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Atrial fibrillation (AF) is common in the elderly. The treatment of this condition is based on anticoagulation to prevent stroke and systemic arterial embolism. Vitamin K antagonists (VKAs) have long been the only anticoagulants available for the management of AF. Administration is complex and is one of the main causes of iatrogenic disease in the elderly. In the past 10 years, direct-acting oral anticoagulants (DOACs) have emerged, and large randomised trials (RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) have demonstrated their superiority over VKAs in the management of AF. These trials were conducted on large numbers of patients (n=71,683), including 27,500 patients aged ≥75 years and nearly 8,000 subjects aged >80 years. Results from 11 recent meta-analyses of randomised trials and observational real-world studies of 660,896 elderly patients indicate that DOACs are more effective than VKA-based prophylaxis in preventing stroke (with a reduction in risk ranging from 13% to 26%), and carry a lower risk of cerebral haemorrhaging (50% reduction in risk). The risk of major haemorrhaging appears to be similar to, or lower than that with DOACs relative to VKAs (depending on the dosage, renal function, haemorrhagic site or type of DOAC). Moreover, improved outcomes with DOACs over VKA therapy have been demonstrated based on subgroup analyses in subjects aged over 75, in patients with renal insufficiency (creatinine clearance: 30-50 mL/min) and in those with a history of falls. Analyses indicate that DOACs are a better choice than VKAs in the elderly because elderly patients are at greatest risk of stroke and cerebral haemorrhaging. In summary, DOACs have a better efficacy/tolerance profile than VKAs, which justifies their first-line use in subjects over 75 years of age.

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥8 days/month) asthma-like symptoms or recurrent (≥2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified.L’asthme fait souvent son apparition avant l’âge de six ans. Cependant, il subsiste des incertitudes relativement à quand et comment un enfant d’âge préscolaire ayant des symptômes de type asthmatique peut être diagnostiqué avec cette condition. Ceci retarde le traitement et contribue à la morbidité à court et à long terme. L’Assemblée clinique sur l’asthme de la Société canadienne de thoracologie s’est associée à la Société canadienne de pédiatrie pour créer un groupe de travail conjoint afin de préparer un document de principes sur le diagnostic et la prise en charge de l’asthme chez les enfants d’âge préscolaire. En l’absence de mesures de la fonction pulmonaire, le diagnostic d’asthme devrait être envisagé chez les enfants de un à cinq ans ayant des symptômes de type asthmatique fréquents (≥8 jours/mois) ou des exacerbations récurrentes (≥2) (épisodes accompagnés de signes compatibles). Le diagnostic nécessite une documentation objective des signes cliniques ou un compte rendu parental convaincant de symptômes d’obstruction des voies respiratoires et de réversibilité de l’ obstruction (amélioration suite à un traitement pour l’asthme), ainsi que l’absence de suspicion clinique de tout autre diagnostic. La respiration sifflante, souvent accompagnée de difficultés respiratoires et de toux, est le signe cardinal de l’obstruction des voies respiratoires. La réversibilité à la suite de la prise de médicaments pour l’asthme se définie par l’observation directe par un professionnel de la santé compétent, d’une amélioration après l’administration de ß

Frailty in the older population is a clinical syndrome which evaluate a risk level. The Frailty syndrome defines a reduction of the adaptation capacity to a stress. It can be modulated by physical, psychological and social factors. The screening of the frailty syndrome is relevant for older people without disability for basic activities of daily living. The clinical criteria of frailty must be predictive of the risk of functional decline and adverse outcomes, consensual at the international level, and easy to perform in primary care as well as in the clinical researches.

Biochemical diagnosis of hereditary metabolic diseases requires the detection and simultaneous identification of a large number of compounds, hence the interest in metabolic profiles. Acylcarnitine profile allows the identification and quantification of more than thirty compounds. As part of the accreditation process for medical biology examinations according to standard NF EN ISO 15189, the group from SFEIM recommends an approach to accredit acylcarnitine profile. Validation parameters and recommendations are discussed in this specific framework.

BACKGROUND & AIMS: This position paper summarizes theoretical and practical aspects of the monitoring of artificial nutrition and metabolism in critically ill patients, thereby completing ESPEN guidelines on intensive care unit (ICU) nutrition. METHODS: Available literature and personal clinical experience on monitoring of nutrition and metabolism was systematically reviewed by the ESPEN group for ICU nutrition guidelines. RESULTS: We did not identify any studies comparing outcomes with monitoring versus not monitoring nutrition therapy. The potential for abnormal values to be associated with harm was clearly recognized. The necessity to create locally adapted standard operating procedures (SOPs) for follow up of enteral and parenteral nutrition is emphasised. Clinical observations, laboratory parameters (including blood glucose, electrolytes, triglycerides, liver tests), and monitoring of energy expenditure and body composition are addressed, focusing on prevention, and early detection of nutrition-related complications. CONCLUSION: Understanding and defining risks and developing local SOPs are critical to reduce specific risks. ispartof: CLINICAL NUTRITION vol:38 issue:2 pages:584-593 ispartof: location:England status: published

Glucose-regulated protein 78 (GRP78) is a chaperone protein that has a high frequency in tumor cells. Normally it is found in the endoplasmic reticulum to assist in protein folding, but under cellular stress, GRP78 influences proliferative signaling pathways at the cell surface. The increased expression elicits autoantibody production, providing a biomarker of ovarian cancer, as well as other types of cancer. This study aims to determine the epitope recognition of GRP78 autoantibodies isolated from serum of ovarian cancer patients and use the identified antibodies to design new drug delivery systems to specifically target cancer cells. We first confirmed that the membrane GRP78 levels are increased in ovarian cancer cells and positively correlate with proliferation. However, the level of circulating GRP78 autoantibodies did not correlate with membrane GRP78 expression in ovarian cancer cells and was lower, although not significantly, compared to control patients. We then determined the epitope recognition of GRP78 autoantibodies and showed that treatment with paclitaxel-loaded nanoparticles coated with anti-GRP78 antibodies significantly decreased tumor development in chick embryo culture of ovarian cancer cell tumors compared to paclitaxel treatment alone. This evidence suggests that nanoparticle drug delivery systems coupled with antibodies against GRP78 has potential as a powerful therapy against ovarian cancer.

Background: Web-based surveys have become a new and popular method for collecting data, but only a few studies have directly compared postal and Web-based surveys among physicians, and none to our knowledge among general practitioners (GPs). Objective: Our aim is to compare two modes of survey delivery (postal and Web-based) in terms of participation rates, response times, and completeness of questionnaires in a study assessing GPs’ preventive practices. Methods: This randomized study was conducted in Western Switzerland (Geneva and Vaud) and in France (Alsace and Pays de la Loire) in 2015. A random selection of community-based GPs (1000 GPs in Switzerland and 2400 GPs in France) were randomly allocated to receive a questionnaire about preventive care activities either by post (n=700 in Switzerland, n=400 in France) or by email (n=300 in Switzerland, n=2000 in France). Reminder messages were sent once in the postal group and twice in the Web-based group. Any GPs practicing only complementary and alternative medicine were excluded from the study. Results: Among the 3400 contacted GPs, 764 (22.47%, 95% CI 21.07%-23.87%) returned the questionnaire. Compared to the postal group, the participation rate in the Web-based group was more than four times lower (246/2300, 10.70% vs 518/1100, 47.09%, P

Cutaneous neurofibromas are benign dermal tumors composed of spindle cells in a myxoid stroma containing numerous blood vessels. Here we describe 6 cases of solitary cutaneous neurofibroma showing unusually higher density of blood vessels in the stroma when compared to that of classical neurofibromas. We propose this lesion to be a new histopathological variant of neurofibroma and name it angioneurofibroma. © 2014 S. Karger AG, Basel

Obstructive Sleep Apnea (OSA) in children, which has a multifactorial origin, can lead, if not treated, to severe medical complications, growth disturbances, behavioural changes and reduced quality of life. Nowadays, it is underdiagnosed whereas early screening, diagnosis and interdisciplinary treatment are essential. Furthermore, many families and health professionals do not often know where to go when there is suspicion of OSA for a child. Orthodontists are uniquely positioned to screen, to refer to the appropriate specialist and to treat, if needed, patients who may be at high risk for OSA. The authors describe the synergistic means to screen, diagnose and treat paediatric OSA in a collaborative and interactive approach between ENT, orthodontists, pneumo-allergologists, sleep physicians, endocrinologists, orofacial myo-functional therapists and speech therapists. These means which are clinically illustrated in this paper fit the guidelines which have been recently published as white papers by official professional specialists organisations involved in paediatric OSA treatment (AAPD, AAO, FFO, SFORL, SFRMS…). The development of multidisciplinary teams gathering specialists who are conscious about the mutual benefits of the specialties involved in paediatric OSA should contribute to optimize the child treatment care pathway and the short, mid and long term outcomes.