Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Influence of Agaricus bisporus establishment and fungicidal treatments on casing soil metataxonomy during mushroom cultivation

The cultivation of edible mushroom is an emerging sector with a potential yet to be discovered. Unlike plants, it is a less developed agriculture where many studies are lacking to optimize the cultivation. In this work we have employed high-throughput techniques by next generation sequencing to screen the microbial structure of casing soil employed in mushroom cultivation (Agaricus bisporus) while sequencing V3-V4 of the 16S rRNA gene for bacteria and the ITS2 region of rRNA for. In addition, the microbiota dynamics and evolution (bacterial and fungal communities) in peat-based casing along the process of incubation of A. bisporus have been studied, while comparing the effect of fungicide treatment (chlorothalonil and metrafenone). Statistically significant changes in populations of bacteria and fungi were observed. Microbial composition differed significantly based on incubation day, changing radically from the original communities in the raw material to a specific microbial composition driven by the A. bisporus mycelium growth. Chlorothalonil treatment seems to delay casing colonization by A. bisporus. Proteobacteria and Bacteroidota appeared as the most dominant bacterial phyla. We observed a great change in the structure of the bacteria populations between day 0 and the following days. Fungi populations changed more gradually, with A. bisporus displacing the rest of the species as the cultivation cycle progresses. A better understanding of the microbial communities in the casing will hopefully allow us to increase the biological efficiency of the crop.This work was co-funded by the FEDER Operational Program La Rioja 2014–2020 (Project CT21_04), the Department of Economic Development and Innovation of La Rioja. Res. n° 1168/2018 and the H2020 Marie Sklodowska-Curie Actions, Grant agreement no. 742966

Elliptic flow of electrons from heavy-flavour hadron decays at mid-rapidity in Pb–Pb collisions at √sNN = 2.76 TeV

The elliptic flow of electrons from heavy-flavour hadron decays at mid-rapidity (|y| < 0.7) is measured in Pb-Pb collisions at sNN−−−√=2.76 TeV with ALICE at the LHC. The particle azimuthal distribution with respect to the reaction plane can be parametrized with a Fourier expansion, where the second coefficient (v2) represents the elliptic flow. The v2 coefficient of inclusive electrons is measured in three centrality classes (0-10%, 10-20% and 20-40%) with the event plane and the scalar product methods in the transverse momentum (pT) intervals 0.5-13 GeV/c and 0.5-8 GeV/c, respectively. After subtracting the background, mainly from photon conversions and Dalitz decays of neutral mesons, a positive v2 of electrons from heavy-flavour hadron decays is observed in all centrality classes, with a maximum significance of 5.9σ in the interval 2< pT < 2.5 GeV/c in semi-central collisions (20-40%). The value of v2 decreases towards more central collisions at low and intermediate pT (0.5 < pT < 3 GeV/c). The v2 of electrons from heavy-flavour hadron decays at mid-rapidity is found to be similar to the one of muons from heavy-flavour hadron decays at forward rapidity (2.5 < y < 4). The results are described within uncertainties by model calculations including substantial elastic interactions of heavy quarks with an expanding strongly-interacting medium

Production of Σ(1385)± and Ξ(1530)0 in p–Pb collisions at √sNN = 5.02 TeV

The transverse momentum distributions of the strange and double-strange hyperon resonances (Σ(1385)±, Ξ(1530)0) produced in p-Pb collisions at sNN−−−√=5.02 TeV were measured in the rapidity range −0.5<yCMS<0 for event classes corresponding to different charged-particle multiplicity densities, ⟨dNch/dηlab⟩. The mean transverse momentum values are presented as a function of ⟨dNch/dηlab⟩, as well as a function of the particle masses and compared with previous results on hyperon production. The integrated yield ratios of excited to ground-state hyperons are constant as a function of ⟨dNch/dηlab⟩. The equivalent ratios to pions exhibit an increase with ⟨dNch/dηlab⟩, depending on their strangeness content

Measurement of electrons from beauty-hadron decays in p–Pb collisions at √sNN = 5.02 TeV and Pb–Pb collisions at √sNN = 2.76 TeV

The production of beauty hadrons was measured via semi-leptonic decays at mid-rapidity with the ALICE detector at the LHC in the transverse momentum interval 1<pT<8 GeV/c in minimum-bias p-Pb collisions at sNN−−−√=5.02 TeV and in 1.3<pT<8 GeV/c in the 20% most central Pb-Pb collisions at sNN−−−√=2.76 TeV. The pp reference spectra at s√=5.02 TeV and s√=2.76 TeV, needed for the calculation of the nuclear modification factors RpPb and RPbPb, were obtained by a pQCD-driven scaling of the cross section of electrons from beauty-hadron decays measured at s√=7 TeV. In the pT interval 3<pT<8 GeV/c a suppression of the yield of electrons from beauty-hadron decays is observed in Pb-Pb compared to pp collisions. Towards lower pT, the RPbPb values increase with large systematic uncertainties. The RpPb is consistent with unity within systematic uncertainties and is well described by theoretical calculations that include cold nuclear matter effects in p-Pb collisions. The measured RpPb and these calculations indicate that cold nuclear matter effects are small at high transverse momentum also in Pb-Pb collisions. Therefore, the observed reduction of RPbPb below unity at high pT may be ascribed to an effect of the hot and dense medium formed in Pb-Pb collisions

Anomalous evolution of the near-side jet peak shape in Pb–Pb collisions at √sNN = 2.76 TeV

The measurement of two-particle angular correlations is a powerful tool to study jet quenching in a pT region inaccessible by direct jet identification. In these measurements pseudorapidity (Δη) and azimuthal (Δφ) differences are used to extract the shape of the near-side peak formed by particles associated to a higher pT trigger particle (1<pT,trig< 8 GeV/c). A combined fit of the near-side peak and long-range correlations is applied to the data allowing the extraction of the centrality evolution of the peak shape in Pb-Pb collisions at sNN−−−√ = 2.76 TeV. A significant broadening of the peak in the Δη direction at low pT is found from peripheral to central collisions, which vanishes above 4 GeV/c, while in the Δφ direction the peak is almost independent of centrality. For the 10% most central collisions and 1<pT,assoc< 2 GeV/c, 1<pT,trig< 3 GeV/c a novel feature is observed: a depletion develops around the centre of the peak. The results are compared to pp collisions at the same centre of mass energy and to AMPT model simulations. The comparison to the investigated models suggests that the broadening and the development of the depletion is connected to the strength of radial and longitudinal flow

Measurement of an excess in the yield of J/ψ at very low pT in Pb–Pb collisions at √sNN = 2.76 TeV

We report on the first measurement of an excess in the yield of J/ψ at very low transverse momentum (pT<0.3 GeV/c) in peripheral hadronic Pb-Pb collisions at sNN−−−√ = 2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor (RAA) of J/ψ in the rapidity range 2.5<y<4 reaches about 7 (2) in the pT range 0-0.3 GeV/c in the 70-90% (50-70%) centrality class. The J/ψ production cross section associated with the observed excess is obtained under the hypothesis that coherent photoproduction of J/ψ is the underlying physics mechanism. If confirmed, the observation of J/ψ coherent photoproduction in Pb-Pb collisions at impact parameters smaller than twice the nuclear radius opens new theoretical and experimental challenges and opportunities. In particular, coherent photoproduction accompanying hadronic collisions may provide insight into the dynamics of photoproduction and nuclear reactions, as well as become a novel probe of the Quark-Gluon Plasma

Linear and non-linear flow modes in Pb–Pb collisions at √sNN = 2.76 TeV

The second and the third order anisotropic flow, V2 and V3, are mostly determined by the corresponding initial spatial anisotropy coefficients, ε2 and ε3, in the initial density distribution. In addition to their dependence on the same order initial anisotropy coefficient, higher order anisotropic flow, Vn (n>3), can also have a significant contribution from lower order initial anisotropy coefficients, which leads to mode-coupling effects. In this Letter we investigate the linear and non-linear modes in higher order anisotropic flow Vn for n=4, 5, 6 with the ALICE detector at the Large Hadron Collider. The measurements are done for particles in the pseudorapidity range |η|<0.8 and the transverse momentum range 0.2<pT<5.0 GeV/c as a function of collision centrality. The results are compared with theoretical calculations and provide important constraints on the initial conditions, including initial spatial geometry and its fluctuations, as well as the ratio of the shear viscosity to entropy density of the produced system