Etude pilote par PET/CT de la réponse à l'ipilimumab dans le traitement du mélanome métastatique.

0 Abstract L'incidence du mélanome est en nette augmentation en Europe et aux Etats-Unis. La Chirurgie peut être curative au stade précoce de la maladie,la radiothérapie se pratique À visée palliative, les chimiothérapies n'ont montré que peu d'effet. Les progress actuels se font via l'immunothérapie. Des traitements par l'interleukine-2 et l'interféron-α se sont montrés efficaces chez certains patients, mais leur utilisation est limitée par leur forte toxicité. Depuis 2011, en Suisse, une nouvelle molécule a été mise sur le marché, l'ipilimumab (Yervoy®). Il s'agit d'un anticorps! monoclonal humain dirigé contre le CTLA4. Il en résulte une activation non spécifique du système immunitaire. Une étude randomisée de phase IIIa été conduite au Etats-Unis. Elle démontre une augmentation de la survie chez les patients atteints de melanoma métastatique traits par ipilimumab, sans traitement préalable des métastases. Le but de cette etude est de determiner s'il est possible, par le biais de l'imagerie PET-CTau 18F-FDG, de prédire la réponse individuelle au traitement par ipilimumab, afin d'optimiser la prise en charge de ces patients. 0.1 Méthode Les patients atteints de mélanome métastatique sont exposés au traitement d'ipilimumab selon les recommandations de Bristol-Myers Squibb. Puis ils effectuent des PET-CT au F-18-FDG selon! le! protocole (CER 400/11, annexé) de l'étude. Les images sont!analysées selon les critères PERCIST (PETResponse Criterias In Solid Tumors) et le TLG (Total Lesion Glycolysis) est calculé. Parallèlement, des prises de sang sont effectuées et les échantillons sont analysés à l'institut Ludwig (LICR, Unil) selon les critères imRC qui determinant la réponse immunologique au traitement. 0.2 Résultats Nous notons une discrépance dans les résultats. Lorsque nous observons une maladie stable avec les critères immunologiques imRC, nous observons une maladie progressive avec lescritères PERCIST. 0.3 Discussion - Conclusion Nous n'avons pu faire entrer que cinq patients dans l'étude, dont trois étaient vivants à trois mois, ce qui a restreint le nombre de données analysables. Les discrépances que nous observons dans nos résultats pourraient être dues au fait que le PET-CT au 18FDG ne nous permet pas de différencier l'activité tumorale de l'activité inflammatoire péri-tumorale. Ce biais pourrait être à l'avenir prévenu en utilisant du 18FLT, un marqueur plus sélectif des cellules tumorales.L'analyse desimages avec les critères de total-lesion glycolysis a été impossible au vu du nombre de lésions que présentaient certains patients. Les critères PERCIST exigent un protocole d'acquisition très strict. La corrélation entre les images, les données immunologiques et la clinique mérite d'être suivie sur le long terme, car il pourrait y avoir une réponse positive plus tardive du traitement par ipilimumab

Understanding Trail Runners' Activity on Online Community Forums: An Inductive Analysis of Discussion Topics

Recreational trail runners often participate in online community forums where they can freely read posted messages, join discussions and/or introduce new discussion topics. This tool can enhance learning as runners connect with other trail runners and reflect on how they can better organize their own practice. Studying forum activity would provide greater insight into the relationship between field practice and dedicated forums. The aim of this study was therefore to detect the topics discussed online by trail runners in order to understand how they collectively look for solutions that help them adapt to issues that emerge during actual practice. The discussion topics (n = 171) on the forum hosted by the Raidlight brand were examined using inductive content analysis, which distinguished two general dimensions. The first dimension was training and had four first-order themes (i.e., "specific trail running sessions", "complementary trail running sessions". "training plans" and "specific questions about races") grouped into two second-order themes (i.e., "training session contents" and "structure and schedule"). The second dimension was health and had seven first-order themes (i.e., "tendinitis", "muscle issues", "foot issues", "sprains and fractures", "pain", "physiology" and "substances and practitioners") grouped into two second-order themes (i.e., "pain and injury" and "prevention"). The results indicate that the issues that trail runners discuss on forums are significant and that the successions of questions and solutions are a fruitful means for building, enriching and adjusting their activity as they cope with constraints. As a practical consequence, suggestions for improving such online platforms are made

The Relationship between Trail Running Withdrawals and Race Topography

Context: A growing amount of recent research in sport psychology has focused on trying to understand withdrawals from ultra-races. However, according to the Four E approach, the studies underestimated the embedded components of these experiences and particularly how they were linked to the specific environmental conditions in which the experiences occurred. Objective: This study aimed to characterize trail running withdrawals in relationship to race topography. Design: Qualitative design, involving self-confrontation interviews and use of a race map. Setting: Use of the race map for description of the race activity and self-confrontation interviews took place 1–3 days after the races. Participants: Ten runners who withdrew during an ultra-trail race. Data Collection and Analysis: Data on past activity traces and experiences were elicited from self-confrontation interviews. Data were coded and compared to identify common sequences and then each type of sequence was counted with regard to race topography. Results: Results showed that each sequence was related to runners’ particular possibilities for acting, feeling, and thinking, which were in turn embedded in the race topography. These sequences allowed the unfolding of the activity and increased its overall effectiveness in relation to the constraints of this specific sport. Conclusion: This study allowed us to highlight important information on how ultra-trail runners manage their races in relationship to the race environment and more specifically to its topography. The result will also help us to recommend potential adjustments to ultra-trail runners’ performance-oriented training and preparation

Heart rate variability in association with frequent use of household sprays and scented products in SAPALDIA

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown.Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction.Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, 1, 1-3, or 4-7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products.Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4-7 days/week was associated with 11% [95% confidence interval (CI): -20%, -2%] and 29% (95% CI: -46%, -8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p > 0.05 for interactions).Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptibl

Comparison of vitality states of finishers and withdrawers in trail running: An enactive and phenomenological perspective.

Studies on ultra-endurance suggest that during the races, athletes typically experience three vitality states (i.e., preservation, loss, and revival) at the phenomenological level. Nevertheless, how these states contribute to the management and outcome of performance remains unclear. The aim of this study was to determine whether and how the vitality states experienced by runners and their evolution during a trail race can be used to distinguish finishers from withdrawers. From an enactive and phenomenological framework, we processed enactive interviews and blog posts of race narratives. We distinguished units of meaning, which were grouped into sequences of experience; each sequence was then categorized as one of the three vitality states: state of vitality preservation (SVP), state of vitality loss (SVL) or state of vitality revival (SVR). We analyzed the distribution of these vitality states and their temporal organization at the beginning, in the second and third quarters, and at the end of the races, and we qualitatively characterized runners' adaptations to SVL. Results showed that finishers completed the race in SVP, with overall significantly more sequences in SVP and significantly fewer sequences in SVL than withdrawers. SVR did not discriminate finishers from withdrawers. The temporal organization of the vitality states showed a significant difference in the emergence of SVP from the second quarter of the race, as well as a significant difference in the emergence of SVL from the third quarter of the race. The analysis of adaptations to SVL confirmed that finishers were more capable of exiting SVL by enacting a preservation world when they felt physical or psychological alerts, whereas withdrawers remained in SVL. Our results showed that finishers and withdrawers did not enact the same phenomenological worlds in the race situation, especially in the organization of vitality adaptations and their relationships to difficulties; the cumulative effect of the succession of experienced vitality states differed, as well

Stabilization of the cubic phase of HfO2 by Y addition in films grown by metal organic chemical vapor deposition

Addition of yttrium in HfO2 thin films prepared on silicon by metal organic chemical vapor deposition is investigated in a wide compositional range (2.0-99.5 at. %). The cubic structure of HfO2 is stabilized for 6.5 at. %. The permittivity is maximum for yttrium content of 6.5-10 at. %; in this range, the effective permittivity, which results from the contribution of both the cubic phase and silicate phase, is of 22. These films exhibit low leakage current density (5x10(-7) A/cm(2) at -1 V for a 6.4 nm film). The cubic phase is stable upon postdeposition high temperature annealing at 900 degrees C under NH3. (c) 2006 American Institute of Physics

Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study

Background: In 2007, WHO launched a global initiative for the elimination of mother-to-child transmission of syphilis (congenital syphilis). An important aspect of the initiative is strengthening surveillance to monitor progress towards elimination. In 2008, using a health systems model with country data inputs, WHO estimated that 1·4 million maternal syphilis infections caused 520 000 adverse pregnancy outcomes. To assess progress, we updated the 2008 estimates and estimated the 2012 global prevalence and cases of maternal and congenital syphilis. Methods: We used a health systems model approved by the Child Health Epidemiology Reference Group. WHO and UN databases provided inputs on livebirths, antenatal care coverage, and syphilis testing, seropositivity, and treatment in antenatal care. For 2012 estimates, we used data collected between 2009 and 2012. We updated the 2008 estimates using data collected between 2000 and 2008, compared these with 2012 estimates using data collected between 2009 and 2012, and performed subanalyses to validate results. Findings: In 2012, an estimated 930 000 maternal syphilis infections caused 350 000 adverse pregnancy outcomes including 143 000 early fetal deaths and stillbirths, 62 000 neonatal deaths, 44 000 preterm or low weight births, and 102 000 infected infants worldwide. Nearly 80% of adverse outcomes (274 000) occurred in women who received antenatal care at least once. Comparing the updated 2008 estimates with the 2012 estimates, maternal syphilis decreased by 38% (from 1 488 394 cases in 2008 to 927 936 cases in 2012) and congenital syphilis decreased by 39% (from 576 784 to 350 915). India represented 65% of the decrease. Analysis excluding India still showed an 18% decrease in maternal and congenital cases of syphilis worldwide. Interpretation: Maternal and congenital syphilis decreased worldwide from 2008 to 2012, which suggests progress towards the elimination of mother-to-child transmission of syphilis. Nonetheless, maternal syphilis caused substantial adverse pregnancy outcomes, even in women receiving antenatal care. Improved access to quality antenatal care, including syphilis testing and treatment, and robust data are all important for achieving the elimination of mother-to child transmission of syphilis. Funding: The UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction in WHO, and the US Centers for Disease Control and Prevention

Need for timely paediatric HIV treatment within primary health care in rural South Africa

<p>Background: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting.</p> <p>Methods: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses.</p> <p>Findings: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%.</p> <p>Conclusion: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.</p&gt

Frailty and use of health and community services by community-dwelling older men: the Concord Health and Ageing in Men Project

Background: frailty is a concept used to describe older people at high risk of adverse outcomes, including falls, functional decline, hospital or nursing home admission and death. The associations between frailty and use of specific health and community services have not been investigated. Methods: the cross-sectional relationship between frailty and use of several health and community services in the last 12 months was investigated in 1,674 community-dwelling men aged 70 or older in the Concord Health and Ageing in Men study, a population-based study conducted in Sydney, Australia. Frailty was assessed using a modified version of the Cardiovascular Health Study criteria. Results: overall, 158 (9.4%) subjects were frail, 679 (40.6%) were intermediate (pre-frail) and 837 (50.0%) were robust. Frailty was associated with use of health and community services in the last 12 months, including consulting a doctor, visiting or being visited by a nurse or a physiotherapist, using help with meals or household duties and spending at least one night in a hospital or nursing home. Frail men without disability in activities of daily living were twice more likely to have seen a doctor in the previous 2 weeks than robust men (adjusted odds ratio 2.04, 95% confidence interval 1.21-3.44), independent of age, comorbidity and socio-economic status. Conclusion: frailty is strongly associated with use of health and community services in community-dwelling older men. The high level of use of medical services suggests that doctors and nurses could play a key role in implementation of preventive intervention