A clinical trial comparing physician prompting with an unprompted automated electronic checklist to reduce empirical antibiotic utilization.

OBJECTIVES: To determine whether face-to-face prompting of critical care physicians reduces empirical antibiotic utilization compared to an unprompted electronic checklist embedded within the electronic health record. DESIGN: Random allocation design. SETTING: Medical ICU with high-intensity intensivist coverage at a tertiary care urban medical center. PATIENTS: Two hundred ninety-six critically ill patients treated with at least 1 day of empirical antibiotics. INTERVENTIONS: For one medical ICU team, face-to-face prompting of critical care physicians if they did not address empirical antibiotic utilization during a patient's daily rounds. On a separate medical ICU team, attendings and fellows were trained once to complete an electronic health record-embedded checklist daily for each patient, including a question asking whether listed empirical antibiotics could be discontinued. MEASUREMENTS AND MAIN RESULTS: Prompting led to a more than four-fold increase in discontinuing or narrowing of empirical antibiotics compared to use of the electronic checklist. Prompted group patients had a lower proportion of patient-days on which empirical antibiotics were administered compared to electronic checklist group patients (63.1% vs 70.0%, p = 0.002). Mean proportion of antibiotic-days on which empirical antibiotics were used was also lower in the prompted group, although not statistically significant (0.78 [0.27] vs 0.83 [0.27], p = 0.093). Each additional day of empirical antibiotics predicted higher risk-adjusted mortality (odds ratio, 1.14; 95% CI, 1.05-1.23). Risk-adjusted ICU length of stay and hospital mortality were not significantly different between the two groups. CONCLUSIONS: Face-to-face prompting was superior to an unprompted electronic health record-based checklist at reducing empirical antibiotic utilization. Sustained culture change may have contributed to the electronic checklist having similar empirical antibiotic utilization to a prompted group in the same medical ICU 2 years prior. Future studies should investigate the integration of an automated prompting mechanism with a more generalizable electronic health record-based checklist.

Ethanol differentially regulates snail family of transcription factors and invasion of premalignant and malignant pancreatic ductal cells.

Pancreatic cancer is one of the deadliest of cancers with a dismal 5-year survival rate. Epidemiological studies have identified chronic pancreatitis as a risk factor for pancreatic cancer. Pancreatic cancer cells also demonstrate increased expression of the transcription factor Snail, a key regulator of epithelial-mesenchymal transition. As ethanol is one of the major causes of pancreatitis, we examined the effect of ethanol on Snail family members in immortalized human pancreatic ductal epithelial (HPDE) cells and in pancreatic cancer cells. Ethanol induced Snail mRNA levels 2.5-fold in HPDE cells, with only 1.5-fold mRNA induction of the Snail-related protein slug. In contrast, ethanol increased Slug mRNA levels 1.5- to 2-fold in pancreatic cancer cells, with minimal effect on Snail. Because Snail increases invasion of cancer cells, we examined the effect of ethanol on invasion of HPDE and pancreatic cancer cells. Surprisingly, ethanol decreased invasion of HPDE cells, but had no effect on invasion of pancreatic cancer cells. Mechanistically, ethanol increased adhesion of HPDE cells to collagen and increased expression of the collagen binding α2- and ß1-integrins. In contrast, ethanol did not affect collagen adhesion or integrin expression in pancreatic cancer cells. Also in contrast to HPDE cells, ethanol did not attenuate ERK1/2 phosphorylation in pancreatic cancer cells; however, inhibiting ERK1/2 decreased pancreatic cancer cell invasion. Overall, our results identify the differential effects of ethanol on premalignant and malignant pancreatic cells, and demonstrate the pleiotropic effects of ethanol on pancreatic cancer progression.

Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction.

BACKGROUND: Pulmonary vascular disease associated with left-side heart failure and preserved ejection fraction (PH-HFpEF) is an increasingly common cause of pulmonary hypertension. The distinction between PH-HFpEF and pulmonary arterial hypertension (PAH) is important because therapies indicated for PAH can be detrimental in HFpEF. The characteristic features of PH-HFpEF are understudied. METHODS AND RESULTS: In a cross-sectional study, we compared the clinical, echocardiographic, and hemodynamic features of PH-HFpEF (n=100), with PAH (n=522), and HFpEF without pulmonary vascular disease (n=45). We determined the clinical characteristics that best differentiated PH-HFpEF from PAH. Compared with patients with PAH, patients with PH-HFpEF were older; had a higher prevalence of cardiovascular comorbidities; had worse exercise capacity and renal function; more frequently had left atrial enlargement; and less frequently had right atrial enlargement. PH was less severe in PH-HFpEF patients than in PAH patients (pulmonary vascular resistance 4.8 [interquartile range 3 to 8.4] versus 10.9 [interquartile range 7.4 to 15.7] Wood units; P<0.001). Old age, the presence of hypertension and coronary artery disease, the absence of right atrial enlargement, higher aortic systolic pressure, higher mean right atrial pressure, and higher cardiac output best differentiated PH-HFpEF from PAH (area under the receiver operating characteristics curve; curve 0.97). Compared with HFpEF patients without pulmonary hypertension, PH-HFpEF patients were often female and more symptomatic, more often had right ventricular hypertrophy and right atrial enlargement, and had higher right atrial pressure. CONCLUSIONS: These data should help better identify PH-HFpEF, an entity that has become increasingly recognized and difficult to treat.

Development of an "all-hazards" hospital disaster preparedness training course utilizing multi-modality teaching.

OBJECTIVES: The objectives of the study were to develop and evaluate an "all-hazards" hospital disaster preparedness training course that utilizes a combination of classroom lectures, skills sessions, tabletop sessions, and disaster exercises to teach the principles of hospital disaster preparedness to hospital-based employees. METHODS: Participants attended a two-day, 16-hour course, entitled Hospital Disaster Life Support (HDLS). The course was designed to address seven core competencies of disaster training for healthcare workers. Specific disaster situations addressed during HDLS included: (1) biological; (2) conventional; (3) radiological; and (4) chemical mass-casualty incidents. The primary goal of HDLS was not only to teach patient care for a disaster, but more importantly, to teach hospital personnel how to manage the disaster itself. Knowledge gained from the HDLS course was assessed by pre- and post-test evaluations. Additionally, participants completed a course evaluation survey at the conclusion of HDLS to assess their attitudes about the course. RESULTS: Participants included 11 physicians, 40 nurses, 23 administrators/directors, and 10 other personnel (n = 84). The average score on the pre-test was 69.1 +/- 12.8 for all positions, and the post-test score was 89.5 +/- 6.7, an improvement of 20.4 points (p < 0.0001, 17.2-23.5). Participants felt HDLS was educational (4.2/5), relevant (4.3/5) and organized (4.3/5). CONCLUSIONS: Identifying an effective means of teaching hospital disaster preparedness to hospital-based employees is an important task. However, the optimal strategy for implementing such education still is under debate. The HDLS course was designed to utilize multiple teaching modalities to train hospital-based employees on the principles of disaster preparedness. Participants of HDLS showed an increase in knowledge gained and reported high satisfaction from their experiences at HDLS. These results suggest that HDLS is an effective way to train hospital-based employees in the area of disaster preparedness.