Background: Aerosolized delivery of antibiotics is hindered by poor penetration within distal and plugged airways. Antibacterial perfluorocarbon ventilation (APV) is a proposed solution in which the lungs are partially or totally filled with perfluorocarbon (PFC) containing emulsified antibiotics. The purpose of this study was to evaluate emulsion stability and rheological, antibacterial, and pharmacokinetic characteristics. Methods: This study examined emulsion aqueous droplet diameter and number density over 24 hr and emulsion and neat PFC viscosity and surface tension. Additionally, Pseudomonas aeruginosa biofilm growth was measured after 2-hr exposure to emulsion with variable aqueous volume percentages (0.25, 1, and 2.5%) and aqueous tobramycin concentrations (C a ¼0.4, 4, and 40 mg/mL). Lastly, the time course of serum and pulmonary tobramycin concentrations was evaluated following APV and conventional aerosolized delivery of tobramycin in rats. Results: The initial aqueous droplet diameter averaged 1.9 -0.2 lm with little change over time. Initial aqueous droplet number density averaged 3.5 -1.7 · 10 9 droplets/mL with a significant ( p < 0.01) decrease over time. Emulsion and PFC viscosity were not significantly different, averaging 1.22 -0.03 · 10 -3 Pa$sec. The surface tensions of PFC and emulsion were 15.0 -0.1 · 10 -3 and 14.6 -0.6 · 10 -3 N/m, respectively, and the aqueous interfacial tensions were 46.7 -0.3 · 10 -3 and 26.9 -11.0 · 10 -3 N/m ( p < 0.01), respectively. Biofilm growth decreased markedly with increasing C a and, to a lesser extent, aqueous volume percentage. Tobramycin delivered via APV yielded 2.5 and 10 times larger pulmonary concentrations at 1 and 4 hr post delivery, respectively, and significantly ( p < 0.05) lower serum concentrations compared with aerosolized delivery. Conclusions: The emulsion is bactericidal, retains the rheology necessary for pulmonary delivery, is sufficiently stable for this application, and results in increased pulmonary retention of the antibiotic.
Researchers have attempted to optimize imaging utilization by describing which clinical variables are more predictive of acute disease and, conversely, what combination of variables can obviate the need for imaging. These results are then used to develop evidence-based clinical pathways, clinical decision instruments, and clinical practice guidelines. Despite the validation of these results in subsequent studies, with some demonstrating improved outcomes, their actual use is often limited. This article outlines a research agenda to promote the dissemination and implementation (also known as knowledge translation) of evidence-based interventions for emergency department (ED) imaging, i.e., clinical pathways, clinical decision instruments, and clinical practice guidelines. We convened a multidisciplinary group of stakeholders and held online and telephone discussions over a 6-month period culminating in an in-person meeting at the 2015 Academic Emergency Medicine consensus conference. We identified the following four overarching research questions: 1) what determinants (barriers and facilitators) influence emergency physicians' use of evidence-based interventions when ordering imaging in the ED; 2) what implementation strategies at the institutional level can improve the use of evidence-based interventions for ED imaging; 3) what interventions at the health care policy level can facilitate the adoption
Introduction:The majority of Indian hospitals do not provide intensive care unit (ICU) care or ward-based noninvasive positive pressure ventilation (NIV). Because no mechanical ventilation or NIV is available in these hospitals, the majority of patients suffering from respiratory failure die.Objective:To perform a cost-effective analysis of two strategies (ward-based NIV with concurrent standard treatment vs standard treatment alone) in chronic obstructive pulmonary disease (COPD) respiratory failure patients treated in Indian hospitals without ICU care.Materials and Methods:A decision-analytical model was created to compare the cost-effectiveness for the two strategies. Estimates from the literature were used for parameters in the model. Future costs were discounted at 3%. All costs were reported in USD (2012). One-way, two-way, and probabilistic sensitivity analysis were performed. The time horizon was lifetime and perspective was societal.Results:The NIV strategy resulted in 17.7% more survival and was slightly more costly (increased cost of $101 (USD 2012) but resulted in increased quality-adjusted life-years (QALYs) (1.67 QALY). The cost-effectiveness (2012 USD)/QALY in the standard and NIV groups was $78/QALY ($535.02/6.82) and $75/QALY ($636.33/8.49), respectively. Incremental cost-effectiveness ratio (ICER) was only $61 USD/QALY. This was substantially lower than the gross domestic product (GDP) per capita for India (1489 USD), suggesting the NIV strategy was very cost effective. Using a 5% discount rate resulted in only minimally different results. Probabilistic analysis suggests that NIV strategy was preferred 100% of the time when willingness to pay was >$250 2012 USD.Conclusion:Ward-based NIV treatment is cost-effective in India, and may increase survival of patients with COPD respiratory failure when ICU is not available.
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