Predictors of Timely Antibiotic Administration for Patients Hospitalized With Community-Acquired Pneumonia From the Cluster-Randomized EDCAP Trial

IntroductionTo identify factors associated with timely initiation of antibiotic therapy for patients hospitalized with pneumonia.DesignSecondary analysis of a cluster-randomized, controlled trial.SettingThirty- two emergency departments (EDs) in Pennsylvania and Connecticut.SubjectsPatients with a clinical and radiographic diagnosis of community-acquired pneumonia.InterventionsFrom January to December 2001, EDs were randomly allocated to guideline implementation strategies of low (n = 8), moderate (n = 12), and high intensity (n = 12) to improve the initial site of treatment and the performance of evidence-based processes of care. Our primary outcome was antibiotic initiation within 4 hours of presentation, which at that time was the recommended process of care for inpatients.ResultsOf the 2076 inpatients enrolled, 1632 (78.6%) received antibiotic therapy within 4 hours of presentation. Antibiotic timeliness ranged from 55.6% to 100% (P < 0.001) by ED and from 77.0% to 79.7% (P = 0.2) across the 3 guideline implementation arms. In multivariable analysis, heart rate ≥ 125 per minute (OR = 1.6, 95% CI 1.1-2.3), respiratory rate ≥ 30 per minute (OR = 2.3, 95% CI 1.6-3.4), and aspiration pneumonia (OR = 3.7, 95% CI 1.1-12.7) were positively associated with timely initiation of antibiotic therapy, whereas a hematocrit < 30% (OR = 0.6, 95% CI 0.4-1.0) was negatively associated with this outcome.ConclusionsTimely initiation of antibiotic therapy is associated primarily with patient-related factors that reflect severity of illness at presentation. Although this study demonstrates an opportunity to improve performance on this quality measure in nearly one quarter of inpatients with pneumonia, we failed to identify any modifiable patient, provider, or hospital level factors to target in such quality improvement efforts.     

Dynamic self-assembly and control of microfluidic particle crystals

Engineered two-phase microfluidic systems have recently shown promise for computation, encryption, and biological processing. For many of these systems, complex control of dispersed-phase frequency and switching is enabled by nonlinearities associated with interfacial stresses. Introducing nonlinearity associated with fluid inertia has recently been identified as an easy to implement strategy to control two-phase (solid-liquid) microscale flows. By taking advantage of inertial effects we demonstrate controllable self-assembling particle systems, uncover dynamics suggesting a unique mechanism of dynamic self-assembly, and establish a framework for engineering microfluidic structures with the possibility of spatial frequency filtering. Focusing on the dynamics of the particle-particle interactions reveals a mechanism for the dynamic self-assembly process; inertial lift forces and a parabolic flow field act together to stabilize interparticle spacings that otherwise would diverge to infinity due to viscous disturbance flows. The interplay of the repulsive viscous interaction and inertial lift also allow us to design and implement microfluidic structures that irreversibly change interparticle spacing, similar to a low-pass filter. Although often not considered at the microscale, nonlinearity due to inertia can provide a platform for high-throughput passive control of particle positions in all directions, which will be useful for applications in flow cytometry, tissue engineering, and metamaterial synthesis.     

Are all n-3 polyunsaturated fatty acids created equal?

N-3 Polyunsaturated fatty acids have been shown to have potential beneficial effects for chronic diseases including cancer, insulin resistance and cardiovascular disease. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular have been studied extensively, whereas substantive evidence for a biological role for the precursor, alpha-linolenic acid (ALA), is lacking. It is not enough to assume that ALA exerts effects through conversion to EPA and DHA, as the process is highly inefficient in humans. Thus, clarification of ALA's involvement in health and disease is essential, as it is the principle n-3 polyunsaturated fatty acid consumed in the North American diet and intakes of EPA and DHA are typically very low. There is evidence suggesting that ALA, EPA and DHA have specific and potentially independent effects on chronic disease. Therefore, this review will assess our current understanding of the differential effects of ALA, EPA and DHA on cancer, insulin resistance, and cardiovascular disease. Potential mechanisms of action will also be reviewed. Overall, a better understanding of the individual role for ALA, EPA and DHA is needed in order to make appropriate dietary recommendations regarding n-3 polyunsaturated fatty acid consumption.     

Longitudinal trends in organophosphate incidents reported to the National Pesticide Information Center, 1995–2007

Background  

Regulatory decisions to phase-out the availability and use of common organophosphate pesticides among the general public were announced in 2000 and continued through 2004. Based on revised risk assessments, chlorpyrifos and diazinon were determined to pose unacceptable risks. To determine the impact of these decisions, organophosphate (OP) exposure incidents reported to the National Pesticide Information Center (NPIC) were analyzed for longitudinal trends.     

Lack of a significant drug interaction between raltegravir and tenofovir

Raltegravir is a novel human immunodeficiency virus type 1 (HIV-1) integrase inhibitor with potent in vitro activity (95% inhibitory concentration of 31 nM in 50% human serum). This article reports the results of an open-label, sequential, three-period study of healthy subjects. Period 1 involved raltegravir at 400 mg twice daily for 4 days, period 2 involved tenofovir disoproxil fumarate (TDF) at 300 mg once daily for 7 days, and period 3 involved raltegravir at 400 mg twice daily plus TDF at 300 mg once daily for 4 days. Pharmacokinetic profiles were also determined in HIV-1-infected patients dosed with raltegravir monotherapy versus raltegravir in combination with TDF and lamivudine. There was no clinically significant effect of TDF on raltegravir. The raltegravir area under the concentration time curve from 0 to 12 h (AUC_0-12) and peak plasma drug concentration (C_max) were modestly increased in healthy subjects (geometric mean ratios [GMRs], 1.49 and 1.64, respectively). There was no substantial effect of TDF on raltegravir concentration at 12 h postdose (C₁₂) in healthy subjects (GMR [TDF plus raltegravir-raltegravir alone], 1.03; 90% confidence interval [CI], 0.73 to 1.45), while a modest increase (GMR, 1.42; 90% CI, 0.89 to 2.28) was seen in HIV-1-infected patients. Raltegravir had no substantial effect on tenofovir pharmacokinetics: C₂₄, AUC, and C_max GMRs were 0.87, 0.90, and 0.77, respectively. Coadministration of raltegravir and TDF does not change the pharmacokinetics of either drug to a clinically meaningful degree. Raltegravir and TDF may be coadministered without dose adjustments.     

In vitro antibacterial activity of CE-156811, a novel analog derived from hygromycin A

We evaluated a novel truncated hygromycin A analog in which the furanose ring was replaced with a 2-fluoro-2-cyclopropylethyl substituent for its activity against multidrug resistant gram-positive bacteria and compared its activity to the activities of linezolid, quinupristin-dalfopristin, and vancomycin. CE-156811 demonstrated robust in vitro activity against gram-positive bacteria that was comparable to that of linezolid.     

A morpholino oligomer targeting highly conserved internal ribosome entry site sequence is able to inhibit multiple species of picornavirus

Members of the genera Enterovirus and Rhinovirus (family Picornaviridae) cause a wide range of human diseases. An established vaccine is available only for poliovirus, and no effective therapy is available for the treatment of infections caused by any pathogenic picornavirus. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded DNA-like antisense agents that readily enter cells. A panel of PPMO was tested for their antiviral activities against various picornaviruses. PPMO targeting conserved internal ribosome entry site (IRES) sequence were highly active against human rhinovirus type 14, coxsackievirus type B2, and poliovirus type 1 (PV1), reducing PV1 titers by up to 6 log(10) in cell cultures. Comparative sequence analysis led us to design a PPMO (EnteroX) targeting 22 nucleotides of IRES sequence that are perfectly conserved across greater than 99% of all human enteroviruses and rhinoviruses. EnteroX reduced PV1 replication in cell culture to an extent similar to that of other IRES-specific PPMO. Resistant PV1 arose in cell cultures after 12 passages in the presence of EnteroX and were found to have two mutations within the EnteroX target sequence. Nevertheless, cPVR transgenic mice treated once daily by intraperitoneal (i.p.) injection with EnteroX before and/or after i.p. infection with 3 x 10(8) PFU (three times the 50% lethal dose) of PV1 had an approximately 80% higher rate of survival than the controls. The viral titer in tissues taken at day 5 postinfection showed that animals in the EnteroX-treated group averaged over 3, 4, and 5 log(10) less virus in the small intestine, spinal cord, and brain, respectively, than the amount in the control animals. These results suggest that EnteroX may have broad therapeutic potential against entero- and rhinoviruses.     

Diabetes in U.S. nursing homes, 2004

The 2004 National Nursing Home Survey collected cross-sectional data for 11,939 nursing home residents aged >or=65 years representing approximately 1.32 million individuals. That year, 24.6% of nursing home residents had diabetes as a primary admission and/or current diagnosis. Diabetes was present in 22.5 and 35.6% of white and nonwhite residents, respectively. Diabetic residents were admitted more often from acute care hospitals (42.5 vs. 35.3%), were more likely to have a length of stay or=65 years had diabetes, and diabetic residents had increased odds of several unfavorable outcomes that are important for care planning.