Intensive care unit admission in chronic obstructive pulmonary disease: patient information and the physician’s decision-making process

International audienceIntroduction: ICU admission is required in more than 25% of patients with chronic obstructive pulmonary disease (COPD) at some time during the course of the disease. However, only limited information is available on how physicians communicate with COPD patients about ICU admission. Methods: COPD patients and relatives from 19 French ICUs were interviewed at ICU discharge about their knowledge of COPD. French pulmonologists self-reported their practices for informing and discussing intensive care treatment preferences with COPD patients. Finally, pulmonologists and ICU physicians reported barriers and facilitators for transfer of COPD patients to the ICU and to propose invasive mechanical ventilation. Results: Self-report questionnaires were filled in by 126 COPD patients and 102 relatives, and 173 pulmonologists and 135 ICU physicians were interviewed. For 41% (n = 39) of patients and 54% (n = 51) of relatives, ICU admission had never been expected prior to admission. One half of patients were not routinely informed by their pulmonologist about possible ICU admission at some time during the course of COPD. Moreover, treatment options (that is, non-invasive ventilation, intubation and mechanical ventilation or tracheotomy) were not explained to COPD patients during regular pulmonologist visits. Pulmonologists and ICU physician have different perceptions of the decision-making process pertaining to ICU admission and intubation. Conclusions: The information provided by pulmonologists to patients and families concerning the prognosis of COPD, the risks of ICU admission and specific care could be improved in order to deliver ICU care in accordance with the patient's personal values and preferences. Given the discrepancies in the decision-making process between pulmonologists and intensivists, a more collaborative approach should probably be discussed

Soluble Isoforms of Vascular Endothelial Growth Factor Are Predictors of Response to Sunitinib in Metastatic Renal Cell Carcinomas

Angiogenesis is the target of several agents in the treatment of malignancies, including renal cell carcinoma (RCC). There is a real need for surrogate biomarkers that can predict selection of patients who may benefit from antiangiogenic therapies, prediction of disease outcome and which may improve the knowledge regarding mechanism of action of these treatments. Tyrosine kinase inhibitors (TKI) have proven efficacy in metastatic RCC (mRCC). However, the molecular mechanisms underlying the clinical response to these drugs remain unclear.The present study aimed to identify molecular biomarkers associated with the response to sunitinib, a Tyrosine kinase inhibitor. To evaluate this relationship, primary tumors from 23 metastatic RCC patients treated by sunitinib were analyzed for a panel of 16 biomarkers involved in tumor pathways targeted by sunitinib, using real-time quantitative reverse-transcriptase PCR. Nine of the 23 patients (39%) responded to sunitinib. Among transcripts analyzed, only the levels of vascular endothelial growth factor (VEGF) soluble isoforms (VEGF(121) and VEGF(165)) were associated with the response to sunitinib (P = 0.04 for both). Furthermore, the ratio of VEGF soluble isoforms (VEGF(121)/VEGF(165)) was significantly associated with prognosis (P = 0.02).This preliminary study provides a promising tool that might help in the management of metastatic RCC, and could be extended to other tumors treated by TKI

Modelisation des données logitudinales complexes en épidémiologie

L'étude de l'évolution et de la valeur pronostique des marqueurs longitudinaux est très fréquente en médecine. Ce travail s'est centré sur la modélisation de données longitudinales en présence de données manquantes ou censure informative à droite. Notre objectif premier a été d'évaluer si un marqueur mesuré de façon répétée au cours du temps pouvait être utilisé comme critère de substitution lors de l'évaluation de l'efficacité d'un nouveau traitement dans le cadre d'un essai thérapeutique. Le premier développement a été de comparer deux stratégies de modélisation pour ces données longitudinales et de survie : un modèle multi-état décrivant les trajectoires des malades entre différents compartiments définis par la valeur du marqueur et la censure informative, et un modèle conjoint du processus longitudinal et du délai de censure informative. Puis, nous avons modélisé l'évolution d'un marqueur en présence de censure informative. Nous proposons une modélisation conjointe des données longitudinales et des données de survie multivariée, lorsque le sous-modèle de survie est un modèle paramétrique pour les fonctions de risque de sous-répartition des événements en compétition. Nous nous sommes alors placés dans un contexte d'inférence bayesienne. Chaque développement a fait l'objet d'une application en épidémiologie clinique, que ce soit dans l'étude de la lymphocytose comme critère de substitution de l'efficacité d'un traitement dans la leucémie, ou dans l'évaluation du bénéfice du remplissage vasculaire chez des malades de réanimation sur un score de gravité mesuré pendant leur séjourPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Natural history of allergic sensitization in infants with early-onset atopic 1 dermatitis: results from ORCA Study

International audienceBACKGROUND: Early-onset atopic dermatitis (AD) is a particular phenotype that may convey a risk of developing multiple sensitizations to allergens but little is known about the pathway of sensitization. The aims of this study were to describe the natural history of sensitization to allergens for this phenotype and to identify the most predictive marker associated with the risk of developing sensitization to inhaled allergens in a well-selected cohort of infants with AD.METHODS: Infants with active AD were enrolled and prospectively explored for biological markers of atopy every year until the age of 6 yr. Allergic sensitization was defined as the presence of positive specific IgEs to allergens and multiple sensitizations as being sensitized to ≥2 allergens. Elevated blood eosinophilia was defined as an eosinophil blood count ≥470 eosinophils/mm3 and elevated total IgE as a serum IgE level ≥45 kU/l.RESULTS: Two hundred and twenty-nine infants were included. Elevated blood eosinophilia was observed at baseline in 60 children (26.2%) and elevated total IgE in 85 (37.1%). When elevated at baseline, eosinophilia and IgE levels remained significantly higher during the follow-up period. Sensitization to food allergens decreased from 58% to 34%, whereas sensitization to inhaled allergens increased over time from 17% to 67%. Initial multiple sensitizations to food allergens were the most predictive factor for the risk of developing sensitization to inhaled allergens at 6 yr (OR 3.72 [1.68-8.30] p < 0.001).CONCLUSIONS: In the early-onset AD phenotype, multiple sensitization to food allergens conveys a higher risk of sensitization to inhaled allergens than single sensitization

The xopJ6 gene encodes a PopP2-like acetyl transferase from Xanthomonas campestris pv. campestris recognized by RRS1/RPS4 R genes in Arabidopsis

International audienc

Early-Onset Atopic Dermatitis in Children: Which Are the Phenotypes at Risk of Asthma? Results from the ORCA Cohort

<div><p>Background</p><p>Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma.</p><p>Methods</p><p>We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6.</p><p>Results</p><p>We identified 3 clusters - <b>cluster 1</b> (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - <b>cluster 2</b> (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - <b>cluster 3</b> (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01).</p><p>Conclusion</p><p>Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.</p></div

Evaluation of the Effects of Pasireotide LAR Administration on Lymphocele Prevention after Axillary Node Dissection for Breast Cancer: Results of a Randomized Non-Comparative Phase 2 Study

International audienceObjectiveThe aim of this study was to assess the efficacy (response rate centered on 80%) of a somatostatin analog with high affinity for 4 somatostatin receptors in reducing the postoperative incidence of symptomatic lymphocele formation following total mastectomy with axillary lymph node dissection.SettingThis prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres.ParticipantsAll female patients for whom mastectomy and axillary lymph node dissection were indicated were eligible for the study, including patients who had received neo-adjuvant chemotherapy. Main exclusion criteria were related to diabetes, cardiac insufficiency, disorder of cardiac conduction or hepatic failure.InterventionsPatients were randomised to receive one injection of either prolonged-release pasireotide 60 mg or placebo (physiological serum), which were administered intramuscularly 7 to 10 days before the scheduled surgery. The study was conducted in a double-blind manner.Primary and Secondary Outcome MeasuresThe primary outcome measure was the percentage of patients who did not develop post-operative axillary symptomatic lymphoceles during the 2 postoperative months. Secondary endpoints were the total quantity of lymph drained, duration and daily volume of drainage and aspirated volumes of lymph.ResultsNinety-one patients were randomised. Ninety patients were evaluable: 42 patients received pasireotide, and 48 patients received placebo. The mean estimated response rate were 62.4% (95% Credibility Interval [CrI]: 48.6%-75.3%) in the treatment group and 50.2% (95% CrI: 37.6%-62.8%) in the placebo group. Overall safety was comparable across groups, and one serious adverse event occurred. In the treatment group, one patient with known insulin-depe*ndent diabetes required hospitalization for hyperglycaemia.ConclusionsWith this phase 2 preliminary study, even if our results indicate a trend towards a reduction in symptomatic lymphocele, pre-operative injection of pasireotide failed to achieve a response rate centered on 80%. Pharmacokinetics analysis suggests that effect of pasireotide could be optimised

Clinical parameters at inclusion in the entire cohort and according to cluster analysis.

<p>All values for categorial or qualitative variables given as percentages. Boldfaced text indicates statistical significance.</p><p>¹AD = atopic dermatitis</p><p>²LS = low sensitization</p><p>³MS = multiple sensitizations</p><p>⁴FHA = familial history of asthma.</p><p>⁵SD = standard deviation</p><p>⁶Analysis of variance and Chi-2 test when conditions allowed, Kruskal-Wallis and Fischer's exact test otherwise.</p><p>Clinical parameters at inclusion in the entire cohort and according to cluster analysis.</p

Biological parameters at inclusion in the entire cohort and according to cluster analysis.

<p>All values for categorial or qualitative variables given as percentages. Boldfaced text indicates statistical significance.</p><p>¹AD = atopic dermatitis</p><p>²LS = low sensitization</p><p>³MS = multiple sensitizations</p><p>⁴FHA = familial history of asthma.</p><p>⁵SD = standard deviation</p><p>⁶Analysis of variance and Chi-2 test when conditions allowed, Kruskal-Wallis and Fischer's exact test otherwise.Boldfaced text indicates statistical significance.</p><p>Biological parameters at inclusion in the entire cohort and according to cluster analysis.</p

Parameters at the end of the follow-up (6 years).

<p>All values given as percentages. Boldfaced text indicates statistical significance.</p><p>¹AD = atopic dermatitis</p><p>²LS = low sensitization</p><p>³MS = multiple sensitizations</p><p>⁴FHA = familial history of asthma.</p><p>⁵Analysis of variance and Chi-2 test when conditions allowed, Kruskal-Wallis and Fischer's exact test otherwise.Boldfaced text indicates statistical significance.</p><p>Parameters at the end of the follow-up (6 years).</p