Population pharmacokinetics of piperacillin and tazobactam in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analysed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (% f T >MIC ) and toxic exposures of greater than 360 mg/L. Tazobactam target of percentage time free concentrations >2 mg/L was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models with body mass index, creatinine clearance and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5 g 6-hourly regimen administered over 4-hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/L while exposing patients to a <3% probability of toxic concentrations. In patients receiving ECMO and RRT a frequency reduction to 12-hourly dosing reduces the probability of toxic concentrations, although this remains at 7 – 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.

Playing to Investigate the Relationship Between Achievement and the Perception of learning

This paper investigates the relationship between achievement and the perception of enjoyment and learning through the serious game, Playing Property. Playing Property is an audience response game forming the basis of workshops to engage junior high students, of 13 to 15 years old, and enhance their knowledge of property investment. The investigation extends to the analysis of trends in audience response decisions from 14 workshops, conducted over three consecutive years. Emerging findings present significant associations between enjoyment and the perception of learning. The relationship between achievement, measured in accumulated game score, and the responders’ perception of enjoyment is present but less significant. Further analysis supports a deeper relationship between play and learning, one where competition and other game play attributes are more effective in engagement than point scoring or rewarding. A more detailed evaluation may include staged testing of what may be learned and how well that learning endures, in comparison with other forms of teaching.

Adaption and Application of the Four Phase Trials to Traditional Chinese Medicines

Four phases of trial are widely used in testing drugs, surgery, and diagnosis in Western medicine (WM). The staged testing process helps protect patients from unnecessary harms and control costs while assessing safety and efficacy. In this paper we adapt the four phase trials for traditional Chinese medicine (TCM). As TCM has been used in humans for thousands of years and there has been good preliminary clinical evidence on safety and efficacy for many of its therapies, in most cases its evaluation can start directly in humans, and preclinical laboratory research can be conducted in phase 4 trials after the efficacy is firmly demonstrated. Furthermore, unlike investigational drugs, TCM therapies are various in the certainty of their safety and efficacy and thus should not enter the evaluation process at the same stage. Unlike in WM, clarifying and refining PICO (patients, intervention, comparator, and outcome) are an important part of evaluation of newly designed TCM therapies. The incommensurability between WM and TCM causes additional difficulties in TCM trials regarding defining and choosing PICO, for which some suggestions are made. Observational studies seem to have a greater role in evaluation for TCM although the efficacy must be confirmed with randomized trials.