Clinical Trials in Paediatrics — Regulatory and Methodological Aspects

The photoautotrophic cyanobacterium Synechocystis PCC6803 has received much attention as a model photosynthetic cell factory for the production of a range of important biotech products. The biomass remaining from this activity may then have further utility in processes such as metal bioremediation. In addition Synechocystis being an inhabitant of many natural aquatic environments is seen as an environmentally friendly alternative to using chemical precipitation methodologies for metal remediation. Synechocystis produces a range of extracellular polysaccharide substances (EPS) that can undergo modification as a function of culture age and growth nutrients which have been implicated in metal biosorption. Many studies have demonstrated that high levels of charged groups present in EPS are important in forming polymeric matrices with metallic ions allowing their biosorption. Genetic studies has revealed genes involved in such metal binding indicating that EPS can be modified for potential enhancement of binding or modification of the types of metals bound. The utility of metal binding to live and dead biomass of Synechocystis has been demonstrated for a range of metals including Cr(VI), Cd(II), Cu(II), Pb(II), Sb, Ni(II), Mn(II), Mn(IV), As(III), As(V), Cs and Hg. The potential of using Synechocystis as a biosorption platform is discussed

Medical Device Development for Children and Young People—Reviewing the Challenges and Opportunities

Development of specific medical devices (MDs) is required to meet the healthcare needs of children and young people (CYP). In this context, MD development should address changes in growth and psychosocial maturation, physiology, and pathophysiology, and avoid inappropriate repurposing of adult technologies. Underpinning the development of MD for CYP is the need to ensure MD safety and effectiveness through pediatric MD-specific regulations. Contrary to current perceptions of limited market potential, the global pediatric healthcare market is expected to generate around USD 15,984 million by 2025. There are 1.8 billion young people in the world today; 40% of the global population is under 24, creating significant future healthcare market opportunities. This review highlights a number of technology areas that have led to successful pediatric MD, including 3D printing, advanced materials, drug delivery, and diagnostic imaging. To ensure the targeted development of MD for CYP, collaboration across multiple professional disciplines is required, facilitated by a platform to foster collaboration and drive innovation. The European Pediatric Translational Research Infrastructure (EPTRI) will be established as the European platform to support collaboration, including the life sciences industrial sector, to identify unmet needs in child health and support the development, adoption, and commercialization of pediatric MDs

Chapter Clinical Trials in Paediatrics — Regulatory and Methodological Aspects

The photoautotrophic cyanobacterium Synechocystis PCC6803 has received much attention as a model photosynthetic cell factory for the production of a range of important biotech products. The biomass remaining from this activity may then have further utility in processes such as metal bioremediation. In addition Synechocystis being an inhabitant of many natural aquatic environments is seen as an environmentally friendly alternative to using chemical precipitation methodologies for metal remediation. Synechocystis produces a range of extracellular polysaccharide substances (EPS) that can undergo modification as a function of culture age and growth nutrients which have been implicated in metal biosorption. Many studies have demonstrated that high levels of charged groups present in EPS are important in forming polymeric matrices with metallic ions allowing their biosorption. Genetic studies has revealed genes involved in such metal binding indicating that EPS can be modified for potential enhancement of binding or modification of the types of metals bound. The utility of metal binding to live and dead biomass of Synechocystis has been demonstrated for a range of metals including Cr(VI), Cd(II), Cu(II), Pb(II), Sb, Ni(II), Mn(II), Mn(IV), As(III), As(V), Cs and Hg. The potential of using Synechocystis as a biosorption platform is discussed

Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen

Abstract Background In the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products. We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children. Results In the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US. No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children. If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered. Conclusions Our data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases

Paediatric Medicines in Europe: The Paediatric Regulation-Is It Time for Reform?

Contains fulltext : 230819.pdf (publisher's version ) (Open Access

Multidisciplinary care in haemoglobinopathies

While most complications are related to haemoglobinopathies and their treatment, it is also possible to observe substantial differences in comorbidities’ onset and seriousness which depend also to the different HPs genotypes. These differences should be carefully considered when health authorities set up and manage adequate care systems and treatments plans. We describe services organisation in Italy including the availability of multispecialty care and tools, in the HPs units participating to the HTA-THAL Multiregional Registry, with the aim to derive the impact of the services and multispecialty care availability on the management of the disease and on the patients wellbeing. The high dispersion and heterogeneity of services demonstrated, exposes the Italian system to a high risk of: a) inappropriate use of economical and medical resources, b) limited access to multidisciplinary care of some patients with apparent inequality among different centres, and c) low patients satisfaction with the services provided. The identification of a ‘standard for HPs services’ is necessary not only at national but also at interventional level in order to implement collaborative research and the identification and networking of reference’ centres worldwide. Following the big efforts provided in the last years here there is a new challenging mission for the TIF

Glucocorticoid receptor mRNA expression in peripheral blood mononuclear cells in high trained compared to low trained athletes and untrained subjects.

8Background: Physiological needs during prolonged exercise are a potent stimulus for the hypothalamic-pituitaryadrenal (HPA) axis. Hence, athletes undergoing daily endurance training sessions may have frequent and prolonged phases of endogenous hypercortisolism. Since chronic glucocorticoids treatment leads to down-regulation of glucocorticoid receptor α (GR-α) mRNA expression, endurance training could lead to modulation of GR expression. Aim: The aim of the study was to evaluate GR-α and GR-β mRNA expressions in peripheral blood mononuclear cells and plasma cortisol, ACTH and cortisol binding globulin (CBG) concentrations at rest in subjects undergoing different training regimes. Subjects and methods: Nine high trained (HT) swimmers (training volume: 21.6±1.7 hours/week in 10-12 sessions) were compared with two age-matched control groups represented by 8 low trained (LT) runners (training volume: 6.4±2.6 h/week in 3-5 sessions) and 9 untrained subjects. Expression of GR was determined by RT-PCR of total RNA. Hormone levels were determined by radioimmunoassay methods. Results: HT athletes showed 10 times less GR-α mRNA expression than the untrained subjects, while LT athletes exhibited values about twofold less than the untrained subjects. GR-β mRNA expression was undetectable in all subjects. No differences were observed among the three groups in hormone levels. Conclusions: GR- α mRNA expression is repressed in proportion to the amount and frequency of the stressful stimuli due to training. Hence, this down-regulation may be a consequence of the frequent and prolonged exposure to cortisol acute elevations induced by training. GR-β did not play an important role in inducing the down-regulation of GR-α mRNA expression observed.nonenoneBONIFAZI M; MENCARELLI M; FEDELE V; CECCARELLI I; PECORELLI A; GRASSO G; ALOISI AM; MUSCETTOLA MBonifazi, Marco; Mencarelli, M; Fedele, V; Ceccarelli, I; Pecorelli, A; Grasso, Giovanni; Aloisi, ANNA MARIA; Muscettola, MARIA MICHEL

Survey by TEDDY European Network of Excellence for Paediatric Clinical Research demonstrates potential for Europe‐wide trials

Aim: The European Network of Excellence for Paediatric Clinical Research, known as the TEDDY Network, carried out a survey to determine the capacity and competence of paediatric centres to perform research studies. Methods: A cross-sectional, web-based pilot survey was conducted from October 2016 to April 2017 with paediatric clinical research centres in 11 countries: Albania, Austria, Belgium, Denmark, Iceland, Ireland, Italy, Norway, Spain, Switzerland and the United Kingdom. All were registered with the TEDDY Network database. Results: We approached 107 centres and 63 provided data on their experiences and expertise in paediatric clinical trials. Four groups of performance indicators were identified, referring to scientific experience, trial readiness, trial competence, regulatory issues, ethics and patients. Most centres were actively involved in paediatric clinical research: 53 centres (84.1%) had received funds for more than five paediatric studies in the last 5 years, and 42 (66.7%) had a specific clinical trial unit and dedicated study coordinators. We concluded that the European centres we studied had the capability and capacity to conduct paediatric trials, but there was still room for improvement, including enhanced collaboration. Conclusion: This pilot survey demonstrated that there is potential for performing paediatric trials across Europe, but improvements are possible