had the highest odds of being associated with professional fulfillment. In contrast, low score responses for meaningfulness of work (OR 0.6, 95% CI 0.5-0.6), self-compassion (0.6, 95% CI 0.5-0.6), and control over schedule (OR 0.6, 95% CI 0.6-0.7) were most associated with burnout. Faculty with professional fulfillment were less likely to report plans for attrition from academics (OR 0.1, 95% CI 0.1-0.2) and from clinical medicine (OR 0.2, 95% CI 0.1-0.4). Faculty with burnout were more likely to report plans for attrition from academics (OR 7, 95% CI 4.8-10.4) and clinical medicine (OR 5.7, 95% CI 3.9-8.6). CONCLUSIONS: Individual and workplace factors that contributed to professional fulfillment and burnout were identified, with meaningfulness of clinical work demonstrating the strongest association with both occupational phenomena. Knowledge of which factors are most impactful in promoting professional fulfillment and mitigating burnout may be useful in guiding efforts to enhance clinician well-being.

Association Between Baseline Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Death Among Patients Tested for COVID-19.

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs may modify risk associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we assessed whether baseline therapy with ACEIs or ARBs was associated with lower mortality, respiratory failure (noninvasive ventilation or intubation), and renal failure (new renal replacement therapy) in SARS-CoV-2-positive patients. This retrospective registry-based observational cohort study used data from a national database of emergency department patients tested for SARS-CoV-2. Symptomatic emergency department patients were accrued from January to October 2020, across 197 hospitals in the United States. Multivariable analysis using logistic regression evaluated end points among SARS-CoV-2-positive cases, focusing on ACEIs/ARBs and adjusting for covariates. Model performance was evaluated using the c statistic for discrimination and Cox plotting for calibration. A total of 13 859 (99.9%) patients had known mortality status, of whom 2045 (14.8%) died. Respiratory failure occurred in 2485/13 880 (17.9%) and renal failure in 548/13 813 (4.0%) patients with available data. ACEI/ARB status was associated with a 25% decrease in mortality odds (odds ratio [OR], 0.75; 95%CI, 0.59-0.94; P = .011; c = .82). ACEIs/ARBs were not significantly associated with respiratory failure (OR, 0.89; 95%CI, 0.78-1.06; P = .206) or renal failure (OR, 0.75; 95%CI, 0.55-1.04; P = .083). Adjusting for covariates, baseline ACEI/ARB was associated with 25% lower mortality in SARS-CoV-2-positive patients. The potential mechanism for ACEI/ARB mortality modification requires further exploration.

Monotherapy Anticoagulation to Expedite Home Treatment of Patients Diagnosed With Venous Thromboembolism in the Emergency Department: A Pragmatic Effectiveness Trial.

BACKGROUND: The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial. METHODS: This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes. RESULTS: We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%-1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%-1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%-0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%-9.5%) and was associated with a risk ratio of 6.0 (2.3-15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled. CONCLUSIONS: Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03404635.

Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments 2-22-2021.

OBJECTIVES: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care. METHODS: Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction score was derived from a 50% random sample (n = 9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables. RESULTS: Multivariable regression yielded a 13-variable score, which was simplified to a 13-point score: +1 point each for age>50 years, measured temperature>37.5°C, oxygen saturation<95%, Black race, Hispanic or Latino ethnicity, household contact with known or suspected COVID-19, patient reported history of dry cough, anosmia/dysgeusia, myalgias or fever; and -1 point each for White race, no direct contact with infected person, or smoking. In the validation sample (n = 9,975), the probability from logistic regression score produced an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.79-0.81), and this level of accuracy was retained across patients enrolled from the early spring to summer of 2020. In the simplified score, a score of zero produced a sensitivity of 95.6% (94.8-96.3%), specificity of 20.0% (19.0-21.0%), negative likelihood ratio of 0.22 (0.19-0.26). Increasing points on the simplified score predicted higher probability of infection (e.g., >75% probability with +5 or more points). CONCLUSION: Criteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decisions about isolation and testing at high throughput checkpoints.

Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: results of a prospective, multicenter study.

STUDY OBJECTIVE: Prediction rules for pulmonary embolism use variables explicitly shown to estimate the probability of pulmonary embolism. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of pulmonary embolism. The objective of this study is to measure the predictive value of 13 implicit variables. METHODS: Patients were enrolled in a prospective cohort study from 12 centers in the United States; all had an objective test for pulmonary embolism (D-dimer, computed tomographic angiography, or ventilation-perfusion scan). Clinical features including 12 predefined previously validated (explicit) variables and 13 variables not part of existing prediction rules (implicit) were prospectively recorded at presentation. The primary outcome was venous thromboembolism (pulmonary embolism or deep venous thrombosis), diagnosed by imaging up to 45 days after enrollment. Variables with adjusted odds ratios from logistic regression with 95% confidence intervals not crossing unity were considered significant. RESULTS: Seven thousand nine hundred forty patients (7.2% venous thromboembolism positive) were enrolled. Mean age was 49 years (standard deviation 17 years) and 67% were female patients. Eight of 13 implicit variables were significantly associated with venous thromboembolism; those with an adjusted odds ratio (OR) greater than 1.5 included non-cancer-related thrombophilia (OR 1.99), pleuritic chest pain (OR 1.53), and family history of venous thromboembolism (OR 1.51). Implicit variables that predicted no venous thromboembolism outcome included substernal chest pain, female sex, and smoking. Nine of 12 explicit variables predicted a positive outcome of venous thromboembolism, including patient history of pulmonary embolism or deep venous thrombosis in the past, unilateral leg swelling, recent surgery, estrogen, hypoxemia, and active malignancy. CONCLUSION: In symptomatic outpatients being considered for possible pulmonary embolism, non-cancer-related thrombophilia, pleuritic chest pain, and family history of venous thromboembolism increase probability of pulmonary embolism or deep venous thrombosis. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US emergency department patients.

12-lead ECG findings of pulmonary hypertension occur more frequently in emergency department patients with pulmonary embolism than in patients without pulmonary embolism.

STUDY OBJECTIVE: Acute pulmonary embolism can produce abnormalities on ECG that reflect severity of pulmonary hypertension. Early recognition of these findings may alter the estimated pretest probability of pulmonary embolism and prompt more aggressive treatment before hemodynamic instability ensues, but it is first important to test whether these findings are specific to patients with pulmonary embolism. We hypothesize that ECG findings consistent with pulmonary hypertension would be observed more frequently in patients with pulmonary embolism. METHODS: Secondary analysis of a prospective, observational cohort of emergency department patients who were tested for pulmonary embolism. ECGs were ordered at clinician's discretion and interpreted at presentation. RESULTS: Six thousand forty-nine patients had an ECG, 354 (5.9%) of whom were diagnosed with pulmonary embolism. The frequency, positive likelihood ratio (LR+) and 95% confidence interval (CI) of each predictor were as follows: S1Q3T3 8.5% with pulmonary embolism versus 3.3% without pulmonary embolism (LR+ 3.7; 95% CI 2.5 to 5.4); nonsinus rhythm, 23.5% versus 16.6% (LR+ 1.4; 95% CI 1.2 to 1.7); inverted T waves in V1 to V2, 14.4% versus 8.1% (LR+ 1.8; 95% CI 1.3 to 2.3); inversion in V1 to V3, 10.5% versus 4.0% (LR+ 2.6; 95% CI 1.9 to 3.6); inversion in V1 to V4, 7.3% versus 2.0% (LR+ 3.7; 95% CI 2.4 to 5.5); incomplete right bundle branch block, 4.8% versus 2.8% (LR+ 1.7; 95% CI 1.0 to 2.7); tachycardia (pulse rate >100 beats/min), 28.8% versus 15.7% (LR+ 1.8; 95% CI 1.5 to 2.2). Likelihood ratios and specificities were similar when patients with previous cardiopulmonary disease were excluded from analysis. CONCLUSION: Findings of acute pulmonary hypertension were infrequent overall but were observed more frequently in patients with the final diagnosis of pulmonary embolism compared with patients who do not have pulmonary embolism.

Multicenter registry of United States emergency department patients tested for SARS-CoV-2.

This paper summarizes the methodology for the registry of suspected COVID-19 in emergency care (RECOVER), a large clinical registry of patients from 155 United States (US) emergency departments (EDs) in 27 states tested for SARS-CoV-2 from March-September 2020. The initial goals are to derive and test: (1) a pretest probability instrument for prediction of SARS-CoV-2 test results, and from this instrument, a set of simple criteria to exclude COVID-19 (the COVID-19 Rule-Out Criteria-the CORC rule), and (2) a prognostic instrument for those with COVID-19. Patient eligibility included any ED patient tested for SARS-CoV-2 with a nasal or oropharyngeal swab. Abstracted clinical data included 204 variables representing the earliest manifestation of infection, including week of testing, demographics, symptoms, exposure risk, past medical history, test results, admission status, and outcomes 30 days later. In addition to the primary goals, the registry will provide a vital platform for characterizing the course, epidemiology, clinical features, and prognosis of patients tested for COVID-19 in the ED setting.

Tandem measurement of D-dimer and myeloperoxidase or C-reactive protein to effectively screen for pulmonary embolism in the emergency department.

OBJECTIVES: The hypothesis was that the tandem measurement of D-dimer and myeloperoxidase (MPO) or C-reactive protein (CRP) could significantly decrease unnecessary pulmonary vascular imaging in emergency department (ED) patients evaluated for pulmonary embolism (PE) compared to D-dimer alone. METHODS: The authors measured the sequential combinations of D-dimer and MPO and D-dimer and CRP in a prospective sample of ED patients evaluated for PE at two centers. Patients were followed for 90 days for venous thromboembolism (VTE, either PE or deep venous thrombosis [DVT]), which required the consensus of two of three blinded physician reviewers. RESULTS: The authors enrolled 304 patients, 22 with VTE (7%; 95% confidence interval [CI] = 5% to 10%). The sensitivity and specificity of a D-dimer alone (cutoff > or = 500 ng/mL) were 100% (95% CI = 85% to 100%) and 59% (95% CI = 53% to 65%), respectively, and was followed by pulmonary vascular imaging negative for PE in 38% (115/304; 95% CI = 32% to 44%). The combination of either a negative D-dimer, or MPO < 22 mg/dL, had a sensitivity of 100% and specificity of 73% (95% CI = 67% to 78%). Thus, tandem measurement of D-dimer and MPO would have decreased the frequency of subsequent negative pulmonary vascular imaging from 38% to 25% (95% CI of the difference of -13% = -5% to -20%). The combination of CRP and D-dimer would not have significantly improved the rate of negative imaging. CONCLUSIONS: The tandem measurement of D-dimer and MPO would have significantly decreased negative pulmonary vascular imaging compared with D-dimer alone and should be validated prospectively.

Direct comparison of the diagnostic accuracy of fifty protein biological markers of pulmonary embolism for use in the emergency department.

OBJECTIVES: Pulmonary embolism (PE) is associated with abnormal concentrations of many proteins involved in inflammation, hemostasis, and vascular injury. The authors quantified the diagnostic accuracy of a battery of protein biological markers for the detection of PE in emergency department (ED) patients. METHODS: A random and a consecutive sample of ED patients evaluated for PE were prospectively enrolled at two academic EDs between August 2005 and April 2006. A plasma sample was obtained at enrollment, and all patients were followed by telephone and medical record review at 90 days for the development of venous thromboembolism (VTE) defined as PE or deep venous thrombosis (DVT), requiring the consensus of two of three blinded physician reviewers. Measurements of potential biological markers were performed by technicians blinded to the study objectives. The diagnostic accuracy of each biological marker was determined by the area under the receiver operating characteristic (ROC) curve. RESULTS: Fifty potential biological markers were measured in 304 ED patients, including 22 patients (7%, 95% confidence interval [CI] = 4% to 10%) with VTE. Fourteen biological markers demonstrated an area under the curve (AUC) with the lower limit of the 95% CI > or = 0.5. Of these, three demonstrated an AUC > or = 0.7: D-dimer (0.90), C-reactive protein (CRP; 0.78), and myeloperoxidase (MPO; 0.78). CONCLUSIONS: From 50 candidate biological markers, only D-dimer, CRP, and MPO demonstrated sufficient diagnostic accuracy to suggest potential utility as biological marker of PE.

Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department.

BACKGROUND: Overuse of resources when evaluating pulmonary embolism (PE) is a concern if the D-dimer assay is improperly used in the evaluation of emergency department patients with suspected PE. The pulmonary embolism rule-out criteria (PERC) rule was derived to prevent unnecessary diagnostic testing in this patient population. The objective of this study was to assess the PERC rule's performance in an external population. METHODS: This was a secondary analysis of a prospectively collected database comparing PERC rule variables to diagnosis of PE in consecutive patients with suspicion for PE. Bivariate analysis on individual variables and the overall accuracy of the PERC rule were performed. RESULTS: Patients on 120 randomly assigned shifts were enrolled with a PE prevalence of 12%. The sensitivity, specificity, positive predictive, and negative predictive values of the PERC rule were 100% (95% confidence interval [CI], 79%-100%), 16% (95% CI, 10%-24%), 14% (95% CI, 8%-14%), and 100% (95% CI, 80%-100%), respectively, for the total patient population, and 100% (95% CI, 25%-100%), 33% (95% CI, 12%-35%), 2% (95% CI, 0%-11%), and 100% (95% CI, 75%-100%), respectively, for the low pretest probability population. Bivariate analysis showed unilateral leg swelling, recent surgery, and a history of venous thromboembolic event to be predictive of the diagnosis of PE. CONCLUSIONS: The PERC rule may identify a cohort of patients with suspected PE for whom diagnostic testing beyond history and physical examination is not indicated.

Radiologic diagnoses of patients who received imaging for venous thromboembolism despite negative D-dimer tests.

OBJECTIVE: The literature supports a negative D-dimer (-DD) excluding venous thromboembolic disease (VTE) in low-risk patients. We determined the radiologic diagnoses in patients where imaging was ordered despite a -DD. METHODS: This is a retrospective chart review of patients with a -DD (Tinaquant; Roche Diagnostics, Mannheim, Germany) and a radiologic study within 48 hours, sought to determine radiologic diagnosis (primary outcome), treatment of VTE, and consensus diagnosis of acute VTE. RESULTS: Among 3462 DD tests, 1678 met the inclusion criteria. Of 1362 patients with DD values of 350 ng/mL or less, 166 (12.2%) had radiologic studies: 93.4% of the final radiologic diagnoses were negative for VTE, 3.6% were indeterminate, and 3.0% (1.0%-6.9%) were positive; 1.8% ultimately had a consensus diagnosis of acute VTE. In 316 patients with DD values between 351 and 500 ng/mL, 88 (27.8%) had radiologic studies: 95.5% were negative, 1.1% were indeterminate, and 3.4% (0.7%-9.6%) were positive. CONCLUSIONS: Of patients who receive radiologic studies despite -DD tests, 3.0% have positive radiologic diagnoses for acute VTE; only 1.8% had acute VTE after the review of their hospital course.

Comparison of acute and convalescent biomarkers of inflammation in patients with acute pulmonary embolism treated with systemic fibrinolysis vs. placebo.

: Previous studies have associated biomarkers indicative of acute inflammation with pulmonary embolism, which may amplify coagulation, inhibit fibrinolysis and increase risk of venous thromboembolism (VTE) recurrence. The aim of this study was to measure inflammatory and hemostatic biomarkers in acute submassive pulmonary embolism at diagnosis and 3-month follow-up and to test the impact of treatment with fibrinolysis. Secondary analysis of a multicenter, double-blinded, randomized controlled trial including patients with submassive pulmonary embolism. Blood samples were obtained within 24 h of diagnosis and prior to bolus-dose tenecteplase (TNK) or placebo; all patients received standard anticoagulation and blood was redrawn 3 months later. Plasma concentrations of inflammatory [Interleukin 6 (IL-6), C-reactive protein (CRP), myeloperoxidase (MPO)] and hemostatic [plasminogen activator inhibitor-1 (PAI-1), fibrinogen, thrombin-activatable fibrinolysis inhibitor and D-dimer] biomarkers were quantified. The median values of the biomarkers of inflammation (IL-6, CRP, MPO) were all significantly decreased at 3-month follow-up, ranging from a 60 to 91% reduction over this time period. Concentrations of PAI-1 and fibrinogen did not change significantly. D-dimer concentration at 3-month follow-up was lower in patients treated with fibrinolysis vs. placebo and appeared to have a trend toward significance (placebo 310 vs. TNK 220 ng/ml, P = 0.051). Acute pulmonary embolism causes marked but transient inflammation, as demonstrated by the significant elevation in the inflammatory biomarkers at diagnosis, followed by their reduction in more than 80% of patients at 3-month follow-up.