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Background: Clostridioides difficile infection (CDI) is a disease that is potentially preventable by vaccination. A good knowledge of its epidemiology, which can change over time, is warranted for prevention purposes and to help decision-making on the use of vaccines in public health programs. The objective of the research was to determine the epidemiology of healthcare-associated CDI (HA-CDI) and community-associated CDI (CA-CDI) in hospitalized patients in Spain using point prevalence data., Methods: Point prevalence survey data on infections of hospitalized patients for years 2012-2019 were analyzed. HA-CDI and CA-CDI prevalence rates were calculated. Both HA-CDI and CA-CDI, as well as age group prevalence rates, were examined for trends. Patient comorbidities were tested for association to CDI., Results: The prevalence of CDI in Spanish hospitals has grown exponentially from 14.1% in 2012 to 35.9% in 2019 (cases/10.000 hospitalized patients). Almost two thirds of the cases are of nosocomial onset. This increase was observed for HA-CDI and CA-CDI at an annual rate of 1.11% (CI 95% 1.08-1.15) and 1.09% (CI 95% 1.04-1.13), respectively. Patients 50 years old or older represent 87% of the total number of cases. Patients suffering from neoplasm (OR 1.39), immunodeficiency (OR 3.26), neutropenia (OR 3.70), cirrhosis (OR 1.92) and chronic renal failure (OR 1.91) have a significant increased risk of developing CDI, after adjusting for age., Conclusion: In Spain, the prevalence rate of both HA-CDI and CA-CDI have been increasing. Burden of CDI as well as clinical and epidemiological characteristics of CDI patients will help to support public health decision-making., (Copyright © 2021 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Chaste (Cancer, Heart And Soft Tissue Environment) is an open source simulation package for the numerical solution of mathematical models arising in physiology and biology. To date, Chaste development has been driven primarily by applications that include continuum modelling of cardiac electrophysiology ('Cardiac Chaste'), discrete cell-based modelling of soft tissues ('Cell-based Chaste'), and modelling of ventilation in lungs ('Lung Chaste'). Cardiac Chaste addresses the need for a high-performance, generic, and verified simulation framework for cardiac electrophysiology that is freely available to the scientific community. Cardiac chaste provides a software package capable of realistic heart simulations that is efficient, rigorously tested, and runs on HPC platforms. Cell-based Chaste addresses the need for efficient and verified implementations of cell-based modelling frameworks, providing a set of extensible tools for simulating biological tissues. Computational modelling, along with live imaging techniques, plays an important role in understanding the processes of tissue growth and repair. A wide range of cell-based modelling frameworks have been developed that have each been successfully applied in a range of biological applications. Cell-based Chaste includes implementations of the cellular automaton model, the cellular Potts model, cell-centre models with cell representations as overlapping spheres or Voronoi tessellations, and the vertex model. Lung Chaste addresses the need for a novel, generic and efficient lung modelling software package that is both tested and verified. It aims to couple biophysically-detailed models of airway mechanics with organ-scale ventilation models in a package that is freely available to the scientific community. Chaste is designed to be modular and extensible, providing libraries for common scientific computing infrastructure such as linear algebra operations, finite element meshes, and ordinary and partial differential equation solvers. This infrastructure is used by libraries for specific applications, such as continuum mechanics, cardiac models, and cell-based models. The software engineering techniques used to develop Chaste are intended to ensure code quality, re-usability and reliability. Primary applications of the software include cardiac and respiratory physiology, cancer and developmental biology.

Background: Lower urinary tract infections (LUTIs) are amongst the most common community acquired infections with frequent antibiotic prescribing. Objectives: To assess empiric antibiotic choice in different types of lower urinary tract infections. We also aimed to identify determinants of fluoroquinolone prescribing, as well as to determine the rate of short antibiotic courses. The frequencies of executing laboratory tests and recommending analgesics/anti-inflammatory drugs were also assessed. Methods: A prospective observational study was performed in 19 different Hungarian primary care practices. Participating general practitioners (GPs) filled out data sheets for each patient with a suspected urinary tract infection. Details of drug use were evaluated. Comparison of different LUTI groups were made by descriptive statistics and univariate analysis. Possible determinants of fluoroquinolone prescribing were assessed by logistic regression. Results: Data sheets of 372 patients were analyzed. The majority of patients (68.82%) had acute uncomplicated cystitis. While antibiotics were prescribed for almost every patient (uncomplicated cases: 92.58%, complicated cases: 94.83%), analgesics/anti-inflammatory drugs were recommended at a rate of 7.81% in uncomplicated, and 13.79% in complicated cystitis cases. Ciprofloxacin was the most commonly prescribed antibacterial agent in both types of cystitis. Short-term antibiotic therapy was prescribed in one third of relevant cases. Logistic regression found a weak association between fluoroquinolone use and patient's age and presence of complicating factors. Conclusions: Many aspects of suboptimal cystitis management were identified (e.g. unnecessarily broad spectra agents, too long antibiotic courses). In this study, patient characteristics has weakly influenced fluoroquinolone prescribing. Based on these results there is considerable room for improvement in primary care antibiotic therapy of cystitis in Hungary., (Copyright © 2019 Benko, Matuz, Juhasz, Bognar, Bordas, Soos, Hajdu and Peto.)

Rationale: Asthma is characterized by disease within the small airways. Several studies have suggested that forced oscillation technique-derived resistance at 5 Hz (R5) - resistance at 20 Hz (R20) is a measure of small airway disease; however, there has been limited validation of this measurement to date. Objectives: To validate the use of forced oscillation R5 - R20 as a measure of small airway narrowing in asthma, and to investigate the role that small airway narrowing plays in asthma. Methods: Patient-based complete conducting airway models were generated from computed tomography scans to simulate the impact of different degrees of airway narrowing at different levels of the airway tree on forced oscillation R5 - R20 ( n  = 31). The computational models were coupled with regression models in an asthmatic cohort ( n  = 177) to simulate the impact of small airway narrowing on asthma control and quality of life. The computational models were used to predict the impact on small airway narrowing of type-2 targeting biologics using pooled data from two similarly design randomized, placebo-controlled biologic trials ( n  = 137). Measurements and Main Results: Simulations demonstrated that narrowing of the small airways had a greater impact on R5 - R20 than narrowing of the larger airways and was associated (above a threshold of approximately 40% narrowing) with marked deterioration in both asthma control and asthma quality of life, above the minimal clinical important difference. The observed treatment effect on R5 - R20 in the pooled trials equated to a predicted small airway narrowing reversal of approximately 40%. Conclusions: We have demonstrated, using computational modeling, that forced oscillation R5 - R20 is a direct measure of anatomical narrowing in the small airways and that small airway narrowing has a marked impact on both asthma control and quality of life and may be modified by biologics.

A cross-national comparison was performed on paediatric (0-19 years) antibiotic use in Hungary, Norway and Portugal to explore and compare the scale and pattern of paediatric antibiotic use in these three European countries. Ambulatory care systemic antibiotic use (ATC: J01) was retrieved from national databases for year 2014. The main outcome measure was number of antibacterial packages per child inhabitant per year (packages/child/year) and was further stratified by age groups. Paediatric antibiotic use peaked in Hungary with 1.3 packages/child/year, followed by Portugal (0.8) and Norway (0.3). This ranking was retained and was most prominent in the 5- to 9-year and 10- to 14-year age groups. The pattern of antibiotic use in different paediatric age groups varied also substantially between countries. Narrow-spectrum penicillins were much commonly used in Norway in all paediatric age subgroups in comparison with Hungary and Portugal. Newer, broad-spectrum cephalosporins and macrolides were widely prescribed for Hungarian and Portuguese children in all paediatric subgroups in contrast to Norway, while tetracyclines were commonly prescribed for Norwegian adolescents. The scale and pattern of paediatric antibiotic use in Hungary and Portugal were very different compared with Norway. The high antibiotic exposure and the high consumption of broad-spectrum penicillins begin in childhood in Hungary and Portugal which underpins the responsibility of paediatric GPs., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

This paper examines the viscous flow resistance in branching tubes as applied to simplified models of the lungs and compares the results of computational fluid dynamics simulations for a range of conditions with measurement data. The results are in good agreement with the available measurement data for both inspiration and expiration. A detailed sensitivity analysis of the dissipation and viscous resistance in a branch then examines the ratio of the viscous resistance to that for a fully developed Poiseuille flow, Z. As other researchers have noted, the calculated resistances give lower values than those from the standard correlation of Pedley et al. The results demonstrate that the resistance is sensitive to the velocity profile upstream of the bifurcations and explain from fluid dynamical considerations the apparent sensitivity of the resistance to the generation number of the branch. The paper also suggests a revised value for the calibration constant in the expression for Z. Finally, a limited set of results are presented for junction losses, and for expiration., (Copyright © 2017 John Wiley & Sons, Ltd.)

Obese women have lower pregnancy rates than normal-weight women undergoing assisted reproductive treatment. We conducted a pilot study to evaluate whether a 12-week diet and exercise intervention before an IVF cycle would influence pregnancy rates in obese women. Forty-one patients were enrolled in this study. They were randomly allocated to two groups: an intervention group (n = 21), who underwent an individualized diet and physical exercise programme supervised by a dietician, and a control group (n = 20), who started IVF with no previous intervention. The primary outcome was clinical pregnancy rate after a single treatment cycle. Mean weight loss in the study group after the intervention was 5.4 kg (range 1.1-14.6 kg). The study and control groups had similar total FSH consumption, number of oocytes and embryos obtained, and number and quality of embryos transferred. There was a non-significant trend towards a higher clinical pregnancy rate after fresh embryo transfer (66.7% versus 41.2%). The intervention group had a significantly higher cumulative live birth rate (61.9% versus 30%, P = 0.045) (odds ratio for intervention group, 3.8; 95% confidence interval, 1.03 to 13.9) The data suggest that weight loss resulted in a significantly increased cumulative live birth rate., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

We construct a stabilized finite-element method to compute flow and finite-strain deformations in an incompressible poroelastic medium. We employ a three-field mixed formulation to calculate displacement, fluid flux and pressure directly and introduce a Lagrange multiplier to enforce flux boundary conditions. We use a low order approximation, namely, continuous piecewise-linear approximation for the displacements and fluid flux, and piecewise-constant approximation for the pressure. This results in a simple matrix structure with low bandwidth. The method is stable in both the limiting cases of small and large permeability. Moreover, the discontinuous pressure space enables efficient approximation of steep gradients such as those occurring due to rapidly changing material coefficients or boundary conditions, both of which are commonly seen in physical and biological applications., (© The Author(s) 2017.)

Many lung diseases lead to an increase in ventilation heterogeneity (VH). Two clinical practices for the measurement of patient VH are in vivo imaging, and the inert gas multiple breath washout (MBW). In this study computational modelling was used to compare the responses of MBW indices LCI and s cond and MRI measured global and local ventilation indices, σ r and σ local , to constriction of airways in the conducting zone of the lungs. The simulations show that s cond , LCI and σ r behave quite similarly to each other, all being sensitive to increases in the severity of constriction, while exhibiting little sensitivity to the depth at which constriction occurs. In contrast, the local MRI index σ local shows strong sensitivity to depth of constriction, but lowered sensitivity to constriction severity. We finish with an analysis of the sensitivity of MRI indices to grid sizes, showing that results should be interpreted with reference to the image resolution. Overall we conclude that the application of both local and global VH measures may help to classify different types of bronchoconstriction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We develop a lung ventilation model based on a continuum poroelastic representation of lung parenchyma that is strongly coupled to a pipe network representation of the airway tree. The continuous system of equations is discretized using a low-order stabilised finite element method. The framework is applied to a realistic lung anatomical model derived from computed tomography data and an artificially generated airway tree to model the conducting airway region. Numerical simulations produce physiologically realistic solutions and demonstrate the effect of airway constriction and reduced tissue elasticity on ventilation, tissue stress and alveolar pressure distribution. The key advantage of the model is the ability to provide insight into the mutual dependence between ventilation and deformation. This is essential when studying lung diseases, such as chronic obstructive pulmonary disease and pulmonary fibrosis. Thus the model can be used to form a better understanding of integrated lung mechanics in both the healthy and diseased states. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

The analysis of high-resolution computed tomography (CT) images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6-10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11) and asthmatic (n = 24) CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47). The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01) in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3-5) versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1) (Spearman ρ = -0.65, p < 0.001) and, at low flow rates (0.00017 L/s), FEV1 over forced vital capacity (FEV1/FVC) (ρ = -0.58, p < 0.001). We conclude that the pipeline and anatomical models can be used directly in mechanistic modelling studies and can form the basis for future patient-based modelling studies.

Complex flow patterns exist within the asymmetric branching airway network in the lungs. These flow patterns are known to become increasingly heterogeneous during disease as a result of various mechanisms such as bronchoconstriction or alterations in lung tissue compliance. Here, we present a coupled model of tissue deformation and network airflow enabling predictions of dynamic flow properties, including temporal flow rate, pressure distribution, and the occurrence of reverse flows. We created two patient-specific airway geometries, one for a healthy subject and one for a severe asthmatic subject, derived using a combination of high-resolution CT data and a volume-filling branching algorithm. In addition, we created virtually constricted airway geometry by reducing the airway radii of the healthy subject model. The flow model was applied to these three different geometries to solve the pressure and flow distribution over a breathing cycle. The differences in wave phase of the flows in parallel airways induced by asymmetric airway geometry and bidirectional interaction between intra-acinar and airway network pressures were small in central airways but were more evident in peripheral airways. The asthmatic model showed elevated ventilation heterogeneity and significant flow disturbance. The reverse flows in the asthmatic model not only altered the local flow characteristics but also affected total lung resistance. The clinical significance of temporal flow disturbance on lung ventilation in normal airway model is obscure. However, increased flow disturbance and ventilation heterogeneity observed in the asthmatic model suggests that reverse flow may be an important factor for asthmatic lung function., (Copyright © 2015 John Wiley & Sons, Ltd.)