Increasing Uptake of Lung Cancer Screening Among Emergency Department Patients: A Pilot Study.

BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Lung cancer screening (LCS) decreases lung cancer mortality. Emergency department (ED) patients are at disproportionately high risk for lung cancer. The ED, therefore, is an optimal environment for interventions to promote LCS. OBJECTIVES: Demonstrate the operational feasibility of identifying ED patients in need of LCS, referring them to LCS services, deploying a text message intervention to promote LCS, and conducting follow-up to determine LCS uptake. METHODS: We conducted a randomized clinical trial to determine the feasibility and provide estimates of the preliminary efficacies of 1) basic referral for LCS and 2) basic referral plus a text messaging intervention, grounded in behavioral change theory, to promote uptake of LCS among ED patients. Participants aged 50 to 80, identified as eligible for LCS, were randomized to study arms and followed up at 150 days to assess interval LCS uptake (primary outcome), barriers to screening, and perceptions of the study interventions. RESULTS: A total of 303 patients were surveyed, with 198 identified as eligible for LCS and subsequently randomized. Results indicated that 24% of participants with follow-up data received LCS (11% of the total randomized sample). Rates of screening at follow-up were similar across study arms. The intervention significantly improved normative perceptions of LCS (p = 0.015; Cohen's d = 0.45). CONCLUSION: This pilot study demonstrates the feasibility of ED-based interventions to increase uptake of LCS among ED patients. A scalable ED-based intervention that increases LCS uptake could reduce lung cancer mortality.

Risk Stratification of Older Adults Who Present to the Emergency Department With Syncope: The FAINT Score.

STUDY OBJECTIVE: Older adults with syncope are commonly treated in the emergency department (ED). We seek to derive a novel risk-stratification tool to predict 30-day serious cardiac outcomes. METHODS: We performed a prospective, observational study of older adults (≥60 years) with unexplained syncope or near syncope who presented to 11 EDs in the United States. Patients with a serious diagnosis identified in the ED were excluded. We collected clinical and laboratory data on all patients. Our primary outcome was 30-day all-cause mortality or serious cardiac outcome. RESULTS: We enrolled 3,177 older adults with unexplained syncope or near syncope between April 2013 and September 2016. Mean age was 73 years (SD 9.0 years). The incidence of the primary outcome was 5.7% (95% confidence interval [CI] 4.9% to 6.5%). Using Bayesian logistic regression, we derived the FAINT score: history of heart failure, history of cardiac arrhythmia, initial abnormal ECG result, elevated pro B-type natriuretic peptide, and elevated high-sensitivity troponin T. A FAINT score of 0 versus greater than or equal to 1 had sensitivity of 96.7% (95% CI 92.9% to 98.8%) and specificity 22.2% (95% CI 20.7% to 23.8%), respectively. The FAINT score tended to be more accurate than unstructured physician judgment: area under the curve 0.704 (95% CI 0.669 to 0.739) versus 0.630 (95% CI 0.589 to 0.670). CONCLUSION: Among older adults with syncope or near syncope of potential cardiac cause, a FAINT score of zero had a reasonably high sensitivity for excluding death and serious cardiac outcomes at 30 days. If externally validated, this tool could improve resource use for this common condition.

Retrospective analysis of the hemodynamic consequences of prehospital supplemental oxygen in acute stroke.

OBJECTIVE: Hyperoxia, the delivery of high levels of supplemental oxygen (sO2) despite normoxia, may increase cerebral oxygenation to penumbral tissue and improve stroke outcomes. However, it may also alter peripheral hemodynamic profiles with potential negative effects on cerebral blood flow (CBF). This study examines the hemodynamic consequences of prehospital sO2 in stroke. METHODS: A retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017 was conducted using demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records. Outcomes were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariable linear regression were used to determine if sO2 was associated with differences in peripheral hemodynamic profiles. RESULTS: All subjects had similar initial EMS vitals except for oxygen saturation. However, both univariate and multivariable analysis revealed that hyperoxia subjects had slightly lower average ED mean arterial pressures (MAP) compared to normoxia (Cohen's d = 0.313). CONCLUSIONS: Prehospital-initiated hyperoxia for acute stroke is associated with a small, but significant decrease in average ED MAP, without changes in heart rate, compared to normoxia. While limited by the inability to link changes in peripheral hemodynamical profiles directly to changes in CBF, this study suggests that hyperoxia may result in a relative hypotension. Further studies are needed to determine if this small change in peripheral vascular resistance translates into a clinically significant reduced CBF.

Prehospital supplemental oxygen for acute stroke - A retrospective analysis.

OBJECTIVE: Brief early administration of supplemental oxygen (sO2) to create hyperoxia may increase oxygenation to penumbral tissue and improve stroke outcomes. Hyperoxia may also result in respiratory compromise and vasoconstriction leading to worse outcomes. This study examines the effects of prehospital sO2 in stroke. METHODS: This is a retrospective analysis of adult acute stroke patients (aged ≥18 years) presenting via EMS to an academic Comprehensive Stroke Center between January 1, 2013 and December 31, 2017. Demographic and clinical characteristics obtained from Get with the Guidelines-Stroke registry and subjects' medical records were compared across three groups based on prehospital oxygen saturation and sO2 administration. Chi-square, ANOVA, and multivariate logistic regression were used to determine if sO2 status was associated with neurological outcomes or respiratory complications. RESULTS: 1352 eligible patients were identified. 62.7% (n = 848) did not receive sO2 ("controls"), 10.7% (n = 144) received sO2 due to hypoxia ("hypoxia"), and 26.6% (n = 360) received sO2 despite normoxia ("hyperoxia"). The groups represented a continuum from more severe deficits (hypoxia) to less severe deficits (controls): mean prehospital GCS (hypoxia -12, hyperoxia - 2, controls - 14 p ≤ 0.001), mean initial NIHSS (hypoxia - 15, hyperoxia - 13, controls - 8 p < 0.001). After controlling for potential confounders, all groups had similar rates of respiratory complications and favorable neurological outcomes. CONCLUSIONS: Hyperoxic subjects had no significant increase in respiratory complications, nor did they differ in neurologic outcomes at discharge when controlling for confounders. While limited by the retrospective nature, this suggests brief, early sO2 for stroke may be safe to evaluate prospectively.

The Accuracy of Interqual Criteria in Determining the Observation versus Inpatient Status in Older Adults with Syncope.

BACKGROUND: McKesson's InterQual criteria are widely used in hospitals to determine if patients should be classified as observation or inpatient status, but the accuracy of the criteria is unknown. OBJECTIVE: We sought to determine whether InterQual criteria accurately predicted length of stay (LOS) in older patients with syncope. METHODS: We conducted a secondary analysis of a cohort study of adults ≥60 years of age who had syncope. We calculated InterQual criteria and classified the patient as observation or inpatient status. Outcomes were whether LOS were less than or greater than 2 midnights. RESULTS: We analyzed 2361 patients; 1227 (52.0%) patients were male and 1945 (82.8%) were white, with a mean age of 73.2 ± 9.0 years. The median LOS was 32.6 h (interquartile range 24.2-71.8). The sensitivity of InterQual criteria for LOS was 60.8% (95% confidence interval 57.9-63.6%) and the specificity was 47.8% (95% confidence interval 45.0-50.5%). CONCLUSIONS: In older adults with syncope, those who met InterQual criteria for inpatient status had longer LOS compared with those who did not; however, the accuracy of the criteria to predict length of stay over 2 days is poor, with a sensitivity of 60% and a specificity of 48%. Future research should identify criteria to improve LOS prediction.

Clinical Benefit of Hospitalization for Older Adults With Unexplained Syncope: A Propensity-Matched Analysis.

STUDY OBJECTIVE: Many adults with syncope are hospitalized solely for observation and testing. We seek to determine whether hospitalization versus outpatient management for older adults with unexplained syncope is associated with a reduction in postdisposition serious adverse events at 30 days. METHODS: We performed a propensity score analysis using data from a prospective, observational study of older adults with unexplained syncope or near syncope who presented to 11 emergency departments (EDs) in the United States. We enrolled adults (≥60 years) who presented with syncope or near syncope. We excluded patients with a serious diagnosis identified in the ED. Clinical and laboratory data were collected on all patients. The primary outcome was rate of post-ED serious adverse events at 30 days. RESULTS: We enrolled 2,492 older adults with syncope and no serious ED diagnosis from April 2013 to September 2016. Mean age was 73 years (SD 8.9 years), and 51% were women. The incidence of serious adverse events within 30 days after the index visit was 7.4% for hospitalized patients and 3.19% for discharged patients, representing an unadjusted difference of 4.2% (95% confidence interval 2.38% to 6.02%). After propensity score matching on risk of hospitalization, there was no statistically significant difference in serious adverse events at 30 days between the hospitalized group (4.89%) and the discharged group (2.82%) (risk difference 2.07%; 95% confidence interval -0.24% to 4.38%). CONCLUSION: In our propensity-matched sample of older adults with unexplained syncope, for those with clinical characteristics similar to that of the discharged cohort, hospitalization was not associated with improvement in 30-day serious adverse event rates.

Comparison of 30-Day Serious Adverse Clinical Events for Elderly Patients Presenting to the Emergency Department With Near-Syncope Versus Syncope.

STUDY OBJECTIVE: Controversy remains in regard to the risk of adverse events for patients presenting with syncope compared with near-syncope. The purpose of our study is to describe the difference in outcomes between these groups in a large multicenter cohort of older emergency department (ED) patients. METHODS: From April 28, 2013, to September 21, 2016, we conducted a prospective, observational study across 11 EDs in adults (≥60 years) with syncope or near-syncope. A standardized data extraction tool was used to collect information during their index visit and at 30-day follow-up. Our primary outcome was the incidence of 30-day death or serious clinical events. Data were analyzed with descriptive statistics and multivariate logistic regression analysis adjusting for relevant demographic or historical variables. RESULTS: A total of 3,581 patients (mean age 72.8 years; 51.6% men) were enrolled in the study. There were 1,380 patients (39%) presenting with near-syncope and 2,201 (61%) presenting with syncope. Baseline characteristics revealed a greater incidence of congestive heart failure, coronary artery disease, previous arrhythmia, nonwhite race, and presenting dyspnea in the near-syncope compared with syncope cohort. There were no differences in the primary outcome between the groups (near-syncope 18.7% versus syncope 18.2%). A multivariate logistic regression analysis identified no difference in 30-day serious outcomes for patients with near-syncope (odds ratio 0.94; 95% confidence interval 0.78 to 1.14) compared with syncope. CONCLUSION: Near-syncope confers risk to patients similar to that of syncope for the composite outcome of 30-day death or serious clinical event.

QTc prolongation as a marker of 30-day serious outcomes in older patients with syncope presenting to the Emergency Department.

BACKGROUND: Syncope is a common chief complaint in the ED, and the electrocardiogram (ECG) is a routine diagnostic tool in the evaluation of syncope. We assessed whether increasingly prolonged QTc intervals are associated with composite 30-day serious outcomes in older adults presenting to the ED with syncope. METHODS: This is a secondary analysis of a prospective, observational study at 11 EDs in adults 60 years or older who presented with syncope or near syncope. We excluded patients presenting without an ECG, measurement of QTc, non-sinus rhythm, bundle branch block or those without 30-day follow-up. We categorized QTc cutoffs into values of <451; 451-470; 471-500, and >500 ms. We determined the rate of composite 30-day serious outcomes including ED serious outcomes and 30-day arrhythmias not identified in ED. RESULTS: The study cohort included 2609 patients. There were 1678 patients (64.3%) that had QTc intervals <451 ms; 544 (20.8%) were 451-470 ms; 302 (11.6%) were 471-500 ms, and 85 (3.3%) had intervals >500 ms. Composite 30-day serious outcomes was associated with increasingly prolonged QTc intervals (13.0%, 15.3%, 18.2%, 22.4%, p = 0.01), but this association did not persist in multivariate analysis. CONCLUSIONS: In a cohort of older patients presenting with syncope, increased QTc interval was a marker of but was not independently predictive of composite 30-day serious outcomes.

Recurrent syncope is not an independent risk predictor for future syncopal events or adverse outcomes.

Almost 20% of patients with syncope will experience another event. It is unknown whether recurrent syncope is a marker for a higher or lower risk etiology of syncope. The goal of this study is to determine whether older adults with recurrent syncope have a higher likelihood of 30-day serious clinical events than patients experiencing their first episode. METHODS: This study is a pre-specified secondary analysis of a multicenter prospective, observational study conducted at 11 emergency departments in the US. Adults 60 years or older who presented with syncope or near syncope were enrolled. The primary outcome was occurrence of 30-day serious outcome. The secondary outcome was 30-day serious cardiac arrhythmia. In multivariate analysis, we assessed whether prior syncope was an independent predictor of 30-day serious events. RESULTS: The study cohort included 3580 patients: 1281 (35.8%) had prior syncope and 2299 (64.2%) were presenting with first episode of syncope. 498 (13.9%) patients had 1 prior episode while 771 (21.5%) had >1 prior episode. Those with recurrent syncope were more likely to have congestive heart failure, coronary artery disease, previous diagnosis of arrhythmia, and an abnormal ECG. Overall, 657 (18.4%) of the cohort had a serious outcome by 30 days after index ED visit. In multivariate analysis, we found no significant difference in risk of events (adjusted odds ratio 1.09; 95% confidence interval 0.90-1.31; p = 0.387). CONCLUSION: In older adults with syncope, a prior history of syncope within the year does not increase the risk for serious 30-day events.

Orthostatic vital signs do not predict 30 day serious outcomes in older emergency department patients with syncope: A multicenter observational study.

BACKGROUND: Syncope is a common chief complaint among older adults in the Emergency Department (ED), and orthostatic vital signs are often a part of their evaluation. We assessed whether abnormal orthostatic vital signs in the ED are associated with composite 30-day serious outcomes in older adults presenting with syncope. METHODS: We performed a secondary analysis of a prospective, observational study at 11 EDs in adults ≥ 60 years who presented with syncope or near syncope. We excluded patients lost to follow up. We used the standard definition of abnormal orthostatic vital signs or subjective symptoms of lightheadedness upon standing to define orthostasis. We determined the rate of composite 30-day serious outcomes, including those during the index ED visit, such as cardiac arrhythmias, myocardial infarction, cardiac intervention, new diagnosis of structural heart disease, stroke, pulmonary embolism, aortic dissection, subarachnoid hemorrhage, cardiopulmonary resuscitation, hemorrhage/anemia requiring transfusion, with major traumatic injury from fall, recurrent syncope, and death) between the groups with normal and abnormal orthostatic vital signs. RESULTS: The study cohort included 1974 patients, of whom 51.2% were male and 725 patients (37.7%) had abnormal orthostatic vital signs. Comparing those with abnormal to those with normal orthostatic vital signs, we did not find a difference in composite 30-serious outcomes (111/725 (15.3%) vs 184/1249 (14.7%); unadjusted odds ratio, 1.05 [95%CI, 0.81-1.35], p = 0.73). After adjustment for gender, coronary artery disease, congestive heart failure (CHF), history of arrhythmia, dyspnea, hypotension, any abnormal ECG, physician risk assessment, medication classes and disposition, there was no association with composite 30-serious outcomes (adjusted odds ratio, 0.82 [95%CI, 0.62-1.09], p = 0.18). CONCLUSIONS: In a cohort of older adult patients presenting with syncope who were able to have orthostatic vital signs evaluated, abnormal orthostatic vital signs did not independently predict composite 30-day serious outcomes.

Predictors of Short Intensive Care Unit Stay for Patients with Diabetic Ketoacidosis Using a Novel Emergency Department-Based Resuscitation and Critical Care Unit.

BACKGROUND: The resuscitation and critical care unit is a novel emergency department-intensive care unit designed to provide early critical care to emergency department patients for ≤24 h. OBJECTIVES: This study sought to identify clinical variables associated with short intensive care unit (ICU) stays in patients with diabetic ketoacidosis (DKA), who commonly require ICU-level care. METHODS: We conducted a retrospective, single-center, cross-sectional study of DKA patients ≥18 years of age who presented to an academic, urban hospital emergency department over 16 months. Patient demographics and clinical variables extracted from medical records were compared between prolonged ICU stay patients of ≥24 h versus short ICU stay patients (SSPs) of <24 h. ICU care was defined as treatment in the resuscitation and critical care unit or inpatient ICU. RESULTS: One hundred sixty-eight emergency department visits with a primary diagnosis of DKA were analyzed. There were 53 prolonged ICU stay patients, 58 SSPs, and 57 patients required no ICU time. SSPs had significantly higher initial serum bicarbonate (13.0 vs. 9.0 mEq/L, p = 0.01) and shorter anion gap closure time (9.8 vs. 14.4 hours, p = 0.003). Medication nonadherence was a significantly more frequent precipitant in SSPs (67.2% vs. 47.2%, p = 0.03). Initial anion gap, glucose, beta-hydroxybutyrate, and severity of illness scores were not significantly different between groups. After multivariate logistic regression adjusting for variables significant from univariate analysis, higher initial bicarbonate (p = 0.04) and medication nonadherence (p = 0.03) remained significantly associated with SSPs. CONCLUSIONS: Patients with DKA with short ICU stays have higher initial bicarbonate levels and are more likely to have medication nonadherence than patients requiring prolonged critical care. These variables may identify patients with DKA who are best treated in an emergency department-intensive care unit to potentially reduce inpatient ICU use.

ECG Predictors of Cardiac Arrhythmias in Older Adults With Syncope.

STUDY OBJECTIVE: Cardiac arrhythmia is a life-threatening condition in older adults who present to the emergency department (ED) with syncope. Previous work suggests the initial ED ECG can predict arrhythmia risk; however, specific ECG predictors have been variably specified. Our objective is to identify specific ECG abnormalities predictive of 30-day serious cardiac arrhythmias in older adults presenting to the ED with syncope. METHODS: We conducted a prospective, observational study at 11 EDs in adults aged 60 years or older who presented with syncope or near syncope. We excluded patients with a serious cardiac arrhythmia diagnosed during the ED evaluation from the primary analysis. The outcome was occurrence of 30-day serous cardiac arrhythmia. The exposure variables were predefined ECG abnormalities. Independent predictors were identified through multivariate logistic regression. The sensitivities and specificities of any predefined ECG abnormality and any ECG abnormality identified on adjusted analysis to predict 30-day serious cardiac arrhythmia were also calculated. RESULTS: After exclusion of 197 patients (5.5%; 95% confidence interval [CI] 4.7% to 6.2%) with serious cardiac arrhythmias in the ED, the study cohort included 3,416 patients. Of these, 104 patients (3.0%; 95% CI 2.5% to 3.7%) had a serious cardiac arrhythmia within 30 days from the index ED visit (median time to diagnosis 2 days [interquartile range 1 to 5 days]). The presence of nonsinus rhythm, multiple premature ventricular conductions, short PR interval, first-degree atrioventricular block, complete left bundle branch block, and Q wave/T wave/ST-segment abnormalities consistent with acute or chronic ischemia on the initial ED ECG increased the risk for a 30-day serious cardiac arrhythmia. This combination of ECG abnormalities had a similar sensitivity in predicting 30-day serious cardiac arrhythmia compared with any ECG abnormality (76.9% [95% CI 67.6% to 84.6%] versus 77.9% [95% CI 68.7% to 85.4%]) and was more specific (55.1% [95% CI 53.4% to 56.8%] versus 46.6% [95% CI 44.9% to 48.3%]). CONCLUSION: In older ED adults with syncope, approximately 3% receive a diagnosis of a serious cardiac arrhythmia not recognized on initial ED evaluation. The presence of specific abnormalities on the initial ED ECG increased the risk for 30-day serious cardiac arrhythmias.

Cervical dysplasia and high-risk human papillomavirus infections among HIV-infected and HIV-uninfected adolescent females in South Africa.

BACKGROUND: HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. METHODS: In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ (2) and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. RESULTS: HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. CONCLUSIONS: HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV.

Transkingdom Analysis of the Female Reproductive Tract Reveals Bacteriophages form Communities.

The female reproductive tract (FRT) microbiome plays a vital role in maintaining vaginal health. Viruses are key regulators of other microbial ecosystems, but little is known about how the FRT viruses (virome), particularly bacteriophages that comprise the phageome, impact FRT health and dysbiosis. We hypothesize that bacterial vaginosis (BV) is associated with altered FRT phageome diversity, transkingdom interplay, and bacteriophage discriminate taxa. Here, we conducted a retrospective, longitudinal analysis of vaginal swabs collected from 54 BV-positive and 46 BV-negative South African women. Bacteriome analysis revealed samples clustered into five distinct bacterial community groups (CGs), and further, bacterial alpha diversity was significantly associated with BV. Virome analysis on a subset of baseline samples showed FRT bacteriophages clustering into novel viral state types (VSTs), a viral community clustering system based on virome composition and abundance. Distinct BV bacteriophage signatures included increased alpha diversity along with discriminant Bacillus, Burkholderia, and Escherichia bacteriophages. Bacteriophage-bacteria transkingdom associations were also identified between Bacillus and Burkholderia viruses and BV-associated bacteria, providing key insights for future studies elucidating the transkingdom interactions driving BV-associated microbiome perturbations. In this cohort, bacteriophage-bacterial associations suggest complex interactions, which may play a role in the establishment and maintenance of BV.

Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction.

Cytosolic phospholipase A2alpha (cPLA2alpha) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as prostaglandins and leukotrienes. Considerable understanding of cPLA2alpha function has been derived from investigations of the enzyme and from cPLA2alpha-null mice, but knowledge of discrete roles for this enzyme in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due to his multiple, complicated small intestinal ulcers despite no use of cyclooxygenase inhibitors. Levels of thromboxane B2 and 12-hydroxyeicosatetraenoic acid produced by platelets and leukotriene B4 released from calcium ionophore-activated blood were markedly reduced, indicating defective enzymatic release of the arachidonic acid substrate for the corresponding cyclooxygenase and lipoxygenases. Platelet aggregation and degranulation induced by adenosine diphosphate or collagen were diminished but were normal in response to arachidonic acid. Two heterozygous single base pair mutations and a known SNP were found in the coding regions of the patient's cPLA2alpha genes (p.[Ser111Pro]+[Arg485His; Lys651Arg]). The total PLA2 activity in sonicated platelets was diminished, and the urinary metabolites of prostacyclin, prostaglandin E2, prostaglandin D2, and thromboxane A2 were also reduced. These findings characterize what we believe is a novel inherited deficiency of cPLA2.

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.

The enteropathy of prostaglandin deficiency.

BACKGROUND: Small intestinal ulcers are frequent complications of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). We present here a genetic deficiency of eicosanoid biosynthesis that illuminates the mechanism of NSAID-induced ulcers of the small intestine. METHODS: Eicosanoids and metabolites were measured by isotope dilution with mass spectrometry. cDNA was obtained by reverse transcription and sequenced following amplification with RT-PCR. RESULTS: We investigated the cause of chronic recurrent small intestinal ulcers, small bowel perforations, and gastrointestinal blood loss in a 45-year-old man who was not taking any cyclooxygenase inhibitor. Prostaglandin metabolites in urine were significantly depressed. Serum thromboxane B2 (TxB2) production was 4.6% of normal controls (P<0.006), and serum 12-HETE was 1.3% of controls (P<0.005). Optical platelet aggregation with simultaneous monitoring of ATP release demonstrated absent granule secretion in response to ADP and a blunted aggregation response to ADP and collagen, but normal response to arachidonic acid (AA). LTB4 biosynthesis by ionophore-activated leukocytes was only 3% of controls, and urinary LTE4 was undetectable. These findings suggested deficient AA release from membrane phospholipids by cytosolic phospholipase A2-alpha (cPLA2-alpha), which regulates cyclooxygenase- and lipoxygenase-mediated eicosanoid production by catalyzing the release of their substrate, AA. Sequencing of cPLA2-alpha cDNA demonstrated two heterozygous nonsynonymous single-base-pair mutations: Ser111Pro (S111P) and Arg485His (R485H), as well as a known single nucleotide polymorphism (SNP), Lys651Arg (K651R). CONCLUSIONS: Characterization of this cPLA2-alpha deficiency provides support for the importance of prostaglandins in protecting small intestinal integrity and indicates that loss of prostaglandin biosynthesis is sufficient to produce small intestinal ulcers.

Do High-sensitivity Troponin and Natriuretic Peptide Predict Death or Serious Cardiac Outcomes After Syncope?

OBJECTIVES: An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high-sensitivity troponin (hscTnT) and natriuretic peptide (NT-proBNP) are unclear. The objective of this study was to determine if hscTnT and NT-proBNP drawn in the ED are independently associated with 30-day death/serious cardiac outcomes in adult patients presenting with syncope. METHODS: A prespecified secondary analysis of a prospective, observational trial enrolling participants ≥ age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow-up. Within 3 hours of consent, hscTnT and NT-proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30-day all-cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods. RESULTS: The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT-proBNP levels. HscTnT levels ≤ 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%-5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%-33%) risk. NT-proBNP levels ≤ 125 ng/L were associated with a 4% (95% CI = 4%-5%) risk, and NT-proBNP > 2,000 ng/L a 29% (95% CI = 25%-32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses excluding ED index serious outcomes demonstrated similar findings. CONCLUSIONS: hscTnT and NT-proBNP are independent predictors of 30-day death and serious outcomes in older ED patients presenting with syncope.

Predictors of Clinically Significant Echocardiography Findings in Older Adults with Syncope: A Secondary Analysis.

BACKGROUND: Syncope is a common reason for visiting the emergency department (ED) and is associated with significant healthcare resource utilization. OBJECTIVE: To develop a risk-stratification tool for clinically significant findings on echocardiography among older adults presenting to the ED with syncope or nearsyncope. DESIGN: Prospective, observational cohort study from April 2013 to September 2016. SETTING: Eleven EDs in the United States. PATIENTS: We enrolled adults (=60 years) who presented to the ED with syncope or near-syncope who underwent transthoracic echocardiography (TTE). MEASUREMENTS: The primary outcome was a clinically significant finding on TTE. Clinical, electrocardiogram, and laboratory variables were also collected. Multivariable logistic regression analysis was used to identify predictors of significant findings on echocardiography. RESULTS: A total of 3,686 patients were enrolled. Of these, 995 (27%) received echocardiography, and 215 (22%) had a significant finding on echocardiography. Regression analysis identified five predictors of significant finding: (1) history of congestive heart failure, (2) history of coronary artery disease, (3) abnormal electrocardiogram, (4) high-sensitivity troponin-T >14 pg/mL, and 5) N-terminal pro B-type natriuretic peptide >125 pg/mL. These five variables make up the ROMEO (Risk Of Major Echocardiography findings in Older adults with syncope) criteria. The sensitivity of a ROMEO score of zero for excluding significant findings on echocardiography was 99.5% (95% CI: 97.4%-99.9%) with a specificity of 15.4% (95% CI: 13.0%-18.1%). CONCLUSIONS: If validated, this risk-stratification tool could help clinicians determine which syncope patients are at very low risk of having clinically significant findings on echocardiography. REGISTRATION: ClinicalTrials.gov Identifier NCT01802398.