Randomized Controlled Trial of Bisacodyl Suppository Versus Placebo for Postoperative Ileus After Elective Colectomy for Colon Cancer

ObjectiveTo compare the use of bisacodyl suppository with placebo in resolving postoperative ileus after elective colectomy in a randomized controlled trial.MethodsTwenty elective colectomy patients were randomized to receive either bisacodyl or placebo suppository on the third postoperative day. Outcomes included time to first defaecation, length of hospital stay, and postoperative complications. Participants and the primary investigator were unaware of the treatment assignment.ResultsAll 10 participants in the bisacodyl group defaecated on the third postoperative day, while participants in the placebo group defaecated on days 3 (2/10), 4 (5/10) and 5 (3/10) (p < 0.001). The average lengths of hospital stay for the bisacodyl and placebo groups were 8.5 ± 2.7 days and 10.4 ± 5.3 days, respectively (p = 0.325). No significant complications occurred in either group.ConclusionBisacodyl suppository seems to be effective and safe in resolving postoperative ileus after elective colectomy in colon cancer patients

Predicting the Area under the Plasma Concentration-Time Curve (AUC) for First Dose Vancomycin Using First-Order Pharmacokinetic Equations

To treat critically ill patients, early achievement of the target area under the plasma concentration-time curve/minimum inhibitory concentration (AUC/MIC) in the first 24 h is recommended. However, accurately calculating the AUC before steady state is an obstacle to this goal. A first-order pharmacokinetic equation to calculate vancomycin AUC after a first dose of vancomycin has never been studied. We sought to estimate AUC using two first-order pharmacokinetic equations, with different paired concentration time points, and to compare these to the actual first dose vancomycin AUC calculated by the linear-log trapezoid rule as a reference. The equations were validated using two independent intensive first dose vancomycin concentration time data sets, one from 10 adults and another from 14 children with severe infection. The equation with compensation for the alpha distribution phase using a first vancomycin serum concentration from 60 to 90 min and the second concentration from 240 to 300 min after the completed infusion showed good agreement and low bias of calculated AUC, with mean differences 0.96. Moreover, it gave an excellent correlation with Pearson’s r > 0.96. Estimating the first dose vancomycin AUC calculated using this first-order pharmacokinetic equation is both reliable and reproducible in clinical practice settings

Comparison of piperacillin plasma concentrations in a prospective randomised trial of extended infusion versus intermittent bolus of piperacillin/tazobactam in paediatric patients

Objectives: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. Methods: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. Results: Ninety patients with a median age (IQR) of 48 months (16–127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6–66.6) versus 6.0 mg/L (4.2–8.6) (P 4xMIC (72.7% versus 30.0%; P = 0.06). Conclusions: PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period

The 8-bromobaicalein alleviated chikungunya-induced musculoskeletal inflammation and reduced the viral load in healthy adult mice

ABSTRACTChikungunya virus is a re-emerging arbovirus that has caused epidemic outbreaks in recent decades. Patients in older age groups with high viral load and severe immunologic response during acute infection are likely to develop chronic arthritis and severe joint pain. Currently, no antiviral drug is available. Previous studies suggested that a flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor in a cell-based system targeting flaviviral polymerase. Here we characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in Vero cells. The molecular target predicted at viral nsP1 methyltransferase using molecular binding and fragment molecular orbital calculation. Additionally, oral administration of 250 mg/kg twice daily treatment alleviated chikungunya-induced musculoskeletal inflammation and reduced viral load in healthy adult mice. Pharmacokinetic analysis indicated that the 250 mg/kg administration maintained the compound level above EC99.9 for 12 h. Therefore, 8-bromobaicalein should be a potential candidate for further development as a pan-arboviral drug