Low concordance between CTPA and echocardiography in identification of right ventricular strain in PERT patients with acute pulmonary embolism.

PURPOSE: Right ventricular strain (RVS) is used to risk stratify patients with acute pulmonary embolism (PE) and influence treatment decisions. Guidelines suggest that either computed tomography pulmonary angiography (CTPA) or transthoracic echocardiography (TTE) can be used to assess RVS. We sought to determine how often CTPA and TTE yield discordant results and to assess the test characteristics of CTPA compared to TTE. METHODS: We analyzed data from a single-center registry of PE cases severe enough to warrant activation of the hospital's Pulmonary Embolism Response Team (PERT). We defined RVS as a right ventricular to left ventricular ratio (RV/LV) ≥ 1 or radiologist's interpretation of RVS on CTPA or as the presence of either RV dilation, hypokinesis, or septal bowing on TTE. RESULTS: We included 554 patients in our analysis, of whom 333 (60%) had concordant RVS findings on CTPA and TTE. Using TTE as the reference standard, CTPA had a sensitivity of 95% (95% CI 92-97%) and a specificity of 4% (95% CI 2-8%) for identifying RVS. CONCLUSIONS: In a selected population of patients with acute PE for which PERT was activated, CTPA is highly sensitive but not specific for the detection of RVS when compared to TTE.

Risk Factors Predicting Cellulitis Diagnosis in a Prospective Cohort Undergoing Dermatology Consultation in the Emergency Department.

Cellulitis is an infection of the skin and skin-associated structures with many clinical mimickers known collectively as pseudocellulitis. Dermatology or infectious disease consultation is considered the gold standard for diagnosis. We evaluated a prospective cohort of adult patients presenting to the emergency department (ED) with concern for lower extremity cellulitis who received dermatology consultation with conferral of a final diagnosis. Possible risk factors independently associated with cellulitis diagnosis (P<.1) were included in a logistic regression model for prediction of cellulitis diagnosis. Factors having odds ratios with a confidence interval excluding 1 were identified as significant independent predictors. The study identified factors that should be considered in evaluation of patients with suspected uncomplicated lower extremity cellulitis.

Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients.

Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls and perform bulk RNA sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between six distinct neutrophil subtypes. At days 3 and 7 post-hospitalization, patients with severe disease display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while patients with resolving disease show a neutrophil progenitor-like signature. Humoral responses are identified as potential drivers of neutrophil effector functions, with elevated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirm that while patient-derived IgG antibodies induce phagocytosis in healthy donor neutrophils, IgA antibodies predominantly induce neutrophil cell death. Overall, our study demonstrates a dysregulated myelopoietic response in severe COVID-19 and a potential role for IgA-dominant responses contributing to mortality.

COVID-19 Seroprevalence in ED Health Care Professionals Study: A Cross-Sectional Study.

INTRODUCTION: ED health care professionals are at the frontline of evaluation and management of patients with acute, and often undifferentiated, illness. During the initial phase of the SARS-CoV-2 outbreak, there were concerns that ED health care professionals may have been at increased risk of exposure to SARS-CoV-2 due to difficulty in early identification of patients. This study assessed the seroprevalence of SARS-CoV-2 antibodies among ED health care professionals without confirmed history of COVID-19 infection at a quaternary academic medical center. METHODS: This study used a cross-sectional design. An ED health care professional was deemed eligible if they had worked at least 4 shifts in the adult emergency department from April 1, 2020, through May 31, 2020, were asymptomatic on the day of blood draw, and were not known to have had prior documented COVID-19 infection. The study period was December 17, 2020, to January 27, 2021. Eligible participants completed a questionnaire and had a blood sample drawn. Samples were run on the Roche Cobas Elecsys Anti-SARS-CoV-2 antibody assay. RESULTS: Of 103 health care professionals (16 attending physicians, 4 emergency residents, 16 advanced practice professionals, and 67 full-time emergency nurses), only 3 (2.9%; exact 95% CI, 0.6%-8.3%) were seropositive for SARS-CoV-2 antibodies. DISCUSSION: At this quaternary academic medical center, among those who volunteered to take an antibody test, there was a low seroprevalence of SARS-CoV-2 antibodies among ED clinicians who were asymptomatic at the time of blood draw and not known to have had prior COVID-19 infection.

Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.

Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89-1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56-2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.

Diffuse Reflectance Spectroscopy with Infrared Thermography for Accurate Prediction of Cellulitis.

Cellulitis is frequently misdiagnosed owing to its clinical mimickers, collectively known as pseudocellulitis. This study investigated diffuse reflectance spectroscopy (DRS) alone and in combination with infrared thermography (IRT) for the differentiation of cellulitis from pseudocellulitis. A prospective cohort study at an urban academic hospital was conducted from March 2017 to March 2018. Patients presenting to the emergency department with presumed cellulitis were screened for eligibility, and 30 adult patients were enrolled. Dermatology consultation conferred a final diagnosis of cellulitis or pseudocellulitis. DRS measurements yielded a spectral ratio between 556 nm (deoxyhemoglobin peak) and 542 nm (oxyhemoglobin peak), and IRT measurements yielded temperature differentials between the affected and unaffected skin. Of the 30 enrolled patients, 30% were diagnosed with pseudocellulitis. DRS revealed higher spectral ratios in patients with cellulitis (P = 0.005). A single parameter model using logistic regression on DRS measurements alone demonstrated a classification accuracy of 77.0%. A dual parameter model using linear discriminant analysis on DRS and IRT measurements combined demonstrated a 95.2% sensitivity, 77.8% specificity, and 90.0% accuracy for cellulitis prediction. DRS and IRT combined diagnoses cellulitis with an accuracy of 90%. DRS and IRT are inexpensive and noninvasive, and their use may reduce cellulitis misdiagnosis.

Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients.

Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19 + patients, 78 COVID-19 âˆ' acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.

Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients.

COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins. By comparing patients who died to severely ill patients who survived, we identify dynamic immunomodulatory and tissue-associated proteins associated with survival, providing insights into which host responses are beneficial and which are detrimental to survival. We identify intracellular death signatures from specific tissues and cell types, and by associating these with angiotensin converting enzyme 2 (ACE2) expression, we map tissue damage associated with severe disease and propose which damage results from direct viral infection rather than from indirect effects of illness. We find that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells. Based on these results, we propose a model of immune and epithelial cell interactions that drive cell-type specific and tissue-specific damage in severe COVID-19.

Highly Elevated Quantitative D-Dimer Assay Values Increase the Likelihood of Venous Thromboembolism.

Objectives In patients with suspected venous thromboembolism (VTE), the D-dimer assay is commonly utilized as part of the workup. The assay is primarily used to determine whether to proceed with radiographic imaging. We compared D-dimer levels in patients suspected of having VTE. We hypothesized that higher D-dimer values predict a higher likelihood of subsequent VTE diagnosis. Methods We conducted a secondary analysis of a multinational, prospective observational study of low- to intermediate-risk adult patients presenting to the emergency department with suspicion of VTE. Demographic and clinical data were collected in a structured manner. Advanced imaging including ultrasound, computed tomography (CT) pulmonary angiography, and ventilation/perfusion scanning was obtained at the discretion of the treating physicians. Imaging was evaluated by board-certified radiologists in real time. D-dimer values' bins were evaluated using a logistic regression model. Results We evaluated 1,752 patients for suspected deep vein thrombosis (DVT), with 191 (10.4%) DVT positive. We evaluated 1,834 patients for suspected pulmonary embolism (PE), with 108 (5.9%) PE positive. Higher D-dimer values in both groups were associated with higher likelihood of subsequent VTE diagnosis, with D-dimer values > 3,999 ng/mL in both groups having the highest incidence of VTE. More than 50% of those patients were VTE positive. Conclusions Increasing D-dimer values predict increased likelihood of being found VTE positive in this patient population. Among those in the highest D-dimer category, > 3,999 ng/mL, over half of patients were VTE positive. Further research could determine additional nuance in D-dimer as a tool to work up suspected VTE.

Multicenter Implementation of a Novel Management Protocol Increases the Outpatient Treatment of Pulmonary Embolism and Deep Vein Thrombosis.

OBJECTIVE: The objective was to determine whether a protocol combining risk stratification, treatment with the direct-acting oral anticoagulant rivaroxaban, and defined follow-up is associated with a greater proportion of patients with venous thromboembolism (VTE) treated as outpatients, without hospital admission. METHODS: We performed a multicenter study of patients diagnosed with VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) in two urban EDs, 18 months before and 18 months after implementation of an outpatient VTE treatment protocol. Patients with radiographically confirmed acute VTE were eligible. Our primary outcome was the proportion of VTE patients discharged from the ED or observation unit (i.e., without hospital admission). We performed subgroup analyses according to hospital, DVT and PE, and low-risk PE. We also assessed 7- and 30-day mortality, major bleeding, and returns to the ED. We compared proportions using chi-square and Fisher's exact tests. RESULTS: We enrolled 2,212 patients, 1,081 (49%) before protocol and 1,131 (51%) after protocol. Mean age (59 years vs. 60 years), female sex (49% vs. 49%), other demographics, comorbid illness, and PE risk stratification were similar before and after. After protocol, more VTE (35% from 26%, p < 0.001), PE (18% from 12%, p = 0.002), low-risk PE (28% from 18%, p < 0.001), and DVT (60% from 49%, p = 0.002) patients were treated as outpatients. Mortality, bleeding, and returns to ED were rare and did not increase after protocol. CONCLUSIONS: A treatment protocol combining risk-stratification, rivaroxaban treatment and defined follow-up is associated with an increase in PE and DVT patients treated as outpatients, with no increase in adverse outcomes.

International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs.

INTRODUCTION: We sought to determine the test characteristics of an automated INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep venous thrombosis (DVT) in emergency department (ED) patients using standard and age-adjusted cut-offs. METHODS: Cross-sectional, international, multicenter study of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6 Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For the standard cut-off, a D-dimer result <500 ng/ml was negative. For the age adjusted cut-off, we used the formula: Age (years) ∗ 10. The diagnostic standard was imaging demonstrating PE or DVT within 3 months. We calculated test characteristics using standard methods. We also explored modifications of the age adjustment multiplier. RESULTS: We included 3837 patients and excluded 251. The mean age of patients evaluated for PE (n = 1834) was 48 ±â€¯16 years, with 676 (37%) male, and 1081 (59%) white. The mean age of evaluated for DVT (n = 1752) was 53 ±â€¯16 years, with 710 (41%) male, and 1172 (67%) white. D-dimer test characteristics for PE were: sensitivity 98.0%, specificity 55.4%, negative predictive value (NPV) 99.8%, positive predictive value (PPV) 11.4%, and for DVT were: sensitivity 92.0%, specificity 44.8%, NPV 98.8%, PPV 10.3%. Age adjustment increased specificity (59.6% [PE], 51.1% [DVT]), but increasing the age-adjustment multiplier decreased sensitivity without increasing specificity. CONCLUSIONS: INNOVANCE D-dimer is highly sensitive and can exclude PE and DVT in ED patients with low- and intermediate- pre-test probability. Age-adjustment increases specificity, without increasing false negatives.

Effect of Dermatology Consultation on Outcomes for Patients With Presumed Cellulitis: A Randomized Clinical Trial.

Importance: Each year, cellulitis leads to 650 000 hospital admissions and is estimated to cost $3.7 billion in the United States. Previous literature has demonstrated a high misdiagnosis rate for cellulitis, which results in unnecessary antibiotic use and health care cost. Objective: To determine whether dermatologic consultation decreases duration of hospital stay or intravenous antibiotic treatment duration in patients with cellulitis. Design, Setting, and Participants: This randomized clinical trial was conducted in a large urban tertiary care hospital between October 2012 and January 2017, with 1-month follow-up duration. Patients were randomized to the control group, which received the standard of care (ie, treatment by primary medicine team), or the intervention group, which received dermatology consultation. Medical chart review of demographic information and hospital courses was performed. Adult patients hospitalized with presumed diagnosis of cellulitis were eligible. A total of 1300 patients were screened, 1125 were excluded, and 175 were included. Statistical analysis was employed to identify significant outcome differences between the 2 groups. Interventions: Dermatology consultation within 24 hours of hospitalization. Main Outcomes and Measures: Length of hospital stay and duration of intravenous antibiotic treatment. Results: Of 175 participants, 70 (40%) were women and 105 (60%) were men. The mean age was 58.8 years. Length of hospital stay was not statistically different between the 2 groups. The duration of intravenous antibiotic treatment (<4 days: 86.4% vs 72.5%; absolute difference, 13.9%; 95% CI, 1.9%-25.9%; P = .04) and duration of total antibiotic treatment was significantly lower in patients who had early dermatology consultation (<10 days: 50.6% vs 32.5%; absolute difference, 18.1%; 95% CI, 3.7%-32.5%; P = .01). Clinical improvement at 2 weeks was significantly higher for those in the intervention group (79 [89.3%] vs 59 [68.3%]; absolute difference, 21.0%; 95% CI, 9.3%-32.7%; P < .001). There was no significant difference in 1-month readmission rate between the groups (4 [4.5%] vs 6 [6.9%]; absolute difference, -2.4%; 95% CI, -9.3% to 4.5%; P = .54). In the intervention group, the rate of cellulitis misdiagnosis was 30.7% (27 of 88 participants). Among the entire cohort, 101 (57.7%) patients were treated with courses of antibiotics longer than what is recommended by guidelines. Conclusions and Relevance: Early dermatologic consultation can improve outcomes in patients with suspected cellulitis by identifying alternate diagnoses, treating modifiable risk factors, and decreasing length of antibiotic treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01706913.

The creation and implementation of an outpatient pulmonary embolism treatment protocol.

The ability to rapidly and accurately risk-stratify patients with venous thromboembolism (VTE), and the availability of direct acting oral anticoagulants have reduced the need for intravenous anticoagulation for patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). Emergency physicians are generally reluctant to discharge patients with VTE without defined and reliable follow up in place, and VTE patients treated with anticoagulants can be at risk for complications related to recurrent VTE and bleeding. In addition, screening for associated diseases (e.g. cancer, hypercoagulable states) may be indicated. Therefore, the outpatient treatment of low risk VTE requires coordinated effort and reliable follow up. By leveraging detailed outcome data and collaborative relationships, we have created a protocol for the safe outpatient treatment of patients with low risk DVT and PE. Our protocol is data driven and designed to address barriers to outpatient VTE management. We expect our protocol to result in improved patient satisfaction, more efficient emergency department (ED) throughput, and decreased cost. Applied nationally, the outpatient treatment of select patients with DVT and PE could have major public health and economic impact.

Comparison of Emergency Department Patients to Inpatients Receiving a Pulmonary Embolism Response Team (PERT) Activation.

OBJECTIVES: The development of pulmonary embolism response teams (PERTs) has been widely adopted nationally with the goal of providing multidisciplinary care to patients with high-risk PE. Most PERT activations originate from the emergency department (ED), while others are from the intensive care unit (ICU) or inpatient floors. It is unclear if ED PERT activations differ from non-ED PERT activation in terms of presentation, management, and outcome. METHODS: We enrolled a consecutive cohort of patients for whom PERT was activated at an urban academic medical center. We compared three groups of PERT activations based on whether the activation originated from the ED, ICU, or a non-ICU inpatient floor. We compared these groups in terms of the proportion of PERT activations that occurred during day, evening, or weekend hours and the proportion of confirmed PE. We also compared PE severity, treatment, and outcomes across locations. We tested differences using chi-square tests, with a two-tailed p-value of <0.05 considered statistically significant. RESULTS: We enrolled 561 patients, of whom 449 (79.5%) had confirmed PE. The mean ± SD age of patients with confirmed PE was 61 ± 17 years, and 300 (53.5%) were male. Activations from the ED (n = 283, 88.4%) or floor (n = 100, 74.6%) were more likely to be for confirmed PE than activations from the ICU (n = 63, 58.9%; p < 0.0001). There was a statistical difference in the time of day of PERT activation with the ED having more activations during night hours than the ICU or floors (p = 0.004). Most activations for confirmed, massive PE originated from the ICU (n = 41, 65.1%), followed by the ED (n = 82, 29%) and inpatient floors (n = 22, 22%; p < 0.0001). Most activations from the ED (n = 155, 54.8%) and floors (n = 55, 55%) were for submassive PE. The use of thrombolysis or thrombectomy was more common among ICU patients (n = 18, 33.3%), followed by ED patients (n = 53, 19.6%) and then floor patients (n = 8, 8.2%). Mortality and major bleeding events were most common among ICU patients and similar among ED and floor patients. CONCLUSIONS: Pulmonary embolism response team activations from different clinical locations differ in terms of patient presentation, PE confirmation, treatments, and outcomes. PERTs should be customized to support the different needs of each clinical area.

The Outpatient Treatment of Venous Thromboembolism: Operational Impact and the Role of Novel Anticoagulants.

Pulmonary embolism (PE) and venous thromboembolism (VTE) are common diagnoses in the emergency department (ED), with significant potential morbidity and mortality. As a result, historically nearly all patients with PE have been admitted to the hospital for observation and treatment. In recent years, the ability to rapidly and accurately risk stratify patients with VTE according to their risk of short-term clinical deterioration has supported outpatient treatment, and non-vitamin K antagonist oral anticoagulants (NOACs) have further facilitated this approach. This review details the historical context and operational impact of managing VTE in the outpatient setting, describes a model for outpatient management of VTE, and suggests potential areas of further inquiry.

Identifying patients with problematic drug use in the emergency department: results of a multisite study.

STUDY OBJECTIVE: Drug-related emergency department (ED) visits have steadily increased, with substance users relying heavily on the ED for medical care. The present study aims to identify clinical correlates of problematic drug use that would facilitate identification of ED patients in need of substance use treatment. METHODS: Using previously validated tests, 15,224 adult ED patients across 6 academic institutions were prescreened for drug use as part of a large randomized prospective trial. Data for 3,240 participants who reported drug use in the past 30 days were included. Self-reported variables related to demographics, substance use, and ED visit were examined to determine their correlative value for problematic drug use. RESULTS: Of the 3,240 patients, 2,084 (64.3%) met criteria for problematic drug use (Drug Abuse Screening Test score ≥ 3). Age greater than or equal to 30 years, tobacco smoking, daily or binge alcohol drinking, daily drug use, primary noncannabis drug use, resource-intense ED triage level, and perceived drug-relatedness of ED visit were highly correlated with problematic drug use. Among primary cannabis users, correlates of problematic drug use were age younger than 30 years, tobacco smoking, binge drinking, daily drug use, and perceived relatedness of the ED visit to drug use. CONCLUSION: Clinical correlates of drug use problems may assist the identification of ED patients who would benefit from comprehensive screening, intervention, and referral to treatment. A clinical decision rule is proposed. The correlation between problematic drug use and resource-intense ED triage levels suggests that ED-based efforts to reduce the unmet need for substance use treatment may help decrease overall health care costs.