Ultrasound Investigation of the Fifth Intercostal Space Landmark for Chest Tube Thoracostomy Site Selection in Pediatric Patients.

OBJECTIVES: Chest tube thoracostomy site selection is typically chosen through landmark identification of the fifth intercostal space (ICS). Using point-of-care ultrasound (POCUS), studies have shown this site to be potentially unsafe in many adults; however, no study has evaluated this in children. The primary aim of this study was to evaluate the safety of the fifth ICS for pediatric chest tube placement, with the secondary aim to identify patient factors that correlate with an unsafe fifth ICS. METHODS: This was an observational study using POCUS to evaluate the safety of the fifth ICS for chest tube thoracostomy placement using a convenience sample of pediatric emergency department patients. Safety was defined as the absence of the diaphragm appearing within or above the fifth ICS during either tidal or maximal respiration. Univariate and multivariable analyses were used to identify patient factors that correlated with an unsafe fifth ICS. RESULTS: Among all patients, 10.3% (95% confidence interval [CI] 6.45-16.1) of diaphragm measurements crossed into or above the fifth ICS during tidal respiration and 27.2% (95% CI 19.0-37.3) during maximal respiration. The diaphragm crossed the fifth ICS more frequently on the right when compared with the left, with an overall rate of 45.0% (95% CI 36.1-54.3) of right diaphragms crossing during maximal respiration. In both univariate and multivariate analyses, a 1-kg/m2 increase in body mass index was associated with an increase of 10% or more in the odds of crossing during both tidal and maximal respiration (P = 0.003 or less). CONCLUSIONS: A significant number of pediatric patients have diaphragms that cross into or above the fifth ICS, suggesting that placement of a chest tube thoracostomy at this site would pose a significant complication risk. POCUS can quickly and accurately identify these unsafe sites, and we recommend it be used before pediatric chest tube thoracostomy.

Determining the joint effect of obesity and diabetes on functional disability at 3-months and on all-cause mortality at 1-year following an ischemic stroke.

BACKGROUND: Obesity and diabetes mellitus, or diabetes, are independently associated with post-ischemic stroke outcomes (e.g., functional disability and all-cause mortality). Although obesity and diabetes are also associated with post-ischemic stroke outcomes, the joint effect of obesity and diabetes on these post-ischemic stroke outcomes has not been explored previously. The purpose of the current study was to explore whether the effect of obesity on post-ischemic stroke outcomes differed by diabetes status in a cohort of acute ischemic stroke subjects with at least a moderate stroke severity. METHODS: Data from the Interventional Management of Stroke (IMS) III clinical trial was analyzed for this post-hoc analysis. A total of 656 subjects were enrolled in IMS III and were followed for one year. The joint effects of obesity and diabetes on functional disability at 3-months and all-cause mortality at 1-year were examined. RESULTS: Of 645 subjects with complete obesity and diabetes information, few were obese (25.74%) or had diabetes (22.64%). Obese subjects with diabetes and non-obese subjects without diabetes had similar odds of functional disability at 3-months following an ischemic stroke (adjusted common odds ratio, 1.038, 95% CI: 0.631, 1.706). For all-cause mortality at 1-year following an ischemic stroke, obese subjects with diabetes had a similar hazard compared with non-obese subjects without diabetes (adjusted hazard ratio, 1.005, 95% CI: 0.559, 1.808). There was insufficient evidence to declare a joint effect between obesity and diabetes on either the multiplicative scale or the additive scale for both outcomes. CONCLUSIONS: In this post-hoc analysis of data from the IMS III clinical trial of acute ischemic stroke patients with at least a moderate stroke severity, there was not sufficient evidence to determine that the effect of obesity differed by diabetes status on post-ischemic stroke outcomes. Additionally, there was not sufficient evidence to determine that either factor was independently associated with all-cause mortality. Future studies could differentiate between metabolically healthy and metabolically unhealthy patients within BMI categories to determine if the effect of obesity on post-stroke outcomes differs by diabetes status.

Diagnostic performance of a biomarker panel as a negative predictor for acute appendicitis in adult ED patients with abdominal pain.

OBJECTIVES: Evaluate the diagnostic accuracy of the APPY1TM biomarker panel, previously described for use in pediatric patients, for identifying adult ED patients with abdominal pain who are at low risk of acute appendicitis. METHODS: This study prospectively enrolled subjects >18years of age presenting to seven U.S. emergency departments with <72hours of abdominal pain suggesting possible acute appendicitis. The APPY1 panel was performed on blood samples drawn from each patient at the time of initial evaluation and results were correlated with the final diagnosis either positive or negative for acute appendicitis. RESULTS: 431 patients were enrolled with 422 completing all aspects of the study. The APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), a negative predictive value of 98.4% (95% CI, 94.4-99.6%), a negative likelihood ratio of 0.07 (95% CI, 0.02-0.27), with a specificity of 36.5% (95% CI, 31.6-41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%) patients who did not have appendicitis with 2 (2.5%) false negatives. The CT utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232 were done for patients who did not have appendicitis and 79 (34%) of these patients were correctly identified as negative with "low risk" biomarker panel results, representing 26% (79/307) of all CT scans performed. CONCLUSION: This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this prospective adult cohort, thereby potentially reducing the dependence on CT for the evaluation of possible acute appendicitis.

Risk Factors for Admission and Prolonged Length of Stay in Pediatric Isolated Skull Fractures.

OBJECTIVES: This study aimed to assess management of pediatric isolated skull fracture (ISF) patients by determining frequency of admission and describing characteristics associated with patients admitted for observation compared with patients discharged directly from the emergency department (ED) and those requiring a prolonged hospitalization. METHODS: We evaluated children younger than 5 years who presented with ISF using the South Carolina Traumatic Brain Injury Surveillance and Registry System data from 2001 to 2011. Outcomes analyzed included discharged from ED, admitted for less than 24 hours, and admitted for more than 24 hours (prolonged hospitalization). Bivariate analyses and a polytomous logistic regression model identified factors associated with patient disposition. RESULTS: Five hundred twenty-seven patients met the study criteria (ED discharge = 283 [53%]; inpatient <24 hours = 156 [29%]; inpatient >24 hours = 88 [18%]). The mean length of stay for admissions was 1.9 (SD, 1.5) days. In the regression model, ED discharges had greater odds of presenting to levels 2 to 3 hospitals (level 2: odds ratio [OR], 6.16; 95% confidence interval [CI], 3.66-10.39; level 3: OR, 30.98; 95% CI, 10.92-87.91) and lower odds of a high poverty status (OR, 0.20; 95% CI, 0.10-0.40). Prolonged hospitalizations had greater odds of concomitant injuries (OR, 2.21; 95% CI, 1.12-4.36). CONCLUSIONS: Admission after ISF is high despite a low risk of deterioration. High-poverty patients presenting to high-acuity medical centers are more commonly admitted for observation. Only presence of concomitant injuries was clinically predictive of prolonged hospitalization. The ability to better stratify risk after pediatric ISF would help providers make more informed decisions regarding ED disposition.

Essential roles of neutral ceramidase and sphingosine in mitochondrial dysfunction due to traumatic brain injury.

In addition to immediate brain damage, traumatic brain injury (TBI) initiates a cascade of pathophysiological events producing secondary injury. The biochemical and cellular mechanisms that comprise secondary injury are not entirely understood. Herein, we report a substantial deregulation of cerebral sphingolipid metabolism in a mouse model of TBI. Sphingolipid profile analysis demonstrated increases in sphingomyelin species and sphingosine concurrently with up-regulation of intermediates of de novo sphingolipid biosynthesis in the brain. Investigation of intracellular sites of sphingosine accumulation revealed an elevation of sphingosine in mitochondria due to the activation of neutral ceramidase (NCDase) and the reduced activity of sphingosine kinase 2 (SphK2). The lack of change in gene expression suggested that post-translational mechanisms are responsible for the shift in the activities of both enzymes. Immunoprecipitation studies revealed that SphK2 is complexed with NCDase and cytochrome oxidase (COX) subunit 1 in mitochondria and that brain injury hindered SphK2 association with the complex. Functional studies showed that sphingosine accumulation resulted in a decreased activity of COX, a rate-limiting enzyme of the mitochondrial electron transport chain. Knocking down NCDase reduced sphingosine accumulation in mitochondria and preserved COX activity after the brain injury. Also, NCDase knockdown improved brain function recovery and lessened brain contusion volume after trauma. These studies highlight a novel mechanism of secondary TBI involving a disturbance of sphingolipid-metabolizing enzymes in mitochondria and suggest a critical role for mitochondrial sphingosine in promoting brain injury after trauma.

The impact of covariate adjustment at randomization and analysis for binary outcomes: understanding differences between superiority and noninferiority trials.

The question of when to adjust for important prognostic covariates often arises in the design of clinical trials, and there remain various opinions on whether to adjust during both randomization and analysis, at randomization alone, or at analysis alone. Furthermore, little is known about the impact of covariate adjustment in the context of noninferiority (NI) designs. The current simulation-based research explores this issue in the NI setting, as compared with the typical superiority setting, by assessing the differential impact on power, type I error, and bias in the treatment estimate as well as its standard error, in the context of logistic regression under both simple and covariate adjusted permuted block randomization algorithms. In both the superiority and NI settings, failure to adjust for covariates that influence outcome in the analysis phase, regardless of prior adjustment at randomization, results in treatment estimates that are biased toward zero, with standard errors that are deflated. However, as no treatment difference is approached under the null hypothesis in superiority and under the alternative in NI, this results in decreased power and nominal or conservative (deflated) type I error in the context of superiority but inflated power and type I error under NI. Results from the simulation study suggest that, regardless of the use of the covariate in randomization, it is appropriate to adjust for important prognostic covariates in analysis, as this yields nearly unbiased estimates of treatment as well as nominal type I error.

Endothelial progenitor cells and a stromal cell-derived factor-1α analogue synergistically improve survival in sepsis.

RATIONALE: Endothelial progenitor cells (EPCs) have been associated with human sepsis but their role is incompletely understood. Stromal cell-derived factor (SDF)-1α facilitates EPC recruitment and is elevated in murine sepsis models. Previous studies have demonstrated that the SDF-1α analog CTCE-0214 (CTCE) is beneficial in polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. OBJECTIVES: We hypothesized that exogenously administered EPCs are also beneficial in CLP sepsis and that CTCE provides synergistic benefit. METHODS: Mice were subjected to CLP and administered EPCs at varying doses, CTCE, or a combination of the two. Mouse survival, plasma miRNA expression, IL-10 production, and lung vascular leakage were determined. The in vitro effect of CTCE on miRNA expression and EPC function were determined. MEASUREMENTS AND MAIN RESULTS: Survival was improved with EPC therapy at a threshold of 10(6) cells. In coculture studies, EPCs augmented LPS-induced macrophage IL-10 production. In vivo EPC administration in sepsis increased plasma IL-10, suppressed lung vascular leakage, attenuated liver and kidney injury, and augmented miR-126 and -125b expression, which regulate endothelial cell function and/or inflammation. When subthreshold numbers of EPCs were coadministered with CTCE in CLP mice they synergistically improved survival. We demonstrated that CTCE recruits endogenous EPCs in septic mice. In in vitro analysis, CTCE enhanced EPC proliferation, angiogenesis, and prosurvival signaling while inhibiting EPC senescence. These cellular effects were, in part, explained by the effect of CTCE on miR-126, -125b, -34a, and -155 expression in EPCs. CONCLUSIONS: EPCs and CTCE represent important potential therapeutic strategies in sepsis.

Abusive head trauma in young children: a population-based study.

OBJECTIVE: The objectives of this study were to provide population-based incidence estimate of abusive head trauma (AHT) in children aged 0 to 5 years from inpatient and emergency department (ED) and identify risk characteristics for recognizing high-risk children to improve public health surveillance. METHODS: This was a retrospective cohort study based on children's first encounter in ED or hospital admission with a diagnosis of head trauma (HT), 2000-2010. The relationship between clinical markers and AHT was examined controlling for covariables in the model using Cox hazards regression. Kaplan-Meier incidence probability was plotted, and the number of weeks elapsing from date of birth to the first encounter with HT established the survival time (T). RESULTS: Twenty-six thousand six hundred eighty-one children had HT, 502 (1.8%) resulted from abuse; 42.4% was captured from ED. Incidence varied from 28.9 (95% confidence interval [CI], 27.9-37.4) in infants to 4.1 (95% CI, 2.4-5.7) in 5-year-olds per 100,000 per year. Adjusted hazard ratio was 20.3 (95% CI, 10.9-38.0) for intracranial bleeding and 11.4 (95% CI, 8.57-15.21) for retinal hemorrhage. CONCLUSIONS: Incidence estimates of AHT are incomplete without including ED. Intracranial bleeding is a cardinal feature of AHT to be considered in case ascertainment to improve public health surveillance.

Abusive head trauma in young children: a population-based study.

OBJECTIVE: The objectives of this study were to provide population-based incidence estimate of abusive head trauma (AHT) in children aged 0 to 5 years from inpatient and emergency department (ED) and identify risk characteristics for recognizing high-risk children to improve public health surveillance. METHODS: This was a retrospective cohort study based on children's first encounter in ED or hospital admission with a diagnosis of head trauma (HT), 2000-2010. The relationship between clinical markers and AHT was examined controlling for covariables in the model using Cox hazards regression. Kaplan-Meier incidence probability was plotted, and the number of weeks elapsing from date of birth to the first encounter with HT established the survival time (T). RESULTS: Twenty-six thousand six hundred eighty-one children had HT, 502 (1.8%) resulted from abuse; 42.4% was captured from ED. Incidence varied from 28.9 (95% confidence interval [CI], 27.9-37.4) in infants to 4.1 (95% CI, 2.4-5.7) in 5-year-olds per 100,000 per year. Adjusted hazard ratio was 20.3 (95% CI, 10.9-38.0) for intracranial bleeding and 11.4 (95% CI, 8.57-15.21) for retinal hemorrhage. CONCLUSIONS: Incidence estimates of AHT are incomplete without including ED. Intracranial bleeding is a cardinal feature of AHT to be considered in case ascertainment to improve public health surveillance.

Heterotrimeric Gα(i) proteins are regulated by lipopolysaccharide and are anti-inflammatory in endotoxemia and polymicrobial sepsis.

Previous studies have implicated a role of heterotrimeric Gα(i) proteins in lipopolysaccharide (LPS)-induced inflammatory responses. We hypothesized that Toll-like receptor (TLR) signaling regulates Gα(i) proteins, which are anti-inflammatory in endotoxemia and polymicrobial sepsis. RAW 264.7 cells were stimulated with LPS and the Gα(i)-GTP protein complex was immunoprecipitated with a Gα(i) protein activation assay. In subsequent in vivo studies, the Gα(i) protein inhibitor pertussis toxin (PTx) or G(i) protein agonist mastoparan (MP-7) were administrated prior to endotoxemia. LPS-induced pro-inflammatory cytokines and mortality were determined. To examine the role of Gα(i2) in sepsis, Gα(i2) (-/-) and wildtype (WT) mice were subjected to cecal ligation and puncture (CLP) and monitored every 24 h for 120 h. Other mice were sacrificed 24 h after CLP. Peritoneal fluid, blood, and tissue samples were collected. Plasma pro-inflammatory cytokine production, bacterial load in peritoneal fluid, blood and lung tissue, myeloperoxidase (MPO) activity in lung and liver and different immune cell populations in spleen were studied. We found that Gα(i) proteins are rapidly activated by LPS followed by rapid inactivation. These studies provide the first direct evidence that Gα(i) proteins are modulated by TLR signaling. In following studies, PTx augmented LPS-induced plasma TNFα, IL-6, whereas MP-7 suppressed LPS-induced TNFα and decreased LPS-induced mortality. In sepsis studies, the survival rate post-CLP was significantly decreased in the Gα(i2) (-/-) mice compared to WT mice. CLP-induced plasma TNFα, IL-6, bacterial load in peritoneal fluid, blood and lung tissue and lung and liver MPO activity were significantly increased in Gα(i2) (-/-) compared to WT mice. Gα(i2) (-/-) mice also exhibited increased Th1 and Th2 responses compared to WT mice. Taken together, Gα(i) proteins are activated by LPS and negatively regulate endotoxemia and sepsis. Understanding the role of Gα(i2) protein in regulation of the inflammatory response in sepsis may provide novel targets for treatment of sepsis.

Beta-arrestin 2 negatively regulates sepsis-induced inflammation.

SUMMARY: Beta-arrestins 1 and 2 are ubiquitously expressed proteins that alter signalling by G-protein-coupled receptors. beta-arrestin 2 plays an important role as a signalling adaptor and scaffold in regulating cellular inflammatory responses. We hypothesized that beta-arrestin 2 is a critical modulator of inflammatory response in experimental sepsis. beta-arrestin 2(-/-) and wild-type (WT) mice were subjected to caecal ligation and puncture (CLP). The survival rate was significantly decreased (P < 0.05) in beta-arrestin 2(-/-) mice (13% survival) compared with WT mice (53% survival). A second group of mice were killed 18 hr after CLP for blood, peritoneal lavage and tissue sample collection. CLP-induced plasma interleukin (IL)-6 was significantly increased 25 +/- 12 fold and caecal myeloperoxidase (MPO) activity was increased 2.4 +/- 0.3 fold in beta-arrestin 2(-/-) compared with WT mice. beta-arrestin 2(-/-) mice exhibited more severe lung damage and higher bacterial loads compared with WT mice post CLP challenge as measured by histopathology and colony-forming unit count. In subsequent experiments, splenocytes, peritoneal macrophages and bone marrow-derived macrophages (BMDMs) were isolated and cultured from beta-arrestin 2(-/-) and WT mice and stimulated in vitro with lipopolysaccharide (LPS). Tumour necrosis factor (TNF)-alpha, IL-6 and IL-10 production induced by LPS was significantly augmented (2.2 +/- 0.2 fold, 1.8 +/- 0.1 fold, and 2.2 +/- 0.4 fold, respectively; P < 0.05) in splenocytes from beta-arrestin 2(-/-) mice compared with WT mice. The splenocyte response was different from that of peritoneal macrophages or BMDMs, which exhibited no difference in TNF-alpha and IL-6 production upon LPS stimulation between WT and beta-arrestin 2(-/-) mice. Our data demonstrate that beta-arrestin 2 functions to negatively regulate the inflammatory response in polymicrobial sepsis.

Prevalence of problem drinking and characteristics of a single-question screen.

Hazardous drinking and alcohol use disorders (i.e, abuse and dependence) are common in Emergency Departments (EDs). This study examined 1) the prevalence of these conditions among ED patients and 2) characteristics of a single screening question (having consumed at least five drinks for males or four for females during a single day). Data from the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed. Logistic regression for clustered data was used to estimate the relative risk for past-year ED use associated with hazardous drinking, abuse, and dependence. Contingency tables were analyzed to estimate the sensitivity and specificity of the single-question screen for detecting these conditions. Hazardous drinking was not associated with ED utilization. Alcohol abuse was associated with a relative risk of 1.3 (95% confidence interval [CI] 1.1-1.5) and alcohol dependence with a relative risk of 1.9 (95% CI 1.6-2.2). For current drinkers, the single question screen was 0.96, 0.85, and 0.90 sensitive for hazardous drinking, alcohol abuse, and alcohol dependence, respectively. Individuals with a positive screen in the past year were considered at least hazardous drinkers, and specificity was 0.80, 0.64, and 0.65 for hazardous drinking, abuse, and dependence, respectively. Specificity was modestly increased in women. Most problem drinkers were hazardous drinkers, but only severe alcohol use disorders were particularly prevalent in the ED. The single heavy-drinking-day item appears sensitive for problem drinking. Positive tests must be followed by additional assessment to differentiate hazardous drinking from alcohol use disorders.

A study of the workforce in emergency medicine: 2007.

INTRODUCTION: This study was undertaken to describe the current status of the emergency medicine workforce in the United States. METHODS: Surveys were distributed in 2008 to 2619 emergency department (ED) medical directors and nurse managers in hospitals in the 2006 American Hospital Association database. RESULTS: Among ED medical directors, 713 responded, for a 27.2% response rate. Currently, 65% of practicing emergency physicians are board certified by the American Board of Emergency Medicine or the American Osteopathic Board of Emergency Medicine. Among those leaving the practice, the most common reasons cited for departure include geographic relocation (46%) and better pay (29%). Approximately 12% of the ED physician workforce is expected to retire in the next 5 years. Among nurse managers, 548 responded, for a 21% response rate. Many nurses (46%) have an associate degree as their highest level of education, 28% have a BSN, and 3% have a graduate degree (MSN or higher). Geographic relocation (44%) is the leading reason for changing employment. Emergency department annual volumes have increased by 49% since 1997, with a mean ED volume of 32 281 in 2007. The average reported ED length of stay is 158 minutes from registration to discharge and 208 minutes from registration to admission. Emergency department spent an average of 49 hours per month in ambulance diversion in 2007. Boarding is common practice, with an average of 318 hours of patient boarding per month. CONCLUSIONS: In the past 10 years, the number of practicing emergency physicians has grown to more than 42 000. The number of board-certified emergency physicians has increased. The number of annual ED visits has risen significantly.

Determining the Joint Effect of Obesity and Diabetes on All-Cause Mortality and Cardiovascular-Related Mortality following an Ischemic Stroke.

Although obesity and diabetes mellitus, or diabetes, are independently associated with mortality-related events (e.g., all-cause mortality and cardiovascular-related mortality) following an ischemic stroke, little is known about the joint effect of obesity and diabetes on mortality-related events following an ischemic stroke. The aim of this study is to evaluate the joint effect of obesity and diabetes on mortality-related events in subjects with a recent ischemic stroke. Data from the multicenter Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial was analyzed for this study. The joint effect of obesity and diabetes on mortality-related events was estimated via Cox proportional hazards regression models. No difference in the hazard of all-cause mortality following an ischemic stroke was observed between obese subjects with diabetes and underweight/normal-weight subjects without diabetes. In contrast, obese subjects with diabetes had an increased hazard of cardiovascular-related mortality following an ischemic stroke compared with underweight/normal-weight subjects without diabetes. Additionally, there was evidence of an attributable proportion due to interaction as well as evidence of a highly statistically significant interaction on the multiplicative scale for cardiovascular-related mortality. In this clinical trial cohort of ischemic stroke survivors, obesity and diabetes synergistically interacted to increase the hazard of cardiovascular-related mortality.

Antimicrobial copper alloys decreased bacteria on stethoscope surfaces.

BACKGROUND: Stethoscopes may serve as vehicles for transmission of bacteria among patients. The aim of this study was to assess the efficacy of antimicrobial copper surfaces to reduce the bacterial concentration associated with stethoscope surfaces. METHODS: A structured prospective trial involving 21 health care providers was conducted at a pediatric emergency division (ED) (n = 14) and an adult medical intensive care unit located in tertiary care facilities (n = 7). Four surfaces common to a stethoscope and a facsimile instrument fabricated from U.S. Environmental Protection Agency-registered antimicrobial copper alloys (AMCus) were assessed for total aerobic colony counts (ACCs), methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and vancomycin-resistant enterococci for 90 days. RESULTS: The mean ACCs collectively recovered from all stethoscope surfaces fabricated from the AMCus were found to carry significantly lower concentrations of bacteria (pediatric ED, 11.7 vs 127.1 colony forming units [CFU]/cm2, P < .00001) than their control equivalents. This observation was independent of health care provider or infection control practices. Absence of recovery of bacteria from the AMCu surfaces (66.3%) was significantly higher (P < .00001) than the control surfaces (22.4%). The urethane rim common to the stethoscopes was the most heavily burdened surface; mean concentrations exceeded the health care-associated infection acquisition concentration (5 CFU/cm2) by at least 25×, supporting that the stethoscope warrants consideration in plans mitigating microbial cross-transmission during patient care. CONCLUSIONS: Stethoscope surfaces fabricated with AMCus were consistently found to harbor fewer bacteria.