Cost-effectiveness of an educational intervention to reduce potentially inappropriate medication

Background Educational interventions can reduce potentially inappropriate medication (PIM) use in older people. Their effectiveness has been measured mainly as changes in PIM use. In this economic evaluation, we analyse the impact of an educational intervention in terms of costs and quality-adjusted life years (QALYs). Methods The educational intervention consisted of activating and interactive training sessions for nursing staff and consulting physicians, and was compared with treatment as usual (TAU). Participants (n = 227) in a cluster randomised trial (cRCT) were residents living permanently in assisted living facilities (n = 20 wards). For economic evaluation, participants' healthcare service use costs and costs for the intervention were estimated for a 12 month period. Incremental cost-effectiveness ratios (ICERs) were estimated for QALYs per participant. Cost-effectiveness analysis was conducted from a healthcare perspective. A bootstrapped cost-effectiveness plane and one-way sensitivity analysis were undertaken to analyse the uncertainty surrounding the estimates. Results The educational intervention was estimated to be less costly and less effective in terms of QALYs than TAU at the 12 month follow-up [incremental costs -euro1,629, confidence interval (CI) -euro5,489 to euro2,240; incremental effect -0.02, CI -0.06 to 0.02]. The base case ICER was >euro80,000/QALY. Conclusion The educational intervention was estimated to be less costly and less effective in terms of QALYs compared with TAU, but the results are subject to some uncertainties. Reduction in PIM use or benefits in quality of life did not seem to translate into improvements in QALYs. Our findings emphasise the need for better understanding of the impact of decreasing PIM use on health outcomes.Peer reviewe

Formation of Highly Oxidized Molecules from NO3 Radical Initiated Oxidation of Delta-3-Carene : A Mechanistic Study

NO3 radical oxidation of most monoterpenes is a significant source of secondary organic aerosol (SOA) in many regions influenced by both biogenic and anthropogenic emissions, but there are very few published mechanistic studies of NO3 chemistry beyond simple first generation products. Here, we present a computationally derived mechanism detailing the unimolecular pathways available to the second generation of peroxy radicals following NO3 oxidation of Delta-3-carene, defining generations based on the sequence of peroxy radicals formed rather than number of oxidant attacks. We assess five different types of unimolecular reactions, including peroxy and alkoxy radical (RO2 and RO) hydrogen shifts, RO2 and RO ring closing (e.g., endoperoxide formation), and RO decomposition. Rate constants calculated using quantum chemical methods indicate that this chemical system has significant contribution from both bimolecular and unimolecular pathways. The dominant unimolecular reactions are endoperoxide formation, RO H-shifts, and RO decomposition. However, the complexity of the overall reaction is tempered as only 1 or 2 radical propagation pathways dominate the fate of each radical intermediate. Chemical ionization mass spectrometry (CIMS) measurements using the NO3- reagent ion during Delta-3-carene + NO3 chamber experiments show products consistent with each of the three types of unimolecular reactions predicted to be important from the computational mechanism. Moreover, the SIMPOL group contribution method for predicting vapor pressures suggests that a majority of the closed-shell products inferred from these unimolecular reactions are likely to have low enough vapor pressure to be able to contribute to SOA formation.Peer reviewe

CHARACTERISATION AND IN VITRO AND IN VIVO EVALUATION OF SUPERCRITICAL-CO2-FOAMED B-TCP/PLCL COMPOSITES FOR BONE APPLICATIONS

Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable beta-tricalciumphosphate/poly(L-lactide-co-epsilon-caprolactone) (beta-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 degrees C, tested samples returned to 95 % of their original height. Hydrolytic degradation of beta-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, beta-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the beta-TCP/PLCL composite. The elastic and highly porous beta-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.Peer reviewe

Estudo da Razão de Bowen em uma Área de Floresta no Sudoeste da Amazônia

The changes mainly occurred in the hydrological cycle are associated with anthropogenic changes. In Brazil are already seen possible changes in the southwestern region that has suffered from water scarcity in their reservoirs. Understanding the Bowen ratio in the Amazon region becomes important to try to understand this ecosystem, since such information connect regional climate change. The latent heat fluxes were analyzed (λE) and sensible heat (H) in REBIO Jaru to determine the reason for Bowen and seek possible climate interactions in humid, wetdry, dry, dry-wet periods in 2009. The results observed in these periods in the Bowen ratio were 0:21; 0:24; 0:30; 0:21, and show that the forest little changes with seasonality during the year unlike the transition of biomes (Amazon - cerrado) and pasture area.As variações ocorridas principalmente no ciclo hidrológico associam-se as mudanças antrópicas. No Brasil já são vistas possíveis alterações na região sudoeste que vem sofrendo com a escassez hídrica em seus reservatórios. Compreender a razão de Bowen na região amazônica torna-se importante para tentar conhecer esse ecossistema, já que tais informações se conectam as alterações climáticas regionais. Foram analisados os fluxos de calor latente (λE) e calor sensível (H) na REBIO Jaru para determinar a razão de Bowen e buscar possíveis interações climáticas nos períodos úmido, úmido-seco, seco e seco-úmido no ano de 2009.  Os resultados observados nesses períodos na razão de Bowen foram: 0.21; 0.24; 0.30;  0.21, e mostram que a floresta pouco se altera com a sazonalidade durante o ano ao contrário dos biomas de transição (Amazônia – cerrado) e da área de pastagem

Simulation of developing human neuronal cell networks

BACKGROUND: Microelectrode array (MEA) is a widely used technique to study for example the functional properties of neuronal networks derived from human embryonic stem cells (hESC-NN). With hESC-NN, we can investigate the earliest developmental stages of neuronal network formation in the human brain. METHODS: In this paper, we propose an in silico model of maturating hESC-NNs based on a phenomenological model called INEX. We focus on simulations of the development of bursts in hESC-NNs, which are the main feature of neuronal activation patterns. The model was developed with data from developing hESC-NN recordings on MEAs which showed increase in the neuronal activity during the investigated six measurement time points in the experimental and simulated data. RESULTS: Our simulations suggest that the maturation process of hESC-NN, resulting in the formation of bursts, can be explained by the development of synapses. Moreover, spike and burst rate both decreased at the last measurement time point suggesting a pruning of synapses as the weak ones are removed. CONCLUSIONS: To conclude, our model reflects the assumption that the interaction between excitatory and inhibitory neurons during the maturation of a neuronal network and the spontaneous emergence of bursts are due to increased connectivity caused by the forming of new synapses.BioMed Central open acces

Changing a semantics: opportunism or courage?

The generalized models for higher-order logics introduced by Leon Henkin, and their multiple offspring over the years, have become a standard tool in many areas of logic. Even so, discussion has persisted about their technical status, and perhaps even their conceptual legitimacy. This paper gives a systematic view of generalized model techniques, discusses what they mean in mathematical and philosophical terms, and presents a few technical themes and results about their role in algebraic representation, calibrating provability, lowering complexity, understanding fixed-point logics, and achieving set-theoretic absoluteness. We also show how thinking about Henkin's approach to semantics of logical systems in this generality can yield new results, dispelling the impression of adhocness. This paper is dedicated to Leon Henkin, a deep logician who has changed the way we all work, while also being an always open, modest, and encouraging colleague and friend.Comment: 27 pages. To appear in: The life and work of Leon Henkin: Essays on his contributions (Studies in Universal Logic) eds: Manzano, M., Sain, I. and Alonso, E., 201

Pathways to Highly Oxidized Products in the Delta 3-Carene + OH System

Oxidation of the monoterpene Delta 3-carene (C10H16) is a potentially important and understudied source of atmospheric secondary organic aerosol (SOA). We present chamber-based measurements of speciated gas and particle phases during photochemical oxidation of Delta 3-carene. We find evidence of highly oxidized organic molecules (HOMs) in the gas phase and relatively low-volatility SOA dominated by C-7-C-10 species. We then use computational methods to develop the first stages of a Delta 3-carene photochemical oxidation mechanism and explain some of our measured compositions. We find that alkoxy bond scission of the cyclohexyl ring likely leads to efficient HOM formation, in line with previous studies. We also find a surprising role for the abstraction of primary hydrogens from methyl groups, which has been calculated to be rapid in the alpha-pinene system, and suggest more research is required to determine if this is more general to other systems and a feature of autoxidation. This work develops a more comprehensive view of Delta 3-carene photochemical oxidation products via measurements and lays out a suggested mechanism of oxidation via computationally derived rate coefficients.Peer reviewe

Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations

Peer reviewe