Rabies postexposure prophylaxis in routine practice in view of the new centers for disease control and prevention and world health organization recommendations.

Background. New recommendations for rabies postexposure prophylaxis (PEP) were published by the Centers for Disease Control and Prevention and the World Health Organization in 2010. In view of these new recommendations, we investigated the adequacy of rabies PEP among patients consulting our travel clinic. Methods. A retrospective analysis of the files of all patients who consulted for rabies PEP at the Travel Clinic of the University Hospital in Lausanne, Switzerland, between January 2005 and August 2011 was conducted. Results. A total of 110 patients who received rabies PEP were identified. The median age of the patients was 34 years (range, 2-79 years), and 53% were women. Ninety subjects were potentially exposed to rabies while travelling abroad. Shortcomings in the management of these patients were (1) late initiation of rabies PEP in travelers who waited to seek medical care until returning to Switzerland, (2) administration of human rabies immunoglobulin (HRIG) to only 7 of 50 travelers (14%) who sought care abroad and for whom HRIG was indicated, and (3) antibody levels <0.5 IU/mL in 6 of 90 patients (6.7%) after 4 doses of vaccine. Conclusions. Patients do not always receive optimal rabies PEP under real-life conditions. A significant proportion of patients did not develop adequate antibody levels after 4 doses of vaccine. These data indicate that the measurement of antibody levels on day 21 of the Essen PEP regimen is useful in order to verify an adequate immune response.

A comparison of the imaging characteristics of the new Kodak Hyper Speed G film with the current T-MAT G/RA film and the CR 9000 system.

Three standard radiation qualities (RQA 3, RQA 5 and RQA 9) and two screens, Kodak Lanex Regular and Insight Skeletal, were used to compare the imaging performance and dose requirements of the new Kodak Hyper Speed G and the current Kodak T-MAT G/RA medical x-ray films. The noise equivalent quanta (NEQ) and detective quantum efficiencies (DQE) of the four screen-film combinations were measured at three gross optical densities and compared with the characteristics for the Kodak CR 9000 system with GP (general purpose) and HR (high resolution) phosphor plates. The new Hyper Speed G film has double the intrinsic sensitivity of the T-MAT G/RA film and a higher contrast in the high optical density range for comparable exposure latitude. By providing both high sensitivity and high spatial resolution, the new film significantly improves the compromise between dose and image quality. As expected, the new film has a higher noise level and a lower signal-to-noise ratio than the standard film, although in the high frequency range this is compensated for by a better resolution, giving better DQE results--especially at high optical density. Both screen-film systems outperform the phosphor plates in terms of MTF and DQE for standard imaging conditions (Regular screen at RQA 5 and RQA 9 beam qualities). At low energy (RQA 3), the CR system has a comparable low-frequency DQE to screen-film systems when used with a fine screen at low and middle optical densities, and a superior low-frequency DQE at high optical density.

The new EASL guidelines for the management of chronic hepatitis B infection adapted for Swiss physicians.

Since the arrival of several new antivirals and due to the growing molecular and clinical knowledge of hepatitis B virus (HBV) infection, therapy of hepatitis B has become complex. Clinical guidelines aim at streamlining medical attitudes: in this respect, the European Association for the Study of the Liver (EASL) recently issued clinical practice guidelines for the management of chronic hepatitis B. Guidelines made by international experts need however to be adapted to local health care systems. Here, we summarise the EASL guidelines with some minor modifications in order to be compatible with the particular Swiss situation, while discussing in more detail some aspects. Chronic hepatitis B is a complex disease with several phases where host and viral factors interact: the features of this continuous interplay need to be evaluated when choosing the most appropriate treatment. The EASL guidelines recommend, as first-line agents, using the most potent antivirals available with the optimal resistance profile, in order to abate HBV DNA as rapidly and as sustainably as possible. Once therapy has been started, the infection evolves and resistant viral strains may emerge. Rescue therapy needs to be started early with more potent agents lacking cross-resistance.

"Public on the outside, private on the inside": the organizational hybridization, sense of belonging and identity strategies of the employees of a public unemployment insurance fund in Switzerland

A number of studies show that New Public Management reforms have altered the current identity benchmarks of public officials, particularly by hybridizing values or management practices. However, existing studies have largely glossed over the sense of belonging of officials when their organization straddles the concerns of public service and private enterprise, so that the boundary between public and private sector is blurred. The purpose of this article is precisely to explore this sense of belonging in the context of organizational hybridization. It does so by drawing on the results of research conducted among the employees of a public unemployment insurance fund in Switzerland. On the one hand, the analysis shows how much their markers of belonging are hybrid, multiple and constructed in negative terms (with regard to the State), while indicating that the working practices of the employees point to an identity that is nevertheless closely bound with the public sector. On the other hand, the analysis shows that the organization plays strategically with its State status, by exploiting either its private or public identity in line with the needs related to its external image. The article concludes with a discussion of the results highlighting the strategic functionality of the hybrid identity of the actors.

Persistence of ultrasound synovitis in patients with rheumatoid arthritis fulfilling the DAS28 and/or the new ACR/EULAR RA remission definitions: results of an observational cohort study.

OBJECTIVE: The primary aim of the study was to evaluate whether rheumatoid arthritis (RA) patients considered to be in remission according to clinical criteria sets still had persisting ultrasound (US) synovitis. We further intended to evaluate the capacity of our US score to discriminate between the patients with a clinically active disease versus those in remission. METHODS: This is an observational study nested within the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) rheumatoid arthritis cohort. A validated US score (SONAR score) based on a semi-quantitative B-mode and Doppler (PwD) score as part of the regular clinical workup by rheumatologists in different clinical settings was used. To define clinically relevant synovitis, the same score was applied to 38 healthy controls and the 90st percentile was used as cut-off for 'relevant' synovitis. RESULTS: Three hundred and seven patients had at least one US examination and concomitant clinical information on disease activity. More than a third of patients in both DAS28 and ACR/EULAR remission showed significant gray scale synovitis (P=0.01 and 0.0002, respectively) and PwD activity (P=0.005 and 0.0005, respectively) when compared to controls. The capacity of US to discriminate between the two clinical remission groups and patients with active disease was only moderate. CONCLUSION: This observational study confirms that many patients considered to be in clinical remission according the DAS and the ACR/EULAR definitions still have residual synovitis on US. The prognostic significance of US synovitis and the exact place of US in patients reaching clinical remission need to be further evaluated.

Facteurs de risque fracturaire, nouveaux traitements: comment evolue la prise en charge de l'ostéoporose de la personne agée [Fracture risk, new treatments: how does the management of the osteoporosis of elderly change?]

Osteoporosis of elderly is a growing medical, economic and health-care problem. It is due to the increase of the life expectancy and the number of osteoporotic fractures. With the new Swiss-specific tool FRAX and the development of inpatients fracture trajectory, we can better identify patients with high risk of fracture. An appropriate treatment can be proposed more quickly. The follow-up of bone markers increases the treatment efficiency. With a better identification, treatment and follow-up of osteoporosis of elderly patients, we can ameliorate the patient's quality of life and decrease the number of osteoporotic fractures with a good cost-effectiveness ratio.

EACTS Day in the new EACTS House.

There is no doubt that the European Association for Cardio-Thoracic Surgery is a success story. In 2011, we celebrated the 25th anniversary of this professional organization. In 2012, we will celebrate the 25th anniversary of the European Journal of Cardio-Thoracic Surgery. In addition, two other journals have been initiated, Interactive CardioVascular and Thoracic Surgery and the Multimedia Manual of Cardio-Thoracic Surgery, and all of them can be accessed through CTSnet (www.ctsnet.org). The most recent development was the birth of EACTS House, and it was to celebrate the official opening of EACTS House on 10 February 2011, that we held the second Strategic meeting, 'EACTS in the Future'. On this occasion, the EACTS council and delegates of the EACTS Domains (Domain of Thoracic Disease, Domain of Vascular Disease, Domain of Congenital Cardiac Disease and Domain of Adult Cardiac Disease) came together with representative thoracic and cardio-vascular surgeons from North America, Asia and BRICS countries as well as senior managers from industry in order to decide where to go from there. As a basis for starting the discussions, a sector analysis of the activities of the Department of Cardio-Vascular Surgery at CHUV in Lausanne, Switzerland was performed in order to identify the trends in the activities of our group of surgeons by pulling the consolidated data for the period running from 1 January 1995 to 31 December 2010. Interestingly enough, the most frequent procedures like coronary artery bypass graft and valve repair/replacement did not increase despite a growing programme. In our setting, the compensation came mainly from vascular surgery and mechanical circulatory support. These data have to be put in perspective by the reports provided by the EACTS domain chairs in order to identify the challenges and opportunities for the future development of our specialties.

European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3--2009 update.

In 2005, several groups, including the European Group for Blood and Marrow Transplantation, the European Organization for Treatment and Research of Cancer, the European Leukemia Net and the Immunocompromised Host Society created the European Conference on Infections in Leukemia (ECIL). The main goal of ECIL is to elaborate guidelines, or recommendations, for the management of infections in leukemia and stem cell transplant patients. The first sets of ECIL slides about the management of invasive fungal disease were made available on the web in 2006 and the papers were published in 2007. The third meeting of the group (ECIL 3) was held in September 2009 and the group updated its previous recommendations. The goal of this paper is to summarize the new proposals from ECIL 3, based on the results of studies published after the ECIL 2 meeting: (1) the prophylactic recommendations for hematopoietic stem cell transplant recipients were formulated differently, by splitting the neutropenic and the GVHD phases and taking into account recent data on voriconazole; (2) micafungin was introduced as an alternative drug for empirical antifungal therapy; (3) although several studies were published on preemptive antifungal approaches in neutropenic patients, the group decided not to propose any recommendation, as the only randomized study comparing an empirical versus a preemptive approach showed a significant excess of fungal disease in the preemptive group.

Towards the validation of "in silico" models and physicochemical filters to identify and characterize new chemical entities

Summary: Lipophilicity plays an important role in the determination and the comprehension of the pharmacokinetic behavior of drugs. It is usually expressed by the partition coefficient (log P) in the n-octanol/water system. The use of an additional solvent system (1,2-dichlorethane/water) is necessary to obtain complementary information, as the log Poct values alone are not sufficient to explain ail biological properties. The aim of this thesis is to develop tools allowing to predict lipophilicity of new drugs and to analyze the information yielded by those log P values. Part I presents the development of theoretical models used to predict lipophilicity. Chapter 2 shows the necessity to extend the existing solvatochromic analyses in order to predict correctly the lipophilicity of new and complex neutral compounds. In Chapter 3, solvatochromic analyses are used to develop a model for the prediction of the lipophilicity of ions. A global model was obtained allowing to estimate the lipophilicity of neutral, anionic and cationic solutes. Part II presents the detailed study of two physicochemical filters. Chapter 4 shows that the Discovery RP Amide C16 stationary phase allows to estimate lipophilicity of the neutral form of basic and acidic solutes, except of lipophilic acidic solutes. Those solutes present additional interactions with this particular stationary phase. In Chapter 5, 4 different IANI stationary phases are investigated. For neutral solutes, linear data are obtained whatever the IANI column used. For the ionized solutes, their retention is due to a balance of electrostatic and hydrophobie interactions. Thus no discrimination is observed between different series of solutes bearing the same charge, from one column to an other. Part III presents two examples illustrating the information obtained thanks to Structure-Properties Relationships (SPR). Comparing graphically lipophilicity values obtained in two different solvent systems allows to reveal the presence of intramolecular effects .such as internai H-bond (Chapter 6). SPR is used to study the partitioning of ionizable groups encountered in Medicinal Chemistry (Chapter7). Résumé La lipophilie joue un .rôle important dans la détermination et la compréhension du comportement pharmacocinétique des médicaments. Elle est généralement exprimée par le coefficient de partage (log P) d'un composé dans le système de solvants n-octanol/eau. L'utilisation d'un deuxième système de solvants (1,2-dichloroéthane/eau) s'est avérée nécessaire afin d'obtenir des informations complémentaires, les valeurs de log Poct seules n'étant pas suffisantes pour expliquer toutes les propriétés biologiques. Le but de cette thèse est de développer des outils permettant de prédire la lipophilie de nouveaux candidats médicaments et d'analyser l'information fournie par les valeurs de log P. La Partie I présente le développement de modèles théoriques utilisés pour prédire la lipophilie. Le chapitre 2 montre la nécessité de mettre à jour les analyses solvatochromiques existantes mais inadaptées à la prédiction de la lipophilie de nouveaux composés neutres. Dans le chapitre 3, la même méthodologie des analyses solvatochromiques est utilisée pour développer un modèle permettant de prédire la lipophilie des ions. Le modèle global obtenu permet la prédiction de la lipophilie de composés neutres, anioniques et cationiques. La Partie II présente l'étude approfondie de deux filtres physicochimiques. Le Chapitre 4 montre que la phase stationnaire Discovery RP Amide C16 permet la détermination de la lipophilie de la forme neutre de composés basiques et acides, à l'exception des acides très lipophiles. Ces derniers présentent des interactions supplémentaires avec cette phase stationnaire. Dans le Chapitre 5, 4 phases stationnaires IAM sont étudiées. Pour les composés neutres étudiés, des valeurs de rétention linéaires sont obtenues, quelque que soit la colonne IAM utilisée. Pour les composés ionisables, leur rétention est due à une balance entre des interactions électrostatiques et hydrophobes. Donc aucune discrimination n'est observée entre les différentes séries de composés portant la même charge d'une colonne à l'autre. La Partie III présente deux exemples illustrant les informations obtenues par l'utilisation des relations structures-propriétés. Comparer graphiquement la lipophilie mesurée dans deux différents systèmes de solvants permet de mettre en évidence la présence d'effets intramoléculaires tels que les liaisons hydrogène intramoléculaires (Chapitre 6). Cette approche des relations structures-propriétés est aussi appliquée à l'étude du partage de fonctions ionisables rencontrées en Chimie Thérapeutique (Chapitre 7) Résumé large public Pour exercer son effet thérapeutique, un médicament doit atteindre son site d'action en quantité suffisante. La quantité effective de médicament atteignant le site d'action dépend du nombre d'interactions entre le médicament et de nombreux constituants de l'organisme comme, par exemple, les enzymes du métabolisme ou les membranes biologiques. Le passage du médicament à travers ces membranes, appelé perméation, est un paramètre important à optimiser pour développer des médicaments plus puissants. La lipophilie joue un rôle clé dans la compréhension de la perméation passive des médicaments. La lipophilie est généralement exprimée par le coefficient de partage (log P) dans le système de solvants (non miscibles) n-octanol/eau. Les valeurs de log Poct seules se sont avérées insuffisantes pour expliquer la perméation à travers toutes les différentes membranes biologiques du corps humain. L'utilisation d'un système de solvants additionnel (le système 1,2-dichloroéthane/eau) a permis d'obtenir les informations complémentaires indispensables à une bonne compréhension du processus de perméation. Un grand nombre d'outils expérimentaux et théoriques sont à disposition pour étudier la lipophilie. Ce travail de thèse se focalise principalement sur le développement ou l'amélioration de certains de ces outils pour permettre leur application à un champ plus large de composés. Voici une brève description de deux de ces outils: 1)La factorisation de la lipophilie en fonction de certaines propriétés structurelles (telle que le volume) propres aux composés permet de développer des modèles théoriques utilisables pour la prédiction de la lipophilie de nouveaux composés ou médicaments. Cette approche est appliquée à l'analyse de la lipophilie de composés neutres ainsi qu'à la lipophilie de composés chargés. 2)La chromatographie liquide à haute pression sur phase inverse (RP-HPLC) est une méthode couramment utilisée pour la détermination expérimentale des valeurs de log Poct.

A look through the new therapeutic window: irbesartan

Although an impressive array of efficacious antihypertensive agents are available to treat hypertension, the optimal use of these agents is limited by dose-related side-effect profiles. This is particularly the case for widely used first-line antihypertensive agents such as diuretics, beta-blockers, calcium antagonists, and alpha1-blockers; this represents a major therapeutic dilemma in treating hypertension. With the development of the angiotensin II receptor antagonists (AIIRAs), this dilemma might have been solved. Irbesartan is a long-acting AIIRA that provides dose-related efficacy with placebo-like tolerability at all clinical doses. The results of placebo and active-control trials of irbesartan have demonstrated that the agent is as effective as the leading members of major antihypertensive classes with respect to blood pressure control, while having superior tolerability. Pooled data from nine multicenter, randomized, placebo-controlled trials with irbesartan have documented no adverse events caused by dose-response. This feature could widen the traditionally narrow therapeutic window in the treatment of hypertension and point to the use of AIIRAs such as irbesartan as first-line therapy in the management of hypertension.

Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area.

Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based management of malaria. The accuracy of an RDT for the detection of clinical malaria and the presence of malarial parasites has recently been evaluated in a high-transmission area of southern Mali. During the same study, the cost-effectiveness of a 'test-and-treat' strategy for the home-based management of malaria (based on an artemisinin-combination therapy) was compared with that of a 'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been considered a presumptive case of uncomplicated malaria by a village healthworker, were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity, and positive and negative predictive values of this test, compared with the results of microscopy and two different definitions of clinical malaria, were then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the detection of parasites by microscopy. In the detection of clinical malaria, it was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%) sensitive but only 30.2% (24.8%-36.2%) specific when compared against the fulfillment of the World Health Organization's (2003) research criteria for uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and-treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0. v. U.S.$0.5). In older subjects, however, the two strategies were equally costly (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs. The question remains whether either of the strategies investigated can be made affordable for the affected population.

Homer and the New Testament as "Multitexts" in the Digital Age ?

The field of classical studies has undergone a radical transformation with the arrival of the digital age, particularly with regard to the editing of ancient texts. As Umberto Eco (2003) pointed out, the digital age may mean the end of the history of variants and of the notion of the "original text." Among the texts of antiquity, the editing of Homer and of the New Testament are more especially susceptible to the effects of digital technology because of their numerous manuscripts. Whereas the "Homer Multitext" project recognizes that the notion of a synthetic critical edition is now seriously brought into question, the prototype of the online Greek New Testament continues to be based on the aim of obtaining a unique text, in the style of a printed critical edition. As it moves from a printed culture to the digital age, the editing of the Greek NT is also confronted by the emergence of non-Western scholarship. For example, the presence is to be noted of Arabic Muslim websites that examine Greek New Testament manuscripts but without directly interacting with Western scholarship.