Towards early inclusion of children in tuberculosis drugs trials : a consensus statement

Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally eff ective, are hampered by high pill burden, long duration of treatment, coexistent toxic eff ects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.National Institute of Allergy and Infectious Diseases and National Institute of Health.Department of Health and Human Services.http://www.thelancet.com/infection2016-06-30hb201

Neonate Born to a Mother with a Diagnosis of Suspected Intra-Amniotic Infection versus COVID-19 or Both

A diagnosis of intra-amniotic infection is typically made based on clinical criteria, including maternal intrapartum fever and one or more of the following: maternal leukocytosis, purulent cervical drainage, or fetal tachycardia. The diagnosis can also be made in patients with an isolated fever of 39°C, or greater, without any other clinical risk factors present. Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been noted to have varying signs and symptoms over the course of the disease including fever, cough, fatigue, anorexia, shortness of breath, sputum production, and myalgia. In this report, we detail a case of a newborn born to a mother with a clinical diagnosis of intra-amniotic infection with maternal fever and fetal tachycardia, who was then found to be SARS-CoV-2 positive on testing. Due to the varying presentation of COVID-19, this case illustrates the low threshold needed to test mothers for SARS-CoV-2 in order to prevent horizontal transmission to neonates and to healthcare providers

Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed clinical case definitions for classification of Intrathoracic Tuberculosis Disease. Consensus from an expert panel

To access this article, click on "Additional Links"There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis

Antenatal manifestations of inborn errors of metabolism: prenatal imaging findings

International audiencePrenatal manifestations of inborn errors of metabolism (IEM) are related to severe disorders involving metabolic pathways active in the fetal period and not compensated by maternal or placental metabolism. Some prenatal imaging findings can be suggestive of such conditions-especially in cases of consanguinity and/or recurrence of symptoms-after exclusion of the most frequent nonmetabolic etiologies. Most of these prenatal imaging findings are nonspecific. They include mainly ascites and hydrops fetalis, intrauterine growth restriction (IUGR), central nervous system (CNS) anomalies, echogenic kidneys, epiphyseal stippling, craniosynostosis, and a wide spectrum of dysostoses. These anomalies can be isolated, but in most cases, an IEM is suggested by an association of features. It must be stressed that the diagnosis of an IEM in the prenatal period is based on a close collaboration between specialists in fetal imaging, medicine, genetics, biology, and pathology

Proceedings of the fourth Resilience Engineering Symposium

These proceedings document the various presentations at the Fourth Resilience Engineering Symposium held on June 8-10, 2011, in Sophia-Antipolis, France. The Symposium gathered participants from five continents and provided them with a forum to exchange experiences and problems, and to learn about Resilience Engineering from the latest scientific achievements to recent practical applications. The First Resilience Engineering Symposium was held in Söderköping, Sweden, on October 25-29 2004. The Second Resilience Engineering Symposium was held in Juan-les-Pins, France, on November 8-10 2006, The Third Resilience Engineering Symposium was held in Juan-les-Pins, France, on October 28-30 2008. Since the first Symposium, resilience engineering has fast become recognised as a valuable complement to the established approaches to safety. Both industry and academia have recognised that resilience engineering offers valuable conceptual and practical basis that can be used to attack the problems of interconnectedness and intractability of complex socio-technical systems. The concepts and principles of resilience engineering have been tested and refined by applications in such fields as air traffic management, offshore production, patient safety, and commercial fishing. Continued work has also made it clear that resilience is neither limited to handling threats and disturbances, nor confined to situations where something can go wrong. Today, resilience is understood as the intrinsic ability of a system to adjust its functioning prior to, during, or following changes and disturbances, so that it can sustain required operations under both expected and unexpected conditions. This definition emphasizes the ability to continue functioning, rather than simply to react and recover from disturbances and the ability to deal with diverse conditions of functioning, expected as well as unexpected. For anyone who is interested in learning more about Resilience Engineering, the books published in the Ashgate Studies in Resilience Engineering provide an excellent starting point. Another sign that Resilience Engineering is coming of age is the establishment of the Resilience Engineering Association. The goal of this association is to provide a forum for coordination and exchange of experiences, by bringing together researchers and professionals working in the Resilience Engineering domain and organisations applying or willing to apply Resilience Engineering principles in their operations. The Resilience Engineering Association held its first General Assembly during the Fourth Symposium, and will in the future play an active role in the organisation of symposia and other activities related to Resilience Engineering