TDM is dead. Long live TCI!

Twenty years ago, target concentration intervention (TCI) was distinguished from therapeutic drug monitoring (TDM). It was proposed that TCI would bring more clinical benefit because of the precision of the approach and the ability to link TCI to principles of pharmacokinetics and pharmacodynamics to predict the dose required by an individual (1). We examine the theory and clinical trial evidence supporting the benefits of TCI over TDM and conclude that in the digital age TDM should be abandoned and replaced by TCI.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation. We compared the percentage of time spent in the international normalized ratio acceptable range (%TIR) during the first 28 days following warfarin initiation, and %TIR and count of bleeding events over the entire follow-up period. Two hundred thirty-four participants were followed up to day 28 (NextDose: 116 and standard of care: 118), and 228 participants (114 per arm) were followed up to the final study visit. Median %TIR tended to be higher for participants receiving NextDose guided warfarin management during the first 28 days (63 vs. 56%, P = 0.13) and over the entire follow-up period (74 vs. 71%, P = 0.04). The hazard of clinically relevant minor bleeding events was lower for participants in the NextDose arm (hazard ratio: 0.21, P = 0.041). In NextDose, there were 89.3% of proposed doses accepted by prescribers. NextDose guided dose management in cardiac surgery patients requiring warfarin was associated with an increase in %TIR across the full follow-up period and fewer hemorrhagic events. A theory-based, pharmacologically guided approach facilitates higher quality warfarin anticoagulation. An important practical benefit is a reduced requirement for clinical experience of warfarin management.

[Comparison of toluene adsorption with two kinds of modified activated carbon].

Granular activated carbon (GAC) was modified by microwave irradiation and electrical heating. The characters and toluene adsorption capacity of modified GAC were studied. The results showed that for microwave heating, with the temperature increasing, the activated carbon's ability of toluene adsorption and content of the surface basic functional group were increased, specific surface area was decreased. After heated at 850 degrees C, GAC had the highest ability for toluene adsorption, at 650 degrees C and 450 degrees C, the ability for toluene adsorption of GAC were similar. For the electrical heating, the same results were obtained. But the GAC modified with electrical heating had lower capacity of toluene adsorption than microwave modified GAC. The SEM photos showed that thermal modification made the porous structure of modified GAC smoother than original GAC, but the structure of GAC shrink at high temperature. Finally, all the experimental data and SEM photos were analyzed; it indicated that due to the difference of heating mechanism and heat transmission direction, the modified GAC have different characters.

[Influence factors of treating waste gas containing benzene and toluene with fungi-biofilter].

Used a two-stage bench-scale temperature adjustable biofilter, biological treatment of medium and high concentration waste benzene and toluene vapor was investigated. The inlet vapor concentration (c(i)) was 0.9 - 5.0 g/m3. The results show that the biofilter can obtained good performance at 30 - 40 degrees C, and at 32.8 degrees C for benzene and toluene, the maximum elimination capacity (EC) of 136 g/(m3 x h) and 150 g/(m3 x h) is obtained at an inlet loading of 673.5 g/(m3 x h) and 665.0 g/(m3 x h), respectively. High media moisture is adverse to the biofilter performance. The optimum moisture for the biofilter is about 45% and the biofilter can obtain good performance at the moisture ranging from 40% to 50%. With the biofilter operation, pressure drop is increasing from 18 Pa to 39 Pa and leachate is changing from colorless to yellow, and these phenomena show that bioaccumulation is existent.