Anticoagulation par antivitamines K: analyse des interactions médicamenteuses et des polymorphismes génétiques à l'origine de la variabilité de la réponse et des risques liés à l'acénocoumarol

La présente thèse s'inscrit dans un contexte global d'amélioration de la qualité et de la sécurité de la prescription de l'acénocoumarol au sein des Hôpitaux Universitaires de Genève. Dans un premier temps, un état des lieux de la prescription de cet anticoagulant oral a été réalisé. Le deuxième grand volet de ce travail a été consacré à la réalisation d'une étude clinique observationnelle de cohorte. Cette étude avait pour but d'évaluer l'impact de certaines variations génétiques sur la réponse au traitement anticoagulant ainsi que sur les interactions médicamenteuses chez des patients hospitalisés débutant un traitement d'acénocoumarol. Finalement, une étude de transport in vitro est venue clore ce travail de recherche afin d'étudier le transport par la P-glycoprotéine des trois principaux dérivés coumariniques utilisés à travers le monde (acénocoumarol, warfarine, phenprocoumone) ainsi que du rivaroxaban, un anticoagulant oral apparu récemment sur le marché

Swiss-Meds: An App Fostering Medication Adherence of Swiss Patient

Medication adherence is a widely recognized problem that is linked to overuse of healthcare system and negative health outcomes. Among the causes of non-adherence, forgetfulness plays a central role. mHealth interventions are particularly interesting to support medication adherence. Unfortunately, there is a lack of information about the quality and effectiveness of the app available on the market. In this article, we present the design and evaluation of an app for the Swiss market. The app was developed with a user-centered approach and was evaluated by both experts and end-users. The app functions include facilitated medication data entry through barcode scanning, and access to educational materials for specific drugs. Although the evaluation by experts and end-users revealed usability issues, such as the inability to customize the app, and a low evaluation of the performance (subjective assessment), it also found that the app contained most of the core functionalities that are expected for a medication adherence app. These are promising results, and will guide the future development of the app to respond to both experts and user expectations

Administration de médicaments au nouveau-né par le cathéter ombilical

RésuméObjectif : Revue de la catheterisation vasculaire ombilicale et des donnees disponibles concernant l’administration de medicaments par le catheter ombilical veineux (CVO) et arteriel (CAO) en neonatologie. Source des données : Revue de la litterature medicale sur PubMed (1970 a 2011) et consultations d’ouvrages de references pediatriques. Sélection des études et extraction des données : Donnees extraites d’articles de revues, d’enquetes et de rapports de cas. Analyse des données : Le positionnement des CVO et CAO est determinant dans la survenue de complications lors de l’administration de medicaments. Peu de donnees bien etayees sont disponibles. L’evaluation s’est basee sur 22 publications. L’administration de medicaments par CVO est tres frequente en neonatologie, et cette pratique peut etre consideree comme sure a condition que le CVO soit place en position centrale. L’administration de medicaments par le CAO est peu frequente, car elle est plus risquee. De nombreuses complications (vasospasme, thrombose, necrose) ont ete observees a la suite de l’administration de medicaments par CAO. Une position basse du CAO augmente le risque de complications. Conclusion : L’administration de medicaments par CVO ne semble pas poser de probleme sous reserve que le CVO soit correctement positionne (central). L’administration de medicaments par CAO etant risquee, une liste des medicaments pouvant etre ou non administres par CAO (medicaments vasoconstricteurs, irritants ou hyperosmolaires) a ete etablie afin de securiser la prise en charge des patients en neonatologie. AbstractObjective: To review umbilical vascular catheterization and the data available regarding the administration of medication by umbilical venous and arterial catheters (UVC and UAC respectively) in neonates.Data sources: Medical literature review on Pub- Med for the period 1970–2011 and consultation of pediatric references. Study selection and data extraction: Data extracted from review articles, surveys, and case reports. Data analysis: When administering medications, positioning of the UVC and UAC is a determining factor in the occurrence of complications. Few data to support this are available. The evaluation was based on 22 publications. The administration of medication by UVC is common in neonatology, and this practice can be considered reliable under the condition that the UVC is placed in a central position. The administration of medication by UAC is infrequent because it is riskier. Numerous complications (vasospasm, thrombosis, necrosis) have been observed following the administration of medication by UAC. Having the UAC in the low position increases the risk of complications. Conclusion: The administration of medication by UVC does not seem to cause any problems under the condition that the UVC is properly positioned centrally. Given that the administration of medication by UAC is risky, a list of medications that may or may not be administered by UAC (vasoconstrictive drugs, irritants, hyperosmolar substances) was developed to improve the safe management of neonatal patients

Introduction de l'acénocoumarol à l'aide d'un algorithme de prescription

Anticoagulant therapy is indicated in many clinical situations. The handling of vitamin K antagonists (VKA) is difficult and their therapeutic range is narrow, requiring close biological monitoring of INR. Introduction of VKA is a particularly critical period. Algorithms for initiation of oral anticoagulant therapy have been proposed but they are generally designed for warfarin, which has a longer half life as compared to acenocoumarol. In this article, algorithms for the prescription of acenocoumarol are proposed, taking into account the patient's age, weight and initial Quick value. The goal of these algorithms, combined with frequent monitoring of INR, is to limit the bleeding risk during the introduction of anticoagulant therapy

SMART-MEDS: Development of a Medication Adherence App for Acute Coronary Syndrome Patients based on a Gamified Behaviour Change Model

Patient adherence to medications is crucial for reducing cardiovascular risk after an acute coronary syndrome (ACS). Although causes for low adherence are diverse, forgetfulness and lack of awareness about treatment importance are accountable for many cases. As a result, medication reminder apps have attempted to tackle this problem. In our work, we present the development of an app with gamification mechanisms to foster adherence and to support the behavior change processes of the Health Access Process Approach (HAPA) theoretical framework. To design our intervention, we relied on a user-centric approach. We listed the main factors related to high and low adherence from the Medication Adherence Reasons Scale (MAR-Scale) and identified functionalities that could address it. We focused in particular on forgetfulness, knowledge and beliefs about medication as the main barriers for adherence. We implemented a quiz and storytelling as gamification strategies to help motivate patients complete their medication journal and to maintain adherence on the long-term

Role of P-glycoprotein in the uptake/efflux transport of oral vitamin K antagonists and rivaroxaban through the Caco-2 cell model

Vitamin K antagonists (VKAs) are prescribed worldwide and remain the oral anticoagulant of choice. These drugs are characterized by a narrow therapeutic index and a large inter- and intra-individual variability. P-glycoprotein could contribute to this variability. The aim of this study was to investigate the involvement of P-gp in the transport of acenocoumarol, phenprocoumon and warfarin using an in vitro Caco-2 cell monolayer model. These results were compared with those obtained with rivaroxaban, a new oral anticoagulant known to be a P-gp substrate. The transport of these four drugs was assessed at pH conditions 6.8/7.4 in the presence or absence of the P-gp inhibitor cyclosporine A (10 μM) and the more potent and specific P-gp inhibitor valspodar (5 μM). Analytical quantification was performed by LC/MS. With an efflux ratio of 1.7 and a significant decrease in the efflux (Papp B-A), in the presence of P-gp inhibitors at a concentration of 50 μM, acenocoumarol can be considered as a weak P-gp substrate. Concerning phenprocoumon, the results suggest that this molecule is a poor P-gp substrate. The P-gp inhibitors did not affect significantly the transport of warfarin. The efflux of rivaroxaban was strongly inhibited by the two P-gp inhibitors. In conclusion, none of the three VKAs tested are strong P-gp substrates. However, acenocoumarol can be considered as a weak P-gp substrate and phenprocoumon as a poor P-gp substrate

Identification and weighting of the most critical "real-life" drug-drug interactions with acenocoumarol in a tertiary care hospital

The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution