High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate.

Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid - BEH - Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48h at room temperature and at +4°C (<6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections.

Violence domestique: guide pratique. Améliorer la prise en charge des femmes concernées

[Table des matières] Généralités sur la violence domestique: Définition de la violence domestique, Prise en charge: possibilités et limites, Dépistage de la violence domestique, Signes et symptômes évoquant un contexte de violence domestique &. La situation spécifique des femmes migrantes. - Documentation: Marche à suivre: check-list, Consentement, Constat médical en cas de violence domestique, Examen physique, Attestation. - Annexes: Bases légales, Gynécologie des enfants et adolescentes, Caisse maladie et éléments financiers, Coordonnées des centres spécialisés, Centres cantonaux d'aide aux victimes d'infraction (Centres LAVI), Littérature et liens. - Suppléments: Marche à suivre: check-list, Spécimens de constat médical [Editorial (extrait)] Le groupe de travail «Abus sexuels au cabinet médical» - constitué voici quelques années par la Société Suisse de Gynécologie et d'Obstétrique - s'est vu chargé par le président de la société d'élaborer un guide pratique pour aborder la violence domestique. En Suisse, des études d'envergure montrent qu'une femme sur quatre au cours de sa vie et une femme sur dix durant les !" derniers mois sont confrontées à la violence. Ces études révèlent un lien étroit entre de nombreux problèmes de santé et le fait de subir de la violence conjugale. La moitié des femmes touchées présentent des problèmes de santé physiques et deux tiers des problèmes de santé psychiques ou des troubles d'ordre psychosomatiques. Et ce sont ces problèmes qui amèneront les femmes à consulter leur médecin. Le groupe de travail poursuit l'objectif d'améliorer la prise en charge des femmes concernées par la violence. En effet, aussi longtemps que la cause réelle des symptômes et des plaintes, à savoir le fait de vivre dans un contexte de violence, n'est pas dépistée, aucune mesure thérapeutique ne pourra avoir d'impact durable sur la santé de la patiente. Les femmes concernées par la violence domestique s'adressent de préférence à leur médecin. De ce fait, les gynécologues, au sein de leur cabinet et dans les cliniques, vont entrer en contact avec ces femmes. Il est donc important que chacun dispose des connaissances nécessaires à leur prise en charge.

Prévention et prise en charge des maladies chroniques : une approche applicable en Suisse

Les maladies chroniques représentent un fardeau important pour la société, en termes de morbidité, dépendance, qualité de vie, mortalité et coûts de la santé. La prise en charge des maladies chroniques constitue ainsi une priorité des systèmes de santé. Tandis que des programmes de prévention et prise en charge des maladies chroniques («prevention and chronic disease management») ont été mis sur pieds depuis plus d'une décennie d'abord en Amérique du Nord puis en Europe, leur développement en Suisse est récent. Ces programmes sont explicitement structurés et organisés, centrés sur les patients et comportent constamment un élément d'éducation thérapeutique. De plus, ils impliquent un travail en équipe ainsi que des prises en charge stratifiées en fonction de la sévérité de la maladie et des besoins des patients, et basées sur les preuves de leur efficacité. Il est important que les médecins et autres professionnels de la santé, ainsi que tous les autres acteurs du système sanitaire reconnaissent la nécessité de mettre en place des modalités adéquates et efficaces de prise en charge des patients présentant des maladies chroniques, participent à leur développement et les soutiennent.

Aspects génétiques de la consommation de tabac et prise en charge clinique [Genetic aspects of smoking and impact on clinical care]

Tobacco smoking is a major public health issue and a better understanding of tobacco addiction represents an important challenge. Many factors are involved in tobacco addiction, including genetic factors. Taking them into account in smoking cessation programs would allow to better adapt these programs to individual characteristics and improve their rate of success. Given enzymatic induction by tobacco smoke, smoking cessation can nevertheless have important consequences on the metabolism of some drugs, that have to be taken into consideration. Here we present different clinical and genetic aspects of smoking and of smoking cessation. A dose adjustment of drugs influenced by tobacco smoke is proposed when quitting smoking.

A doubling measure on R(d) can charge a rectifiable curve

"Vegeu el resum a l'inici del document del fitxer adjunt"

Polyanalgesic Consensus Conference--2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel.

INTRODUCTION: Trialing for intrathecal pump placement is an essential part of the decision-making process in placing a permanent device. In both the United States and the international community, the proper method for trialing is ill defined. METHODS: The Polyanalgesic Consensus Conference (PACC) is a group of well-published experienced practitioners who meet to update the state of care for intrathecal therapies on the basis of current knowledge in the literature and clinical experience. Anexhaustive search is performed to create a base of information that the panel considers when making recommendations for best clinical practices. This literature, coupled with clinical experience, is the basis for recommendations and for identification of gaps in the base of knowledge regarding trialing for intrathecal pump placement. RESULTS: The panel has made recommendations for the proper methods of trialing for long-term intrathecal drug delivery. CONCLUSION: The use of intrathecal drug delivery is an important part of the treatment algorithm for moderate to severe chronic pain. It has become common practice to perform a temporary neuroaxial infusion before permanent device implantation. On the basis of current knowledge, the PACC has developed recommendations to improve care. The need to update these recommendations will be very important as new literature is published.

Clinical use of temporary percutaneous left ventricular assist devices.

Background: Temporary percutaneous left ventricular assist devices (TPLVAD) can be inserted and removed in awake patients. They substitute left ventricular function for a period of up to a few weeks and provide an excellent backup and bridge to recovery or decision. Methods: Retrospective analysis of 75 patients who received TPLVAD to treat cardiogenic shock (n = 49) or to facilitate high-risk percutaneous coronary intervention (PCI) (n = 26). Forty-two patients with cardiogenic shock and 16 patients with high-risk PCI received a TandemHeart and 7 patients and 10 patients, respectively, received an Impella Recover LP 2.5. Outcome and related complications up to 1 month are reported with reference to device depending function. Results: One-month survival was 53% in patients with shock and 96% in patients with PCI. Conclusion: TPLVADs can support the failing heart with acceptable risk. Outcome is better in prophylactic use than in patients with cardiogenic shock. (C) 2011 Wiley-Liss, Inc.

Ultimate test bench for pediatric biventricular assist device based on artificial muscles.

Ventricular assist devices (VADs) are used in treatment for terminal heart failure or as a bridge to transplantation. We created biVAD using the artificial muscles (AMs) that supports both ventricles at the same time. We developed the test bench (TB) as the in vitro evaluating system to enable the measurement of performance. The biVAD exerts different pressure between left and right ventricle like the heart physiologically does. The heart model based on child's heart was constructed in silicone. This model was fitted with the biVAD. Two pipettes containing water with an ultrasonic sensor placed on top of each and attached to ventricles reproduced the preload and the after load of each ventricle by the real-time measurement of the fluid height variation proportionally to the exerted pressure. The LabVIEW software extrapolated the displaced volume and the pressure generated by each side of our biVAD. The development of a standardized protocol permitted the validation of the TB for in vitro evaluation, measurement of the performances of the AM biVAD herein, and reproducibility of data.

Direct electrical stimulation using a battery-operated device for induction and modulation of colonic contractions in pigs.

Direct electrical stimulation of the colon offers a promising approach for the induction of propulsive colonic contractions by using an implantable device. The objective of this study was to assess the feasibility to induce colonic contractions using a commercially available battery-operated stimulator (maximum pulse width of 1 ms and maximum amplitude of 10 V). Three pairs of pacing electrodes were inserted into the cecal seromuscular layer of anesthetized pigs. During a first set of in vivo experiments conducted on six animals, a pacing protocol leading to cecum contractions was determined: stimulation bursts with 1 ms pulse width, 10 V amplitude (7-15 mA), 120 Hz frequency, and 30-s burst duration, repeated every 2-5 min. In a second testing phase, an evaluation of the pacing protocol was performed in four animals (120 stimulation bursts in total). By using the battery-operated stimulator, contractions of the cecum and movement of contents could be induced in 92% of all stimulations. A cecal shortening of about 30% and an average intraluminal pressure increase of 10.0 +/- 6.0 mmHg were observed.

In vivo testing of a novel adjustable glaucoma drainage device.

PURPOSE: We report on the in vivo testing of a novel noninvasively adjustable glaucoma drainage device (AGDD), which features an adjustable outflow resistance, and assess the safety and efficiency of this implant. METHODS: Under general anesthesia, the AGDD was implanted on seven white New Zealand rabbits for a duration of 4 months under a scleral flap in a way analogous to the Ex-PRESS device and set in an operationally closed position. The IOP was measured on a regular basis on the operated and control eyes using a rebound tonometer. Once a month the AGDD was adjusted noninvasively from its fully closed to its fully open position and the resulting pressure drop was measured. The contralateral eye was not operated and served as control. After euthanization, the eyes were collected for histology evaluation. RESULTS: The mean preoperative IOP was 11.1 ± 2.4 mm Hg. The IOP was significantly lower for the operated eye (6.8 ± 2 mm Hg) compared to the nonoperated eye (13.1 ± 1.6 mm Hg) during the first 8 days after surgery. When opening the AGDD from its fully closed to fully open position, the IOP dropped significantly from 11.2 ± 2.9 to 4.8 ± 0.9 mm Hg (P < 0.05). CONCLUSIONS: Implanting the AGDD is a safe and uncomplicated surgical procedure. The fluidic resistance was noninvasively adjustable during the postoperative period with the AGDD between its fully closed and fully open positions.