Person:

Kabrhel, Christopher

Purpose: Clinical decision rules for the disposition of patients with pulmonary embolism (PE) are typically validated against an outcome of 30-day mortality or disease recurrence. There is little justification for this time frame, nor is it clear whether this outcome reflects emergency department (ED) decision making. Aims: To determine which outcomes emergency physicians (EP) consider most relevant to disposition decisions. Methods: Survey of attending EPs in geographically diverse US states using acute PE as the diagnostic framework. Responses required single-answer multiple choice, a numerical percentage, rank-ordered responses, or a five-point Likert scale. We distributed the survey via e-mail to 608 EPs. Results: We received responses from 292 (48%) EPs: 88% board certified, 91% trained in emergency medicine, and 70% work in academics. Respondents reported discharging 1% of patients with PE from the ED, but 21% reported being asked to do so by an admitting service. EPs were more interested in knowing 5-day (in hospital) outcomes [192/265, 72% (95% exact CI=66%–78%)] than 30-day outcomes [39/261, 15% (95% exact CI=11%–20%)] or 90-day outcomes [29/263, 11% (95% exact CI=8%–15%)]. On a Likert scale, 212/241 (88%, 95% exact CI=83%–92%) agreed or strongly agreed that they considered 5-day (in hospital) clinical deterioration when making a decision to admit or discharge a patient from the ED compared to 184/242 (76%, 95% exact CI=70%–81%) and 73/242 (30%, 95% exact CI=24%–36%) for 30 and 90 days, respectively. A wide variety of clinical outcomes beyond death or recurrent PE were considered indicative of clinical deterioration. Conclusions: Five-day (in hospital) outcomes that incorporate a variety of clinical deterioration events are of interest to EPs when determining the disposition of ED patients with PE. Researchers should consider this when developing and validating clinical decision rules.

Background: Pulmonary embolism (PE) is the most serious manifestation of venous thromboembolism and a leading cause of sudden death. Several studies have suggested associations of venous thromboembolism with short-term particulate matter (PM) exposure; evidence on long-term PM and traffic exposure is mixed. Objectives: We examined the association of long-term exposure to PM2.5, PM2.5–10, and PM10 (PM with diameter of ≤ 2.5, 2.5–10, and ≤ 10 μm) and distance to roadways with overall incident PE and with PE subtypes in a cohort of U.S. women. Methods: The study included 115,745 women from the Nurses’ Health Study, followed from 1992 through 2008. Incident PE cases were self-reported biennially. Nonidiopathic PE were cases for which the medical record revealed an underlying health condition related to PE (i.e., surgery, trauma, or malignancy); idiopathic PE were cases with no such history. We used spatiotemporal models combining spatial smoothing and geographic covariates to quantify exposure at residential addresses, and Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CIs). Results: PM2.5 averaged over 1 month (HR = 1.22; 95% CI: 1.04, 1.44) or 12 months (HR = 1.17; 95% CI: 0.93, 1.48) was associated with incident PE, after adjusting for known risk factors and PM2.5–10. Equivalent analyses restricted to PE subtypes showed a positive association for PM2.5 with nonidiopathic PE, but not with idiopathic PE. We did not find evidence of an association between distance to roadways and PE risk. Conclusions: We provide evidence that PM in the prior 1 and 12 months is associated with PE risk. Our results also suggest that women with underlying health conditions may be more susceptible to PE after PM exposure. Citation Pun VC, Hart JE, Kabrhel C, Camargo CA Jr, Baccarelli AA, Laden F. 2015. Prospective study of ambient particulate matter exposure and risk of pulmonary embolism in the Nurses’ Health Study cohort. Environ Health Perspect 123:1265–1270; http://dx.doi.org/10.1289/ehp.1408927

Background: Trauma exposure and posttraumatic stress disorder (PTSD) have been linked to myocardial infarction and stroke in women, with biological and behavioral mechanisms implicated in underlying risk. The third most common cardiovascular illness, venous thromboembolism (VTE), is a specific health risk for women. Given previous associations with other cardiovascular diseases, we hypothesized that high levels of trauma and PTSD symptoms would be associated with higher risk of incident VTE in younger and middle‐aged women. Methods and Results: We used proportional hazards models to estimate hazard ratios (HRs) and 95% CIs for new‐onset VTE (960 events) over 22 years in 49 296 women in the Nurses’ Health Study II. Compared to no trauma exposure, both trauma exposure and PTSD symptoms were significantly associated with increased risk of developing VTE, adjusting for demographics, family history, and childhood adiposity. Women with the most PTSD symptoms exhibited the greatest risk elevation: trauma/6 to 7 symptoms: HR=2.42 (95% CI, 1.83–3.20); trauma/4 to 5 symptoms: HR=2.00 (95% CI, 1.55–2.59); trauma/1 to 3 symptoms: HR=1.44 (95% CI, 1.12–1.84); trauma/no symptoms: HR=1.72 (95% CI, 1.43–2.08). Results were similar, although attenuated, when adjusting for VTE‐relevant medications, medical conditions, and health behaviors. Conclusions: Women with the highest PTSD symptom levels had nearly a 2‐fold increased risk of VTE compared to women without trauma exposure in fully adjusted models. Trauma exposure alone was also associated with elevated VTE risk. Trauma and PTSD symptoms may be associated with a hypercoagulable state. Treatment providers should be aware that women with trauma exposure and PTSD symptoms may be vulnerable to VTE.

The diagnosis or exclusion of pulmonary embolism (PE) remains challenging for emergency physicians. Symptoms can be vague or non-existent, and the clinical presentation shares features with many other common diagnoses. Diagnostic testing is complicated, as biomarkers, like the D-dimer, are frequently false positive, and imaging, like computed tomography pulmonary angiography, carries risks of radiation and contrast dye exposure. It is therefore incumbent on emergency physicians to be both vigilant and thoughtful about this diagnosis. In recent years, several advances in treatment have also emerged. Novel, direct-acting oral anticoagulants make the outpatient treatment of low risk PE easier than before. However, the spectrum of PE severity varies widely, so emergency physicians must be able to risk-stratify patients to ensure the appropriate disposition. Finally, PE response teams have been developed to facilitate rapid access to advanced therapies (e.g., catheter directed thrombolysis) for patients with high-risk PE. This review will discuss the clinical challenges of PE diagnosis, risk stratification and treatment that emergency physicians face every day.

The Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95% CI: 1.79–2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.

Introduction: The American College of Emergency Physicians guidelines recommend more aggressive workup beyond imaging alone in patients with a high pretest probability (PTP) of pulmonary embolism (PE). However, the ability of multiple tests to safely rule out PE in high PTP patients is not known. We sought to measure the ability of negative computed tomography pulmonary angiography (CTPA) along with negative D-dimer to rule out PE in these high-risk patients. Methods: We analyzed data from a previous prospective observational study conducted in 12 emergency departments (ED). Wells score criteria were entered by providers before final PE testing. PE was diagnosed by imaging on the index ED visit, or within 45 days, demonstrating either PE or deep vein thrombosis (DVT), or if the patient died of PE during the 45-day, follow-up period. Testing threshold was set at 1.8%. Results: A total of 7,940 patients were enrolled and tested for PE, and 257 had high PTP (Wells >6). Sixteen of these high-risk patients had negative CTPA and negative D-dimer, of whom two were positive for PE (12.5% [95% confidence interval {2.2%–40.0%}]). One of these patients had a DVT on CT venogram and the other was diagnosed at follow-up. Conclusion: Our analysis suggests that in patients with high PTP of PE, neither negative CTPA by itself nor a negative CTPA plus a negative D-dimer are sufficient to rule out PE. More aggressive workup strategies may be required for these patients.