Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis

Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including <100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations

Enhanced Tissue Integration During Cartilage RepairIn VitroCan Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge

Objective: Experimental wounding of articular cartilage results in cell death at the lesion edge. The objective of this study was to investigate whether inhibition of this cell death results in enhanced integrative cartilage repair. Methods: Bovine articular cartilage discs (6mm) were incubated in media containing inhibitors of necrosis (Necrostatin-1, Nec-1) or apoptosis (Z-VAD-FMK, ZVF) before cutting a 3mm inner core. This core was left in situ to create disc/ring composites, cultured for up to 6 weeks with the inhibitors, and analyzed for cell death, sulfated glycosaminoglycan release, and tissue integration. Results: Creating the disc/ring composites resulted in a significant increase in necrosis. ZVF significantly reduced necrosis and apoptosis at the wound edge. Nec-1 reduced necrosis. Both inhibitors reduced the level of wound-induced sulfated glycosaminoglycan loss. Toluidine blue staining and electron microscopy of cartilage revealed significant integration of the wound edges in disc/ring composites treated with ZVF. Nec-1 improved integration, but to a lesser extent. Push-out testing revealed that ZVF increased adhesive strength compared to control composites. Conclusions: This study shows that treatment of articular cartilage with cell death inhibitors during wound repair increases the number of viable cells at the wound edge, prevents matrix loss, and results in a significant improvement in cartilage-cartilage integration

Non-tariff measures affecting agro-food trade between the EU and Africa Summary of a workshop

This report contains the presentations and the summary of the IPTS workshop "Non Tariff Measures (NTMs) affecting agro-food trade between the EU and Africa" held in September 2010 in Seville. The workshop brought together experts from research, policy making and business in order to exchange knowledge and discuss about NTMs and the issues associated with them. The workshop first gave an overview of NTM classifications as well as the methods in the analysis of NTMs. With this background case studies were presented, focusing on NTMs from the perspective of African exporters of agro-food products.JRC.DDG.J.5-Agriculture and Life Sciences in the Econom

Catalogue des habitats forestiers de Guyane

Grâce à de nombreux efforts de prospections et d'inventaires naturalistes, la biodiversité guyanaise est de mieux en mieux connue et les listes d'espèces nouvelles ne cessent de s'allonger années après années. Cependant l'écosystème forestier ne se résume pas à une juxtaposition d'individus et d'espèces : de complexes relations interspécifiques régissent le fonctionnement des communautés qui sont elles-mêmes influencées par les conditions environnementales. dans lesquelles elles se développent. Gérer et conserver la biodiversité guyanaise implique de mieux cerner ces interactions entre faune, flore et environnement ; interactions qui façonnent toute une diversité d'habitats forestiers avec des dynamiques propres et des compositions originales. Plusieurs programmes de recherche se sont attelés à démêler cet écheveau écologique en se concentrant tout d'abord sur quelques plateformes scientifiques (Paracou, Nouragues, Piste de Saint-Elie) puis en élargissant la focale à l'ensemble de notre territoire sous l'impulsion des gestionnaires publics et des associations naturalistes guyanaises (programmes de recherche DIME, ECOTROP, HABITATS, etc.). Ce catalogue des habitats forestiers présente une synthèse de ces résultats sous la forme de fiches descriptives dressant un portrait précis des différents habitats naturels rencontrés en forêt guyanaise et des mécanismes qui les ont peu à peu façonnés. Un travail collectif important a été accompli pour fournir des éléments précis concernant les cortèges de grande faune, les peuplements d'arbres qui les abritent et la qualité des sols qui les supportent

PDMS COATED UV SENSOR FOR CONTINUOUS MONITORING OF BTEX IN GROUNDWATER

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