Emily L. Wilson

Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome: Study Rationale and Design (ASTRO-APS)

Background: Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by thrombosis, pregnancy morbidity, and the presence of characteristic antibodies. Current therapy for patients having APS with a history of thrombosis necessitates anticoagulation with the vitamin K antagonist warfarin, a challenging drug to manage. Apixaban, approved for the treatment and prevention of venous thrombosis with a low rate of bleeding observed, has never been studied among patients with APS. Aims and Methods: We report study rationale and design of Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome (ASTRO-APS), a prospective randomized open-label blinded event pilot study that will randomize patients with a clinical diagnosis of APS receiving therapeutic anticoagulation to either adjusted-dose warfarin or apixaban 2.5 mg twice a day. We aim to report our ability to identify, recruit, randomize, and retain patients with APS randomized to apixaban compared with warfarin. We will report clinically important outcomes of thrombosis and bleeding. All clinical outcomes will be adjudicated by a panel blinded to the treatment arm. A unique aspect of this study is the enrollment of patients with an established clinical diagnosis of APS. Also unique is our use of electronic medical record interrogation techniques to identify patients who would likely meet our inclusion criteria and use of an electronic portal for follow-up visit data capture. Conclusion: ASTRO-APS will be the largest prospective study to date comparing a direct oral anticoagulant with warfarin among patients with APS for the secondary prevention of thrombosis. Our inclusion criteria assure that outcomes obtained will be clinically applicable to the routine management of patients with APS receiving indefinite anticoagulation.

Application of a simplified definition of diastolic function in severe sepsis and septic shock.

BackgroundLeft ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition.MethodsIn this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24xa0h of onset of sepsis (median 4.3xa0h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition.ResultsWe studied 167 patients. The ASE 2009 definition categorized only 35xa0% of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e′ and E/e′, omitting the other measurements. The simplified definition categorized 87xa0% of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension.ConclusionsA novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

Characteristics associated with clinician diagnosis of aspiration pneumonia: a descriptive study of afflicted patients and their outcomes.

BACKGROUNDnAspiration pneumonia is a common disease, although less well characterized than other pneumonia syndromes.nnnOBJECTIVEnWe analyzed patient-level covariates associated with clinician-defined aspiration pneumonia.nnnMETHODSnWe used the Community-Acquired Pneumonia Organization database, a multicenter, international population of patients with community-acquired pneumonia, using data from 2001 to 2012. Aspiration pneumonia was determined by the treating clinician. We analyzed covariates associated with clinician-defined diagnosis of aspiration pneumonia using logistic regression. We compared aspiration pneumonia patients to propensity-matched cases with nonaspiration pneumonia.nnnRESULTSnWe studied 5185 patients. Four hundred fifty-one of these patients had aspiration pneumonia. Patients with aspiration pneumonia were older, had greater disease severity, and more comorbidities than patients with nonaspiration pneumonia. They were more likely cared for in the intensive care unit (19% vs 13%, Pu2009=u20090.002), had longer unadjusted hospital length of stay (9 vs 7 days, Pu2009<u20090.001), and took longer to achieve clinical stability (unadjusted 8 vs 4 days, Pu2009<u20090.001). Confusion, nursing home residence, and cerebrovascular disease were most associated with clinician diagnosis of aspiration pneumonia (odds ratio: 4.4, 2.9, 2.3, respectively). Unadjusted inpatient mortality was higher (23% vs 9%, Pu2009<u20090.001). Aspiration pneumonia conferred a 2.3 odds ratio for inpatient mortality after adjusting for age, disease severity, and comorbidities.nnnCONCLUSIONSnAmong pneumonia patients, confusion, nursing home residence, and cerebrovascular disease are associated with a clinician diagnosis of aspiration. Aspiration pneumonia is associated with greater mortality among patients with community-acquired pneumonia, which is not explained by older age, measured indices of severity, or comorbidities.

In-hospital outcomes and costs of surgical stabilization versus nonoperative management of severe rib fractures.

BACKGROUND One factor that has precluded the wide adoption of surgical stabilization of rib fractures (SSRF) is the perception that it is too expensive to surgically repair an injury that will eventually heal without intervention. The purpose of this study was to compare in-hospital outcomes, costs, and charges for SSRF patients with a series of propensity-matched, nonoperatively managed rib fracture (NON-OP) patients at a single Level 1 trauma center. METHODS All patients admitted with rib fractures between January 2009 and June 2013 were identified. Patient demographics, injury, cost, and charge data were collected. Two-to-one propensity score matching was used to identify NON-OP patients who were similar to the SSRF patients. Zero-inflated negative binomial regression was conducted to assess the relationship among SSRF, intensive care unit (ICU) length of stay (LOS), and ventilator days. Cost and charge information was compared using Wilcoxon rank-sum tests. RESULTS A total of 411 patients (137 SSRF, 274 NON-OP) were included in the analysis. Ventilator days and ICU LOS in days were not different between the SSRF and NON-OP groups when compared using the Wilcoxon rank-sum test. Ventilator and ICU days were less for SSRF by 2.24 days and 1.62 days, respectively, using zero-inflated negative binomial analysis to exclude the large number of patients who had 0 day on the ventilator and/or in the ICU. SSRF patients had higher hospital costs and total relevant charges compared with the NON-OP patients. Subgroup analysis of patients requiring mechanical ventilation who did not have head injury showed decreased ventilator days (median, 3 days vs. 5 days; p = 0.03) and need for tracheostomy (5% vs. 23%, p = 0.02) in SSRF versus NON-OP, respectively. In this subgroup, there was no difference in hospital costs and charges between SSRF and NON-OP. CONCLUSION SSRF patients have shorter ICU LOS and less ventilator days than NON-OP across a diverse group of patients. Hospital costs and charges for SSRF patients are higher. In mechanically ventilated patients who do not have head injury, in-hospital outcomes are better, and there is no difference in hospital costs and charges. Further prospective cost-effectiveness research will determine whether improved quality of life and ability to return to meaningful activity sooner outweighs the increased costs of the acute care episode for SSRF patients. LEVEL OF EVIDENCE Epidemiologic study, level III.

Association of left ventricular longitudinal strain with central venous oxygen saturation and serum lactate in patients with early severe sepsis and septic shock.

IntroductionIn septic shock, assessment of cardiac function often relies on invasive central venous oxygen saturation (ScvO2). Ventricular strain is a non-invasive method of assessing ventricular wall deformation and may be a sensitive marker of heart function. We hypothesized that it may have a relationship with ScvO2 and lactate.MethodsWe prospectively performed transthoracic echocardiography in patients with severe sepsis or septic shock and measured (1) left ventricular longitudinal strain from a four-chamber view and (2) ScvO2. We excluded patients for whom image quality was inadequate or for whom ScvO2 values were unobtainable. We determined the association between strain and ScvO2 with logistic and linear regression, using covariates of mean arterial pressure, central venous pressure, and vasopressor dose. We determined the association between strain and lactate. We considered strain greater than −17 % as abnormal and strain greater than −10 % as severely abnormal.ResultsWe studied 89 patients, 68 of whom had interpretable images. Of these patients, 42 had measurable ScvO2. Sixty percent of patients had abnormal strain, and 16 % had severely abnormal strain. Strain is associated with low ScvO2 (linear coefficient −1.05, p =0.006; odds ratio 1.23 for ScvO2 <60 %, p =0.016). Patients with severely abnormal strain had significantly lower ScvO2 (56.1 % vs. 67.5 %, p <0.01) and higher lactate (2.7 vs. 1.9 mmol/dl, p =0.04) than those who did not. Strain was significantly different between patients, based on a threshold ScvO2 of 60 % (−13.7 % vs. -17.2 %, p =0.01) but not at 70 % (−15.0 % vs. −18.2 %, p =0.08).ConclusionsLeft ventricular strain is associated with low ScvO2 and hyperlactatemia. It may be a non-invasive surrogate for adequacy of oxygen delivery during early severe sepsis or septic shock.

The prevalence and impact of defensive medicine in the radiographic workup of the trauma patient: a pilot study

BACKGROUNDnDefensive medicine is estimated to cost the United States

Predictors of 6-month health utility outcomes in survivors of acute respiratory distress syndrome

210 billion annually. Trauma surgeons are at risk of practicing defensive medicine in the form of reflexively ordering computed tomography (CT) scans. The aim of this study is to quantify the monetary impact and radiation exposure related to the radiographic workup of trauma patients.nnnMETHODSnWe conducted a prospective, observational study involving 295 trauma patients at Level I trauma center. Physicians were surveyed regarding specific CT scans ordered, likelihood of significant injuries found on scans, and which scans would have been ordered in a hypothetical, litigation-free environment.nnnRESULTSnFour hundred sixteen of 1,097 CT scans (38%) were ordered out of defensive purposes. Nine CT scans (2.2%) that would not have been ordered resulted in a change in management. Defensively ordered CT scans resulted in nearly

Surgical stabilization of severe rib fractures decreases incidence of retained hemothorax and empyema

120,000 in excess charges and 8.8xa0mSv of unnecessary radiation per patient.nnnCONCLUSIONnDefensively ordered CT scan in the workup of trauma patients is a prevalent and costly practice that exposes patients to potentially unnecessary and harmful radiation.

Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes

Background With improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding and improving quality of life (QOL) outcomes in ARDS survivors is a clinical and research priority. We sought to identify variables associated with QOL, as measured by the EQ-5D health utility score, after ARDS using contemporary data science methods. Methods Analysis of prospectively acquired baseline variables and 6-month EQ-5D health utility scores for adults with ARDS enrolled in the ARDS Network Long-Term Outcomes Study (ALTOS). Penalised regression identified predictors of health utility, with results validated using 10-fold cross-validation. Results Among 616 ARDS survivors, several predictors were associated with 6-month EQ-5D utility scores, including two lifestyle factors. Specifically, older age, female sex, Hispanic/Latino ethnicity, current smoking and higher body mass index were associated with lower EQ-5D utilities, while living at home without assistance at baseline and AIDS were associated with higher EQ-5D utilities in ARDS survivors. No acute illness variables were associated with EQ-5D utility. Conclusions Acute illness variables do not appear to be associated with postdischarge QOL among ARDS survivors. Functional independence and lifestyle factors, such as obesity and tobacco smoking, were associated with worse QOL. Future analyses of postdischarge health utility among ARDS survivors should incorporate measures of demographics and functional independence at baseline. Trial registration numbers NCT00719446 (ALTOS), NCT00434993 (ALTA), NCT00609180 (EDEN/OMEGA), and NCT00883948 (EDEN); Post-results.

Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy

BACKGROUNDnRetained hemothorax (RH) is relatively common after chest trauma and can lead to empyema. We hypothesized that patients who have surgical fixation of rib fractures (SSRF) have less RH and empyema than those who have medical management of rib fractures (MMRF).nnnMETHODSnAdmitted rib fracture patients from January 2009 to June 2013 were identified. A 2:1 propensity score model identified MMRF patients who were similar to SSRF. RH, and empyema and readmissions, were recorded. Variables were compared using Fisher exact test and Wilcoxon rank-sum tests.nnnRESULTSnOne hundred thirty-seven SSRF and 274 MMRF were analyzed; 31 (7.5%) had RH requiring 35 interventions; 3 (2.2%) SSRF patients had RH compared with 28 (10.2%) MMRF (P = .003). Four (14.3%) MMRF subjects with RH developed empyema versus zero in the SSRF group (P = .008); 6 (19.3%) RH patients required readmission versus 14 (3.7%) in the non-RH group (P = .002).nnnCONCLUSIONSnPatients with rib fractures who have SSRF have less RH compared with similar MMRF patients. Although not a singular reason to perform SSRF, this clinical benefit should not be overlooked.