Unsuspected Pulmonary Embolism in Observation Unit Patients

Objective: Many emergency department (ED) patients with cardiopulmonary symptoms such as chest pain or dyspnea are placed in observation units but do not undergo specific diagnostic testing for pulmonary embolism (PE). The role of observation units in the diagnosis of PE has not been studied. We hypothesized that there was a small but significant rate of unsuspected PE in our observation unit population.Methods: We performed a retrospective chart review at an urban academic hospital of all ED patients with an International Classification of Diseases, Ninth Revision diagnosis of PE between January 2005 and July 2006. The number of such patients assigned to observation at any point in their stay was recorded, in addition to events leading to diagnosis and subsequent in-hospital outcomes.Results: Thirteen of the 190 ED patients diagnosed with PE were placed in the observation unit. Six of these either had a known recent diagnosis of PE or had testing for PE initiated prior to placement in the observation unit. Two of the remaining seven patients with undiagnosed PE were placed in observation for undifferentiated chest pain, accounting for 0.09% of the 2190 patients under the chest pain protocol. Twelve of 13 PE patients (92%) were admitted with an average stay of 4.3 days. Of the 13 patients, five were ultimately determined after admission to not have PE, leaving a rate of confirmed PE in the observation unit population of 0.12% (8/6182), with five of eight being classified as unsuspected prior to assignment to observation (0.08% rate).Conclusion: We identified a small number of patients assigned to observation with unsuspected PE. The high rate of hospital admission and prolonged hospital stay suggests that patients with PE are inappropriate for observation status. Given the low incidence of unsuspected PE, there may be a need for a specific approach to screening for PE in observation unit patients.[WestJEM. 2009;10:130-134.

The Impact of For-Profit Hospital Status on the Care and Outcomes of Patients With Non–ST-Segment Elevation Myocardial Infarction Results From the CRUSADE Initiative

ObjectivesWe sought to determine whether for-profit status influenced hospitals’ care or outcomes among non–ST-segment elevation myocardial infarction (NSTEMI) patients.BackgroundWhile for-profit hospitals potentially have financial incentives to selectively care for younger, healthier patients, perform highly reimbursed procedures, reduce costs by limiting access to expensive medications, and encourage shorter in-patient length of stay, there are limited data available to investigate these issues objectively.MethodsUsing data from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines) Initiative, we investigated whether for-profit status influenced hospitals’ patient case mix, care, or outcomes among 145,357 patients with NSTEMI treated between January 1, 2001, and December 31, 2005, at 532 U.S. hospitals. Impact of for-profit status on care and outcomes was analyzed overall and after adjustment for clinical and facility factors using regression modeling.ResultsPatients (n = 11,658) treated at 58 for-profit hospitals were of similar age and gender, but were more likely to be nonwhite (black, Asian, Hispanic, and other) and have health maintenance organization/private insurance, diabetes mellitus, congestive heart failure, hypertension, and renal insufficiency compared with 133,699 patients treated at 474 nonprofit hospitals. For-profit hospitals were less likely to use discharge beta-blockers, but all other treatments were similar including the use of interventional procedures (cardiac catheterization and revascularization procedures) compared with nonprofit centers. In-hospital length of stay and mortality were also similar by hospital type.ConclusionsWe found no evidence that for-profit hospitals selectively treat less sick patients, provide less evidence-based care, limit in-hospital stays, or have patients with worse acute outcomes than nonprofit centers

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients

Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9$1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1$1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8$50,000 per life-year saved. Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development

Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department With Sepsis

Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed

Discriminative Value of Inflammatory Biomarkers for Suspected Sepsis

Circulating biomarkers can facilitate sepsis diagnosis enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers

Gene Expression-Based Classifiers Identify Staphylococcus aureus Infection in Mice and Humans

Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host’s inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues

Renal systems biology of patients with systemic inflammatory response syndrome

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate were inversely correlated with the majority of significantly down-regulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness

An integrated transcriptome and expressed variant analysis of sepsis survival and death

BackgroundSepsis, a leading cause of morbidity and mortality, is not a homogeneous disease but rather a syndrome encompassing many heterogeneous pathophysiologies. Patient factors including genetics predispose to poor outcomes, though current clinical characterizations fail to identify those at greatest risk of progression and mortality.MethodsThe Community Acquired Pneumonia and Sepsis Outcome Diagnostic study enrolled 1,152 subjects with suspected sepsis. We sequenced peripheral blood RNA of 129 representative subjects with systemic inflammatory response syndrome (SIRS) or sepsis (SIRS due to infection), including 78 sepsis survivors and 28 sepsis non-survivors who had previously undergone plasma proteomic and metabolomic profiling. Gene expression differences were identified between sepsis survivors, sepsis non-survivors, and SIRS followed by gene enrichment pathway analysis. Expressed sequence variants were identified followed by testing for association with sepsis outcomes.ResultsThe expression of 338 genes differed between subjects with SIRS and those with sepsis, primarily reflecting immune activation in sepsis. Expression of 1,238 genes differed with sepsis outcome: non-survivors had lower expression of many immune function-related genes. Functional genetic variants associated with sepsis mortality were sought based on a common disease-rare variant hypothesis. VPS9D1, whose expression was increased in sepsis survivors, had a higher burden of missense variants in sepsis survivors. The presence of variants was associated with altered expression of 3,799 genes, primarily reflecting Golgi and endosome biology.ConclusionsThe activation of immune response-related genes seen in sepsis survivors was muted in sepsis non-survivors. The association of sepsis survival with a robust immune response and the presence of missense variants in VPS9D1 warrants replication and further functional studies.Trial registrationClinicalTrials.gov NCT00258869. Registered on 23 November 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0111-5) contains supplementary material, which is available to authorized users

Variation in the Use of 12‐Lead Electrocardiography for Patients With Chest Pain by Emergency Medical Services in North Carolina

BACKGROUND: Prehospital 12‐lead electrocardiography (ECG) is critical to timely STEMI care although its use remains inconsistent. Previous studies to identify reasons for failure to obtain a prehospital ECG have generally only focused on individual emergency medical service (EMS) systems in urban areas. Our study objective was to identify patient, geographic, and EMS agency‐related factors associated with failure to perform a prehospital ECG across a statewide geography. METHODS AND RESULTS: We analyzed data from the Prehospital Medical Information System (PreMIS) in North Carolina from January 2008 to November 2010 for patients >30 years of age who used EMS and had a prehospital chief complaint of chest pain. Among 3.1 million EMS encounters, 134 350 patients met study criteria. From 2008–2010, 82 311 (61%) persons with chest pain received a prehospital ECG; utilization increased from 55% in 2008 to 65% in 2010 (trend P<0.001). Utilization by health referral region ranged from 22.9% to 74.2% and was lowest in rural areas. Men were more likely than women to have an ECG performed (63.0% vs 61.3%, adjusted RR 1.02, 95% CI 1.01 to 1.04). The certification‐level of the EMS provider (paramedic vsbasic/intermediate) and system‐level ECG equipment availability were the strongest predictors of ECG utilization. Persons in an ambulance with a certified paramedic were significantly more likely to receive a prehospital ECG than nonparamedics (RR 2.15, 95% CI 1.55, 2.99). CONCLUSIONS: Across a large geographic area prehospital ECG use increased significantly, although important quality improvement opportunities remain. Increasing ECG availability and improving EMS certification and training levels are needed to improve overall care and reduce rural‐urban treatment differences