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Aims Methods Results Conclusion The accuracy of model‐informed precision dosing largely depends on selecting the most appropriate population pharmacokinetic (popPK) model from many available options. This study aims to evaluate the concordance of optimal initial simulated doses among various vancomycin popPK models developed in neonates and to explore the role of predictive performance in explaining the variability in probability of target attainment (PTA).A virtual neonatal patient population was created and 26 previously externally evaluated vancomycin popPK models were used to simulate 5 different dosing regimens. For each simulated scenario, the area under the concentration–time curve and PTA were calculated to assess the agreement on optimal initial doses across the 26 models. A multiple regression was performed to explore the impact of the models' predictive performance on PTA.For most models (15/26), there was an agreement on the optimal dosing regimen. The highest PTA being achieved by the model with the best a priori predictive performance. The multiple regression model significantly predicted mean ln‐transformed PTA, with F(2, 23) = 5.406 and P = .010, yielding an adjusted R2 of .21. PTA was significantly influenced by imprecision (P = .048) but not bias (P = .469).In conclusion, our study demonstrated that, despite the variability in bias and imprecision, there was a consensus on the initial optimal doses for the majority of models; however, models with superior a priori predictive performance yielded higher PTA values. Bias and imprecision alone only seem to predict a small proportion of the variability in PTA, with imprecision having a more pronounced effect. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration‐time curve over first‐order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models. Methods: Models were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction‐based diagnostics, then by simulation‐based diagnostics and a posteriori analyses only if deemed satisfactory; model‐informed vancomycin exposure was also compared with reference first‐order pharmacokinetic equations. The best‐performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target. Results: A total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias ≤ ± 15% and imprecision ≤ 30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et al. and Mehrotra et al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment. Discussion: We externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations. [ABSTRACT FROM AUTHOR]

An optimization problem arising when planning forest harvesting operations is the location of new access roads. The new roads must cover several areas to be harvested at minimum cost. This problem is of economical and environmental relevance in the domain of forestry. In this study, the problem is expressed as a P-forest problem in a graph. It consists of determining a set of tree structures in a graph that covers a set of vertices corresponding to harvest areas. The objective is to minimize the sum of construction costs and harvesting costs. In addition to the location of roads, the P-forest problem has several relevant applications, including public transport, electricity transmission, roads, pipelines, and communication networks design. This paper presents a greedy randomized adaptive search procedure (GRASP) to solve this problem. The heuristic was implemented on a decision support system, and computational experiments were conducted on randomly generated and real instances to demonstrate the performance and practical efficiency of the proposed approach. A comparison with manually designed forest road networks in the real instances shows a clear advantage for the proposed method. Resume: Un probleme important d'optimisation intervenant dans le cadre de la planification des operations forestieres est la localisation de nouveaux chemins d'acces pour le debardage. Les nouveaux chemins forestiers doivent couvrir un ensemble de zones de recolte a un cout minimum. Ce probleme est d'une importance economique et environnementale majeure pour le secteur forestier. Dans cet article, le probleme est exprime sous la forme d'un probleme de P-arbres dans un graphe. Il consiste a determiner un ensemble de structures arborescentes dans un graphe de maniere a couvrir indirectement les points qui correspondent aux zones a debarder. L'objectif est de minimiser les couts de debardage et de construction de chemin. Ce probleme d'optimisation trouve egalement des applications dans differents domaines tels que la conception de reseaux de transports, de reseaux electriques, de routes, de conduites et de reseaux de telecommunications. Nous proposons une procedure de recherche gloutonne adaptative pour resoudre ce probleme. Cette heuristique a ete integree a un systeme d'aide a la decision et testee sur des instances generees aleatoirement ainsi que sur des scenarios reels. Afin de demontrer l'efficacite ainsi que l'aspect operationnel de l'approche, les resultats ont ete compares a des reseaux concus manuellement. Cette comparaison indique un net avantage en faveur de notre approche., 1. Introduction Due to the evolution of environmental and economical aspects in forestry, there is a continuing need to find efficient optimization methods in this application field. Forest harvesting planning [...]

Background: Sutureless aortic valve replacement (AVR) is an emerging alternative to standard AVR in elderly and high-risk patients. This procedure is associated with a high rate of postoperative permanent pacemaker implantation (PPI). The study aim was to assess the impact on the rate of PPI of implanting the Perceval prosthesis without using balloon inflation., Methods: A total of 159 patients who underwent sutureless AVR using the Perceval prosthesis was included. Balloon inflation was used in 132 patients (Balloon group) and not used in the remaining 27 (No-Balloon group). Clinical, echocardiographic and electrocardiographic outcomes were assessed., Results: There was no significant difference in PPI rate between the two groups (26% for Balloon group versus 22% in No-Balloon group; p = 0.700). Balloon inflation had no significant impact on the incidence of paravalvular leaks (p = 0.839), or on the need to return to cardiopulmonary bypass (CPB) intraoperatively due to paravalvular leak or unsatisfactory deployment (p >0.999). Mean and peak transaortic pressure gradients were similar between the two groups (p = 0.417 and p = 0.522, respectively). Cross-clamp and CPB times were shorter in the No-Balloon group (49.6 ± 15.9 min versus 61.1 ± 25.6 min and 64.1 ± 26.3 min versus 79.6 ± 35.4 min, respectively; p = 0.027 and p = 0.012, respectively)., Conclusions: The two groups had similar postoperative PPI rates. Implanting the Perceval prosthesis without balloon inflation is safe and had no impact on paravalvular leaks, intraoperative complications or hemodynamic results. Reductions in aortic cross-clamp time and CPB time were observed when the balloon was not used.