Daren M. Beam

2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial.

OBJECTIVES The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge). BACKGROUND Patients presenting with possible acute coronary syndrome (ACS), who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays. METHODS This prospective observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infarction (TIMI) score, electrocardiography, and 0 + 2 h values of laboratory troponin I as the sole biomarker. Patients presenting with chest pain due to suspected ACS were included. The primary endpoint was major adverse cardiac event (MACE) within 30 days. RESULTS Of 1,975 patients, 302 (15.3%) had a MACE. The ADP classified 392 patients (20%) as low risk. One (0.25%) of these patients had a MACE, giving the ADP a sensitivity of 99.7% (95% confidence interval [CI]: 98.1% to 99.9%), negative predictive value of 99.7% (95% CI: 98.6% to 100.0%), specificity of 23.4% (95% CI: 21.4% to 25.4%), and positive predictive value of 19.0% (95% CI: 17.2% to 21.0%). Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up. CONCLUSIONS Using the ADP, a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. (An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin; ACTRN12611001069943).

Incidence and Predictors of Repeated Computed Tomographic Pulmonary Angiography in Emergency Department Patients

STUDY OBJECTIVE Use of contrast-enhanced computed tomography (CT) of the pulmonary arteries to evaluate for pulmonary embolism has increased, raising concern about radiation and contrast toxicity. We sought to measure the frequency of repeat CT pulmonary angiography in emergency department (ED) patients. METHODS This was a prospective, longitudinal follow-up of ED patients who underwent first-time CT pulmonary angiography as part of a research protocol for diagnosis of pulmonary embolism in 2001 to 2002. Two authors (DMB and MCK) searched electronic medical record databases to measure the frequency of repeated CT scans performed within 5 years. Primary outcome was greater than or equal to 1 repeated CT pulmonary angiography examination. Radiologist-written interpretations of CT pulmonary angiography were categorized by 2 observers (DMB and JAK). Cox regression was used to estimate hazard ratios for 24 clinical variables. RESULTS A cohort of 675 ED patients was observed for a median of 1,989 days: 226 of 675 (33%) had at least 1 additional CT pulmonary angiography scan, and 60 died with no repeated CT pulmonary angiography, leading to a mortality-adjusted frequency of repeated CT pulmonary angiography scanning of 226 of 615, or 37%. Seventy-three percent of the cohort had 1 or more subsequent CT scans of any body part, and 31 patients (5%) had 5 or more repeated CT pulmonary angiography scans. The pulmonary embolism (positive) prevalence was 57 of 675 (8.4%; 95% confidence interval [CI] 6.5% to 10.8%) on the first CT pulmonary angiography versus 8 of 226 (3.5%; 95% CI 1.5% to 6.9%) on the second CT pulmonary angiography scan. Hazard ratios indicated that respiratory rate, active malignancy, previous coronary artery disease, and previous or new diagnosis of venous thromboembolism were positively associated with repeated CT pulmonary angiography scanning. CONCLUSION At least one third of ED patients who undergo CT pulmonary angiography scanning will have a second CT pulmonary angiography result that will be negative for pulmonary embolism. New methods are needed to exclude pulmonary embolism recurrence without use of ionizing radiation.

Factors Associated With Positive D-dimer Results in Patients Evaluated for Pulmonary Embolism

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.

Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure: Quantifying the opportunity for improvement

BACKGROUND 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. χ(2) 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.

Risk of Thromboembolism Varies, Depending on Category of Immobility in Outpatients

STUDY OBJECTIVE Immobility predisposes to venous thromboembolism, but this risk may vary, depending on the underlying cause of immobility. METHODS This was a prospective, longitudinal outcome study of self-presenting emergency department (ED) patients who were from 12 hospitals and had suspected venous thromboembolism. Using explicit written criteria, clinicians recorded clinical features of each patient in the ED by using a Web-based data form. The form required one of 6 types of immobility: no immobility, general or whole-body immobility greater than 48 hours, limb (orthopedic) immobility, travel greater than 8 hours causing immobility within the previous 7 days, neurologic paralysis, or other immobility not listed above. Patients were followed for 45 days for outcome of venous thromboembolism, which required positive imaging results and clinical plan to treat. Odds ratios (ORs) were derived from logistic regression including 12 covariates. RESULTS From 7,940 patients enrolled, 545 of 7,940 (6.9%) were diagnosed with venous thromboembolism (354 pulmonary embolism, 72 deep venous thrombosis, 119 pulmonary embolism and deep venous thrombosis). Risk of venous thromboembolism varied, depending on immobility type: limb (OR=2.24; 95% confidence interval [CI] 1.40 to 3.60), general (OR=1.76; 95% CI 1.26 to 2.44), other (OR=1.97; 95% CI 1.25 to 3.09), neurologic (OR=2.23; 95% CI 1.01 to 4.92), and travel (OR=1.19; 95% CI 0.85 to 1.67). Other significant risk factors from multivariate analysis included age greater than 50 years (OR =1.5; 95% CI 1.25 to 1.82), unilateral leg swelling (OR=2.68; 95% CI 2.13 to 3.37), previous venous thromboembolism (OR=2.99; 95% CI 2.41 to 3.71), active malignancy (OR=2.23; 95% CI 1.69 to 2.95), and recent surgery (OR=2.12; 95% CI 1.61 to 2.81). CONCLUSION In a large cohort of symptomatic ED patients, risk of venous thromboembolism was substantially increased by presence of limb, whole-body, or neurologic immobility but not by travel greater than 8 hours. These data show the importance of clarifying the cause of immobility in risk assessment of venous thromboembolism.

Immediate Discharge and Home Treatment With Rivaroxaban of Low‐risk Venous Thromboembolism Diagnosed in Two U.S. Emergency Departments: A One‐year Preplanned Analysis

Abstract Objectives The study hypothesis was that a target‐specific anticoagulant would allow successful home treatment of selected patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) diagnosed in two urban emergency departments (EDs). Methods A protocol was established for treating low‐risk DVT or PE patients with rivaroxaban and clinic, follow‐up at both 2 to 5 weeks, and 3 to 6 months. Patients were determined to be low‐risk by using a modified version of the Hestia criteria, supplemented by additional criteria for patients with active cancer. Acceptable outcome rates were defined as venous thromboembolism (VTE) recurrence ≤ 2.1% or bleeding ≤ 9.4% during treatment. VTE recurrence required positive imaging of any VTE. The International Society of Thrombosis and Hemostasis definition of major or clinically relevant nonmajor bleeding was used. Results From March 2013 through April 2014, a total of 106 patients were treated. Seventy‐one (68%) had DVT, 30 (28%) had PE, and five (3%) had both, representing 51% of all DVTs and 27% of all PEs diagnosed in both EDs during the period of study. The 106 patients have been followed for a mean (±SD) of 389 (±111) days (range = 213 to 594 days). No patient had VTE recurrence, and no patient had a major or clinically relevant bleeding event while on therapy (none of the 106, 0%, 95% confidence interval [CI] = 0% to 3.4%). However, three patients 2.8% (95% CI = 1% to 8%) had recurrent DVT after cessation of therapy. Conclusions Patients diagnosed with VTE and immediately discharged from the ED while treated with rivaroxaban had a low rate of VTE recurrence and bleeding.

Potential Impact of Adjusting the Threshold of the Quantitative D-dimer Based on Pretest Probability of Acute Pulmonary Embolism

OBJECTIVES The utility of D-dimer testing for suspected pulmonary embolism (PE) can be limited by test specificity. The authors tested if the threshold of the quantitative D-dimer can be varied according to pretest probability (PTP) of PE to increase specificity while maintaining a negative predictive value (NPV) of >99%. METHODS This was a prospective, observational multicenter study of emergency department (ED) patients in the United States. Eligible patients had a diagnostic study ordered to evaluate possible PE. PTP was determined by the clinicians unstructured estimate and the Wells score. Five different D-dimer assays were used. D-dimer test performance was measured using 1) standard thresholds and 2) variable threshold values: twice (for low PTP patients), equal (intermediate PTP patients), or half (high PTP patients) of standard threshold. Venous thromboembolism (VTE) within 45 days required positive imaging plus decision to treat. RESULTS The authors enrolled 7,940 patients tested for PE, and clinicians ordered a quantitative D-dimer for 4,357 (55%) patients who had PTPs distributed as follows: low (74%), moderate (21%), or high (4%). At standard cutoffs, across all PTP strata, quantitative D-dimer testing had a test sensitivity of 94% (95% confidence interval [CI] = 91% to 97%), specificity of 58% (95% CI = 56% to 60%), and NPV of 99.5% (95% CI = 99.1% to 99.7%). If variable cutoffs had been used the overall sensitivity would have been 88% (95% CI = 83% to 92%), specificity 75% (95% CI = 74% to 76%), and NPV 99.1% (95% CI = 98.7% to 99.4%). CONCLUSIONS This large multicenter observational sample demonstrates that emergency medicine clinicians currently order a D-dimer in the majority of patients tested for PE, including a large proportion with intermediate PTP and high PTP. Varying the D-dimers cutoff according to PTP can increase specificity with no measurable decrease in NPV.

Comparison of the Simplify D-dimer assay performed at the bedside with a laboratory-based quantitative D-dimer assay for the diagnosis of pulmonary embolism in a low prevalence emergency department population

Background: The immunofiltration D-dimer assay could allow point-of-care testing for pulmonary embolism (PE). A study was undertaken to compare a clinician-performed qualitative D-dimer assay with the automated quantitative D-dimer test. Methods: A prospective observational study was conducted from January to October 2005 at an urban academic emergency department (ED). 1193 patients of mean (SD) age 47 (16) years (66% female) were enrolled. The study protocol combined pretest probability estimation, D-dimer testing by both a qualitative immunochromatographic assay (Simplify) performed at the point of care by 192 different clinicians and a quantitative D-dimer test performed in a CLIA-certified laboratory. The criterion standard was image-proven PE or deep venous thrombosis within 45 days after enrolment. To test interobserver agreement for the qualitative assay, two blinded observers independently read 841 Simplify cartridges. Results: Of 1193 patients enrolled, 45 were PE+ (3.8%, 95% CI 2.8% to 5.0%). Qualitative results were available for 1169 (98%) and quantitative results were available for 1136 (95%). Comparison of the qualitative and quantitative D-dimer tests gave the following results: sensitivity 91% (95% CI 78% to 98%) vs 93% (95% CI 80% to 98%); specificity 57% (95% CI 54% to 60%) vs 57% (95% CI 54% to 60%); likelihood ratio negative 0.16 (95% CI 0.06 to 0.37) vs 0.13 (95% CI 0.05 to 0.35). The weighted Cohen’s κ for interpretation of the qualitative assay was 0.69 (95% CI 0.63 to 0.76). Conclusions: In this very low-risk ED population, a qualitative D-dimer assay performed at the point of care had similar diagnostic accuracy to the quantitative D-dimer test. Interobserver agreement for the qualitative test was good.

Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance

Background Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE) in outpatients. Objectives The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. Methods Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms questionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]). The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT) to those with pulmonary embolism (PE). Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. Results From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/253 patients had recurrent DVT and 2/253 had major hemorrhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively) and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively), consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians’ (N=116) before-to-after protocol comfort level with home treatment of PE increased 48% on visual analog scale. Conclusion Hestia-negative VTE patients treated with oral monotherapy at home had low rates of VTE recurrence and bleeding, as well as quality of life measurements similar to prior reports.

Cost of Treating Venous Thromboembolism With Heparin and Warfarin Versus Home Treatment With Rivaroxaban.

BACKGROUND Target-specific anticoagulants such as rivaroxaban facilitate immediate discharge of low-risk venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) allowing treatment at home instead of hospitalization. OBJECTIVES The objective was to compare costs accrued over 6 months by patients diagnosed with low-risk VTE and treated at home with rivaroxaban versus usual care with heparin-warfarin. METHODS This case-control study calculated costs using the established charge-to-cost ratio from UB-04 billing claims of patients diagnosed at two metropolitan hospitals. Patients were defined as low risk by the Hestia criteria. All patients were anticoagulated for 6 months. Control patients were treated with usual care using low-molecular-weight heparin (LMWH) and then warfarin. Case patients were treated with an initial dose of rivaroxaban in the ED followed by same-day discharge home with rivaroxaban. Medians were compared by Mann-Whitney U-test. RESULTS Fifty cases and 47 controls were identified. Groups were well matched according to mean age, Charlson comorbidity score, and proportions by sex and location of thrombus. For all VTEs, median hospital charges for 6 months after diagnosis were