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.

Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population.

BACKGROUND: Obesity and African American ethnicity are established independent risk factors for the development of chronic kidney disease. No data exist about the association between obesity and renal hemodynamics in the African region. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 301 nondiabetic participants (97 lean, 108 overweight, and 96 obese) of African descent with a positive family history of hypertension from the Seychelles islands. PREDICTOR: Body mass index (BMI). OUTCOMES: Glomerular hyperfiltration, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction. MEASUREMENTS: GFR and ERPF were measured using inulin and para-aminohippurate clearances, respectively. Participants' baseline demographics, laboratory data, and blood pressure were measured using standard techniques. RESULTS: The prevalence of glomerular hyperfiltration (defined as GFR >or=140 mL/min) increased across BMI categories (7.2%, 14.8%, and 27.1% for lean, overweight, and obese participants, respectively; P < 0.001). Higher BMI was associated with higher median GFR (99, 110, and 117 mL/min for lean, overweight, and obese participants, respectively; P < 0.001), ERPF (424, 462, and 477 mL/min, respectively; P = 0.01), and filtration fraction (0.23, 0.24, and 0.25; P < 0.001). Multivariate analyses adjusting for age, sex, blood pressure, fasting glucose level, and urinary sodium excretion and accounting for familial correlations confirmed the associations between high BMI (>25 kg/m(2)) and increased GFR, ERPF, and filtration fraction. No association between BMI categories and GFR was found with adjustment for body surface area. LIMITATIONS: Participants had a positive family history of hypertension. CONCLUSION: Overweight and obesity are associated with increased GFR, ERPF, and filtration fraction and a high prevalence of glomerular hyperfiltration in nondiabetic individuals of African descent. The absence of associations between BMI categories and GFR indexed for body surface area raises questions regarding the appropriateness of indexing GFR for body surface area in overweight populations.

Risk factors of stroke mortality in the African region: a cohort study

Background: Population-based cohort studies of risk factors of stroke are scarce in developing countries and none has been done in the African region. We conducted a longitudinal study in the Seychelles (Indian Ocean, east of Kenya), a middle-income island state where the majority of the population is of African descent. Such data in Africa are important for international comparison and for advocacy in the region. Methods: Three examination surveys of cardiovascular risk factors were performed in independent samples representative of the general population aged 25-64 in 1989, 1994 and 2004 (n=1081, 1067, and 1255, respectively). Baseline risk factors data were linked with cause-specific mortality from vital statistics up to May 2007 (all deaths are medically certified in the Seychelles and kept in an electronic database). We considered stroke (any type) as a cause of death if the diagnosis was reported in any of the 4 fields in the death certificates for underlying and concomitant causes of death. Results. Among the 2479 persons aged 35-64 at baseline, 280 died including 56 with stroke during follow up (maximum: 18.2 years; mean: 10.2 years). In this age range, age-adjusted mortality rates (/100'000/year) were 969 for all cause and 187 for stroke; age-adjusted prevalence of high blood pressure (≥140/90 mmHg) was 48%. In multivariate Cox survival time regression, stroke mortality was increased by 18% and 35% for a 10-mmHg increase in systolic, respectively diastolic BP (p<0.001). Stroke mortality was also associated with age, smoking ≥5 cigarettes vs. no smoking (HR: 2.4; 95% CI: 1.2-4.8) and diabetes (HR: 1.9; 1.02-3.6) but not with sex, LDL-cholesterol intake, alcohol intake and professional occupation. Conclusion. This first population-based cohort study in the African region demonstrates high mortality rates from stroke in middle-aged adults and confirms associations with high BP and other risk factors. This emphasizes the importance of reducing BP and other modifiable risk factors in high risk individuals and in the general population as a main strategy to reduce the burden of stroke.

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.

Perspectives for Forensic Intelligence in anti-doping: Thinking outside of the box.

Today's approach to anti-doping is mostly centered on the judicial process, despite pursuing a further goal in the detection, reduction, solving and/or prevention of doping. Similarly to decision-making in the area of law enforcement feeding on Forensic Intelligence, anti-doping might significantly benefit from a more extensive gathering of knowledge. Forensic Intelligence might bring a broader logical dimension to the interpretation of data on doping activities for a more future-oriented and comprehensive approach instead of the traditional case-based and reactive process. Information coming from a variety of sources related to doping, whether directly or potentially, would feed an organized memory to provide real time intelligence on the size, seriousness and evolution of the phenomenon. Due to the complexity of doping, integrating analytical chemical results and longitudinal monitoring of biomarkers with physiological, epidemiological, sociological or circumstantial information might provide a logical framework enabling fit for purpose decision-making. Therefore, Anti-Doping Intelligence might prove efficient at providing a more proactive response to any potential or emerging doping phenomenon or to address existing problems with innovative actions or/and policies. This approach might prove useful to detect, neutralize, disrupt and/or prevent organized doping or the trafficking of doping agents, as well as helping to refine the targeting of athletes or teams. In addition, such an intelligence-led methodology would serve to address doping offenses in the absence of adverse analytical chemical evidence.

Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.