Population genetics and conservation of recently discovered springsnails in Arizona.

Establishing baseline geographical distributions of extant genetic diversity is increasingly important for future conservation efforts of freshwater species. We analyse the mitochondrial cytochrome c oxidase subunit I (COI) gene to taxonomically characterize 233 samples from recently discovered springsnail populations throughout 17 sites in Arizona, USA. A total of 28 unique COI haplotypes were recovered, with the number of haplotypes ranging from 1 to 4 by population in Arizona. Phylogenetic analyses resulted in haplotypes from 13 of 17 locations in Arizona being successfully identified to species, with five described and three undescribed species in the genus Pyrgulopsis (Hydrobiidae). Future work will require in-depth morphological work to clarify the taxonomic status of these putatively novel species. Importantly, among recovered species, we identified haplotype diversity of the critically endangered Three Forks springsnail, Pyrgulopsis trivialis, in the eastern Gila watershed, which will inform wildlife managers in deciding which source populations to use in reintroduction efforts. We discuss possible causes for observed population structure of Arizona's springsnail populations, with suggestions for the future sampling schemes necessary for the conservation of this uniquely important freshwater mollusc.

Artificial intelligence in pulmonary medicine: computer vision, predictive model and COVID-19.

Artificial intelligence (AI) is transforming healthcare delivery. The digital revolution in medicine and healthcare information is prompting a staggering growth of data intertwined with elements from many digital sources such as genomics, medical imaging and electronic health records. Such massive growth has sparked the development of an increasing number of AI-based applications that can be deployed in clinical practice. Pulmonary specialists who are familiar with the principles of AI and its applications will be empowered and prepared to seize future practice and research opportunities. The goal of this review is to provide pulmonary specialists and other readers with information pertinent to the use of AI in pulmonary medicine. First, we describe the concept of AI and some of the requisites of machine learning and deep learning. Next, we review some of the literature relevant to the use of computer vision in medical imaging, predictive modelling with machine learning, and the use of AI for battling the novel severe acute respiratory syndrome-coronavirus-2 pandemic. We close our review with a discussion of limitations and challenges pertaining to the further incorporation of AI into clinical pulmonary practice.

Intravenous Vancomycin Therapeutic Drug Monitoring in Children: Evaluation of a Pharmacy-Driven Protocol and Collaborative Practice Agreement.

BACKGROUND: Vancomycin optimization is challenging, requiring careful therapeutic drug monitoring (TDM) to avoid toxicity and ensure an efficacious concentration. Most prescriptions are empiric and often discontinued within 72 hours, which makes early TDM unnecessary. Although TDM using trough levels is common, the area under the concentration-time curve (AUC) is the preferred pharmacodynamic target. We studied the effect of a pharmacy-driven vancomycin collaborative practice agreement (CPA) at a children's hospital that delayed TDM up to 72 hours and targeted a 2-point 24-hour AUC of ≥400 mg × h/L. METHODS: We retrospectively reviewed vancomycin courses in patients aged ≥30 days who received vancomycin between April 1, 2011, and August 30, 2017. We implemented the CPA on June 1, 2014. Outcomes included CPA use, use of TDM, dosage adjustments, and development of acute kidney injury; we compared courses given while monitoring only trough levels (TO-TDM) with those given while using the CPA (AUC-TDM). We performed interrupted time series analyses to account for preintervention trends. RESULTS: We included 2379 courses in the TO-TDM period and 2155 in the AUC-TDM period. During AUC-TDM, 87% of the courses were managed by the CPA. In adjusted interrupted time series analyses, CPA implementation was associated with an initial change in level of -0.265 (95% confidence interval [CI], -0.336 to -0.189) TDM and an initial change in level of -0.332 (95% CI, -0.506 to -0.163) dosage adjustments. The 1-year risk of acute kidney injury decreased after CPA implementation (odds ratio, 0.695 [95% CI, 0.539-0.91]). CONCLUSION: The pharmacy-driven vancomycin CPA resulted in less monitoring and fewer dose adjustments without increasing AKI.

Variables that Influence Basic Prosthetic Mobility in People With Non-Vascular Lower Limb Amputation.

BACKGROUND: There exists a dearth of evidence on rehabilitation factors that influence prosthetic mobility in people with lower limb amputation (LLA). Examining variables that contribute to prosthetic mobility can inform rehabilitation interventions, providing guidance in developing more comprehensive care for these individuals. OBJECTIVE: To determine the influence of modifiable and non-modifiable variables related to LLA and their impact on prosthetic mobility, using the International Classification of Functioning, Disability and Health (ICF) model. Secondarily, to determine if personal factors and self-reported balance and mobility are predictive of Component timed-up-and-go (cTUG) performance. DESIGN: Cross-sectional study of a convenience sample. SETTING: National conference. PARTICIPANTS: People (N=68) with non-vascular causes of unilateral LLA. METHODS: Assessment of anthropometrics, mobility, bilateral hip extensor strength, hip range of motion, single limb balance, and self report measures. Lasso linear regression and extreme gradient boosting analyses were used to determine influence of variables on prosthetic mobility. MAIN OUTCOME MEASURE: Timed performance of the cTUG. RESULTS: The following five variables were found to influence basic prosthetic mobility (P ≤ .05) in people with transtibial amputation: hip extensor strength, hip range of motion, single limb balance, waist circumference, and age. In the transfemoral cohort, number of comorbidities and waist circumference primarily influenced prosthetic mobility. Additionally, 66% of the variance in cTUG total time for the entire sample could be explained by simply regressing on level of amputation, number of comorbidities, age and Activities-specific Balance Confidence scale score, all variables easily collected in a waiting room. CONCLUSION: Variables that are modifiable with physical therapy intervention including hip extensor strength, hip range of motion, single limb balance, and waist circumference significantly influenced basic prosthetic mobility. These variables can be affected by targeted rehabilitation interventions and lifestyle changes. LEVEL OF EVIDENCE: II.

Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), low tidal volume ventilation has been associated with reduced mortality. Driving pressure (tidal volume normalized to respiratory system compliance) may be an even stronger predictor of ARDS survival than tidal volume. We sought to study whether these associations hold true in acute respiratory failure patients without ARDS. METHODS: This is a retrospectively cohort analysis of mechanically ventilated adult patients admitted to ICUs from 12 hospitals over 2 years. We used natural language processing of chest radiograph reports and data from the electronic medical record to identify patients who had ARDS. We used multivariable logistic regression and generalized linear models to estimate associations between tidal volume, driving pressure, and respiratory system compliance with adjusted 30-day mortality using covariates of Acute Physiology Score (APS), Charlson Comorbidity Index (CCI), age, and PaO2/FiO2 ratio. RESULTS: We studied 2641 patients; 48% had ARDS (n = 1273). Patients with ARDS had higher mean APS (25 vs. 23, p < .001) but similar CCI (4 vs. 3, p = 0.6) scores. For non-ARDS patients, tidal volume was associated with increased adjusted mortality (OR 1.18 per 1 mL/kg PBW increase in tidal volume, CI 1.04 to 1.35, p = 0.010). We observed no association between driving pressure or respiratory compliance and mortality in patients without ARDS. In ARDS patients, both ΔP (OR1.1, CI 1.06-1.14, p < 0.001) and tidal volume (OR 1.17, CI 1.04-1.31, p = 0.007) were associated with mortality. CONCLUSIONS: In a large retrospective analysis of critically ill non-ARDS patients receiving mechanical ventilation, we found that tidal volume was associated with 30-day mortality, while driving pressure was not.

Antibiotic Use and Outcomes After Implementation of the Drug Resistance in Pneumonia Score in ED Patients With Community-Onset Pneumonia.

BACKGROUND: To guide rational antibiotic selection in community-onset pneumonia, we previously derived and validated a novel prediction tool, the Drug-Resistance in Pneumonia (DRIP) score. In 2015, the DRIP score was integrated into an existing electronic pneumonia clinical decision support tool (ePNa). METHODS: We conducted a quasi-experimental, pre-post implementation study of ePNa with DRIP score (2015) vs ePNa with health-care-associated pneumonia (HCAP) logic (2012) in ED patients admitted with community-onset pneumonia to four US hospitals. Using generalized linear models, we used the difference-in-differences method to estimate the average treatment effect on the treated with respect to ePNa with DRIP score on broad-spectrum antibiotic use, mortality, hospital stay, and cost, adjusting for available patient-level confounders. RESULTS: We analyzed 2,169 adult admissions: 1,122 in 2012 and 1,047 in 2015. A drug-resistant pathogen was recovered in 3.2% of patients in 2012 and 2.8% in 2015; inadequate initial empirical antibiotics were prescribed in 1.1% and 0.5%, respectively (P = .12). A broad-spectrum antibiotic was administered in 40.1% of admissions in 2012 and 33.0% in 2015 (P < .001). Vancomycin days of therapy per 1,000 patient days in 2012 were 287.3 compared with 238.8 in 2015 (P < .001). In the primary analysis, the average treatment effect among patients using the DRIP score was a reduction in broad-spectrum antibiotic use (OR, 0.62; 95% CI, 0.39-0.98; P = .039). However, the average effects for ePNa with DRIP on mortality, length of stay, and cost were not statistically significant. CONCLUSIONS: Electronic calculation of the DRIP score was more effective than HCAP criteria for guiding appropriate broad-spectrum antibiotic use in community-onset pneumonia.

ED Door-to-Antibiotic Time and Long-term Mortality in Sepsis.

BACKGROUND: The impact of antibiotic timing on sepsis outcomes remains controversial due to conflicting results from previous studies. OBJECTIVES: This study investigated the association of door-to-antibiotic time with long-term mortality in ED patients with sepsis. METHODS: This retrospective cohort study included nontrauma adult ED patients with clinical sepsis admitted to four hospitals from 2013 to 2017. Only patients' first eligible encounter was included. Multivariable logistic regression was used to measure the adjusted association between door-to-antibiotic time and 1-year mortality. Secondary analyses used alternative antibiotic timing measures (antibiotic initiation within 1 or 3 h and separate comparison of antibiotic exposure at each hour up to hour 6), alternative outcomes (hospital, 30-day, and 90-day mortality), and alternative statistical methods to mitigate indication bias. RESULTS: Among 10,811 eligible patients, median door-to-antibiotic time was 166 min (interquartile range, 115-230 min), and 1-year mortality was 19%. After adjustment, each additional hour from ED arrival to antibiotic initiation was associated with a 10% (95% CI, 5-14; P < .001) increased odds of 1-year mortality. The association remained linear when each 1-h interval of door-to-antibiotic time was independently compared with door-to-antibiotic time ≤ 1 h and was similar for hospital, 30-day, and 90-day mortality. Mortality at 1 year was higher when door-to-antibiotic times were > 3 h vs ≤ 3 h (adjusted OR, 1.27; 95% CI, 1.13-1.43) but not > 1 h vs ≤ 1 h (adjusted OR, 1.26; 95% CI, 0.98-1.62). CONCLUSIONS: Delays in ED antibiotic initiation time are associated with clinically important increases in long-term, risk-adjusted sepsis mortality.

Clinician Perspectives Regarding In-Hospital Cardiac Arrest Resuscitation: A Multicenter Survey.

OBJECTIVES: Evaluate clinicians' sentiments about participating in cardiac arrest resuscitations and identify factors associated with confidence in resuscitation of cardiac arrest. DESIGN: Electronic survey. SETTING: Twenty-one hospitals in Utah and Idaho. SUBJECTS: All attending physicians, residents, and nurses in a multilevel healthcare system likely to participate in an in-hospital cardiac arrest resuscitation at least once every 2 years. INTERVENTIONS: None. MEASUREMENTS AND METHODS: A survey instrument evaluating clinician perceptions of in-hospital cardiac arrest resuscitation participation was developed after literature review and iteratively revised based on expert input and cognitive pretesting. Survey responses were collected anonymously. Sixty percent of 1,642 contacted clinicians (n = 977) submitted complete responses, of whom 874 met study inclusion criteria (190 attending physicians, 576 nurses, and 110 residents). Most respondents (74%) participated in less than or equal to six in-hospital cardiac arrest events per year, and 41% of respondents were most likely to participate in in-hospital cardiac arrest resuscitation at a community, rural, or critical access hospital. Confidence in in-hospital cardiac arrest participation was high overall (92%), but lower among residents (86%) than nurses (91%) or attending physicians (96%; p = 0.008). Fewer residents (52%) than nurses (73%) or attending physicians (95%; p < 0.001) reported feeling confident leading in-hospital cardiac arrest teams. Residents (63%) and attending physicians (36%) were more likely to worry about making errors during an in-hospital cardiac arrest event than nurses (18%; p < 0.001). Only 15% of residents and 50% of respondents overall reported they were both confident participating in in-hospital cardiac arrest resuscitation and did not worry about making errors. In-hospital cardiac arrest participation frequency was the dominant predictor of respondents' confidence leading or participating in an in-hospital cardiac arrest resuscitation. CONCLUSIONS: Many clinicians, especially residents, who participate in or lead in-hospital cardiac arrest resuscitation events lack confidence or worry about management errors. Hospitals-particularly smaller hospitals-should consider methods to provide in-hospital cardiac arrest teams additional "effective experience," potentially using simulation or telemedicine consultation.

Emergency Department Crowding Is Associated With Delayed Antibiotics for Sepsis.

STUDY OBJECTIVE: Barriers to early antibiotic administration for sepsis remain poorly understood. We investigated the association between emergency department (ED) crowding and door-to-antibiotic time in ED sepsis. METHODS: We conducted a retrospective cohort study of ED sepsis patients presenting to 2 community hospitals, a regional referral hospital, and a tertiary teaching hospital. The primary exposure was ED occupancy rate, defined as the ratio of registered ED patients to licensed ED beds. We defined ED overcrowding as an ED occupancy rate greater than or equal to 1. We used multivariable regression to measure the adjusted association between ED crowding and door-to-antibiotic time (elapsed time from ED arrival to first antibiotic initiation). Using Markov multistate models, we also investigated the association between ED crowding and pre-antibiotic care processes. RESULTS: Among 3,572 eligible sepsis patients, 70% arrived when the ED occupancy rate was greater than or equal to 0.5 and 14% arrived to an overcrowded ED. Median door-to-antibiotic time was 158 minutes (interquartile range 109 to 216 minutes). When the ED was overcrowded, 46% of patients received antibiotics within 3 hours of ED arrival compared with 63% when it was not (difference 14.4%; 95% confidence interval 9.7% to 19.2%). After adjustment, each 10% increase in ED occupancy rate was associated with a 4.0-minute increase (95% confidence interval 2.8 to 5.2 minutes) in door-to-antibiotic time and a decrease in the odds of antibiotic initiation within 3 hours (odds ratio 0.90; 95% confidence interval 0.88 to 0.93). Increasing ED crowding was associated with slower initial patient assessment but not further delays after the initial assessment. CONCLUSION: ED crowding was associated with increased sepsis antibiotic delay. Hospitals must devise strategies to optimize sepsis antibiotic administration during periods of ED crowding.

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation.

BACKGROUND: CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. RESULTS: Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380]). All received preemptive CMV antiviral therapy at first detectable DNAemia. CMV-I occurred in 34.8% of allogeneic and 2.1% of autologous transplants; median time to onset was 45 days. In allogeneic HSCT recipients, the primary risk factor for CMV-I was CMV donor/recipient (D/R) serostatus. In a Markov multi-state model for allogeneic HSCT recipients, the hazard ratio for CMV-I and relapse was 1.5 (95% CI 0.8-2.8) and for CMV-I and mortality 2.4 (95% CI 0.9-6.5). In a multivariable model for all patients, CMV-I was associated with increased total cost (coefficient = 0.21, estimated incremental daily cost USD $500; P = 0.02). Cost was attenuated in allogeneic HSCT recipients (coefficient = 0.13, USD $699 vs $613, or $24 892 per transplant episode; P = 0.23). CMV disease (CMV-D) complicated 29.6% of CMV-I events in allogeneic HSCT recipients, but was not associated with an incrementally increased adjusted risk of mortality compared with CMV-I alone. CMV-I (56.4%) and CMV-D (19.8%) were significantly overrepresented in D-/R+ serostatus HSCT recipients, and mortality was higher in R+ HSCT recipients. CONCLUSIONS: Despite early preemptive antiviral treatment, CMV-I impacts clinical outcomes and cost after HSCT, but the impact on cost is less pronounced in allogeneic HSCT recipients compared with autologous HSCT recipients.

Weight-based enoxaparin dosing and deep vein thrombosis in hospitalized trauma patients: A double-blind, randomized, pilot study.

BACKGROUND: Venous thromboembolism is a cause of morbidity and mortality in trauma patients. Chemoprophylaxis with low-molecular-weight heparin at a standardized dose is recommended. Conventional chemoprophylaxis may be inadequate. We hypothesized that a weight-adjusted enoxaparin prophylaxis regimen would reduce the frequency of venous thromboembolism in hospitalized trauma patients and at 90-day follow-up. METHODS: This prospective, randomized pilot study enrolled adult patients admitted to a level 1 trauma center between July 2013 and January 2015. Subjects were randomized to receive either standard (30 mg subcutaneously every 12 hours) or weight-based (0.5mg/kg subcutaneously every 12 hours) enoxaparin. Surveillance duplex ultrasound for lower extremity deep vein thrombosis was performed on hospital days 1, 3, and 7, and weekly thereafter. The primary outcome was deep vein thrombosis during hospitalization. Secondary outcomes included venous thromboembolism at 90 days and significant bleeding events. RESULTS: Two hundred thirty-four (124 standard, 110 weight-based) subjects were enrolled. There was no difference between standard and weight-based regarding age, body mass index, percentage female gender, injury severity score, or percentage that had surgery. There was a trend toward less in-hospital deep vein thrombosis in weight-based (12 [9.7%] standard vs 4 [3.6%] weight-based, P = .075). At 90 days, there was no difference in venous thromboembolism (12 [9.7%] standard vs 6 [5.5%] weight-based, P =.34). There was 1 bleeding event, which occurred in a standard subject. CONCLUSION: Weight-based enoxaparin dosing for venous thromboembolism chemoprophylaxis in trauma patients may provide better protection against venous thromboembolism than standard. A definitive study is necessary to determine whether weight-based dosing is superior to standard.

Predictive Variables for Failure in Administration of Intrapleural Tissue Plasminogen Activator/Deoxyribonuclease in Patients With Complicated Parapneumonic Effusions/Empyema.

BACKGROUND: Combined intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has been shown to reduce the need for surgical intervention for complicated pleural effusion/empyema (CPE/empyema). For patients in whom tPA/DNase is likely to fail, however, receipt of this therapy may simply delay the inevitable. The goal of this study was to identify risk factors for failure of combined intrapleural therapy. METHODS: We performed a retrospective chart review of patients who received intrapleural tPA/DNase for the treatment of CPE/empyema. Clinical variables included demographic data, radiographic parameters at time of diagnosis, and results from pleural fluid analysis. We used gradient boosted trees-an ensemble machine learning technique, with hyperparameter tuning to mitigate overfitting-to rank the importance of 19 candidate clinical variables with respect to their ability to predict failure of tPA/DNase therapy. RESULTS: We identified 84 patients who received intrapleural tPA/DNase for the treatment of complicated pleural effusions/empyema over a 5-year period. Resolution of CPE/empyema with intrapleural tPA/DNase was achieved in two-thirds of the patients (n = 57). Of the 19 candidate predictors of tPA/DNase failure, the presence of pleural thickening was found to be the most important (48% relative importance), followed by the presence of an abscess or necrotizing pneumonia (24%), the pleural protein level (6%), and the presence of loculated effusion (4%). CONCLUSIONS: Our analysis found that the presence of pleural thickening and the presence of an abscess/necrotizing pneumonia helps to triage patients in whom combined intrapleural therapy is likely to fail. The results warrant further study and validation in a prospective multicenter study.

Three-Factor Versus Four-Factor Prothrombin Complex Concentrate for the Emergent Management of Warfarin-Associated Intracranial Hemorrhage.

BACKGROUND: Four-factor prothrombin complex concentrates (PCC) produce a more rapid and complete INR correction compared with 3-factor PCC in patients receiving warfarin. It is unknown if this improves clinical outcomes in the setting of intracranial hemorrhage (ICH). METHODS: This multicenter, retrospective cohort study included patients presenting with warfarin-associated ICH reversed with either 4- or 3-factor PCC. The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, discharge location, intensive care unit (ICU) and hospital-free days, INR reversal, and thromboembolic (TE) events at 90 days. Each was analyzed using regression analysis. Continuous and binary outcomes were analyzed using linear and logistic regression, respectively, while ordinal regression was used for discharge location. RESULTS: Of the 103 patients, 63 received 4-factor PCC. Median age was 79 years [interquartile intervals(IQI 73-84)], median presenting INR was 2.7 (2.2-3.3), and presenting ICH was intraparenchymal in 51% of patients. In-hospital and 30-day mortality were 25 and 35%, respectively. In-hospital mortality was greater among those who received 4-factor PCC, yet was not statistically significant (OR 2.2, 95% CI 0.59-9.4, p = 0.26), as having Glasgow Coma Scale (GCS) ≤8 explained most of the difference (OR 48, 95% CI 14-219, p <0.001). The effect of 4-factor PCC was not statistically significant in any of the secondary analyses. Crude rates of TE events were higher in the 4-factor PCC group (19 vs. 10%), though not significantly. CONCLUSIONS: In-hospital mortality was not improved with the use of 4- versus 3-factor PCC in the emergent reversal of warfarin-associated ICH. Secondary clinical outcomes were similarly nonsignificant.

Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock.

BACKGROUND: Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. METHODS: We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min. RESULTS: We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration. CONCLUSIONS: Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.

Pleural Effusions at First ED Encounter Predict Worse Clinical Outcomes in Patients With Pneumonia.

BACKGROUND: Pleural effusions are present in 15% to 44% of hospitalized patients with pneumonia. It is unknown whether effusions at first presentation to the ED influence outcomes or should be managed differently. METHODS: We studied patients in seven hospital EDs with International Statistical Classification of Disease and Health Related Problems-Version 9 codes for pneumonia, or empyema, sepsis, or respiratory failure with secondary pneumonia. Patients with no confirmatory findings on chest imaging were excluded. Pleural effusions were identified with the use of radiographic imaging. RESULTS: Over 24 months, 4,771 of 458,837 adult ED patients fulfilled entry criteria. Among the 690 (14.5%) patients with pleural effusions, their median age was 68 years, and 46% were male. Patients with higher Elixhauser comorbidity scores (OR, 1.13 [95% CI, 1.09-1.18]; P < .001), brain natriuretic peptide levels (OR, 1.20 [95% CI, 1.12-1.28]; P < .001), bilirubin levels (OR, 1.07 [95% CI, 1.00-1.15]; P = .04), and age (OR, 1.15 [95% CI, 1.09-1.21]; P < .001) were more likely to have parapneumonic effusions. In patients without effusion, electronic version of CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years accurately predicted mortality (4.7% predicted vs 5.0% actual). However, eCURB underestimated mortality in those with effusions (predicted 7.0% vs actual 14.0%; P < .001). Patients with effusions were more likely to be admitted (77% vs 57%; P < .001) and had a longer hospital stay (median, 2.8 vs 1.3 days; P < .001). After severity adjustment, the likelihood of 30-day mortality was greater among patients with effusions (OR, 2.6 [CI, 2.0-3.5]; P < .001), and hospital stay was disproportionately longer (coefficient, 0.22 [CI, 0.14-0.29]; P < .001). CONCLUSIONS: Patients with pneumonia and pleural effusions at ED presentation in this study were more likely to die, be admitted, and had longer hospital stays. Why parapneumonic effusions are associated with adverse outcomes, and whether different management of these patients might improve outcome, needs urgent investigation.

Use of Tracheal Aspirate Culture in Newly Intubated Patients with Community-Onset Pneumonia.

RATIONALE: Successful treatment of life-threatening community-acquired pneumonia requires appropriate empiric antibiotic coverage. But using conventional diagnostic techniques, a microbiological diagnosis is often not achieved. The diagnostic usefulness of tracheal aspirate at the time of intubation in patients with severe pneumonia has not been well studied. OBJECTIVES: The purpose of this study was to evaluate the use of tracheal aspirate culture in identifying pneumonia pathogens. METHODS: We identified all patients older than 18 years of age with International Classification of Disease, Ninth Revision codes and radiographic evidence of pneumonia seen in the emergency departments at 2 university-affiliated Utah hospitals from December 2009 to November 2010 and from December 2011 to November 2012. Patients intubated within 24 hours of arrival were then identified electronically. Postintubation orders instructed respiratory therapists to obtain tracheal aspirate for culture. All culture results were reviewed individually and defined as positive if a pneumonia pathogen was identified. Results of other microbiology studies were obtained from the electronic medical record. MEASUREMENTS AND MAIN RESULTS: Of 2,011 patients with pneumonia, 94 were intubated and 84 had a tracheal aspirate obtained. Of these 84 patients, 47 (56%) had a pulmonary pathogen identified by tracheal aspirate culture, 80 also had blood cultures, and 71 underwent Pneumococcal and Legionella urinary antigen testing. A microbiological diagnosis was made in 55 patients (65.5%) by any diagnostic method. In 39% of patients (32 of 82), the tracheal aspirate culture was the only positive test, resulting in a unique microbiological diagnosis in patients who would have otherwise been classified as "culture negative." CONCLUSIONS: Tracheal aspirate cultures obtained as part of routine care identified a plausible pneumonia pathogen in more than one-half of emergency department adult patients with severe pneumonia requiring intubation. Tracheal aspirate culture offers important additive diagnostic value to other routine tests.

Pneumococcal urinary antigen test use in diagnosis and treatment of pneumonia in seven Utah hospitals.

The pneumocococcal urine antigen test increases specific microbiological diagnosis over conventional culture methods in pneumonia patients. Data are limited regarding its yield and effect on antibiotic prescribing among patients with community-onset pneumonia in clinical practice. We performed a secondary analysis of 2837 emergency department patients admitted to seven Utah hospitals over 2 years with international diagnostic codes version 9 codes and radiographic evidence of pneumonia. Mean age was 64.2 years, 47.2% were male and all-cause 30-day mortality was 9.6%. Urinary antigen testing was performed in 1110 (39%) patients yielding 134 (12%) positives. Intensive care unit patients were more likely to undergo testing, and have a positive result (15% versus 8.8% for ward patients; p<0.01). Patients with risk factors for healthcare-associated pneumonia had fewer urinary antigen tests performed, but 8.4% were positive. Physicians changed to targeted antibiotic therapy in 20 (15%) patients, de-escalated antibiotic therapy in 76 patients (57%). In 38 (28%) patients, antibiotics were not changed. Only one patient changed to targeted therapy suffered clinical relapse. Length of stay and mortality were lower in patients receiving targeted therapy. Pneumococcal urinary antigen testing is an inexpensive, noninvasive test that favourably influenced antibiotic prescribing in a "real world", multi-hospital observational study.

YouTube as an information source for pediatric adenotonsillectomy and ear tube surgery.

OBJECTIVES: Assess the overall quality of information on adenotonsillectomy and ear tube surgery presented on YouTube (www.youtube.com) from the perspective of a parent or patient searching for information on surgery. METHODS: The YouTube website was systematically searched on select dates with a formal search strategy to identify videos pertaining to pediatric adenotonsillectomy and ear tube surgery. Only videos with at least 5 (ear tube surgery) or 10 (adenotonsillectomy) views per day were included. Each video was viewed and scored by two independent scorers. Videos were categorized by goal and scored for video/audio quality, accuracy, comprehensiveness, and procedure-specific content. STUDY DESIGN: Cross-sectional study. SETTING: Public domain website. RESULTS: Fifty-five videos were scored for adenotonsillectomy and forty-seven for ear tube surgery. The most common category was educational (65.3%) followed by testimonial (28.4%), and news program (9.8%). Testimonials were more common for adenotonsillectomy than ear tube surgery (41.8% vs. 12.8%, p=0.001). Testimonials had a significantly lower mean accuracy (2.23 vs. 2.62, p=0.02), comprehensiveness (1.71 vs. 2.22, p=0.007), and TA specific content (0.64 vs. 1.69, p=0.001) score than educational type videos. Only six videos (5.9%) received high scores in both video/audio quality and accuracy/comprehensiveness of content. There was no significant association between the accuracy and comprehensive score and views, posted "likes", posted "dislikes", and likes/dislikes ratio. There was an association between "likes" and mean video quality (Spearman's rho=0.262, p=0.008). CONCLUSION: Parents/patients searching YouTube for information on pediatric adenotonsillectomy and ear tube surgery will generally encounter low quality information with testimonials being common but of significantly lower quality. Viewer perceived quality ("likes") did not correlate to formally scored content quality.

Amelioration of hepatic inflammation in a mouse model of NASH using a dithiocarbamate derivative.

PURPOSE: The process whereby liver inflammation develops in non-alcoholic steatohepatitis (NASH) is not fully understood. While modification of the inflammatory milieu is an attractive target to prevent the development of hepatocellular injury, most antiinflammatory agents have proven ineffective in this setting. Tetraethylthiuram disulfide (TDSF) is able to induce S-glutathionylation of NF-κB along with critical signaling proteins involved with inflammation, especially when complexed with a heavy metal. For this reason, we hypothesized that administration of TDSF would function to ameliorate necroinflammatory activity in a mouse model of NASH. METHODS: Mice were divided into five groups and received control chow versus a methionine-choline-deficient diet. After 6 weeks of TDSF versus sham gavage, animals were necropsied. Using conventional H&E staining, livers were examined using the Brunt scoring system by a hepatopathologist blinded to treatment groups. Validated mouse primer sets were used for quantitative real-time PCR to evaluate changes in mRNA expression. RESULTS: Livers treated with TDSF demonstrated a qualitative reduction in lobular inflammation, lipogranuloma formation, and Kupffer cell accumulation, but not steatosis. Significant reductions in inflammatory transcripts for α-1-collagen, TGF-ß, Mmp2, MCP-1, and TNF-1α were also observed. CONCLUSIONS: Animals treated with TDSF exhibit a reduction in lobular inflammation that is independent of lipid accumulation when administered MCD diet. Similar reductions are seen in several inflammatory transcripts associated with NASH. Additional work in this area may reveal a therapeutic role for TDSF or similar agents in curtailing inflammatory signaling within the liver.