Suivi de l'adhésion thérapeutique des patients hypertendus ou dyslipi- démiques par les cercles de qualité médecins-pharmaciens [Monitoring drug adherence for hypertensive and dyslipidemic patients in networks of community-based pharmacists and physicians].

Patient adherence is often poor for hypertension and dyslipidaemia. A monitoring of drug adherence might improve these risk factors control, but little is known in ambulatory care. We conducted a randomised controlled study in networks of community-based pharmacists and physicians in the canton of Fribourg to examine whether monitoring drug adherence with an electronic monitor (MEMS) would improve risk factor control among treated, but uncontrolled hypertensive and dyslipidemic patients. The results indicate that MEMS achieve a better blood pressure control and lipid profile, although its implementation requires considerable resources. The study also shows the value of collaboration between physicians and pharmacists in the field of patient adherence to improve ambulatory care of patients with cardiovascular risk factors.

Conservation genetics and population monitoring of the Alpine Salamander (Salamandra Atra) :

SUMMARYIn the context of the biodiversity crisis, amphibians are experiencing the most severe worldwide decline of all vertebrates and are in urgent need of better management. Efficient conservation strategies rely on sound knowledge of the species biology and of the genetic and demographic processes that might impair their welfare. Nonetheless, these processes are poorly understood in amphibians. Delineating population boundaries remains consequently problematic for these species, while it is of critical importance to define adequate management units for conservation. In this study, our attention focused on the alpine salamander (Salamandra atra), a species that deserves much interest in terms of both conservation biology and evolution. This endemic alpine species shows peculiar life-history traits (viviparity, reduced activity period, slow maturation) and has a slow population turnover, which might be problematic for its persistence in a changing environment. Due to its elusive behaviour (individuals spend most of their time underground and are unavailable for sampling), dynamic processes of gene and individuals were poorly understood for that species. Consequently, its conservation status could hardly be reliably assessed. Similarly the fire salamander (Salamandra salamandra) also poses special challenges for conservation, as no clear demarcation of geographical populations exists and dispersal patterns are poorly known. Through a phylogeographic analysis, we first studied the evolutionary history of the alpine salamander to better document the distribution of the genetic diversity along its geographical range. This study highlighted the presence of multiple divergent lineages in Italy together with a clear genetic divergence between populations from Northern and Dinaric Alps. These signs of cryptic genetic differentiation, which are not accounted for by the current taxonomy of the species, should not be neglected for further definition of conservation units. In addition, our data supported glacial survival of the species in northern peripheral glacial réfugia and nunataks, a pattern rarely documented for long-lived species. Then, we evaluated the level of gene flow between populations at the local scale and tested for asymmetries in male versus female dispersal using both field-based (mark-recapture) and genetic approaches. This study revealed high level of gene flow between populations, which stems mainly from male dispersal. This corroborated the idea that salamanders are much better dispersers than hitherto thought and provided a well- supported example of male-biased dispersal in amphibians. In a third step, based on a mark- recapture survey, we addressed the problem of sampling unavailability in alpine salamanders and evaluated its impact on two monitoring methods. We showed that about three quarters of individuals were unavailable for sampling during sampling sessions, a proportion that can vary with climatic conditions. If not taken into account, these complexities would result in false assumptions on population trends and misdirect conservation efforts. Finally, regarding the daunting task of delineating management units, our attention was drawn on the fire salamander. We conducted a local population genetic study that revealed high levels of gene flow among sampling sites. Management units for this species should consequently be large. Interestingly, despite the presence of several landscape features often reported to act as barriers, genetic breaks occurred at unexpected places. This suggests that landscape features may rather have idiosyncratic effects on population structure. In conclusion, this work brought new insights on both genetic and demographic processes occurring in salamanders. The results suggest that some biological paradigms should be taken with caution when particular species are in focus. Species- specific studies remain thus fundamental for a better understanding of species evolution and conservation, particularly in the context of current global changes.RESUMEDans le contexte de la crise de la biodiversité actuelle, les amphibiens subissent le déclin le plus important de tous les vertébrés et ont urgemment besoin d'une meilleure protection. L'établissement de stratégies de conservation efficaces repose sur des connaissances solides de la biologie des espèces et des processus génétiques et démographiques pouvant menacer leur survie. Ces processus sont néanmoins encore peu étudiés chez les amphibiens.Dans cette étude, notre attention s'est portée sur la salamandre noire (Salamandra atra), une espèce endémique des Alpes dont les traits d'histoire de vie atypiques (viviparité, phase d'activité réduite, lent turnover des populations) pourraient la rendre très vulnérable face aux changements environnementaux. Par ailleurs, en raison de son comportement cryptique (les individus passent la plupart de leur temps sous terre) la dynamique des gènes et des individus est mal comprise chez cette espèce. Il est donc difficile d'évaluer son statut de conservation de manière fiable. La salamandre tachetée {Salamandra salamandra), pour qui il n'existe aucune démarcation géographique apparente des populations, pose également des problèmes en termes de gestion. Dans un premier temps, nous avons étudié l'histoire évolutive de la salamandre noire afin de mieux décrire la distribution de sa diversité génétique au sein de son aire géographique. Cela a permis de mettre en évidence la présence de multiples lignées en Italie, ainsi qu'une nette divergence entre les populations du nord des Alpes et des Alpes dinariques. Ces résultats seront à prendre en compte lorsqu'il s'agira de définir des unités de conservation pour cette espèce. D'autre part, nos données soutiennent l'hypothèse d'une survie glaciaire dans des refuges nordiques périglaciaires ou dans des nunataks, fait rarement documenté pour une espèce longévive. Nous avons ensuite évalué la différentiation génétique des populations à l'échelle locale, ce qui a révélé d'important flux de gènes, ainsi qu'une asymétrie de dispersion en faveur des mâles. Ces résultats corroborent l'idée que les amphibiens dispersent mieux que ce que l'on pensait, et fournissent un exemple robuste de dispersion biaisée en faveur des mâles chez les amphibiens. Nous avons ensuite abordé le problème de Γ inaccessibilité des individus à la capture. Nous avons montré qu'environ trois quarts des individus sont inaccessibles lors des échantillonnages, une proportion qui peut varier en fonction des conditions climatiques. Ignoré, ce processus pourrait entraîner une mauvaise interprétation des fluctuations de populations ainsi qu'une mauvaise allocation des efforts de conservation. Concernant la définition d'unités de gestion pour la salamandre tachetée, nous avons pu mettre en évidence un flux de gènes important entre les sites échantillonnés. Les unités de gestion pour cette espèce devraient donc être étendues. Etonnamment, malgré la présence de nombreuses barrières potentielles au flux de gènes, les démarcations génétiques sont apparues à des endroits inattendus. En conclusion, ce travail a apporté une meilleure compréhension des processus génétiques et démographiques en action chez les salamandres. Les résultats suggèrent que certains paradigmes biologiques devraient être considérés avec précaution quand il s'agit de les appliquer à des espèces particulières. Les études spécifiques demeurent donc fondamentales pour une meilleure compréhension de l'évolution des espèces et leur conservation, tout particulièrement dans le contexte des changements globaux actuels.

Postoperative management of adult central neurosurgical patients: systemic and neuro-monitoring.

Postoperative neurosurgical patients are at risk of developing complications. Systemic and neuro-monitoring are used to identify patients who deteriorate in order to treat the underlying cause and minimize the impact on outcome. Hypotension and hypoxia are likely to be the most frequent insults and can be detected easily with blood pressure monitoring and pulse oximetry. Repeated clinical examination, however, is probably the most important monitor in the postoperative setting. Clinical scores such as the Glasgow Coma Score and the more recently introduced FOUR Score are important tools to standardize the clinical assessment. Intracranial pressure monitoring, cerebral blood flow monitoring, electroencephalography, and brain imaging are often used postoperatively. Despite the numerous publications on this topic only few studies address the impact of postoperative monitoring on outcome. Accordingly, in most patients the decision on which monitors are to be used must be based on the patient's presentation and clinical judgment.

Patterns of Adherence to Raltegravir-Based Regimens and the Risk of Virological Failure Among HIV-Infected Patients: The RALTECAPS Cohort Study.

ABSTRACT:: Adherence patterns and their influence on virologic outcome are well characterized for protease inhibitor (PI)- and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We aimed to determine how patterns of adherence to raltegravir influence the risk of virological failure. We conducted a prospective multicenter cohort following 81 HIV-infected antiretroviral-naive or experienced subjects receiving or starting twice-a-day raltegravir-based antiretroviral therapy. Their adherence patterns were monitored using the Medication Events Monitoring System. During follow-up (188 days, ±77), 12 (15%) of 81 subjects experienced virological failure. Longer treatment interruption [adjusted odds ratio per 24-hour increase: 2.4; 95% confidence interval: 1.2 to 6.9; P < 0.02] and average adherence (odds ratio per 5% increase: 0.68; 95% confidence interval: 0.46 to 1.00, P < 0.05) were both independently associated with virological failure controlling for prior duration of viral suppression. Timely interdose intervals and high levels of adherence to raltegravir are both necessary to control HIV replication.

Antidoping programme and biological monitoring before and during the 2014 FIFA World Cup Brazil.

BACKGROUND: The FIFA has implemented an important antidoping programme for the 2014 FIFA World Cup. AIM: To perform the analyses before and during the World Cup with biological monitoring of blood and urine samples. METHODS: All qualified players from the 32 teams participating in the World Cup were tested out-of-competition. During the World Cup, 2-8 players per match were tested. Over 1000 samples were collected in total and analysed in the WADA accredited Laboratory of Lausanne. RESULTS: The quality of the analyses was at the required level as described in the WADA technical documents. The urinary steroid profiles of the players were stable and consistent with previously published papers on football players. During the competition, amphetamine was detected in a sample collected on a player who had a therapeutic use exemption for attention deficit hyperactivity disorder. The blood passport data showed no significant difference in haemoglobin values between out-of-competition and postmatch samples. CONCLUSIONS: Logistical issues linked to biological samples collection, and the overseas shipment during the World Cup did not impair the quality of the analyses, especially when used as the biological passport of football players.

Eumelanin-based coloration and fitness parameters in birds: a meta-analysis

Although melanin is the most common pigment in animal integuments, the adaptive function of variation in melanin-based coloration remains poorly understood. The individual fitness returns associated with melanin pigments can be variable across species as these pigments can have physical and biological protective properties and genes involved in melanogenesis may vary in the intensity of pleiotropic effects. Moreover, dark and pale coloration can also enhance camouflage in alternative habitats and melanin-based coloration can be involved in social interactions. We investigated whether darker or paler individuals achieve a higher fitness in birds, a taxon wherein associations between melanin-based coloration and fitness parameters have been studied in a large number of species. A meta-analysis showed that the degree of melanin-based coloration was not significantly associated with laying date, clutch size, brood size, and survival across 26 species. Similar results were found when restricting the analyses to non-sexually dimorphic birds, colour polymorphic and monomorphic species, in passerines and non-passerines and in species for which inter-individual variation in melanism is due to colour intensity. However, eumelanic coloration was positively associated with clutch and brood size in sexually dimorphic species and those that vary in the size of black patches, respectively. Given that greater extent of melanin-based coloration was positively associated with reproductive parameters and survival in some species but negatively in other species, we conclude that in birds the sign and magnitude of selection exerted on melanin-based coloration is species- or trait-specific.

Ambulatory Blood Pressure and Adherence Monitoring: Diagnosing Pseudoresistant Hypertension.

A small proportion of the treated hypertensive population consistently has a blood pressure greater than 140/90 mm Hg despite a triple therapy including a diuretic, a calcium channel blocker, and a blocker of the renin-angiotensin system. According to guidelines, these patients have so-called resistant hypertension. The prevalence of this clinical condition is higher in tertiary than primary care centers and often is associated with chronic kidney disease, diabetes, obesity, and sleep apnea syndrome. Exclusion of pseudoresistant hypertension using ambulatory or home blood pressure monitoring is a crucial step in the investigation of patients with resistant hypertension. Thus, among the multiple factors to consider when investigating patients with resistant hypertension, ambulatory blood pressure monitoring should be performed very early. Among other factors to consider, physicians should investigate patient adherence to therapy, assess the adequacy of treatment, exclude interfering factors, and, finally, look for secondary forms of hypertension. Poor adherence to therapy accounts for 30% to 50% of cases of resistance to therapy depending on the methodology used to diagnose adherence problems. This review discusses the clinical factors implicated in the pathogenesis of resistant hypertension with a particular emphasis on pseudoresistance, drug adherence, and the use of ambulatory blood pressure monitoring for the diagnosis and management of resistant hypertension.

The mzTab Data Exchange Format: Communicating Mass-spectrometry-based Proteomics and Metabolomics Experimental Results to a Wider Audience.

The HUPO Proteomics Standards Initiative has developed several standardized data formats to facilitate data sharing in mass spectrometry (MS)-based proteomics. These allow researchers to report their complete results in a unified way. However, at present, there is no format to describe the final qualitative and quantitative results for proteomics and metabolomics experiments in a simple tabular format. Many downstream analysis use cases are only concerned with the final results of an experiment and require an easily accessible format, compatible with tools such as Microsoft Excel or R. We developed the mzTab file format for MS-based proteomics and metabolomics results to meet this need. mzTab is intended as a lightweight supplement to the existing standard XML-based file formats (mzML, mzIdentML, mzQuantML), providing a comprehensive summary, similar in concept to the supplemental material of a scientific publication. mzTab files can contain protein, peptide, and small molecule identifications together with experimental metadata and basic quantitative information. The format is not intended to store the complete experimental evidence but provides mechanisms to report results at different levels of detail. These range from a simple summary of the final results to a representation of the results including the experimental design. This format is ideally suited to make MS-based proteomics and metabolomics results available to a wider biological community outside the field of MS. Several software tools for proteomics and metabolomics have already adapted the format as an output format. The comprehensive mzTab specification document and extensive additional documentation can be found online.

Anti-basal ganglia antibodies and Tourette's syndrome: a voxel-based morphometry and diffusion tensor imaging study in an adult population.

Anti-basal ganglia antibodies (ABGAs) have been suggested to be a hallmark of autoimmunity in Gilles de la Tourette's syndrome (GTS), possibly related to prior exposure to streptococcal infection. In order to detect whether the presence of ABGAs was associated with subtle structural changes in GTS, whole-brain analysis using independent sets of T(1) and diffusion tensor imaging MRI-based methods were performed on 22 adults with GTS with (n = 9) and without (n = 13) detectable ABGAs in the serum. Voxel-based morphometry analysis failed to detect any significant difference in grey matter density between ABGA-positive and ABGA-negative groups in caudate nuclei, putamina, thalami and frontal lobes. These results suggest that ABGA synthesis is not related to structural changes in grey and white matter (detectable with these methods) within frontostriatal circuits.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population (epublish)

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder.

Background: Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear. Methods: We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI). Results: We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls. Limitations: The major limitation of our study is the small number of patients with bipolar disorder. Conclusion: Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.

Impact and cost of a 2-week community-based screening and awareness program for diabetes and cardiovascular risk factors in a Swiss canton.

BACKGROUND: Community-based diabetes screening programs can help sensitize the population and identify new cases. However, the impact of such programs is rarely assessed in high-income countries, where concurrent health information and screening opportunities are common place. INTERVENTION AND METHODS: A 2-week screening and awareness campaign was organized as part of a new diabetes program in the canton of Vaud (population of 697,000) in Switzerland. Screening was performed without appointment in 190 out of 244 pharmacies in the canton at the subsidized cost of 10 Swiss Francs per participant. Screening included questions on risk behaviors, measurement of body mass index, blood pressure, blood cholesterol, random blood glucose (RBG), and A1c if RBG was >/=7.0 mmol/L. A mass media campaign promoting physical activity and a healthy diet was channeled through several media, eg, 165 spots on radio, billboards in 250 public places, flyers in 360 public transport vehicles, and a dozen articles in several newspapers. A telephone survey in a representative sample of the population of the canton was performed after the campaign to evaluate the program. RESULTS: A total of 4222 participants (0.76% of all persons aged >/=18 years) underwent the screening program (median age: 53 years, 63% females). Among participants not treated for diabetes, 3.7% had RBG >/= 7.8 mmol/L and 1.8% had both RBG >/= 7.0 mmol/L and A1c >/= 6.5. Untreated blood pressure >/=140/90 mmHg and/or untreated cholesterol >/=5.2 mmol/L were found in 50.5% of participants. One or several treated or untreated modifiable risk factors were found in 78% of participants. The telephone survey showed that 53% of all adults in the canton were sensitized by the campaign. Excluding fees paid by the participants, the program incurred a cost of CHF 330,600. CONCLUSION: A community-based screening program had low efficiency for detecting new cases of diabetes, but it identified large numbers of persons with elevated other cardiovascular risk factors. Our findings suggest the convenience of A1c for mass screening of diabetes, the usefulness of extending diabetes screening to other cardiovascular risk factors, and the importance of a robust background communication campaign.

Model-based Segmentation and Fusion of 3D Computed Tomography and 3D Ultrasound of the Eye for Radiotherapy Planning

Computed Tomography (CT) represents the standard imaging modality for tumor volume delineation for radiotherapy treatment planning of retinoblastoma despite some inherent limitations. CT scan is very useful in providing information on physical density for dose calculation and morphological volumetric information but presents a low sensitivity in assessing the tumor viability. On the other hand, 3D ultrasound (US) allows a highly accurate definition of the tumor volume thanks to its high spatial resolution but it is not currently integrated in the treatment planning but used only for diagnosis and follow-up. Our ultimate goal is an automatic segmentation of gross tumor volume (GTV) in the 3D US, the segmentation of the organs at risk (OAR) in the CT and the registration of both modalities. In this paper, we present some preliminary results in this direction. We present 3D active contour-based segmentation of the eye ball and the lens in CT images; the presented approach incorporates the prior knowledge of the anatomy by using a 3D geometrical eye model. The automated segmentation results are validated by comparing with manual segmentations. Then, we present two approaches for the fusion of 3D CT and US images: (i) landmark-based transformation, and (ii) object-based transformation that makes use of eye ball contour information on CT and US images.

Investigations on hydrogen isotope ratios of endogenous urinary steroids: reference-population-based thresholds and proof-of-concept.

Carbon isotope ratio (CIR) analysis has been routinely and successfully used in sports drug testing for many years to uncover the misuse of endogenous steroids. One limitation of the method is the availability of steroid preparations exhibiting CIRs equal to endogenous steroids. To overcome this problem, hydrogen isotope ratios (HIR) of endogenous urinary steroids were investigated as a potential complement; results obtained from a reference population of 67 individuals are presented herein. An established sample preparation method was modified and improved to enable separate measurements of each analyte of interest where possible. From the fraction of glucuronidated steroids; pregnanediol, 16-androstenol, 11-ketoetiocholanolone, androsterone (A), etiocholanolone (E), dehydroepiandrosterone (D), 5α- and 5β-androstanediol, testosterone and epitestosterone were included. In addition, sulfate conjugates of A, E, D, epiandrosterone and 17α- and 17β-androstenediol were considered and analyzed after acidic solvolysis. The obtained results enabled the calculation of the first reference-population-based thresholds for HIR of urinary steroids that can readily be applied to routine doping control samples. Proof-of-concept was accomplished by investigating urine specimens collected after a single oral application of testosterone-undecanoate. The HIR of most testosterone metabolites were found to be significantly influenced by the exogenous steroid beyond the established threshold values. Additionally, one regular doping control sample with an extraordinary testosterone/epitestosterone ratio of 100 without suspicious CIR was subjected to the complementary methodology of HIR analysis. The HIR data eventually provided evidence for the exogenous origin of urinary testosterone metabolites. Despite further investigations on HIR being advisable to corroborate the presented reference-population-based thresholds, the developed method proved to be a new tool supporting modern sports drug testing procedures.