Therapeutic monitoring of antidepressants in the era of pharmacogenetics studies.

As for other drugs, there is a large interindividual variability of the plasma concentrations of antidepressants for a given dose. Within the last 2 decades, a very large number of pharmacogenetic studies have made it possible to understand the importance of genetic factors on the disposition of drugs in the organism, many of them at the levels of drug metabolism. Polymorphism of CYP2D6 and of other drug-metabolizing enzymes may thus lead to very large differences in drug exposure between patients and possibly also to toxicity or ineffective drug concentrations in some subjects. In consequence, dose recommendations of antidepressants based on genotypes, justified by the principle of administering bioequivalent individualized drug doses, are now proposed. However, blood (and thus possibly brain) concentrations also depend on other factors than the genetic makeup of the patients. Therapeutic drug monitoring of antidepressants allows us to take into account the influence of factors such as comedications, diet, smoking habit, impaired organ function, and compliance. Therapeutic drug monitoring and genotyping are thus complementary, and their combined use contributes to improve pharmacotherapy with antidepressants and other drugs.

Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer.

Multifocal and recurrent epithelial tumors, originating from either dormant or de novo cancer cells, are major causes of morbidity and mortality. The age-dependent increase of cancer incidence has long been assumed to result from the sequential accumulation of cancer-driving or -facilitating mutations with induction of cellular senescence as a protective mechanism. However, recent evidence suggests that the initiation and development of epithelial cancer results from a close interplay with its altered tissue microenvironment, with chronic inflammation, stromal senescence, autophagy, and the activation of cancer-associated fibroblasts (CAFs) playing possible primary roles. We will discuss recent progress in these areas, and highlight how this understanding may be used for devising novel preventive and therapeutic approaches to the epithelial cancer problem.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Introduction: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on measurement of blood concentrations. Maintaining concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. In the last decades computer programs have been developed to assist clinicians in this assignment. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Method: Literature and Internet search was performed to identify software. All programs were tested on common personal computer. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software's characteristics. Numbers of drugs handled vary widely and 8 programs offer the ability to the user to add its own drug model. 10 computer programs are able to compute Bayesian dosage adaptation based on a blood concentration (a posteriori adjustment) while 9 are also able to suggest a priori dosage regimen (prior to any blood concentration measurement), based on individual patient covariates, such as age, gender, weight. Among those applying Bayesian analysis, one uses the non-parametric approach. The top 2 software emerging from this benchmark are MwPharm and TCIWorks. Other programs evaluated have also a good potential but are less sophisticated (e.g. in terms of storage or report generation) or less user-friendly.¦Conclusion: Whereas 2 integrated programs are at the top of the ranked listed, such complex tools would possibly not fit all institutions, and each software tool must be regarded with respect to individual needs of hospitals or clinicians. Interest in computing tool to support therapeutic monitoring is still growing. Although developers put efforts into it the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capacity of data storage and report generation.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

Neural differentiation and therapeutic potential of adipose tissue derived stem cells.

Neural tissue has historically been regarded as having poor regenerative capacity but recent advances in the growing fields of tissue engineering and regenerative medicine have opened new hopes for the treatment of nerve injuries and neurodegenerative disorders. Adipose tissue has been shown to contain a large quantity of adult stem cells (ASC). These cells can be easily harvested with low associated morbidity and because of their potential to differentiate into multiple cell types, their use has been suggested for a wide variety of therapeutic applications. In this review we examine the evidence indicating that ASC can stimulate nerve regeneration by both undergoing neural differentiation and through the release of a range of growth factors. We also discuss some of the issues that need to be addressed before ASC can be developed as an effective cellular therapy for the treatment of neural tissue disorders.

Aptitudes communicationnelles et formations à la communication en oncologie : Discussion critique

Cet article consiste en une discussion critique de la question de la communication en matière de prise en charge du patient atteint de cancer et de l'enseignement des aptitudes communicationnelles en oncologie. Nous avons d'abord essayé de définir les contours de ce qu'est (ou devrait être) une communication adéquate en oncologie, pour ensuite aborder les concepts sous-tendant les formations à la communication dans ce domaine, le problème des recommandations d'experts et du type dominant d'évaluation se rapportant à ces formations ainsi que les contenus enseignés et ainsi véhiculés.

Choix thérapeutique dans les tumeurs costales primaires [Therapeutic choice in primary costal tumors].

Primary rib tumors constitute a rare entity and have only seldom been studied separately. In a retrospective study based on 21 cases, with the help of the literature, we try to specify the specific problems encountered with rib tumors and the therapeutic consequences that follow. Our series comprises 10 benign tumors, 3 malignant tumors and 8 cartilaginous tumors. The benign tumors were resected and all the patients recovered uneventfully. One of the patients died of a plasmocytoma 92 months after resection. Among the cartilaginous tumors, we observed two recurrences after 9 and 24 months from which the patient died eventually at 20 and 72 months after resection. The histologic diagnosis of a rib tumor must be made through an excisional biopsy. Cartilaginous tumors are potentially malignant. They must be treated as malignant tumors by radical resection and primary reconstruction. The long-term follow-up of every patient carrying a rib tumor is mandatory because of the risk of late recurrence.

The impact of communication skills training in oncology: a linguistic analysis.

This study aimed to investigate the impact of a communication skills training (CST) in oncology on clinicians' linguistic strategies. A verbal communication analysis software (Logiciel d'Analyse de la Communication Verbale) was used to compare simulated patients interviews with oncology clinicians who participated in CST (N = 57) (pre/post with a 6-month interval) with a control group of oncology clinicians who did not (N = 56) (T1/T2 with a 6-month interval). A significant improvement of linguistic strategies related to biomedical, psychological and social issues was observed. Analysis of linguistic aspects of videotaped interviews might become in the future a part of individualised feedback in CST and utilised as a marker for an evaluation of training.

Designing pheromone communication in swarm robotics: Group foraging behavior mediated by chemical substance

In swarm robotics, communication among the robots is essential. Inspired by biological swarms using pheromones, we propose the use of chemical compounds to realize group foraging behavior in robot swarms. We designed a fully autonomous robot, and then created a swarm using ethanol as the trail pheromone allowing the robots to communicate with one another indirectly via pheromone trails. Our group recruitment and cooperative transport algorithms provide the robots with the required swarm behavior. We conducted both simulations and experiments with real robot swarms, and analyzed the data statistically to investigate any changes caused by pheromone communication in the performance of the swarm in solving foraging recruitment and cooperative transport tasks. The results show that the robots can communicate using pheromone trails, and that the improvement due to pheromone communication may be non-linear, depending on the size of the robot swarm.