Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Post-discharge venous thromboembolism prophylaxis in hospitalized trauma patients: A retrospective comparison of patients receiving versus not receiving post-discharge prophylaxis.

BACKGROUND: Risk of venous thromboembolism (VTE) in many trauma patients extends beyond hospitalization, but there is a paucity of evidence to guide the use of post-discharge prophylaxis (PDP). METHODS: A retrospective cohort study of trauma patients deemed moderate-to-high risk for VTE (risk assessment profile score [RAP] ≥5) who were prescribed PDP based on an internal clinical guideline assessing injury pattern and mobility status. PDP patients were compared with those that did not receive post-discharge prophylaxis (NPDP). RESULTS: 1512 patients were included. PDP group had higher mean RAP score (7.3 vs. 6.4, p â€‹< â€‹0.001), more likely to have a complex orthopedic fracture and underwent a longer median hospital (4.7 vs. 2.9 days, p â€‹< â€‹0.001). No difference between groups in 90-day VTE (11 [1.5 â€‹%] (PDP) vs. 8 [1.0 â€‹%] (NPDP), p â€‹= â€‹0.50), clinically relevant bleeding (p â€‹= â€‹0.58), or readmission (p â€‹= â€‹0.46). CONCLUSIONS: VTE incidence, clinically relevant bleeding, and readmission 90-days after hospital discharge were low and similar between PDP and NPDP groups. PDP prescribed in a presumably higher VTE risk trauma population may mitigate the long-term risk of VTE.

First steps toward a BIG change: A pilot study to implement the Brain Injury Guidelines across a 24-hospital system.

INTRODUCTION: The modified Brain Injury Guidelines (mBIG) support a subset of low-risk patients to be managed without repeat head computed tomography (RHCT), neurosurgical consult (NSC), or hospital transfer/admission. This pilot aimed to assess mBIG implementation at a single facility to inform future systemwide implementation. METHODS: Single cohort pilot trial at a level I trauma center, December 2021-August 2022. Adult patients included if tICH meeting BIG 1 or 2 criteria. BIG 3 patients excluded. RESULTS: No patients required neurosurgical intervention. 72 RHCT and 83 NSC were prevented. 21 isolated BIG 1 were safely discharged home from the ED. No hospital readmissions for tICH. Protocol adherence rate was 92%. CONCLUSION: Implementation of the mBIG at a single trauma center is feasible and optimizes resource utilization. This pilot study will inform an implementation trial of the mBIG across a 24-hospital integrated health system.

Concordance Between Initial Presumptive and Final Adjudicated Diagnoses of Infection Among Patients Meeting Sepsis-3 Criteria in the Emergency Department.

BACKGROUND: Guidelines emphasize rapid antibiotic treatment for sepsis, but infection presence is often uncertain at initial presentation. We investigated the incidence and drivers of false-positive presumptive infection diagnosis among emergency department (ED) patients meeting Sepsis-3 criteria. METHODS: For a retrospective cohort of patients hospitalized after meeting Sepsis-3 criteria (acute organ failure and suspected infection including blood cultures drawn and intravenous antimicrobials administered) in 1 of 4 EDs from 2013 to 2017, trained reviewers first identified the ED-diagnosed source of infection and adjudicated the presence and source of infection on final assessment. Reviewers subsequently adjudicated final infection probability for a randomly selected 10% subset of subjects. Risk factors for false-positive infection diagnosis and its association with 30-day mortality were evaluated using multivariable regression. RESULTS: Of 8267 patients meeting Sepsis-3 criteria in the ED, 699 (8.5%) did not have an infection on final adjudication and 1488 (18.0%) patients with confirmed infections had a different source of infection diagnosed in the ED versus final adjudication (ie, initial/final source diagnosis discordance). Among the subset of patients whose final infection probability was adjudicated (n = 812), 79 (9.7%) had only "possible" infection and 77 (9.5%) were not infected. Factors associated with false-positive infection diagnosis included hypothermia, altered mental status, comorbidity burden, and an "unknown infection source" diagnosis in the ED (odds ratio: 6.39; 95% confidence interval: 5.14-7.94). False-positive infection diagnosis was not associated with 30-day mortality. CONCLUSIONS: In this large multihospital study, <20% of ED patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication.

Synoptic reporting accuracy for computed tomography pulmonary arteriography among patients suspected of pulmonary embolism.

Background: Structured reporting is an efficient and replicable method of presenting diagnostic results that eliminates variability inherent in narrative descriptive reporting and may improve clinical decisions. Synoptic element reporting can generate discrete coded data that then may inform clinical decision support and trigger downstream actions in computerized electronic health records. Objective: Limited evidence exists for use of synoptic reporting for computed tomography pulmonary arteriography (CTPA) among patients suspected of pulmonary embolism. We reported the accuracy of synoptic reporting for the outcome of pulmonary embolism among patients who presented to an integrated health care system with CTPA performed for suspected pulmonary embolism. Methods: Structured radiology reports with embedded synoptic elements were implemented for all CTPA examinations on March 1, 2018. Four hundred CTPA reports between January 4, 2019 and July 30, 2020 (200 reports each for which synoptic reporting recorded the presence or absence of pulmonary embolism [PE]) were selected at random. One non-diagnostic study was excluded from analysis. We then assessed the accuracy of synoptic reporting compared with the gold standard of manual chart review. Results: Synoptic reporting and manual review agreed in 99.2% of patients undergoing CTPA for suspected PE, agreed on the presence of PE in 196 of 199 (98.5%) cases, the absence of PE in 200 of 200 (100%) cases with a sensitivity of 87.6% (76.1-96.1) a specificity of 99.9% (99.7%-100%), a positive predictive value of 99.5% (98.1-100), and a negative predictive value of 98% (95.7%-99.5%). Conclusion: The overall rate of agreement was 99.2%, but we observed an unacceptable false-negative rate for clinical reliance on synoptic element reporting in isolation from dictated reports.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation.

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

Biomarker derived risk scores predict venous thromboembolism and major bleeding among patients with COVID-19.

Background: Venous thromboembolism (VTE) risk is increased in patients with COVID-19 infection. Understanding which patients are likely to develop VTE may inform pharmacologic VTE prophylaxis decision making. The hospital-associated venous thromboembolism-Intermountain Risk Score (HA-VTE IMRS) and the hospital-associated major bleeding-Intermountain Risk Score (HA-MB IMRS) are risk scores predictive of VTE and bleeding that were derived from only patient age and data found in the complete blood count (CBC) and basic metabolic panel (BMP). Objectives: We assessed the HA-VTE IMRS and HA-MB IMRS for predictiveness of 90-day VTE and major bleeding, respectively, among patients diagnosed with COVID-19, and further investigated if adding D-dimer improved these predictions. We also reported 30-day outcomes. Patients/Methods: We identified 5047 sequential patients with a laboratory confirmed diagnosis of COVID-19 and a CBC and BMP between 2 days before and 7 days following the diagnosis of COVID-19 from March 12, 2020, to February 28, 2021. We calculated the HA-VTE IMRS and the HA-MB IMRS for all patients. We assessed the added predictiveness of D-dimer obtained within 48 hours of the COVID test. Results: The HA-VTE IMRS yielded a c-statistic of 0.70 for predicting 90-day VTE and adding D-dimer improved the c-statistic to 0.764 with the corollary sensitivity/specificity/positive/negative predictive values of 49.4%/75.7%/6.7%/97.7% and 58.8%/76.2%/10.9%/97.4%, respectively. Among hospitalized and ambulatory patients separately, the HA-VTE IMRS performed similarly. The HA-MB IMRS predictiveness for 90-day major bleeding yielded a c-statistic of 0.64. Conclusion: The HA-VTE IMRS and HA-MB IMRS predict 90- and 30-day VTE and major bleeding among COVID-19 patients. Adding D-dimer improved the predictiveness of the HA-VTE IMRS for VTE.

Association of the Intermountain Risk Score with major adverse health events in patients positive for COVID-19: an observational evaluation of a US cohort.

OBJECTIVES: The Intermountain Risk Score (IMRS), composed using published sex-specific weightings of parameters in the complete blood count (CBC) and basic metabolic profile (BMP), is a validated predictor of mortality. We hypothesised that IMRS calculated from prepandemic CBC and BMP predicts COVID-19 outcomes and that IMRS using laboratory results tested at COVID-19 diagnosis is also predictive. DESIGN: Prospective observational cohort study. SETTING: Primary, secondary, urgent and emergent care, and drive-through testing locations across Utah and in sections of adjacent US states. Viral RNA testing for SARS-CoV-2 was conducted from 3 March to 2 November 2020. PARTICIPANTS: Patients aged ≥18 years were evaluated if they had CBC and BMP measured in 2019 and tested positive for COVID-19 in 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a composite of hospitalisation or mortality, with secondary outcomes being hospitalisation and mortality separately. RESULTS: Among 3883 patients, 8.2% were hospitalised and 1.6% died. Subjects with low, mild, moderate and high-risk IMRS had the composite endpoint in 3.5% (52/1502), 8.6% (108/1256), 15.5% (152/979) and 28.1% (41/146) of patients, respectively. Compared with low-risk, subjects in mild-risk, moderate-risk and high-risk groups had HR=2.33 (95% CI 1.67 to 3.24), HR=4.01 (95% CI 2.93 to 5.50) and HR=8.34 (95% CI 5.54 to 12.57), respectively. Subjects aged <60 years had HR=3.06 (95% CI 2.01 to 4.65) and HR=7.38 (95% CI 3.14 to 17.34) for moderate and high risks versus low risk, respectively; those ≥60 years had HR=1.95 (95% CI 0.99 to 3.86) and HR=3.40 (95% CI 1.63 to 7.07). In multivariable analyses, IMRS was independently predictive and was shown to capture substantial risk variation of comorbidities. CONCLUSIONS: IMRS, a simple risk score using very basic laboratory results, predicted COVID-19 hospitalisation and mortality. This included important abilities to identify risk in younger adults with few diagnosed comorbidities and to predict risk prior to SARS-CoV-2 infection.

Prevalence, Characteristics, and Outcomes of Emergency Department Discharge Among Patients With Sepsis.

Importance: Sepsis guidelines and research have focused on patients with sepsis who are admitted to the hospital, but the scope and implications of sepsis that is managed in an outpatient setting are largely unknown. Objective: To identify the prevalence, risk factors, practice variation, and outcomes for discharge to outpatient management of sepsis among patients presenting to the emergency department (ED). Design, Setting, and Participants: This cohort study was conducted at the EDs of 4 Utah hospitals, and data extraction and analysis were performed from 2017 to 2021. Participants were adult ED patients who presented to a participating ED from July 1, 2013, to December 31, 2016, and met sepsis criteria before departing the ED alive and not receiving hospice care. Exposures: Patient demographic and clinical characteristics, health system parameters, and ED attending physician. Main Outcomes and Measures: Information on ED disposition was obtained from electronic medical records, and 30-day mortality data were acquired from Utah state death records and the US Social Security Death Index. Factors associated with ED discharge rather than hospital admission were identified using penalized logistic regression. Variation in ED discharge rates between physicians was estimated after adjustment for potential confounders using generalized linear mixed models. Inverse probability of treatment weighting was used in the primary analysis to assess the noninferiority of outpatient management for 30-day mortality (noninferiority margin of 1.5%) while adjusting for multiple potential confounders. Results: Among 12 333 ED patients with sepsis (median [IQR] age, 62 [47-76] years; 7017 women [56.9%]) who were analyzed in the study, 1985 (16.1%) were discharged from the ED. After penalized regression, factors associated with ED discharge included age (adjusted odds ratio [aOR], 0.90 per 10-y increase; 95% CI, 0.87-0.93), arrival to ED by ambulance (aOR, 0.61; 95% CI, 0.52-0.71), organ failure severity (aOR, 0.58 per 1-point increase in the Sequential Organ Failure Assessment score; 95% CI, 0.54-0.60), and urinary tract (aOR, 4.56 [95% CI, 3.91-5.31] vs pneumonia), intra-abdominal (aOR, 0.51 [95% CI, 0.39-0.65] vs pneumonia), skin (aOR, 1.40 [95% CI, 1.14-1.72] vs pneumonia) or other source of infection (aOR, 1.67 [95% CI, 1.40-1.97] vs pneumonia). Among 89 ED attending physicians, adjusted ED discharge probability varied significantly (likelihood ratio test, P < .001), ranging from 8% to 40% for an average patient. The unadjusted 30-day mortality was lower in discharged patients than admitted patients (0.9% vs 8.3%; P < .001), and their adjusted 30-day mortality was noninferior (propensity-adjusted odds ratio, 0.21 [95% CI, 0.09-0.48]; adjusted risk difference, 5.8% [95% CI, 5.1%-6.5%]; P < .001). Alternative confounder adjustment strategies yielded odds ratios that ranged from 0.21 to 0.42. Conclusions and Relevance: In this cohort study, discharge to outpatient treatment of patients who met sepsis criteria in the ED was more common than previously recognized and varied substantially between ED physicians, but it was not associated with higher mortality compared with hospital admission. Systematic, evidence-based strategies to optimize the triage of ED patients with sepsis are needed.

Outpatient Randomized Controlled Trials in the Covid-19 Era and Beyond.

Outpatient Trials in the Covid-19 Era and BeyondA group of investigators had a meeting at the National Heart, Lung, and Blood Institute in May 2020 to discuss ways to decrease thrombotic complications among symptomatic outpatients with Covid-19. The investigators discuss their approach to three specific challenges: conducting a trial remotely, working through regulatory hurdles, and recruiting a diverse population of participants.

Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial.

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.

Post-discharge thrombosis and bleeding in medical patients: A novel risk score derived from ubiquitous biomarkers.

BACKGROUND: Some hospitalized medical patients experience venous thromboembolism (VTE) following discharge. Prophylaxis extended beyond hospital discharge (extended duration thromboprophylaxis [EDT]) may reduce this risk. However, EDT is costly and can cause bleeding, so selecting appropriate patients is essential. We formerly reported the performance of a mortality risk prediction score (Intermountain Risk Score [IMRS]) that was minimally predictive of 90-day hospital-associated venous thromboembolism (HA-VTE) and major bleeding (HA-MB). We used the components of the IMRS to calculate de novo risk scores to predict 90-day HA-VTE (HA-VTE IMRS) and major bleeding (HA-MB IMRS). METHODS: From 45 669 medical patients we randomly assigned 30 445 to derive the HA-VTE IMRS and the HA-MB IMRS. Backward stepwise regression and bootstrapping identified predictor covariates from the blood count and basic chemistry. These candidate variables were split into quintiles, and the referent quintile was that with the lowest event rate for HA-VTE and HA-MB; respectively. A clinically relevant rate of HA-VTE and HA-MB was used to inform outcome rates. Performance was assessed in the derivation set of 15 224 patients. RESULTS: The HA-VTE IMRS and HA-MB IMRS area under the receiver operating curve (AUC) in the derivation set were 0.646, and 0.691, respectively. In the validation set, the HA-VTE IMRS and HA-MB IMRS AUCs were 0.60 and 0.643. CONCLUSIONS: Risk scores derived from components of routine labs ubiquitous in clinical care identify patients that are at risk for 90-day postdischarge HA-VTE and major bleeding. This may identify a subset of patients with high HA-VTE risk and low HA-MB risk who may benefit from EDT.

Electronic pulmonary embolism clinical decision support and effect on yield of computerized tomographic pulmonary angiography: ePE-A pragmatic prospective cohort study.

OBJECTIVE: Multiple professional societies recommend pre-test probability (PTP) assessment prior to imaging in the evaluation of patients with suspected pulmonary embolism (PE), however, PTP testing remains uncommon, with imaging occurring frequently and rates of confirmed PE remaining low. The goal of this study was to assess the impact of a clinical decision support tool embedded into the electronic health record to improve the diagnostic yield of computerized tomography pulmonary angiography (CTPA) in suspected patients with PE in the emergency department (ED). METHODS: Between July 24, 2014 and December 31, 2016, 4 hospitals from a healthcare system embedded an optional electronic clinical decision support system to assist in the diagnosis of pulmonary embolism (ePE). This system employs the Pulmonary Embolism Rule-out Criteria (PERC) and revised Geneva Score (RGS) in series prior to CT imaging. We compared the diagnostic yield of CTPA) among patients for whom the physician opted to use ePE versus the diagnostic yield of CTPA when ePE was not used. RESULTS: During the 2.5-year study period, 37,288 adult patients were eligible and included for study evaluation. Of eligible patients, 1949 of 37,288 (5.2%) were enrolled by activation of the tool. A total of 16,526 CTPAs were performed system-wide. When ePE was not engaged, CTPA was positive for PE in 1556 of 15,546 scans for a positive yield of 10.0%. When ePE was used, CTPA identified PE in 211 of 980 scans (21.5% yield) (P < 0.001). CONCLUSIONS: ePE significantly increased the diagnostic yield of CTPA without missing 30-day clinically overt PE.

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.

Trauma patients at risk for venous thromboembolism who undergo routine duplex ultrasound screening experience fewer pulmonary emboli: A prospective randomized trial.

BACKGROUND: Although guidelines are established for the prevention and management of venous thromboembolism (VTE) in trauma, no consensus exists regarding protocols for the diagnostic approach. We hypothesized that at-risk trauma patients who undergo duplex ultrasound (DUS) surveillance for lower extremity deep venous thrombosis (DVT) will have a lower rate of symptomatic or fatal pulmonary embolism (PE) than those who do not undergo routine surveillance. METHODS: Prospective, randomized trial between March 2017 and September 2019 of trauma patients admitted to a single, level 1 trauma center, with a risk assessment profile score of ≥5. Patients were randomized to receive either bilateral lower extremity DUS surveillance on days 1, 3, and 7 and weekly during hospitalization ultrasound group (US) or no surveillance no ultrasound group (NoUS). Rates of in-hospital and 90-day DVT and PE were reported as was DVT propagation and all-cause mortality. Standard care for the prevention and management of VTE per established institutional protocols was provided to all patients. RESULTS: A total of 3,236 trauma service admissions were screened, and 1,989 moderate- and high-risk patients were randomized (US, 995; NoUS, 994). The mean ± SD age was 62 ± 20.1 years, Injury Severity Score was 14 ± 9.7, risk assessment profile was 7.1 ± 2.4, and 97% suffered blunt trauma. There was no difference in demographics or VTE risk factors between the groups. There were significantly fewer in-hospital PE in the US group than the NoUS group (1 [0.1%] vs. 9 [0.9%], p = 0.01). The US group experienced more in-hospital below-knee DVTs (124 [12.5%] vs. 8 [0.8%], p < 0.001) and above-knee DVTs (19 [1.9%] vs. 8 [0.8%], p = 0.05). There was no difference in 90-day PE or DVT, or overall mortality. CONCLUSION: The implementation of a selective routine DUS protocol was associated with significantly fewer in-hospital PE. More DVTs were identified with routine screening; however, surveillance bias appears to exist primarily with distal DVT. Larger trials are needed to further characterize the relationship between routine DUS screening and VTE outcomes in the high-risk trauma population. LEVEL OF EVIDENCE: Therapeutic/care management, level II.

Cost-effectiveness of managing low-risk pulmonary embolism patients without hospitalization. The low-risk pulmonary embolism prospective management study.

OBJECTIVE: Evaluate the cost-effectiveness and difference in length-of-stay when patients in the ED diagnosed with low-risk pulmonary embolism (PE) are managed with early discharge or observation. METHODS: Single cohort prospective management study from January 2013 to October 2016 of patients with PE diagnosed in the ED and evaluated for a primary composite endpoint of mortality, recurrent venous thromboembolism, and/or major bleeding event at 90 days. Low-risk patients had a PE Severity Index score < 86, no evidence of proximal deep vein thrombosis on venous compression ultrasonography of both lower extremities, and no evidence of right heart strain on echocardiography. Patients were managed either in the ED or in the hospital on observation status. Primary outcomes were total length of stay, total encounter costs, and 30-day costs. RESULTS: 213 patients were enrolled. 13 were excluded per the study protocol. Of the remaining 200, 122 were managed with emergency department observation (EDO) and 78 with hospital observation (HO). One patient managed with EDO met the composite outcome due to a major bleeding event on day 61. The mean length of stay for EDO was 793.4 min (SD -169.7, 95% CI:762-823) and for HO was 1170 (SD -211.4, 95% CI:1122-1218) with a difference of 376.8 (95% CI: 430-323, p < 0.0001). Total encounter mean costs for EDO were $1982.95 and $2759.59 for HO, with a difference of $776.64 (95% CI: 972-480, p > 0.0001). 30-day total mean costs for EDO were $2864.14 and $3441.52 for HO, with a difference of $577.38 (95% CI: -1372-217, p = 0.15). CONCLUSIONS: Patients with low-risk PE managed with ED-based observation have a shorter length of stay and lower total encounter costs than patients managed with Hospital-based observation.