Sepsis Bundle Adherence Is Associated with Improved Survival in Severe Sepsis or Septic Shock.

INTRODUCTION: There have been conflicting data regarding the relationship between sepsis-bundle adherence and mortality. Moreover, little is known about how this relationship may be moderated by the anatomic source of infection or the location of sepsis declaration. METHODS: This was a multi-center, retrospective, observational study of adult patients with a hospital discharge diagnosis of severe sepsis or septic shock. The study included patients who presented to one of three Los Angeles County Department of Health Services (DHS) full-service hospitals January 2012 to December 2014. The primary outcome of interest was the association between sepsis-bundle adherence and in-hospital mortality. Secondary outcome measures included in-hospital mortality by source of infection, and the location of sepsis declaration. RESULTS: Among the 4,582 patients identified with sepsis, overall mortality was lower among those who received bundle-adherent care compared to those who did not (17.9% vs. 20.4%; p=0.035). Seventy-five percent (n=3,459) of patients first met sepsis criteria in the ED, 9.6% (n=444) in the intensive care unit (ICU) and 14.8% (n=678) on the ward. Bundle adherence was associated with lower mortality for those declaring in the ICU (23.0% adherent [95% confidence interval{CI} {16.8-30.5}] vs. 31.4% non-adherent [95% CI {26.4-37.0}]; p=0.063), but not for those declaring in the ED (17.2% adherent [95% CI {15.8-18.7}] vs. 15.1% non-adherent [95% CI {13.0-17.5}]; p=0.133) or on the ward (24.8% adherent [95% CI {18.6-32.4}] vs. 24.4% non-adherent [95% CI {20.9-28.3}]; p=0.908). Pneumonia was the most common source of sepsis (32.6%), and patients with pneumonia had the highest mortality of all other subsets receiving bundle non-adherent care (28.9%; 95% CI [25.3-32.9]). Although overall mortality was lower among those who received bundle-adherent care compared to those who did not, when divided into subgroups by suspected source of infection, a statistically significant mortality benefit to bundle-adherent sepsis care was only seen in patients with pneumonia. CONCLUSION: In a large public healthcare system, adherence with severe sepsis/septic shock management bundles was found to be associated with improved survival. Bundle adherence seems to be most beneficial for patients with pneumonia. The overall improved survival in patients who received bundle-adherent care was driven by patients declaring in the ICU. Adherence was not associated with lower mortality in the large subset of patients who declared in the ED, nor in the smaller subset of patients who declared in the ward.

Reasons for Energy Drink Use and Reported Adverse Effects Among Adolescent Emergency Department Patients.

OBJECTIVES: There is concern of energy drink use by adolescents. The objective of this study was to evaluate the energy drink consumption use, frequency, age of first use, reasons for use, influences of choice of brand, and adverse events recorded in a predominant Latino adolescent population. METHODS: Subjects between the ages of 13 and 19 years utilizing emergency department services for any reason at a large county hospital answered a questionnaire about energy drink usage. RESULTS: There were 192 subjects, of which 49% were male and 51% were female. Latino adolescents were 85% of the participants, although other ethnic groups participated including African American, white, and Asian. Reasons for use include 61% to increase energy, 32% as study aide, 29% to improve sports performance, and 9% to lose weight. Twenty-four percent reported using energy drinks with ethanol or illicit drugs including marijuana, cocaine, and methamphetamine. Adverse reactions were reported in 40% of the subjects including insomnia (19%), feeling "jittery" (19%), palpitations (16%), gastrointestinal upset (11%), headache (8%), chest pain (5%), shortness of breath (4%), and seizures (1%). CONCLUSIONS: Both brand name and packaging influenced the choice of energy drink in most subjects. Forty percent reported at least 1 adverse effect. While most adverse effects were not severe, a small number are serious. In addition, we showed intentional ingestion with ethanol and illicit drugs. Of additional concern is that both brand and packaging seem to directly affect choice of energy drink consumed.

The diagnosis of right heart thrombus by focused cardiac ultrasound in a critically ill patient in compensated shock.

Right heart thrombus (RHT) is a life-threatening diagnosis that is rarely made in the emergency department (ED), but with the increasing use of focused cardiac ultrasound (FocUS), more of these cases may be identified in a timely fashion. We present a case of an ill-appearing patient who had an immediate change in management due to the visualization of RHT soon after arrival to the ED. The diagnosis was confirmed after a cardiology-performed ultrasound (US). This case illustrates the value of the recognition of RHT on FocUS and how US protocols designed for the evaluation of shock and shortness of breath may potentially be expanded to patients in a 'compensated' or 'pre-shock' state to expedite the correct diagnosis and to facilitate more timely management.

Compliance with outpatient stress testing in low-risk patients presenting to the emergency department with chest pain.

Recent evidence suggests that stress testing prior to emergency department (ED) release in low-risk chest pain patients identifies those who can be safely discharged home. When immediate stress testing is not feasible, rapid outpatient stress testing has been recommended. The objective of this study was to determine compliance rate and incidence of adverse cardiac events in patients presenting to the ED with low-risk chest pain referred for outpatient stress testing. Retrospective chart and social security death index review were conducted in 448 consecutive chest pain patients who presented to a university hospital and level I trauma center between April 30 and December 31, 2007. Patients were evaluated with an accelerated chest pain protocol defined as a 4-hour ED rule out and referral for outpatient stress testing within 72 hours of ED release. Only patients without known cardiac disease, a thrombolysis in myocardial infarction risk score ≤2, negative serial ECGs and cardiac biomarkers, and benign ED course were eligible for the protocol. Primary outcome measures included compliance with outpatient stress testing and documented 30-day incidence of adverse cardiac events following ED release. The social security death index was queried to determine 12-month incidence of all-cause mortality in enrolled patients. Logistic regression analysis of characteristics associated with outpatient stress test compliance was determined and incidence of adverse cardiac events in those who were and were not compliant with outpatient stress testing was compared. Significance was set at P < 0.05. A total of 188 patients (42%) completed outpatient stress testing, but only 27 (6%) completed testing within 72 hours of ED discharge. Compliance was correlated with insurance and race, but not patient age, gender, or thrombolysis in myocardial infarction risk score. No significant differences in adverse cardiac events were documented in patients who did and did not comply with outpatient stress testing. Compliance with outpatient stress testing is poor in low-risk chest pain patients following ED release. Despite poor compliance, the documented incidence of adverse cardiac events in this low-risk cohort was lower than that reported in patients with negative provocative testing prior to ED release.

The ngram chief complaint classifier: a novel method of automatically creating chief complaint classifiers based on international classification of diseases groupings.

INTRODUCTION: The ngram classifier is created by using text fragments to measure associations between chief complaints (CC) and a syndromic grouping of ICD-9-CM codes. OBJECTIVES: For gastrointestinal (GI) syndrome to determine: (1) ngram CC classifier sensitivity/specificity. (2) Daily volumes for ngram CC and ICD-9-CM classifiers. DESIGN: Retrospective cohort. SETTING: 19 Emergency Departments. PARTICIPANTS: Consecutive visits (1/1/2000-12/31/2005). PROTOCOL: (1) Used an existing ICD-9-CM filter for "lower GI" to create the ngram CC classifier from a training set and then measured sensitivity/specificity in a test set using an ICD-9-CM classifier as criterion. (2) Compare daily volumes based on ICD-9-CM with that predicted by the ngram classifier. RESULTS: For a specificity of 0.96, sensitivity was 0.70. The daily volume correlation for ngram vs. ICD-9-CM was R=0.92. CONCLUSION: The ngram CC classifier performed similarly to manually developed CC classifiers and has advantages of rapid automated creation and updating, and may be used independent of language or dialect.

Volunteerism among surgeons: an exploration of attitudes and barriers.

BACKGROUND: In a recent survey, the American College of Surgeons found great interest in surgically related volunteerism, but it was unclear if the interest reflected participation. The purpose of the current study was to explore attitudes and barriers to volunteering. METHODS: To assess surgeons' experiences and beliefs about volunteerism, we mailed a questionnaire to Nathan A. Womack Society members. We analyzed respondents' demographics and attitudes, and associations between physician characteristics and volunteer status. RESULTS: The response rate was 42.5%. More than half (56%) of respondents volunteered surgical skills at least once, and 48% actively volunteer a mean of 9 days per year. Full-time practicing status was associated with being an active volunteer (57.8% vs 17.2% not full-time, P <.001). Modifiable barriers were identified. CONCLUSIONS: Many different kinds of surgeons volunteer their surgical skills, reflecting the interest found by the College. Knowledge of barriers can be used to develop strategies to help interested surgeons pursue volunteer interests.

Intestinal ischemia-reperfusion injury alters purinergic receptor expression in clinically relevant extraintestinal organs.

BACKGROUND: Intestinal ischemia-reperfusion (IIR) injury is known to initiate the systemic inflammatory response syndrome, which often progresses to multiple organ failure. We investigated changes in purinoceptor expression in clinically relevant extra-intestinal organs following IIR injury. MATERIALS AND METHODS: Anesthetized adult male BalbC mice were randomized to sham laparotomy (control, n = 5), or 15 min of superior mesenteric artery occlusion. Experimental ischemia was followed by a period of reperfusion [1 min (n = 6) or 1 h (n = 6)]. Mice were then sacrificed and lung, kidney, and intestinal tissues were harvested. Following RNA extraction, purinoceptor mRNA expression for P2Y2, A3, P2X7, A2b, P2Y4, and P2Y6 was analyzed using real-time RT-PCR. RESULTS: Significant differences in purinoceptor expression were observed in the lungs and kidneys of mice exposed to IIR injury when compared to controls. Pulmonary P2Y2 receptor expression was increased in the 1 h IIR group when compared to control, while pulmonary A3 receptor expression was incrementally elevated following IIR injury. In the kidney, P2Y2 receptor expression was increased in the 1 h IIR group compared to both 1 min IIR and control, and A3 receptor expression was decreased in the 1 h IIR group compared to the 1 min IIR group. No significant changes were observed in the intestinal purinoceptor profiles. CONCLUSION: Purinoceptor expression is altered in the murine lung and kidney, but not intestine following experimental IIR injury. These findings may implicate extracellular nucleotides and purinoceptors as possible mediators of the extra-intestinal organ dysfunction associated with IIR injury.

Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways.

Extracellular nucleotides can mediate a variety of cellular functions via interactions with purinergic receptors. We previously showed that mechanical ventilation (MV) induces airway IL-6 and ATP release, modifies luminal nucleotide composition, and alters lung purinoceptor expression. Here we hypothesize that extracellular nucleotides induce secretion of IL-6 by small airway epithelial cells (SAEC). Human SAEC were stimulated with nucleotides in the presence or absence of inhibitors. Supernatants were analyzed for IL-6 and lysates for p38 MAPK activity by ELISA. RNA was analyzed by real-time RT-PCR. Rats (n=51) were randomized to groups as follows: control, small-volume MV, large-volume MV, large-volume MV-intratracheal apyrase, or small-volume MV-intratracheal adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS). After 1 h of MV, bronchoalveolar lavage fluid was analyzed for ATP and IL-6 by luminometry and ELISA. ATP and ATPgammaS increased SAEC IL-6 secretion in a time- and dose-dependent manner, an effect inhibited by apyrase. Agonists were ranked in the following order: ATPgammaS>ATP=UTP>ADP=adenosine>2-methylthio-ADP=control. SB-203580, but not U-0126 or JNK1 inhibitor, decreased nucleotide effects. Additionally, nucleotides induced p38 MAPK phosphorylation. Inhibitors of Ca2+ signaling, phospholipase C, transcription, and translation decreased IL-6 release. Furthermore, nucleotides increased IL-6 expression. In vivo, large-volume MV increased airway ATP and IL-6 concentrations. IL-6 release was decreased by apyrase and increased by ATPgammaS. Extracellular nucleotides induce P2Y2-mediated secretion of IL-6 by SAEC via Ca2+, phospholipase C, and p38 MAPK-dependent pathways. This effect is dependent on transcription and translation. Our findings were confirmed in an in vivo model, thus demonstrating a novel mechanism of nucleotide-induced IL-6 secretion by airway epithelia.

ATP stimulates MMP-2 release from human aortic smooth muscle cells via JNK signaling pathway.

Aortic smooth muscle cell release of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) has been implicated in aortic aneurysm pathogenesis, but proximal modulation of release is poorly understood. Extracellular nucleotides regulate vascular smooth muscle cell metabolism in response to physiochemical stresses, but nucleotide modulation of MMP and/or TIMP release has not been reported. We hypothesized that nucleotides modulate MMP-2 and TIMP-2 release from human aortic smooth muscle cells (HASMCs) via distinct purinergic receptors and signaling pathways. We exposed HASMCs to exogenous ATP and other nucleotides with and without interleukin-1beta (IL-1beta). HASMCs were pretreated in some experiments with apyrase, which degrades ATP, and inhibitors of ERK1/2, JNK, and p38 MAPK. MMP-2 and TIMP-2 released into supernatant were assessed using ELISA and Western blotting. ATP, adenosine, and UTP significantly stimulated MMP-2 release in the presence of IL-1beta (300 nM ATP: 181 +/- 22%, P = 0.003; 30 microm adenosine: 244 +/- 150%, P = 0.001; and 200 microm UTP: 153 +/- 40%, P = 0.015; vs. 100% constitutive). ATP also stimulated MMP-2 release in the absence of IL-1beta (100 microm ATP: 148 +/- 38% vs. 100% constitutive). Apyrase significantly reduced ATP-stimulated MMP-2 release (apyrase + 500 nM ATP: 59 +/- 3% vs. 124 +/- 7% with 500 nM ATP). Rank-order agonist potency for MMP-2 release was consistent with ATP activation of PAY and PAY receptors. ATP induced phosphorylation of intracellular JNK, and inhibition of the JNK pathway blocked ATP-stimulated MMP-2 release, indicating signaling via this pathway. Nucleotides are thus novel stimulants of MMP-2 release from HASMCs and may provide a mechanistic link between physiochemical stress in the aorta and aneurysms, especially in the context of inflammation.

Cardiac events in New Jersey after the September 11, 2001, terrorist attack.

The higher stress associated with the World Trade Center (WTC) attacks on September 11, 2001, may have resulted in more cardiac events particularly in those living in close proximity. Our goal was to determine if there was an increase in cardiac events in a subset of emergency departments (EDs) within a 50-mi radius of the WTC. We performed a retrospective analysis of consecutive patients seen by ED physicians in 16 EDs for the 60 days before and after September 11 in 2000-2002. We determined the number of patients admitted to an inpatient bed with a primary or secondary diagnosis of acute myocardial infarction (MI) or tachyarrhythmia. In each year, we compared patient visits for the 60 days before and after September 11 using the chi-square statistic. For the 360 days during the 3 years, there were 571,079 patient visits in the database of which 110,766 (19.4%) were admitted. Comparing the 60 days before and after September 11, 2001, we found a statistically significant increase in patients with MIs (79 patients before versus 118 patients after, P =.01), representing an increase of 49%. There were no statistically significant differences for MIs in 2000 and 2002 and in tachyarrhythmias for all three years. For the 60-day period after September 11, 2001, we found a statistically significant increase in the number of patients presenting with acute MI but no increase in patients admitted with tachyarrhythmias.

Measurement of free and bound fractions of extracellular ATP in biological solutions using bioluminescence.

Measurement of extracellular ATP in biological solutions is complicated by protein-binding and rapid enzymatic degradation. We hypothesized that the concentration of extracellular ATP could be determined luminometrically by limiting degradation and measuring the free and protein-bound fractions. ATP was added (a) at constant concentration to solutions containing varying albumin concentrations; (b) at varying concentrations to a physiological albumin solution (4 gm/dL); (c) at varying concentrations to plasma. After centrifugation, a fraction of each supernatant was heated. ATP in heated and unheated samples was measured luminometrically. Blood was drawn into saline or an ATP-stabilizing solution and endogenous plasma ATP measured. ATP-albumin binding was a linear function of albumin concentration (3.5% ATP bound at 100 micromol/L to 33.2% ATP bound at 1000 micromol/L) but independent of ATP concentration (29.3%, 10-1000 nmol/L ATP in 602 micromol/L albumin). Heating released the majority of bound ATP from albumin-containing solutions (94.8 +/- 1.7%) and plasma (97.6 +/- 5.1%). Total endogenous plasma ATP comprised 93 +/- 27 nmol/L (free) and 150 +/- 40 nmol/L (total fraction). Without stabilizing solution, degradation of free endogenous plasma ATP occurred. Within a physiological range (10-1000 nmol/L), ATP binds albumin independently of ATP concentration. Heating releases bound ATP, enabling accurate luminometric measurement of total extracellular ATP (free and bound) in biological samples.

Conversion of five-, six-, and seven-membered lactams to racemic or scalemic 2-substituted heterocycles by amidoalkylation.

An efficient method for the synthesis of 2-alkyl- and 2-aryl pyrrolidines, piperidines, and azepanes from lactams, in either racemic or enantiopure form, is presented. The lactam nitrogens are acylated with either Boc anhydride or trans-cumylcyclohexyl (TCC) chloroformate. Selective reduction of the lactam carbonyl to the carbinolamide is followed by treatment with benzotriazole. Substitution of the benzotriazole is accomplished by treatment with organometallics, yielding the 2-substituted heterocycles. With TCC, up to 90% diastereoselectivity is achieved. After diastereomer purification, reductive removal of the auxiliary affords enantiopure 2-substituted heterocycles. A mechanistic hypothesis is presented that details the conformational equilibria of the key step.

Socioeconomic and health status differences between depressed and nondepressed ED elders.

The objective of the study was to describe differences in demographics, medical conditions, and social situation between depressed and nondepressed elderly emergency department (ED) patients. We studied a prospective convenience sample of English-speaking ED patients greater-than-or-equal 65 years, without altered mental status, obvious dementia or delirium, participating in a depression screening study during an ED visit for a nonpsychiatric complaint. Demographics were collected. Research personnel administered the Geriatric Depression Scale (GDS), the Folstein Mini-Mental State Examination and a health questionnaire. A total of 103 subjects were enrolled. GDS identified 33 patients (32%) with DEP. DEP patients were more likely to report the following: lower income, lower education level, more medical conditions, less independence, assisted living, and poorer overall health than ND patients. A third of these elderly ED patients report symptoms consistent with depression. There are significant differences in socioeconomic characteristics, health status, and functional ability. Future depression studies should focus on elders with these characteristics.

Validation of a brief screening tool to detect depression in elderly ED patients.

Although depression is the most common psychiatric disorder in the elderly, it is often unrecognized by physicians. The objective of the study was to assess the utility of a 3-question screening instrument (ED-DSI) to detect depression among elderly emergency department (ED) patients. We used a prospective convenience sample of English-speaking ED patients >or=65yr. Patients were excluded for being too ill to participate, having obvious dementia, or acute changes in mentation. A physician administered the ED-DSI. Trained research personnel blinded to ED-DSI answers then administered the 30 question Geriatric Depression Scale (GDS). The ED-DSI was considered positive if the patient answered yes to one or more questions and subjects were considered depressed when the GDS score was >or=10. ED-DSI was compared to GDS using contingency tables. A total of 103 subjects were enrolled. Average age was 75 years and subjects were predominately female (66%) and white (85%). GDS identified 33 patients (32%) as depressed. Of these, 26 were correctly identified by ED-DSI giving an ED-DSI sensitivity of 79% (95%CI (65%, 93%)) specificity of 66% (95%CI (54%, 78%)) and a negative predictive value of 87% (95%CI (79%, 95%)). The 3-question ED-DSI is a useful tool to detect depression in this population of ED patients.