Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors.

BACKGROUND: Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors. METHODS: We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin). RESULTS: Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage. CONCLUSIONS: In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.).

Emergence of Extended-Spectrum ß-Lactamase Urinary Tract Infections Among Hospitalized Emergency Department Patients in the United States.

STUDY OBJECTIVE: Enterobacteriaceae resistant to ceftriaxone, mediated through extended-spectrum ß-lactamases (ESBLs), commonly cause urinary tract infections worldwide, but have been less prevalent in North America. Current US rates are unknown. We determine Enterobacteriaceae antimicrobial resistance rates among US emergency department (ED) patients hospitalized for urinary tract infection. METHODS: We prospectively enrolled adults hospitalized for urinary tract infection from 11 geographically diverse university-affiliated hospital EDs during 2018 to 2019. Among participants with culture-confirmed infection, we evaluated prevalence of antimicrobial resistance, including that caused by ESBL-producing Enterobacteriaceae, resistance risk factors, and time to in vitro-active antibiotics. RESULTS: Of 527 total participants, 444 (84%) had cultures that grew Enterobacteriaceae; 89 of 435 participants (20.5%; 95% confidence interval 16.9% to 24.5%; 4.6% to 45.4% by site) whose isolates had confirmatory testing had bacteria that were ESBL producing. The overall prevalence of ESBL-producing Enterobacteriaceae infection among all participants with urinary tract infection was 17.2% (95% confidence interval 14.0% to 20.7%). ESBL-producing Enterobacteriaceae infection risk factors were hospital, long-term care, antibiotic exposure within 90 days, and a fluoroquinolone- or ceftriaxone-resistant isolate within 1 year. Enterobacteriaceae resistance rates for other antimicrobials were fluoroquinolone 32.3%, gentamicin 13.7%, amikacin 1.3%, and meropenem 0.3%. Ceftriaxone was the most common empirical antibiotic. In vitro-active antibiotics were not administered within 12 hours of presentation to 48 participants (53.9%) with ESBL-producing Enterobacteriaceae infection, including 17 (58.6%) with sepsis. Compared with other Enterobacteriaceae infections, ESBL infections were associated with longer time to in vitro-active treatment (17.3 versus 3.5 hours). CONCLUSION: Among adults hospitalized for urinary tract infection in many US locations, ESBL-producing Enterobacteriaceae have emerged as a common cause of infection that is often not initially treated with an in vitro-active antibiotic.

Cancer pain management in the emergency department: a multicenter prospective observational trial of the Comprehensive Oncologic Emergencies Research Network (CONCERN).

PURPOSE: Many patients with cancer seek care for pain in the emergency department (ED). Prospective research on cancer pain in this setting has historically been insufficient. We conducted this study to describe the reported pain among cancer patients presenting to the ED, how pain is managed, and how pain may be associated with clinical outcomes. METHODS: We conducted a multicenter cohort study on adult patients with active cancer presenting to 18 EDs in the USA. We reported pain scores, response to medication, and analgesic utilization. We estimated the associations between pain severity, medication utilization, and the following outcomes: 30-day mortality, 30-day hospital readmission, and ED disposition. RESULTS: The study population included 1075 participants. Those who received an opioid in the ED were more likely to be admitted to the hospital and were more likely to be readmitted within 30 days (OR 1.4 (95% CI: 1.11, 1.88) and OR 1.56 (95% CI: 1.17, 2.07)), respectively. Severe pain at ED presentation was associated with increased 30-day mortality (OR 2.30, 95% CI: 1.05, 5.02), though this risk was attenuated when adjusting for clinical factors (most notably functional status). CONCLUSIONS: Patients with severe pain had a higher risk of mortality, which was attenuated when correcting for clinical characteristics. Those patients who required opioid analgesics in the ED were more likely to require admission and were more at risk of 30-day hospital readmission. Future efforts should focus on these at-risk groups, who may benefit from additional services including palliative care, hospice, or home-health services.

Validation of the Emergency Severity Index (Version 4) for the Triage of Adult Emergency Department Patients With Active Cancer.

BACKGROUND: Patients with active cancer account for a growing percentage of all emergency department (ED) visits and have a unique set of risks related to their disease and its treatments. Effective triage for this population is fundamental to facilitating their emergency care. OBJECTIVES: We evaluated the validity of the Emergency Severity Index (ESI; version 4) triage tool to predict ED-relevant outcomes among adult patients with active cancer. METHODS: We conducted a prespecified analysis of the observational cohort established by the National Cancer Institute-supported Comprehensive Oncologic Emergencies Research Network's multicenter (18 sites) study of ED visits by patients with active cancer (N = 1075). We used a series of χ2 tests for independence to relate ESI scores with 1) disposition, 2) ED resource use, 3) hospital length of stay, and 4) 30-day mortality. RESULTS: Among the 1008 subjects included in this analysis, the ESI distribution skewed heavily toward high acuity (>95% of subjects had an ESI level of 1, 2, or 3). ESI was significantly associated with patient disposition and ED resource use (p values < 0.05). No significant associations were observed between ESI and the non-ED based outcomes of hospital length of stay or 30-day mortality. CONCLUSION: ESI scores among ED patients with active cancer indicate higher acuity than the general ED population and are predictive of disposition and ED resource use. These findings show that the ESI is a valid triage tool for use in this population for outcomes directly relevant to ED care.

Emergency Department Intubation Success With Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study.

STUDY OBJECTIVE: Although both succinylcholine and rocuronium are used to facilitate emergency department (ED) rapid sequence intubation, the difference in intubation success rate between them is unknown. We compare first-pass intubation success between ED rapid sequence intubation facilitated by succinylcholine versus rocuronium. METHODS: We analyzed prospectively collected data from the National Emergency Airway Registry, a multicenter registry collecting data on all intubations performed in 22 EDs. We included intubations of patients older than 14 years who received succinylcholine or rocuronium during 2016. We compared the first-pass intubation success between patients receiving succinylcholine and those receiving rocuronium. We also compared the incidence of adverse events (cardiac arrest, dental trauma, direct airway injury, dysrhythmias, epistaxis, esophageal intubation, hypotension, hypoxia, iatrogenic bleeding, laryngoscope failure, laryngospasm, lip laceration, main-stem bronchus intubation, malignant hyperthermia, medication error, pharyngeal laceration, pneumothorax, endotracheal tube cuff failure, and vomiting). We conducted subgroup analyses stratified by paralytic weight-based dose. RESULTS: There were 2,275 rapid sequence intubations facilitated by succinylcholine and 1,800 by rocuronium. Patients receiving succinylcholine were younger and more likely to undergo intubation with video laryngoscopy and by more experienced providers. First-pass intubation success rate was 87.0% with succinylcholine versus 87.5% with rocuronium (adjusted odds ratio 0.9; 95% confidence interval 0.6 to 1.3). The incidence of any adverse event was also comparable between these agents: 14.7% for succinylcholine versus 14.8% for rocuronium (adjusted odds ratio 1.1; 95% confidence interval 0.9 to 1.3). We observed similar results when they were stratified by paralytic weight-based dose. CONCLUSION: In this large observational series, we did not detect an association between paralytic choice and first-pass rapid sequence intubation success or peri-intubation adverse events.

Clinical Severity Alone Does Not Determine Disposition Decisions for Patients in the Emergency Department with Suicide Risk.

BACKGROUND: Boarding of patients with suicide risk in emergency departments (EDs) negatively affects both patients and society. Factors other than clinical severity may frequently preclude safe outpatient dispositions among suicidal patients boarding for psychiatric admission in the ED. OBJECTIVE: To determine the extent to which nonclinical factors preclude safe outpatient discharge from the ED among patients boarding for psychiatric admission based on suicide risk. METHODS: A survey regarding the importance of 13 clinical and 19 nonclinical barriers to safe outpatient disposition was administered in the ED to 40 adults who were determined by psychiatrists to require inpatient level of psychiatric care due to suicide risk. A second survey regarding whether addressing the nonclinical factors would have enabled a safe outpatient disposition in each case was administered to the psychiatrists who evaluated each patient participant. RESULTS: Out of 40 patient participants, 39 cited at least one nonclinical factor that could have enabled a safe outpatient disposition had it been correctable in the ED. According to the psychiatrists who made the decision to hospitalize, 10 (25%) of the patient participants could have been discharged had social support become available. CONCLUSION: Both clinical and nonclinical factors affect disposition from the ED after an evaluation for suicide risk. Attention to nonclinical factors should be considered in programmatic efforts to reduce ED boarding of patients with suicide risk.

Management of Major Bleeding Events in Patients Treated With Dabigatran for Nonvalvular Atrial Fibrillation: A Retrospective, Multicenter Review.

STUDY OBJECTIVE: There are limited data on the clinical presentations and management of dabigatran-associated major bleeding outside the clinical trial setting. The aim of this study is to describe clinical characteristics, interventions, and outcomes in patients with dabigatran-associated major bleeding who present to the emergency department (ED). METHODS: We performed a retrospective observational chart review study of dabigatran-treated patients with nonvalvular atrial fibrillation who presented with acute major bleeding to the ED. We searched electronic medical record databases cross-referencing medication lists and hemorrhage International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes. We studied the resulting charts to yield confirmed nonvalvular atrial fibrillation in patients with an index event of major bleeding and at least 1 dose of dabigatran in the 5 preceding days. RESULTS: The electronic search yielded 284 cases, and we assessed 93 as ineligible, leaving 191 in the final cohort. Of these, 118 patients (62%) had gastrointestinal hemorrhage; 36 (19%) had intracranial hemorrhage, 8 (4%) of which were nontraumatic cases and 28 (15%) traumatic. Thirty-six (19%) of the index events were in "other" locations and 1 (0.5%) "unknown." There were 12 deaths (6%): 8 from patients presenting with gastrointestinal bleeding events, 2 from intracranial hemorrhage (both nontraumatic), and 2 from other. Although RBC and plasma transfusions were common, only 11 patients (6%) received purified coagulation factors. CONCLUSION: Despite rare use of reversal strategies, mortality was low and outcomes were favorable, similar to reported outcomes from clinical trials, in this sample of patients with major bleeding while receiving dabigatran.

Cost and Utility of Microbiological Cultures Early After Intensive Care Unit Admission for Intracerebral Hemorrhage.

BACKGROUND: Fever is common among intensive care unit (ICU) patients. Clinicians may use microbiological cultures to differentiate infectious and aseptic fever. However, their utility depends on the prevalence of infection; and false-positive results might adversely affect patient care. We sought to quantify the cost and utility of microbiological cultures in a cohort of ICU patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We performed a secondary analysis of a cohort with spontaneous ICH requiring mechanical ventilation. We collected baseline data, measures of systemic inflammation, microbiological culture results for the first 48 h, and daily antibiotic usage. Two physicians adjudicated true-positive and false-positive culture results using standard criteria. We calculated the cost per true-positive result and used logistic regression to test the association between false-positive results with subsequent antibiotic exposure. RESULTS: Overall, 697 subjects were included. A total of 233 subjects had 432 blood cultures obtained, with one true-positive (diagnostic yield 0.1 %, $22,200 per true-positive) and 11 false-positives. True-positive urine cultures (5 %) and sputum cultures (13 %) were more common but so were false-positives (6 and 17 %, respectively). In adjusted analysis, false-positive blood and sputum results were associated with increased antibiotic exposure. CONCLUSIONS: The yield of blood cultures early after spontaneous ICH was very low. False-positive results significantly increased the odds of antibiotic exposure. Our results support limiting the use of blood cultures in the first two days after ICU admission for spontaneous ICH.

Techniques and Trends, Success Rates, and Adverse Events in Emergency Department Pediatric Intubations: A Report From the National Emergency Airway Registry.

STUDY OBJECTIVE: We describe emergency department (ED) intubation practices for children younger than 16 years through multicenter prospective surveillance. METHODS: Academic and community EDs in the United States, Canada, and Australia recorded data electronically, from 2002 to 2012, with verified greater than or equal to 90% reporting. RESULTS: Ten of 18 participating centers provided qualifying data, reporting 1,053 encounters. Emergency physicians initiated 85% of intubations. Trainees initiated 83% (95% confidence interval [CI] 81% to 85%). Premedication became uncommon, reaching less than 30% by the last year. Etomidate was used in 78% of rapid sequence intubations. Rocuronium use increased during the period of study, whereas succinylcholine use declined. Video laryngoscopy increased, whereas direct laryngoscopy declined. The first attempt was successful in 83% of patients (95% CI 81% to 85%) overall. The risk of first-attempt failure was highest for infants (relative risk versus all others 2.3; 95% CI 1.8 to 3.0). Odds of first-attempt success for girls relative to boys were 0.57. The odds were 3.4 times greater for rapid sequence intubation than sedation without paralysis. The ultimate success rate was 99.5%. CONCLUSION: Because we sampled only 10 centers and most of the intubations were by trainees, our results may not be generalizable to the typical ED setting. We found that premedication is now uncommon, etomidate is the predominant induction agent, and rocuronium and video laryngoscopy are used increasingly. First-attempt failure is most common in infants.

Failure of antibiotics in cellulitis trials: a systematic review and meta-analysis.

OBJECTIVES: The objectives of the study are to quantify trial-to-trial variability in antibiotic failure rates, in randomized clinical trials of cellulitis treatment and to provide a point estimate for the treatment failure rate across trials. METHODS: We conducted a structured search for clinical trials evaluating antibiotic treatment of cellulitis, indexed in PubMed by August 2015. We included studies published in English and excluded studies conducted wholly outside of developed countries because the pathophysiology of cellulitis is likely to be different in such settings. Two authors reviewed all abstracts identified for possible inclusion. Of studies identified initially, 5% met the selection criteria. Two reviewers extracted data independently, and data were pooled using the Freeman-Tukey transformation under a random-effects model. Our primary outcome was the summary estimate of treatment failure across intent-to-treat and clinically evaluable participants. RESULTS: We included 19 articles reporting data from 20 studies, for a total of 3935 patients. Treatment failure was reported in 6% to 37% of participants in the 9 trials reporting intent-to-treat results, with a summary point estimate of 18% failing treatment (95% confidence interval, 15%-21%). In the 15 articles evaluating clinically evaluable participants, treatment failure rates ranged from 3% to 42%, and overall, 12% (95% confidence interval, 10%-14%) were designated treatment failures. CONCLUSIONS: Treatment failure rates vary widely across cellulitis trials, from 6% to 37%. This may be due to confusion of cellulitis with its mimics and perhaps problems with construct validity of the diagnosis of cellulitis. Such factors bias trials toward equivalence and, in routine clinical care, impair quality and antibiotic stewardship. Objective diagnostic tools are needed.

A Qualitative Study of Factors Facilitating Clinical Nurse Engagement in Emergency Department Catheter-Associated Urinary Tract Infection Prevention.

OBJECTIVE: The aim of this study was to explore the actions of nurse leaders that facilitated clinical nurses' active involvement in emergency department (ED) catheter-associated urinary tract infection (CAUTI) prevention programs. BACKGROUND: Hospitals face increasing financial pressures to reduce CAUTI. Urinary catheters, often inserted in the ED, expose patients to CAUTI risk. Nurses are the principal champions of ED CAUTI prevention programs. METHODS: This was a qualitative analysis from a multisite, comparative case study project. A total of 52 interviews and 9 focus groups were analyzed across 6 enrolled EDs. Using a conventional content analysis, members of the research team coded data and developed site summaries to describe themes that had emerged across transcripts. Subsequently, all codes and site summaries were reviewed to identify the actions of nurse leaders that facilitated clinical nurses' engagement in CAUTI prevention efforts. RESULTS: Nurse leaders were the principal champions of CAUTI prevention programs and successfully engaged clinical nurses in CAUTI prevention efforts by (1) reframing urinary catheters as a source of potential patient harm; (2) empowering clinical nurses to identify and address CAUTI improvement opportunities; (3) fostering a culture of teamwork, which facilitated interdisciplinary communication around urinary catheter appropriateness and alternatives; and (4) holding clinical nurses accountable for CAUTI process and outcome measures. CONCLUSIONS: The prevention of CAUTI is an important opportunity for nurse leaders to engage clinical nurses in meaningful improvement efforts. Clinical nurses are best positioned to examine urinary catheter insertion workflow and to suggest improvements in avoiding use and improving placement and maintenance. To engage clinical nurses in CAUTI prevention, nurse leaders should focus on how urinary catheters expose patients to potential harm, involve nurses in designing and implementing practice changes, and provide local data to show the impact of nursing practices on patient outcomes.

Techniques, success, and adverse events of emergency department adult intubations.

STUDY OBJECTIVE: We describe the operators, techniques, success, and adverse event rates of adult emergency department (ED) intubation through multicenter prospective surveillance. METHODS: Eighteen EDs in the United States, Canada, and Australia recorded intubation data onto a Web-based data collection tool, with a greater than or equal to 90% reporting compliance requirement. We report proportions with binomial 95% confidence intervals (CIs) and regression, with year as the dependent variable, to model change over time. RESULTS: Of 18 participating centers, 5 were excluded for failing to meet compliance standards. From the remaining 13 centers, we report data on 17,583 emergency intubations of patients aged 15 years or older from 2002 to 2012. Indications were medical in 65% of patients and trauma in 31%. Rapid sequence intubation was the first method attempted in 85% of encounters. Emergency physicians managed 95% of intubations and most (79%) were physician trainees. Direct laryngoscopy was used in 84% of first attempts. Video laryngoscopy use increased from less than 1% in the first 3 years to 27% in the last 3 years (risk difference 27%; 95% CI 25% to 28%; mean odds ratio increase per year [ie, slope] 1.7; 95% CI 1.6 to 1.8). Etomidate was used in 91% and succinylcholine in 75% of rapid sequence intubations. Among rapid sequence intubations, rocuronium use increased from 8.2% in the first 3 years to 42% in the last 3 years (mean odds ratio increase per year 1.3; 95% CI 1.3 to 1.3). The first-attempt intubation success rate was 83% (95% CI 83% to 84%) and was higher in the last 3 years than in the first 3 (86% versus 80%; risk difference 6.2%; 95% CI 4.2% to 7.8%). The airway was successfully secured in 99.4% of encounters (95% CI 99.3% to 99.6%). CONCLUSION: In the EDs we studied, emergency intubation has a high and increasing success rate. Both drug and device selection evolved significantly during the study period.

Sepsis visits and antibiotic utilization in U.S. emergency departments*.

OBJECTIVES: To monitor the frequency of sepsis visits in U.S. emergency departments and assess the appropriateness of antibiotic utilization. DESIGN: We analyzed data from the National Hospital Ambulatory Medical Care Survey, defining sepsis as an explicit diagnosis of sepsis via International Classification of Diseases, 9th Revision, Clinical Modification codes 038, 995.91, 995.92, or 785.52. We also monitored trends using cases inferred by infection plus organ dysfunction without explicit diagnosis of sepsis, which we refer to as implicit sepsis cases. We assess changes in visit frequency and ascertain emergency department antibiotic administration rates. SETTING: Four-stage probability sample of visits to U.S. emergency departments, excluding Federal/military. PATIENTS: Adult emergency department visits, United States, 1994-2009. MEASUREMENTS AND MAIN RESULTS: Sepsis was diagnosed explicitly at 260,000 visits per year in U.S. emergency departments (95% CI, 251,000-270,000) or 1.23 visits per 1,000 U.S. population. The visit rate remained stable from 1994 to 2009 (p for trend 0.42). By contrast, the rate of visits with an implicit diagnosis of sepsis increased by 0.07 every 2 years (95% CI, 0.04-0.10; p for trend 0.002). Antibiotics were prescribed in the emergency department during 61% (95% CI, 57-65) of explicit sepsis visits. This increased from 52% in 1994-1997 to 69% in 2006-2009 (difference, 17%; 95% CI, 16.8-17.2). Of antibiotic regimens, 18% covered methicillin-resistant Staphylococcus aureus, 27% Pseudomonas, and 10% extended-spectrum beta-lactamase-producing bacteria, without evidence of targeting according to known risk factors. Of explicit sepsis cases, 31% were admitted to the ICU with 40% mortality (95% CI, 30-51). Overall hospital mortality was 17% (95% CI, 11-22). CONCLUSIONS: Explicitly diagnosed sepsis visits did not become more common during 1994-2009. Our data suggest that many emergency department patients with sepsis do not receive antibiotics until they arrive on the inpatient unit. When antibiotics are used among septic emergency department patients, drug-resistant bacteria are covered infrequently. These methods provide a simple approach to tracking the frequency with which sepsis is diagnosed among emergency department patients and to monitoring antibiotic therapy.

Long-acting neuromuscular paralysis without concurrent sedation in emergency care.

OBJECTIVE: Neuromuscular paralysis without sedation is an avoidable medical error with negative psychologic and potentially physiologic consequences. We determine the frequency of long-acting paralysis without concurrent sedation among patients intubated in our emergency department (ED) or before arrival. METHODS: We performed a retrospective cohort study from July 2007 to August 2009. We chose this time interval because in 2006, our institution developed a multidisciplinary plan designed to improve care of intubated patients. We identified all mechanically ventilated patients using billing codes. We reviewed all records to identify use of long-acting neuromuscular blocking agents. We captured data on patient characteristics and location of intubation, using a standardized data collection form. We report bivariate risk ratios to quantify associations with lack of concurrent sedation. A priori, we defined concurrent sedation as administration of any sedative during the 60 minutes preceding and the 15 minutes after administration of the long-acting paralytic. RESULTS: Over the 26-month period of study, 292 patients received a long-acting paralytic. Of the 212 available for analysis, 39 (18%) did not receive concurrent sedation. Every decade of age increased the risk of paralysis without concurrent sedation by 1.2 (95% confidence interval [CI], 1.1-1.4). Paralysis for intubation (vs for transport or ventilation management) increased the odds of no sedation by 2.1 (95% CI, 1.2-3.7). No other covariates predicted nonsedation. CONCLUSION: Absence of concurrent sedation was common among patients receiving long-acting neuromuscular paralysis before arrival or at our ED, despite implementation of a guideline to improve practice.

Death or revascularization among nonadmitted ED patients with low-positive vs negative troponin T results.

STUDY OBJECTIVE: Compare outcomes among emergency department (ED) patients with low-positive (0.01-0.02 ng/mL) vs negative troponin T. METHODS: Retrospective cohort study of nonadmitted ED patients with troponin testing at a tertiary-care hospital. Trained research assistants used a structured tool to review charts from all nonadmitted ED patients with troponin testing, 12/1/2009 to 11/30/2010. Outcomes of death and coronary revascularization were assessed at 30 days and 6 months via medical record review, Social Security Death Index searches, and patient contact. RESULTS: There were 57596 ED visits; with 33388 (58%) discharged immediately, 6410 (11%) assigned to the observation unit, and 17798 (31%) admitted or other. Troponin was measured in 2684 (6.7%) of the nonadmitted cases. Troponin was negative in 2523 (94.0%), low positive in 78 (2.9%), and positive (≥0.03 ng/mL) in 83 (3.1%). Of troponin-negative cases, 0.8% (95% CI, 0.4-1.1%) died or were revascularized by 30 days, vs 2.8% (95% CI, 0.0-6.7%) of low-positive cases (risk difference [RD], 2.0%; 95% CI, -1.8 to 5.9%). At 6 months, the rates were 1.7% (95% CI, 1.1-2.2%) and 12.9% (95% CI, 5.0-20.7%) (RD, 11%; 95% CI, 3.3-19.1%). Death alone at 30 days occurred in 0.4% (95% CI, 0.1-0.6%) vs 1.3% (95% CI, 0.0-3.8%) (RD, 0.9%; 95% CI, -1.6 to 3.4%). Death at 6 months occurred in 1.2% (95% CI, 0.8-1.6%) vs 11.7% (95% CI, 4.5-18.9%) (RD, 10%; 95% CI, 3.3-17.7%). CONCLUSION: Among patients not initially admitted, rates of death and coronary revascularization differed insignificantly at 30 days but significantly at 6 months. Detailed inspection of our results reveals that the bulk of the added risk at 6 months was due to non-cardiac mortality.

Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial.

BACKGROUND: Community-associated methicillin-resistant S. aureus (CA-MRSA) is the most common organism isolated from purulent skin infections. Antibiotics are usually not beneficial for skin abscess, and national guidelines do not recommend CA-MRSA coverage for cellulitis, except purulent cellulitis, which is uncommon. Despite this, antibiotics targeting CA-MRSA are prescribed commonly and increasingly for skin infections, perhaps due, in part, to lack of experimental evidence among cellulitis patients. We test the hypothesis that antibiotics targeting CA-MRSA are beneficial in the treatment of cellulitis. METHODS: We performed a randomized, multicenter, double-blind, placebo-controlled trial from 2007 to 2011. We enrolled patients with cellulitis, no abscesses, symptoms for <1 week, and no diabetes, immunosuppression, peripheral vascular disease, or hospitalization (clinicaltrials.gov NCT00676130). All participants received cephalexin. Additionally, each was randomized to trimethoprim-sulfamethoxazole or placebo. We provided 14 days of antibiotics and instructed participants to continue therapy for ≥1 week, then stop 3 days after they felt the infection to be cured. Our main outcome measure was the risk difference for treatment success, determined in person at 2 weeks, with telephone and medical record confirmation at 1 month. RESULTS: We enrolled 153 participants, and 146 had outcome data for intent-to-treat analysis. Median age was 29, range 3-74. Of intervention participants, 62/73 (85%) were cured versus 60/73 controls (82%), a risk difference of 2.7% (95% confidence interval, -9.3% to 15%; P = .66). No covariates predicted treatment response, including nasal MRSA colonization and purulence at enrollment. CONCLUSIONS: Among patients diagnosed with cellulitis without abscess, the addition of trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes overall or by subgroup. CLINICAL TRIALS REGISTRATION: NCT00676130.

Acute respiratory distress syndrome after spontaneous intracerebral hemorrhage*.

OBJECTIVES: Acute respiratory distress syndrome develops commonly in critically ill patients in response to an injurious stimulus. The prevalence and risk factors for development of acute respiratory distress syndrome after spontaneous intracerebral hemorrhage have not been reported. We sought to determine the prevalence of acute respiratory distress syndrome after intracerebral hemorrhage, characterize risk factors for its development, and assess its impact on patient outcomes. DESIGN: Retrospective cohort study at two academic centers. PATIENTS: We included consecutive patients presenting from June 1, 2000, to November 1, 2010, with intracerebral hemorrhage requiring mechanical ventilation. We excluded patients with age less than 18 years, intracerebral hemorrhage secondary to trauma, tumor, ischemic stroke, or structural lesion; if they required intubation only during surgery; if they were admitted for comfort measures; or for a history of immunodeficiency. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected both prospectively as part of an ongoing cohort study and by retrospective chart review. Of 1,665 patients identified by database query, 697 met inclusion criteria. The prevalence of acute respiratory distress syndrome was 27%. In unadjusted analysis, high tidal volume ventilation was associated with an increased risk of acute respiratory distress syndrome (hazard ratio, 1.79 [95% CI, 1.13-2.83]), as were male sex, RBC and plasma transfusion, higher fluid balance, obesity, hypoxemia, acidosis, tobacco use, emergent hematoma evacuation, and vasopressor dependence. In multivariable modeling, high tidal volume ventilation was the strongest risk factor for acute respiratory distress syndrome development (hazard ratio, 1.74 [95% CI, 1.08-2.81]) and for inhospital mortality (hazard ratio, 2.52 [95% CI, 1.46-4.34]). CONCLUSIONS: Development of acute respiratory distress syndrome is common after intubation for intracerebral hemorrhage. Modifiable risk factors, including high tidal volume ventilation, are associated with its development and in-patient mortality.