Magnitude and determinants of antibiotic dispensing without prescription in Spain: a simulated patient study

Objectives: Excessive and inappropriate use of antibiotics increases antimicrobial resistance. The aim of this study was to determine the magnitude and determinants of antibiotic dispensing without prescription in Spain by the simulated patient technique. Methods: A cross-sectional study was conducted with all the pharmacies in a region of north-west Spain (n = 977), between December 2016 and January 2017. Four actors visited the pharmacies simulating a respiratory infection. Four incremental levels of pressure were used to obtain an antibiotic. The education and sex of the person who was dispensing and the area where the pharmacy was located were recorded. The effect of these independent variables on the dispensing of an antibiotic without prescription (1 = yes, 0 = no) was modelled by logistic regression. Results: An antibiotic was obtained in 18.83% (95% CI = 16.5%-21.41%) of the visits. The area influenced the dispensing of antibiotics without a medical prescription, with a greater likelihood of dispensing in rural (OR = 1.79; 95% CI = 1.20-2.68) or semi-rural (OR = 1.66; 95% CI = 1.13-2.44) areas than in urban areas. No association was found with the sex or the training of the person who dispensed the antibiotic. In the pharmacies in urban areas, a lower level of pressure was needed to obtain the antibiotic. Conclusions: This study shows that one-fifth of the pharmacies still dispense antibiotics without prescription, especially under patient pressure. A rural setting has been identified as a risk factor for dispensing without prescription, so it must be taken into account for future interventions

Reaction mechanism and characteristics of T_{20} in d + ^3He backward elastic scattering at intermediate energies

For backward elastic scattering of deuterons by ^3He, cross sections \sigma and tensor analyzing power T_{20} are measured at E_d=140-270 MeV. The data are analyzed by the PWIA and by the general formula which includes virtual excitations of other channels, with the assumption of the proton transfer from ^3He to the deuteron. Using ^3He wave functions calculated by the Faddeev equation, the PWIA describes global features of the experimental data, while the virtual excitation effects are important for quantitative fits to the T_{20} data. Theoretical predictions on T_{20}, K_y^y (polarization transfer coefficient) and C_{yy} (spin correlation coefficient) are provided up to GeV energies.Comment: REVTEX+epsfig, 17 pages including 6 eps figs, to be published in Phys. Rev.

Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer

Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients

Pharmaceutical companies information and antibiotic prescription patterns: A follow-up study in Spanish primary care

OBJECTIVES: To assess the impact of sources of drug information on antibiotic prescribing patterns (quantity and quality) among primary care physicians. METHODS: We conducted a cohort study on primary care physicians who were actively engaged in medical practice in 2010 in a region in north-west Spain (Galicia), fulfilling inclusion criteria (n = 2100). As the independent variable, we took the perceived utility of 6 sources of information on antibiotics, as measured by the validated KAAR-11 questionnaire. As dependent variables, we used: (1) a quality indicator (appropriate quality, defined as any case where 6 of the 12 indicators proposed by the European Surveillance of Antimicrobial Consumption Network [ESAC-Net] were better than the mean values for Spain); and, (2) a quantity indicator (high prescribing), defined as any case where defined daily doses (DDD) per 1 000 inhabitants per day of antibacterials for systemic use were higher than the mean values for Spain. The adjusted odds ratio for a change in the interquartile range (IqOR) for each sources of information on antibiotics was calculated using Generalized Linear Mixed Models. RESULTS: The questionnaire response rate was 68%. Greater perceived utility of pharmaceutical sales representatives increases the risk of having high prescribing (1/IqOR = 2.50 [95%CI: 1.63-3.66]) and reduces the probability of having appropriate quality (1/IqOR = 2.28 [95%CI: 1.77-3.01]). Greater perceived utility of clinical guidelines increases the probability of having appropriate quality (1/IqOR = 1.25 [95%CI: 1.02-1.54]) and reduces the probability of high prescribing (1/IqOR = 1.25 [95%CI: 1.02-1.54]). CONCLUSIONS: Sources of information on antibiotics are an important determinant of the quantity and quality of antibiotic prescribing in primary care. Commercial sources of information influence prescribing negatively, and clinical guidelines are associated with better indicators.Instituto de Salud Carlos IIIThe European Regional Development Fund (ERDF)Mutua Madrileñ

The European construction social partners: gender equality in theory and practice

This article explores the social partners' role in the gender equality agenda in construction at skilled operative level. It draws on a survey of the European construction social partners that investigated the presence of women in skilled trades and the policies, collective agreements and practices that play a role in women's integration. The responses indicate that the construction industry still displays inertia and conservatism, and that the social partners corroborate rather than counter this. They express a 'discourse' of gender equality, but this does not automatically lead to equal opportunity policies or programmes. The social partners have the platform to make inroads and to change the industry from within, but need further encouragement to put this on their agenda

Measurement of the tensor analyzing power T20 in the dd->^3Hen and dd->^3Hp at intermediate energies and at zero degree

The data on the tensor analyzing power T20 in the dd->^3Hen and dd-> ^3Hp reactions at 140, 200 and 270 MeV of the deuteron kinetic energy and at zero degree obtained at RIKEN Accelerator Research Facility are presented. The observed positive sign of T20 clearly demonstrates the sensitivity to the D/S wave ratios in the ^3He and ^3H in the energy domain of the measurements. The T20 data for the ^3He-n and ^3H-p channels are in agreement within experimental accuracy.Comment: 9 pages, 3 figures, submitted in Phys.Lett.

Direct Observation of the Myosin Va Recovery Stroke That Contributes to Unidirectional Stepping along Actin

Myosins are ATP-driven linear molecular motors that work as cellular force generators, transporters, and force sensors. These functions are driven by large-scale nucleotide-dependent conformational changes, termed “strokes”; the “power stroke” is the force-generating swinging of the myosin light chain–binding “neck” domain relative to the motor domain “head” while bound to actin; the “recovery stroke” is the necessary initial motion that primes, or “cocks,” myosin while detached from actin. Myosin Va is a processive dimer that steps unidirectionally along actin following a “hand over hand” mechanism in which the trailing head detaches and steps forward ∼72 nm. Despite large rotational Brownian motion of the detached head about a free joint adjoining the two necks, unidirectional stepping is achieved, in part by the power stroke of the attached head that moves the joint forward. However, the power stroke alone cannot fully account for preferential forward site binding since the orientation and angle stability of the detached head, which is determined by the properties of the recovery stroke, dictate actin binding site accessibility. Here, we directly observe the recovery stroke dynamics and fluctuations of myosin Va using a novel, transient caged ATP-controlling system that maintains constant ATP levels through stepwise UV-pulse sequences of varying intensity. We immobilized the neck of monomeric myosin Va on a surface and observed real time motions of bead(s) attached site-specifically to the head. ATP induces a transient swing of the neck to the post-recovery stroke conformation, where it remains for ∼40 s, until ATP hydrolysis products are released. Angle distributions indicate that the post-recovery stroke conformation is stabilized by ≥5 kBT of energy. The high kinetic and energetic stability of the post-recovery stroke conformation favors preferential binding of the detached head to a forward site 72 nm away. Thus, the recovery stroke contributes to unidirectional stepping of myosin Va

Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning

Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient's immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy. Developing predictive methods to identify patients with high risk of severe COVID-19 disease is of crucial importance. Authors show here that by measuring anti-SARS-CoV-2 antibody and cytokine levels at the time of hospital admission and integrating the data by unsupervised hierarchical clustering/machine learning, it is possible to predict unfavourable outcome