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Item A clinical decision framework to guide the outpatient treatment of emergency department patients diagnosed with acute pulmonary embolism or deep vein thrombosis: Results from a multidisciplinary consensus panel(Wiley, 2021-12-15) Kabrhel, Christopher; Vinson, David R.; Mitchell, Alice Marina; Rosovsky, Rachel P.; Chang, Anna Marie; Hernandez-Nino, Jackeline; Wolf, Stephen J.; Emergency Medicine, School of MedicineThe outpatient treatment of select emergency department patients with acute pulmonary embolism (PE) or deep vein thrombosis (DVT) has been shown to be safe, cost effective and associated with high patient satisfaction. Despite this, outpatient PE and DVT treatment remains uncommon. To address this, the American College of Emergency Physicians assembled a multidisciplinary team of content experts to provide evidence-based recommendations and practical advice to help clinicians safely treat patients with low-risk PE and DVT without hospitalization. The emergency clinician must stratify the patient's risk of clinical decompensation due to their PE or DVT as well as their risk of bleeding due to anticoagulation. The clinician must also select and start an anticoagulant and ensure that the patient has access to the medication in a timely manner. Reliable follow-up is critical, and the patient must also be educated about signs or symptoms that should prompt a return to the emergency department. To facilitate access to these recommendations, the consensus panel also created 2 web-based "point-of-care tools."Item 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, multi-center study(2010-04) Courtney, Mark; Kline, Jeffrey A.; Kabrhel, Christopher; Moore, Christopher L; Smithline, Howard A; Nordenholz, Kristen E; Richman, Peter B; Plewa, Michael CStudy Objective—Prediction rules for pulmonary embolism (PE) employ variables explicitly shown to estimate the probability of PE. However, clinicians often use variables that have not been similarly validated, yet are implicitly believed to modify probability of PE. The objective of this study was 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 PE (D-dimer, CT angiography, or V/Q 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 VTE (venous thromboembolism: PE 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—7,940 patients (7.2% VTE+) were enrolled. Mean age was 49±17 years and 67% were female. Eight of 13 implicit variables were significantly associated with VTE; those with an adjusted OR >1.5 included non-cancer related thrombophilia (1.99), pleuritic chest pain (1.53), and family history of VTE (1.51). Implicit variables that predicted no VTE outcome included: substernal chest pain, female gender, and smoking. Nine of 12 explicit variables predicted a positive outcome of VTE, including unilateral leg swelling, recent surgery, estrogen, hypoxemia and active malignancy. Conclusions—In symptomatic outpatients being considered for possible PE, non-cancer related thrombophilia, pleuritic chest pain, and family history of VTE increase probability of PE or DVT. Other variables that are part of existing pretest probability systems were validated as important predictors in this diverse sample of US Emergency department patients.Item Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments 2-22-2021(PloS, 2021-03) Kline, Jeffrey A.; Camargo, Carlos A.; Courtney, D. Mark; Kabrhel, Christopher; Nordenholz, Kristen E.; Aufderheide, Thomas; Baugh, Joshua J.; Beiser, David G.; Bennett, Christopher L.; Bledsoe, Joseph; Castillo, Edward; Chisolm-Straker, Makini; Goldberg, Elizabeth M.; House, Hans; House, Stacey; Jang, Timothy; Lim, Stephen C.; Madsen, Troy E.; McCarthy, Danielle M.; Meltzer, Andrew; Moore, Stephen; Newgard, Craig; Pagenhardt, Justine; Pettit, Katherine L.; Pulia, Michael S.; Puskarich, Michael A.; Southerland, Lauren T.; Sparks, Scott; Turner-Lawrence, Danielle; Vrablik, Marie; Wang, Alfred; Weekes, Anthony J.; Westafer, Lauren; Wilburn, John; Emergency Medicine, School of MedicineObjectives 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.Item Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism(Springer US, 2015-08) Stewart, Lauren K.; Peitz, Geoffrey W.; Nordenholz, Kristen E.; Courtney, D. Mark; Kabrhel, Christopher; Jones, Alan E.; Rondina, Matthew T.; Diercks, Deborah B.; Klinger, James R.; Kline, Jeffrey A.; Department of Emergency Medicine, School of MedicineAcute 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 R2 = 0.303. Obesity had the largest effect on PCS (β = −8.6, P<0.001), with tenecteplase second (β = 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.Item Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure: Quantifying the opportunity for improvement(2012-07) Venkatesh, Arjun K; Kline, Jeffrey A.; Courtney, D Mark; Camargo Jr, Carlos A; Plewa, Michael C; Nordenholz, Kristen E; Moore, Christopher L; Richman, Peter B; Smithline, Howard A; Beam, Daren M; Kabrhel, ChristopherBackground The National Quality Forum (NQF) has endorsed a performance measure designed to increase imaging efficiency for the evaluation of pulmonary embolism (PE) in the emergency department (ED). To our knowledge, no published data have examined the effect of patient-level predictors on performance. Methods To quantify the prevalence of avoidable imaging in ED patients with suspected PE, we performed a prospective, multicenter observational study of ED patients evaluated for PE from 2004 through 2007 at 11 US EDs. Adult patients tested for PE were enrolled, with data collected in a standardized instrument. The primary outcome was the proportion of imaging that was potentially avoidable according to the NQF measure. Avoidable imaging was defined as imaging in a patient with low pretest probability for PE, who either did not have a D-dimer test ordered or who had a negative D-dimer test result. We performed subanalyses testing alternative pretest probability cutoffs and imaging definitions on measure performance as well as a secondary analysis to identify factors associated with inappropriate imaging. χ2 Test was used for bivariate analysis of categorical variables and multivariable logistic regression for the secondary analysis. Results We enrolled 5940 patients, of whom 4113 (69%) had low pretest probability of PE. Imaging was performed in 2238 low-risk patients (38%), of whom 811 had no D-dimer testing, and 394 had negative D-dimer test results. Imaging was avoidable, according to the NQF measure, in 1205 patients (32%; 95% CI, 31%-34%). Avoidable imaging owing to not ordering a D-dimer test was associated with age (odds ratio [OR], 1.15 per decade; 95% CI, 1.10-1.21). Avoidable imaging owing to imaging after a negative D-dimer test result was associated with inactive malignant disease (OR, 1.66; 95% CI, 1.11-2.49). Conclusions One-third of imaging performed for suspected PE may be categorized as avoidable. Improving adherence to established diagnostic protocols is likely to result in significantly fewer patients receiving unnecessary irradiation and substantial savings.Item Factors Associated With Positive D-dimer Results in Patients Evaluated for Pulmonary Embolism(2010-06) Kabrhel, Christopher; Courtney, D Mark; Camargo, Carlos A Jr; Plewa, Michael C; Nordenholz, Kristen E; Moore, Christopher L; Richman, Peter B; Smithline, Howard A; Beam, Daren M; Kline, Jeffrey A.Objectives: Available D-dimer assays have low specificity and may increase radiographic testing for pulmonary embolism (PE). To help clinicians better target testing, this study sought to quantify the effect of risk factors for a positive quantitative D-dimer in patients evaluated for PE. Methods: This was a prospective, multicenter, observational study. Emergency department (ED) patients evaluated for PE with a quantitative D-dimer were eligible for inclusion. The main outcome of interest was a positive D-dimer. Odds ratio (ORs) and 95% confidence intervals (CIs) were determined by multivariable logistic regression. Adjusted estimates of relative risk were also calculated. Results: A total of 4,346 patients had D-dimer testing, of whom 2,930 (67%) were women. A total of 2,500 (57%) were white, 1,474 (34%) were black or African American, 238 (6%) were Hispanic, and 144 (3%) were of other race or ethnicity. The mean (±SD) age was 48 (±17) years. Overall, 1,903 (44%) D-dimers were positive. Model fit was adequate (c-statistic = 0.739, Hosmer and Lemeshow p-value = 0.13). Significant positive predictors of D-dimer positive included female sex; increasing age; black (vs. white) race; cocaine use; general, limb, or neurologic immobility; hemoptysis; hemodialysis; active malignancy; rheumatoid arthritis; lupus; sickle cell disease; prior venous thromboembolism (VTE; not under treatment); pregnancy and postpartum state; and abdominal, chest, orthopedic, or other surgery. Warfarin use was protective. In contrast, several variables known to be associated with PE were not associated with positive D-dimer results: body mass index (BMI), estrogen use, family history of PE, (inactive) malignancy, thrombophilia, trauma within 4 weeks, travel, and prior VTE (under treatment). Conclusions: Many factors are associated with a positive D-dimer test. The effect of these factors on the usefulness of the test should be considered prior to ordering a D-dimer.Item Incidence and characteristics of arterial thromboemboli in patients with COVID-19(Springer Nature, 2021-12-20) Glober, Nancy; Stewart, Lauren; Seo, JangDong; Kabrhel, Christopher; Nordenholz, Kristen; Camargo, Carlos; Kline, Jeffrey; Emergency Medicine, School of MedicineBackground: Studies have reported COVID-19 as an independent risk factor for arterial thromboemboli. Methods: From a cross-sectional sample, we determined the incidence and location of arterial thromboemboli (myocardial infarction, ischemic stroke, peripheral artery), stratified by COVID-19 status, in the RECOVER database, which included data on patients at 45 United States medical centers in 22 states. Epidemiological factors, clinical characteristics and outcomes were collected through a combination of individual chart review and automatic electronic query and recorded in REDCap®. We investigated the association of baseline comorbidities on the development of arterial thromboemboli and analyzed results based on the presence or absence of concomitant COVID-19 infection, testing this association with Chi-squared. We also described use of anticoagulants and statins. Results: Data were collected on 26,974 patients, of which 13,803 (51.17%) tested positive for COVID-19. Incidence of arterial thromboemboli during hospitalization was 0.13% in patients who tested positive for COVID-19 and 0.19% in patients who tested negative. Arterial thromboemboli tended to be more common in extremities than in core organs (heart, kidney, lung, liver) in patients with COVID-19, odds ratio 2.04 (95% CI 0.707 - 5.85). Patients with COVID-19 were less likely to develop an arterial thrombus when on baseline statin medication (p=0.014). Presence of metabolic syndrome predicted presence of core arterial thrombus (p=0.001) and extremity arterial thrombus (p=0.010) in those with COVID-19. Arterial thromboemboli were less common in patients with COVID-19 than in those who tested negative for COVID-19. Conclusions: Presence of a composite metabolic syndrome profile may be associated with arterial clot formation in patients with COVID-19 infection.Item Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath(WB Saunders, 2015-04) Russell, Frances M.; Moore, Christopher L.; Courtney, D. Mark; Kabrhel, Christopher; Smithline, Howard A.; Nordenholz, Kristen E.; Richman, Peter B.; O’Neil, Brian J.; Plewa, Michael C.; Beam, Daren M.; Mastouri, Ronald; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBACKGROUND: 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.Item Multicenter registry of United States emergency department patients tested for SARS-CoV-2(Wiley, 2020-11-12) Kline, Jeffrey A.; Pettit, Katherine L.; Kabrhel, Christopher; Courtney, D. Mark; Nordenholz, Kristen E.; Camargo, Carlos A.; Emergency Medicine, School of MedicineThis 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.Item Predicting 30-day return hospital admissions in patients with COVID-19 discharged from the emergency department: A national retrospective cohort study(Wiley, 2021) Beiser, David G.; Jarou, Zachary J.; Kassir, Alaa A.; Puskarich, Michael A.; Vrablik, Marie C.; Rosenman, Elizabeth D.; McDonald, Samuel A.; Meltzer, Andrew C.; Courtney, D. Mark; Kabrhel, Christopher; Kline, Jeffrey A.; RECOVER Investigators; Emergency Medicine, School of MedicineObjectives: Identification of patients with coronavirus disease 2019 (COVID-19) at risk for deterioration after discharge from the emergency department (ED) remains a clinical challenge. Our objective was to develop a prediction model that identifies patients with COVID-19 at risk for return and hospital admission within 30 days of ED discharge. Methods: We performed a retrospective cohort study of discharged adult ED patients (n = 7529) with SARS-CoV-2 infection from 116 unique hospitals contributing to the National Registry of Suspected COVID-19 in Emergency Care. The primary outcome was return hospital admission within 30 days. Models were developed using classification and regression tree (CART), gradient boosted machine (GBM), random forest (RF), and least absolute shrinkage and selection (LASSO) approaches. Results: Among patients with COVID-19 discharged from the ED on their index encounter, 571 (7.6%) returned for hospital admission within 30 days. The machine-learning (ML) models (GBM, RF, and LASSO) performed similarly. The RF model yielded a test area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI], 0.71–0.78), with a sensitivity of 0.46 (95% CI, 0.39–0.54) and a specificity of 0.84 (95% CI, 0.82–0.85). Predictive variables, including lowest oxygen saturation, temperature, or history of hypertension, diabetes, hyperlipidemia, or obesity, were common to all ML models. Conclusions: A predictive model identifying adult ED patients with COVID-19 at risk for return for return hospital admission within 30 days is feasible. Ensemble/boot-strapped classification methods (eg, GBM, RF, and LASSO) outperform the single-tree CART method. Future efforts may focus on the application of ML models in the hospital setting to optimize the allocation of follow-up resources.