Exploring the thermally-controlled fentanyl transdermal therapy to provide constant drug delivery by physics-based digital twins.

Transdermal drug delivery is suitable for low-molecular-weight drugs with specific lipophilicity, like fentanyl, which is widely used for cancer-induced pain management. However, fentanyl's transdermal therapy displays high intra-individual variability. Factors like skin characteristics at application sites and ambient temperature contribute to this variation. In this study, we developed a physics-based digital twin of the human body to cope with this variability and propose better adapted setups. This twin includes an in-silico skin model for drug penetration, a pharmacokinetic model, and a pharmacodynamic model. Based on the results of our simulations, applying the patch on the flank (side abdominal area) showed a 15.3 % higher maximum fentanyl concentration in the plasma than on the chest. Additionally, the time to reach this maximum concentration when delivered through the flank was 19.8 h, which was 10.3 h earlier than via the upper arm. Finally, this variation led to an 18 % lower minimum pain intensity for delivery via the flank than the chest. Moreover, the impact of seasonal changes on ambient temperature and skin temperature by considering the activity level was investigated. Based on our result, the fentanyl uptake flux by capillaries increased by up to 11.8 % from an inactive state in winter to an active state in summer. We also evaluated the effect of controlling fentanyl delivery by adjusting the temperature of the patch to alleviate the pain to reach a mild pain intensity (rated three on the VAS scale). By implementing this strategy, the average pain intensity decreased by 1.1 points, and the standard deviation for fentanyl concentration in plasma and average pain intensity reduced by 37.5 % and 33.3 %, respectively. Therefore, our digital twin demonstrated the efficacy of controlled drug release through temperature regulation, ensuring the therapy toward the intended target outcome and reducing therapy outcome variability. This holds promise as a potentially useful tool for physicians.

It's worth cleaning - The examination of the female taper could identify a particular cause of trunnionosis at revision 16 years after total hip arthroplasty.

Adverse reaction to metal debris (ARMD) is an issue in metal-on-metal (MoM) total hip replacements (THR). It mainly affects large-head MoM THR, whereas 28-32 mm MoM pairings are associated with low long-term revision rates. However, the bearing surface is not necessarily the only cause of metal debris. This report documents with advanced analysis of the retrievals a particular cause of trunnionosis in late failure of a small diameter MoM THR and illustrates the importance of cleaning of the taper when seating the head in THR. A 65-year-old patient was revised due to ARMD 16 years after small diameter MoM THR. Debridement and exchange of the inlay and the head had been performed through an anterior approach. While the cup and the outer surface of the head were accessible to direct analysis by an optical coordinate measuring machine, the female taper had to be analysed indirectly by measuring an imprint. Wear from the cup and the head was within expected low ranges. The analysis of the female taper identified bone fragments, which contributed to trunnionosis. Failure due to ARMD after MoM THR is not necessarily caused by the bearing, but can be due to trunnionosis. Bone fragments within the taper contact in this case highlight the importance of meticulous cleaning of the taper before seating the head, to avoid trunnionosis.