Early career academic productivity among emergency physicians with R01 grant funding.

OBJECTIVES: The objective was to describe the early academic career activities of emergency physician (EP) scientists with recent Research Project Grant Program (R01) grant funding from the National Institutes of Health (NIH). METHODS: The curricula vitae of all EP scientists in the United States currently funded by the NIH were analyzed for evidence of advanced research training and frequency and type of publication and grant writing. Each investigator was surveyed for demographic features and estimation of protected time during their early career development. RESULTS: Eighteen investigators were identified. The median length of time from completion of residency to receipt of their first R01 grant was 11 years (interquartile range [IQR] = 11 to 15 years), and the median age of investigators at the time of this award was 43 years (IQR = 39 to 47 years). At the time of their award, researchers were publishing five peer-reviewed manuscripts a year (IQR = 1 to 8 manuscripts) and had already received considerable external funding. Ninety-four percent of those studied had pursued a research fellowship, an advanced degree, or an NIH K-award following residency. CONCLUSIONS: For EPs, receipt of an R01 from the NIH requires more than a decade of work following the completion of training. This period is characterized by pursuit of advanced research training, active and accelerating publication and collaboration, and acquisition of smaller extramural grants.

Forecasting models of emergency department crowding.

OBJECTIVES: The authors investigated whether models using time series methods can generate accurate short-term forecasts of emergency department (ED) bed occupancy, using traditional historical averages models as comparison. METHODS: From July 2005 through June 2006, retrospective hourly ED bed occupancy values were collected from three tertiary care hospitals. Three models of ED bed occupancy were developed for each site: 1) hourly historical average, 2) seasonal autoregressive integrated moving average (ARIMA), and 3) sinusoidal with an autoregression (AR)-structured error term. Goodness of fits were compared using log likelihood and Akaike's Information Criterion (AIC). The accuracies of 4- and 12-hour forecasts were evaluated by comparing model forecasts to actual observed bed occupancy with root mean square (RMS) error. Sensitivity of prediction errors to model training time was evaluated, as well. RESULTS: The seasonal ARIMA outperformed the historical average in complexity adjusted goodness of fit (AIC). Both AR-based models had significantly better forecast accuracy for the 4- and the 12-hour forecasts of ED bed occupancy (analysis of variance [ANOVA] p < 0.01), compared to the historical average. The AR-based models did not differ significantly from each other in their performance. Model prediction errors did not show appreciable sensitivity to model training times greater than 7 days. CONCLUSIONS: Both a sinusoidal model with AR-structured error term and a seasonal ARIMA model were found to robustly forecast ED bed occupancy 4 and 12 hours in advance at three different EDs, without needing data input beyond bed occupancy in the preceding hours.

In vitro and in silico analysis of annexin V binding to lymphocytes as a biomarker in emergency department sepsis studies.

BACKGROUND: Peripheral blood lymphocyte apoptosis is a recognized feature of serious infection and sepsis and can be easily quantified by flow cytometric measurement of annexin V binding to the cell surface. Use of apoptosis as a biomarker in emergency department (ED) studies of sepsis is potentially difficult because of sample processing requirements and limited availability of a research cytometer with which to measure patient samples. OBJECTIVES: To assess, in vitro and in simulation, the relationship between sample stability, timing of patient enrollment, and diagnostic performance of a flow cytometric assay for sepsis in patients evaluated in EDs. METHODS: Assuming any clinical trial would require daily sample batching, the authors measured the stability of lymphocyte samples over time, noting the rate at which annexin V-negative cells became positive as ED processing delays increased. With these data, they then optimized a study design that could evaluate lymphocyte apoptosis as a sepsis biomarker by using a series of Monte Carlo-based simulated clinical trials. RESULTS: The authors found that annexin V-negative lymphocytes become positive during storage delays that would be encountered in an ED sepsis trial. The extent of this deterioration was least among cells left as whole blood at room temperature until just before analysis or when lymphocytes were isolated early and stored in culture media at 4 degrees C until analysis. When the expected rate of sample deterioration was considered in simulated clinical trials, an inverse relationship was found between the rate at which patients are enrolled and the best achievable receiver operating characteristic curve a study could produce. CONCLUSIONS: Peripheral blood samples being analyzed for lymphocyte apoptosis degrade at a rate relevant to the design of ED trials of sepsis. Because of sample processing delays inherent in studying unscheduled septic patients, the performance of annexin V binding as a biomarker for sepsis can approach, but not be expected to exceed, its performance in a comparable intensive care unit-based study.

Lipopolysaccharide O-antigen promotes persistent murine bacteremia.

Bacteremia is a common complication of pneumonia with Klebsiella pneumoniae. In the previous work, we have shown that the lipopolysaccharide (LPS) O-antigen in K. pneumoniae O1:K2 contributes to lethality during pneumonia in part by promoting bacteremia. In the current work, we studied an O-antigen-deficient K. pneumoniae strain to further evaluate this polysaccharide's role in bloodstream infection. Cultured macrophage and murine bacteremia models were studied. In vitro, O-antigen-deficient bacteria, compared with wild-type organisms, were stronger activators of the murine alveolar macrophage cell line MH-S as assessed by nuclear localization of RelA/p65 and by secretion of cytokines and chemokines. O-antigen-deficient Klebsiellae were also more susceptible to killing by murine neutrophils. In vivo, the absence of O-antigen allowed more rapid and complete clearance of bacteria from the bloodstream, liver, and spleen after intravenous injection in mice. Survival was also greater among animals infected with bacteria missing the O-antigen. Gene expression profiling (via reverse transcriptase-polymerase chain reaction of 84 inflammatory mediator complementary DNA) revealed that by 24 h postinfection, the livers and spleens of animals infected with O-antigen-deficient organisms had significantly downregulated cytokine and chemokine expression compared with wild-type infected animals. The O-antigen surface carbohydrate of O1:K2 serotype K. pneumoniae appears to contribute to bacterial virulence by lessening the activation of macrophages, conveying resistance to killing by neutrophils, and by promoting persistent infection in the blood, liver, and spleen after the onset of bacteremia.

Status report: Development of emergency medicine research since the Macy Report.

In Williamsburg, VA, April 17 to 20, 1994, the Josiah Macy, Jr. Foundation sponsored a conference entitled "The Role of Emergency Medicine in the Future of American Medical Care," a report on which was published in Annals in 1995. This report promulgated recommendations for the development and enhancement of academic departments of emergency medicine and a conference to develop an agenda for research in emergency medicine. The American College of Emergency Physicians' Research Committee, along with several ad hoc members, presents updates in several of the areas addressed by the Macy Report and subsequent conferences, as a status report for the development of emergency medicine research as a whole, as of late 2002.