When "enough" is not enough: new perspectives on optimal methadone maintenance dose.

Some methadone maintenance treatment (MMT) programs prescribe inadequate daily methadone doses. Patients complain of withdrawal symptoms and continue illicit opioid use, yet practitioners are reluctant to increase doses above certain arbitrary thresholds. Serum methadone levels (SMLs) may guide practitioners dosing decisions, especially for those patients who have low SMLs despite higher methadone doses. Such variation is due in part to the complexities of methadone metabolism. The medication itself is a racemic (50:50) mixture of 2 enantiomers: an active "R" form and an essentially inactive "S" form. Methadone is metabolized primarily in the liver, by up to five cytochrome P450 isoforms, and individual differences in enzyme activity help explain wide ranges of active R-enantiomer concentrations in patients given identical doses of racemic methadone. Most clinical research studies have used methadone doses of less than 100 mg/day [d] and have not reported corresponding SMLs. New research suggests that doses ranging from 120 mg/d to more than 700 mg/d, with correspondingly higher SMLs, may be optimal for many patients. Each patient presents a unique clinical challenge, and there is no way of prescribing a single best methadone dose to achieve a specific blood level as a "gold standard" for all patients. Clinical signs and patient-reported symptoms of abstinence syndrome, and continuing illicit opioid use, are effective indicators of dose inadequacy. There does not appear to be a maximum daily dose limit when determining what is adequately "enough" methadone in MMT.

The future of longevity: background and perspectives

In many developed countries, including Switzerland, the ongoing increase in life expectancy is driven by the mortality decline among older persons. This has important consequences for both the provision of health care and the management of pension funds. In this context, the Swiss Federal Office of Statistics mandated a small group of experts to provide a critical review on the future evolution of mortality in developed countries. The report starts with an analysis of the past trends in life expectancy. Longevity is defined here as the duration (or the length) of life as observed in population or in individuals. The oldest and still most used indicators of longevity are life expectancy at birth (LE0) at a population level, and maximum life span (MLS) at the individual level (page 9) and in healthy life expectancy (page 19). A discussion on the future evolution of mortality and health is then presented (page 27). A set of recommendations is finally proposed (page 39).

Concept de first responders en Suisse romande: état des lieux et perspectives [Concept of first responders in Western Switzerland: current situation and future perspectives].

The notion of "First Responder" (FR) refers to the system of first-aid volunteers who act to initiate the first-aid care before the classical emergency help arrives. In 2011, the French-speaking Switzerland counts 19 groups, divided up between four cantons (Fribourg, Vaud, Neuchâtel, Valais). The geographical distribution of those FR shows the stakes of these peripherical areas, with the accessibility difficulties for the emergency services, and a low demography of ambulances and doctors. The number of interventions carried out by the FR has significantly increased during the last years. The association of a quality formation, an excellent knowledge of the ground and a quick intervention has a positive impact on the survival of the patients with vital emergency or traumatic conditions.

Utility scores associated with the world health organisation drinking risk-level classification in alcohol dependence

BACKGROUND: Extensive research exists estimating the effect hazardous alcohol¦use on morbidity and mortality, but little research quantifies the association between¦alcohol consumption and utility scores in patients with alcohol dependence.¦In the context of comparative research, the World Health Organisation (WHO)¦proposed to categorise the risk for alcohol-related acute and chronic harm according¦to patients' average daily alcohol consumption. OBJECTIVES: To estimate utility¦scores associated with each category of the WHO drinking risk-level classification¦in patients with alcohol dependence (AD). METHODS: We used data from¦CONTROL, an observational cohort study including 143 AD patients from the Alcohol¦Treatment Center at Lausanne University Hospital, followed for 12 months.¦Average daily alcohol consumption was assessed monthly using the Timeline Follow-¦back method and patients were categorised according to the WHO drinking¦risk-level classification: abstinent, low, medium, high and very high. Other measures¦as sociodemographic characteristics and utility scores derived from the EuroQoL¦5-Dimensions questionnaire (EQ-5D) were collected every three months.¦Mixed models for repeated measures were used to estimate mean utility scores¦associated with WHO drinking risk-level categories. RESULTS: A total of 143 patients¦were included and the 12-month follow-up permitting the assessment of¦1318 person-months. At baseline the mean age of the patients was 44.6 (SD 11.8)¦and the majority of patients was male (63.6%). Using repeated measures analysis,¦utility scores decreased with increasing drinking levels, ranging from 0.80 in abstinent¦patients to 0.62 in patients with very high risk drinking level (p_0.0001).¦CONCLUSIONS: In this sample of patients with alcohol dependence undergoing¦specialized care, utility scores estimated from the EQ-5D appeared to substantially¦and consistently vary according to patients' WHO drinking level.

Transnational authority in the knowledge-based economy: Who sets the standards of ICT training and certification?

This article examines the extent and limits of nonstate forms of authority in international relations. It analyzes how the information and communication technology (ICT) infrastructure for the tradability of services in a global knowledge-based economy relies on informal regulatory practices for the adjustment of ICT-related skills. By focusing on the challenge that highly volatile and short-lived cycles of demands for this type of knowledge pose for ensuring the right qualification of the labor force, the article explores how companies and associations provide training and certification programs as part of a growing market for educational services setting their own standards. The existing literature on non-conventional forms of authority in the global political economy has emphasized that the consent of actors, subject to informal rules and some form of state support, remains crucial for the effectiveness of those new forms of power. However, analyses based on a limited sample of actors tend toward a narrow understanding of the issues concerned and fail to fully explore the differentiated space in which non state authority is emerging. This article develops a three-dimensional analytical framework that brings together the scope of the issues involved, the range of nonstate actors concerned, and the spatial scope of their authority. The empirical findings highlight the limits of these new forms of nonstate authority and shed light on the role of the state and international governmental organizations in this new context.

The First World War and coal trade geography in Latin America and the Caribbean (1890-1930)

This paper aims to illustrate the dynamics of coal trade between Latin America and its main trade partners, i.e. the USA, Great Britain and Germany, before and after the enormous disruption caused by the First World War. The coal trade was used as an indicator of modernization for Latin American countries, given that oil was at that time of secondary importance. Energy imports have determined the possibilities of each Latin American country in its process of development. Here we address this question and place special emphasis on supply channels, concluding that the trade link with main suppliers was of key significance. Although this was very clear by the end of the period, the process had started well before the First World War, at least for the majority of LA&C countries. These points are developed through a gravity model applied to the bilateral coal trade. The importance of the market supplier share is addressed through cluster methodologies.

Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport.

The highly pathogenic Old World arenavirus Lassa virus (LASV) and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) use α-dystroglycan as a cellular receptor and enter the host cell by an unusual endocytotic pathway independent of clathrin, caveolin, dynamin, and actin. Upon internalization, the viruses are delivered to acidified endosomes in a Rab5-independent manner bypassing classical routes of incoming vesicular trafficking. Here we sought to identify cellular factors involved in the unusual and largely unknown entry pathway of LASV and LCMV. Cell entry of LASV and LCMV required microtubular transport to late endosomes, consistent with the low fusion pH of the viral envelope glycoproteins. Productive infection with recombinant LCMV expressing LASV envelope glycoprotein (rLCMV-LASVGP) and LCMV depended on phosphatidyl inositol 3-kinase (PI3K) as well as lysobisphosphatidic acid (LBPA), an unusual phospholipid that is involved in the formation of intraluminal vesicles (ILV) of the multivesicular body (MVB) of the late endosome. We provide evidence for a role of the endosomal sorting complex required for transport (ESCRT) in LASV and LCMV cell entry, in particular the ESCRT components Hrs, Tsg101, Vps22, and Vps24, as well as the ESCRT-associated ATPase Vps4 involved in fission of ILV. Productive infection with rLCMV-LASVGP and LCMV also critically depended on the ESCRT-associated protein Alix, which is implicated in membrane dynamics of the MVB/late endosomes. Our study identifies crucial cellular factors implicated in Old World arenavirus cell entry and indicates that LASV and LCMV invade the host cell passing via the MVB/late endosome. Our data further suggest that the virus-receptor complexes undergo sorting into ILV of the MVB mediated by the ESCRT, possibly using a pathway that may be linked to the cellular trafficking and degradation of the cellular receptor.

The efficacy of a protective cream in a real-world apprentice hairdresser environment.

The object of this study was to compare the protective action of a new barrier cream (Excipial Protect, Spirig Pharma AG, Egerkingen, Switzerland) to its vehicle in the context of hand irritation of apprentice hairdressers caused by repeated shampooing and exposure to hair-care products. This was a double-blind cross-over comparing Excipial Protect (containing aluminium chlorohydrate 5% as active ingredient) against its vehicle alone. The efficacy of the creams was evaluated taking into account: (1) clinical scores by researchers, (2) biometric measurements, (3) subjective opinions of the subjects. An analysis of variance was performed considering order of application, degree of atopy, and reported number of shampoos. We observed very little difference in efficacy between the protective cream and its vehicle. The presence, however, of aluminium chlorhydrate in the protective cream was shown to have a positive effect against work-related irritation. The cosmetic qualities of the creams seemed, to the participants, to be as important as their real protective and hydrating properties, an important factor in compliance issues.

Pertinence de la trace: étude théorique et perspectives expérimentales

Pour faire évoluer la science forensique, il faut pouvoir analyser des notions élémentaires appartenant au quotidien et non se focaliser exclusivement sur le développement de nouvelles techniques. Encore non étudiée sous cette perspective, la pertinence fait partie de ces notions fondamentales forensiques pour lesquelles une telle analyse mérite d'être menée. En tenant compte du constat formulé par Inman et Rudin (2000), à savoir que la tâche la plus compliquée est de pouvoir reconnaître des traces matérielles pertinentes, s'interroger sur la pertinence de la trace soulève bien plus qu'une question. Cela met en évidence une multitude de paramètres intervenant dans les processus de raisonnement et de décision opérés sur les lieux d'investigations. Du reste trois facteurs susceptibles d'avoir une influence notable sur la recherche de traces apparaissent : Savoir, Formation et Expérience ou S.F.E. Ils forment, en étant regroupés, un bagage spécifique au spécialiste, composant sa connaissance dans le domaine et à même de jouer un rôle d'importance dans son travail opéré sur les lieux. Afin de déterminer l'influence de ce bagage sur le concept de pertinence, la démarche expérimentale se conduit en deux temps. Dans une première phase, l'approche se veut exploratoire au travers d'un stage réalisé dans une unité d'interventions, permettant de poser des bases statistiques et de dresser une réalité du travail sur le terrain. Puis au cours de la phase expérimentale, la conduite d'entretiens semi-directifs, couplés à un sondage, vise à déterminer quelle perception du concept de pertinence ressort parmi les volontaires interrogés. Ces derniers sont issus de groupes composés de futurs criminalistes, qui suivent une formation forensique à l'Université de Lausanne, et de praticiens expérimentés de formation police et / ou scientifique. En tentant de clarifier le concept de pertinence, l'objectif est de fournir des outils pour renforcer ou orienter la formation de spécialistes sur le terrain, en ayant permis d'amorcer une démarche de réflexion logique face aux champs d'investigations. En se voulant utile pour mieux formaliser la détection et la collecte des traces pertinentes sur les lieux, cela constitue une aide à la gestion : un atout non négligeable à l'heure où les contrôles qualité et les standards ne sont plus seulement une tendance mais une réalité qui s'impose.