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.

OBJECTIVE: The 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. SETTING: This prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres. PARTICIPANTS: All 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. INTERVENTIONS: Patients 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 MEASURES: The 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. RESULTS: Ninety-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. CONCLUSIONS: With 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01356862.

Differential Perceptions of Noninvasive Ventilation in Intensive Care among Medical Caregivers, Patients, and Their Relatives: A Multicenter Prospective Study-The PARVENIR Study.

BACKGROUND: Noninvasive ventilation (NIV) requires a close "partnership" between a conscious patient and the patient's caregivers. Specific perceptions of NIV stakeholders and their impact have been poorly described to date. The objectives of this study were to compare the perceptions of NIV by intensive care unit (ICU) physicians, nurses, patients, and their relatives and to explore factors associated with caregivers' willingness to administer NIV and patients' and relatives' anxiety in relation to NIV. METHODS: This is a prospective, multicenter questionnaire-based study. RESULTS: Three hundred and eleven ICU physicians, 752 nurses, 396 patients, and 145 relatives from 32 ICUs answered the questionnaire. Nurses generally reported more negative feelings and more frequent regrets about providing NIV (median score, 3; interquartile range, [1 to 5] vs. 1 [1 to 5]; P < 0.0001) compared to ICU physicians. Sixty-four percent of ICU physicians and only 32% of nurses reported a high level of willingness to administer NIV, which was independently associated with NIV case-volume and workload. A high NIV session-related level of anxiety was observed in 37% of patients and 45% of relatives. "Dyspnea during NIV," "long NIV session," and "the need to have someone at the bedside" were identified as independent risk factors of high anxiety in patients. CONCLUSIONS: Lack of willingness of caregivers to administer NIV and a high level of anxiety of patients and relatives in relation to NIV are frequent in the ICU. Most factors associated with low willingness to administer NIV by nurses or anxiety in patients and relatives may be amenable to change. Interventional studies are now warranted to evaluate how to reduce these risk factors and therefore contribute to better management of a potentially traumatic experience. (Anesthesiology 2016; 124:1347-59).

Early-onset atopic dermatitis in children: which are the phenotypes at risk of asthma? Results from the ORCA cohort.

BACKGROUND: 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. METHODS: 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. RESULTS: We identified 3 clusters - cluster 1 (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"; - cluster 2 (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" - cluster 3 (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). CONCLUSION: Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.