Factors associated with the provision of targeted temperature management: A balanced factorial experiment.

AIM: This study examined the influence of patient attributes and provider or organizational factors on the decision to apply targeted temperature management (TTM) to resuscitated out-of-hospital cardiac arrest (OHCA) patients. METHODS: A balanced factorial experiment was conducted among emergency medicine physicians (EMPs). Sixteen OHCA patient scenarios with balanced factors were presented. The balancing factors were dichotomous categories of patient age (45 ±â€¯2 vs. 70 ±â€¯2 years), patient sex (men vs. women), socioeconomic status (SES; higher vs. lower), and guardian attitudes (positive vs. reluctant) regarding TTM. Information on participant and organizational characteristics was collected. The outcome variable was a score (0-100) based on responses to questions that indicated how likely the participants were to apply TTM. RESULTS: Seventy-five EMPs completed the experiment. The median score for the likelihood of TTM application was 85 (interquartile range, 70-95). Scores differed significantly for patient age (90% vs. 80%, p = 0.001), SES (90% vs. 80%, p = 0.001), and guardian attitude regarding TTM (90% vs. 70%, p = 0.001). The likelihood of TTM application was associated with EMP experience with TTM (more or <50 times) (90% vs. 80%, p = 0.001). EMPs working in hospitals with commercial TTM devices or operating protocols were more likely to use TTM than those working in hospitals without TTM devices or protocols (88 vs. 80 and 90 vs. 80; p = 0.001, respectively). CONCLUSION: Patient demographics and provider and organizational factors significantly affected the decision to apply TTM.

Development of sildenafil-loaded orally disintegrating tablet with new lactate salt.

To develop a sildenafil lactate-loaded orally disintegrating tablet with a faster drug effect onset and immediate action of erection, the orally disintegrating tablets were prepared with various amounts of menthol and colloidal silica using the direct compression technique followed by vacuum drying. Their tablet properties such as friability, hardness, wetting time and disintegration time were investigated. The oral bioavailability of sildenafil in the orally disintegrating tablet was then compared with the sildenafil citrate-loaded commercial tablet (Viagra(®)) in rabbits. Sildenafil lactate was a new salt form with more improved solubility and alleviated bitterness compared with commercial salt, sildenafil citrate. As the amount of menthol in the orally disintegrating tablet increased, the friability increased and hardness decreased, resulting in a shorter wetting time and disintegration time. Colloidal silica did the opposite. The sildenafil lactate-loaded orally disintegrating tablet prepared with 45 mg/tab of menthol and 1.5 mg/tab of colloidal silica gave a hardness of 3-4 KP, friability less than 0.5% and disintegration time less than 30 s, suggesting that it was a practical and commercial product with good tablet property and excellent efficacy. Furthermore, it gave higher AUC and C(max), and shorter T(max) values than did the commercial tablet, indicating that it improved the oral bioavailability of sildenafil in rabbits compared with the commercial tablet. Thus, the sildenafil lactate-loaded orally disintegrating tablet might induce a fast onset of action and immediate erection compared with the sildenafil citrate-loaded commercial tablet.

Transcriptional up-regulation of antioxidant genes by PPARδ inhibits angiotensin II-induced premature senescence in vascular smooth muscle cells.

This study evaluated peroxisome proliferator-activated receptor (PPAR) δ as a potential target for therapeutic intervention in Ang II-induced senescence in human vascular smooth muscle cells (hVSMCs). Activation of PPARδ by GW501516, a specific agonist of PPARδ, significantly inhibited the Ang II-induced premature senescence of hVSMCs. Agonist-activated PPARδ suppressed the generation of Ang II-triggered reactive oxygen species (ROS) with a concomitant reduction in DNA damage. Notably, GW501516 up-regulated the expression of antioxidant genes, such as glutathione peroxidase 1, thioredoxin 1, manganese superoxide dismutase and heme oxygenase 1. siRNA-mediated down-regulation of these antioxidant genes almost completely abolished the effects of GW501516 on ROS production and premature senescence in hVSMCs treated with Ang II. Taken together, the enhanced transcription of antioxidant genes is responsible for the PPARδ-mediated inhibition of premature senescence through sequestration of ROS in hVSMCs treated with Ang II.

Comparison of the solubility and pharmacokinetics of sildenafil salts.

To develop sildenafil lactate, a salt form of sildenafil with improved solubility and bioavailability of poorly water-soluble sildenafil base, this salt form was prepared using a spray dryer. Its solubility and pharmacokinetics in rabbits were evaluated compared with sildenafil base and sildenafil citrate. Sildenafil lactate improved the solubility of sildenafil in various solvents including distilled water compared with sildenafil citrate. It provided higher AUC and C(max) and, shorter t(1/2) values than did the other materials, indicating that it improved the oral bioavailability of sildenafil in rabbits. Our results suggest that sildenafil lactate would be useful to deliver sildenafil in a pattern that allows fast absorption and late metabolism. Furthermore, the plasma concentration at 0.25 h in sildenafil lactate was similar to the C(max) value at T(max) (0.5 h) in sildenafil citrate. Thus, sildenafil lactate might provide a faster onset of action and immediate erection compared with sildenafil citrate, the conventional drug.