Wide systematic variations in potentially avoidable hospitalisations of chronically ill patients: Ecological study of basic health areas and healthcare areas. / Amplias variaciones sistemáticas en hospitalizaciones potencialmente evitables en pacientes crónicos: estudio ecológico sobre zonas básicas de salud y áreas sanitarias.

BACKGROUND AND OBJECTIVE: Potentially avoidable hospitalisations (PAHs) due to chronic conditions are a healthcare problem that could reflect healthcare of insufficient quality. This study reports the systematic variations in PAHs for the collection of providers of the Spanish National Health System. MATERIALS AND METHODS: We conducted an ecological study on government data, analysing the systematic variation in PAHs for 6 chronic conditions during 2013-2015. To determine the variation, we performed a small area analysis using Bayesian methodology. RESULTS: Between 2013 and 2015, 439,878 admissions for PAHs were recorded in the Spanish National Health System. There was an up to 4-fold difference in PAH rates between certain basic health areas (BHA), with highly variable differences depending on the analysed condition. Forty percent of the BHAs showed a greater than expected risk of PAH. Beyond the systematic variation observed between BHAs, the healthcare areas of the patients' residence explained 33% of the variation in PAHs. We observed specific differences in these general results according to clinical condition, age and sex. CONCLUSIONS: The wide systematic variation in PAHs suggests a problem of quality in the care provided to chronically ill patients by the providers of healthcare areas in Spain. Identifying and analysing these areas and other healthcare areas with better results could provide a reference for improving the care of other suppliers with poorer performance.

ECG-based estimation of dispersion of APD restitution as a tool to stratify sotalol-induced arrhythmic risk.

BACKGROUND: Increased spatial dispersion of restitution properties has been associated to arrhythmic risk. An ECG-based index quantifying restitution dispersion, DRest, is evaluated in patients who experienced Torsades de Pointes (TdP) under sotalol challenge and compared with the response in healthy subjects. METHODS AND RESULTS: ECG recordings were analyzed for quantification of DRest and QTc, among others biomarkers. DRest provides improved discrimination following sotalol administration between TdP and healthy subjects ([min-max]: [0.18-0.22] vs [0.02-0.12]), compared to other biomarkers including QTc ([436-548ms] vs [376-467ms]). Results in healthy subjects are in agreement with simulations of sotalol effects on a human tissue electrophysiological model. CONCLUSIONS: This case study supports the potential of DRest for improved arrhythmia risk stratification even with QTc values below 450ms.

Wide systematic variations in potentially avoidable hospitalizations of chronically ill patients: Ecological study of primary care areas and healthcare areas.

BACKGROUND AND OBJECTIVE: Potentially avoidable hospitalisations (PAHs) due to chronic conditions are a healthcare problem that could reflect healthcare of insufficient quality. This study reports the systematic variations in PAHs for the collection of providers of the Spanish National Health System. MATERIALS AND METHODS: We conducted an ecological study on government data, analysing the systematic variation in PAHs for 6 chronic conditions during 2013-2015. To determine the variation, we performed a small area analysis using Bayesian methodology. RESULTS: Between 2013 and 2015, 439,878 admissions for PAHs were recorded in the Spanish National Health System. There was an up to 4-fold difference in PAH rates between certain basic health areas (BHA), with highly variable differences depending on the analyzed condition. Forty percent of the BHAs showed a greater than expected risk of PAH. Beyond the systematic variation observed between BHAs, the healthcare areas of the patients' residence explained 33% of the variation in PAHs. We observed specific differences in these general results according to clinical condition, age and sex. CONCLUSIONS: The wide systematic variation in PAHs suggests a problem of quality in the care provided to chronically ill patients by the providers of healthcare areas in Spain. Identifying and analysing these areas and other healthcare areas with better results could provide a reference for improving the care of other suppliers with poorer performance.

Effects of aging and heat treatment on whole yeast cells and yeast cell walls and on adsorption of ochratoxin A in a wine model system.

A wine model was evaluated to determine the influence of aging on the ability of whole yeast cells (WY) and yeast cell walls (YCW) to remove ochratoxin A (OTA). Aging and autolysis were monitored for 214 h in the model wine. The original concentration of OTA in the model wine was 10 microg/liter, and WY and YCW were added at a final concentration of 1 g/liter. YCW mannoproteins were involved in the removal of OTA from the model wine through adsorption mechanisms. Aging affected the capacity of WY to remove OTA, but YCW removal capacity remained constant during aging. A previous heat treatment (85 degrees C for 10 min) of WY and YCW increased their removal capacity and increased the efficiency of the decontamination process.

Correction: Experimentally-Based Computational Investigation into Beat-To-Beat Variability in Ventricular Repolarization and Its Response to Ionic Current Inhibition.

[This corrects the article DOI: 10.1371/journal.pone.0151461.].

Experimentally-Based Computational Investigation into Beat-To-Beat Variability in Ventricular Repolarization and Its Response to Ionic Current Inhibition.

Beat-to-beat variability in repolarization (BVR) has been proposed as an arrhythmic risk marker for disease and pharmacological action. The mechanisms are unclear but BVR is thought to be a cell level manifestation of ion channel stochasticity, modulated by cell-to-cell differences in ionic conductances. In this study, we describe the construction of an experimentally-calibrated set of stochastic cardiac cell models that captures both BVR and cell-to-cell differences in BVR displayed in isolated canine action potential measurements using pharmacological agents. Simulated and experimental ranges of BVR are compared in control and under pharmacological inhibition, and the key ionic currents determining BVR under physiological and pharmacological conditions are identified. Results show that the 4-aminopyridine-sensitive transient outward potassium current, Ito1, is a fundamental driver of BVR in control and upon complete inhibition of the slow delayed rectifier potassium current, IKs. In contrast, IKs and the L-type calcium current, ICaL, become the major contributors to BVR upon inhibition of the fast delayed rectifier potassium current, IKr. This highlights both IKs and Ito1 as key contributors to repolarization reserve. Partial correlation analysis identifies the distribution of Ito1 channel numbers as an important independent determinant of the magnitude of BVR and drug-induced change in BVR in control and under pharmacological inhibition of ionic currents. Distributions in the number of IKs and ICaL channels only become independent determinants of the magnitude of BVR upon complete inhibition of IKr. These findings provide quantitative insights into the ionic causes of BVR as a marker for repolarization reserve, both under control condition and pharmacological inhibition.

Polydimethylsiloxane solid-phase microextraction-gas chromatography method for the analysis of volatile compounds in wines. Its application to the characterization of varietal wines.

A study was made of the validity of the solid-phase microextraction method, using a polydimethylsiloxane coated fused-silica fiber, for the extraction-desorption of the minor volatile compounds from wine before their gas chromatographic analysis. The aspects considered were the influence of ethanol on extraction, repeatability, limits of detection, linearity and recovery of compounds. This method, together with the direct injection of the major volatile compounds, was applied to 16 varietal wines. The findings indicate that the method is a highly suitable technique for the analysis of wines and that the volatile composition of wines depends, at least partly, on the grapes with which they have been made.

Release of lipids during yeast autolysis in a model wine system.

The release of lipids during the aging of sparkling wines in contact with yeast can influence wine sensory attributes and, especially, foam characteristics. Model systems allow study of the autolysis process in a reasonable period of time compared to natural conditions, at which it can last several months. In this paper, the release of the different classes of lipids during the autolysis of three commercial yeast strains in a model wine medium has been monitored. Due to the absence of accurate quantitative methods, an HPLC method for separating and quantifying the different neutral and polar yeast lipid classes was developed. Lipids were eluted through a YMC PVA-Sil column with a complex solvent mixture. Detection was carried out with a light-scattering detector. The yeasts were suspended in the model wine buffer and incubated at 30 degrees C for up to 12 days. A release of triacylglycerols, 1,3-diacylglycerols, 2-monoacylglycerols, free fatty acids, sterol esters, and sterols was observed over the first 2 days, a period that corresponded to the maximum loss of yeast viability. A decrease in most of these lipids was observed from day 2, possibly indicative of the release of yeast hydrolytic enzymes due to the breakdown of the cell wall. Phospholipids were not detected in any of the autolysates. The mean lipid content in the autolysates as a percentage of the total lipid content in the yeasts was 8.6% for sterol esters, 3.8% for sterols, 2% for triacylglycerols, and <2% for 1,3-diacylglycerols and free fatty acids.

Assessment of the native electrophoretic analysis of total grape must proteins for the characterization of Vitis vinifera L. cultivars.

The findings of an ampelographic analysis of vines belonging to a Germoplasm Bank were compared to the results of native electrophoresis of the total proteins in their musts. Cluster analysis of the data from the morphological description produced correct groupings, in terms of variety, for all samples. When cluster analysis was performed on the electrophoretic data, 10 of the 11 musts studied were grouped correctly. Electrophoresis was also performed on 30 musts made from a mixture of grapes from large vineyards. In the cluster analysis of the electrophoretic data on the proteins of the 41 musts studied, all the musts are grouped correctly in terms of variety. Electrophoretic analysis of proteins is a simple technique that can be used routinely, provides complementary information to morphological analysis for varietal characterization of vines, and in the majority of cases, makes it possible to ascertain the grape variety from which musts originate.

Sensory and analytical study of rose sparkling wines manufactured by second fermentation in the bottle.

The sensory and analytical characteristics of five rose sparkling wines manufactured by the traditional method have been determined. Moreover, the changes that take place in the nitrogen and volatile fraction of the wines during the second fermentation and the aging with the yeasts have been studied. Each of these wines was made from a single industrial rose base wine of the Garnacha Tinta variety, with five selected yeasts strains. The base wine had a low content in free amino acids, 16 mg/L, and the yeast consumed more peptides than free amino acids during second fermentation. From the application of the two-way analysis of variance, yeast strain, and aging time factors to the data of volatile compounds, it has been found that most of the differences between these sparkling wines are due to the aging time. It has been verified that these rose sparkling wines have foam of good quality and that the grape variety Garnacha Tinta is suitable for the production of rose sparkling wines.

Time course of ECG depolarization and repolarization changes during ischemia in PTCA recordings.

OBJECTIVES: In this work we studied the temporal evolution of changes in the electrocardiogram (ECG) as a consequence of the induced ischemia during prolonged coronary angioplasty, comparing the time course of indexes reflecting depolarization and those reflecting repolarization. METHODS: We considered both local (measured at specific points of the ECG) and global (obtained from the Karhunen-Loève transform) indexes. In particular, the evolution of Q, R and S wave amplitudes during ischemia was analyzed with respect to classical indexes such as ST level. As a measurement of sensitivity we used an Ischemic Changes Sensor (ICS), which reflects the capacity of an index to detect changes in the ECG. RESULTS: The results showed that, in leads with low-amplitude ST-T complexes, the S wave amplitude was more sensitive in detecting ischemia than was the commonly used index ST60. It was found that in such leads the S wave amplitude initially exhibited a delayed response to ischemia when compared to ST60, but its performance was better from the second minute of occlusion. The global indexes describing the ST-T complex were, in terms of the ICS, superior to the S wave amplitude for ischemia detection. CONCLUSIONS: Ischemic ECG changes occur both at repolarization and depolarization, with alterations in the depolarization period appearing later in time. Local indexes are less sensitive to ischemia than global ones.

Modeling and quantification of repolarization feature dependency on heart rate.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". OBJECTIVES: This work aims at providing an efficient method to estimate the parameters of a non linear model including memory, previously proposed to characterize rate adaptation of repolarization indices. METHODS: The physiological restrictions on the model parameters have been included in the cost function in such a way that unconstrained optimization techniques such as descent optimization methods can be used for parameter estimation. The proposed method has been evaluated on electrocardiogram (ECG) recordings of healthy subjects performing a tilt test, where rate adaptation of QT and Tpeak-to-Tend (Tpe) intervals has been characterized. RESULTS: The proposed strategy results in an efficient methodology to characterize rate adaptation of repolarization features, improving the convergence time with respect to previous strategies. Moreover, Tpe interval adapts faster to changes in heart rate than the QT interval. CONCLUSIONS: In this work an efficient estimation of the parameters of a model aimed at characterizing rate adaptation of repolarization features has been proposed. The Tpe interval has been shown to be rate related and with a shorter memory lag than the QT interval.

Assessing real-time RR-QT frequency-domain measures of coupling and causality through inhomogeneous point-process bivariate models.

Ventricular repolarization instability is known to be related to arrhythmogenesis and increased risk of sudden cardiac death. These repolarization dynamics are linked to the distance between T-wave and Q-wave occurrences (QT) on the ECG, and they are coupled with R-wave to R-wave interval variability (RRV). Several efforts have been dedicated to the analysis of QT-RR interactions in order to provide both a quantification of the coupling and estimates of intrinsic repolarization dynamics. However, a methodology able to quantify dynamic changes in repolarization variability unrelated to RRV dynamics is still needed. In this study, we propose a bivariate model embedded within a multiple inhomogeneous point-process framework to obtain time-varying tracking of (causal) interactions between QT variability (QTV), a marker of repolarization variability, and RRV. Data from 15 healthy subjects undergoing a tilt table test were analyzed. Our results demonstrate that the model effectively captures the time-varying mutual QTV-RRV interactions. The analysis of time-varying coherence confirms that head-up tilt is associated with a decrease in linear QTV-RRV coupling, while time-varying directed coherence shows that intrinsic QTV becomes more prominent during head-up tilt.

Amplias variaciones sistemáticas en hospitalizaciones potencialmente evitables en pacientes crónicos: estudio ecológico sobre zonas básicas de salud y áreas sanitarias / Wide systematic variations in potentially avoidable hospitalisations of chronically ill patients: Ecological study of basic health areas and healthcare areas

Antecedentes y objetivo Las hospitalizaciones potencialmente evitables (HPE) por condiciones crónicas constituyen un problema sanitario que puede ser reflejo de una atención sanitaria de insuficiente calidad. En este trabajo se describen las variaciones sistemáticas en HPE para el conjunto de proveedores del Sistema Nacional de Salud. Materiales y métodos Estudio ecológico sobre datos administrativos en el que se analiza la variación sistemática en las HPE por 6 condiciones crónicas en el período 2013-2015. Para la estimación de la variación se realiza análisis de área pequeña utilizando metodología bayesiana. Resultados Entre 2013 y 2015 se registraron 439.878 ingresos por HPE en el Sistema Nacional de Salud. La variación de tasas de HPE entre zonas básicas de salud (ZBS) extremas fue de hasta 4 veces, con diferencias muy variables dependiendo de la condición analizada El 40% de las ZBS presentó un riesgo de HPE por encima de la esperado. Más allá de la variación sistemática observada entre ZBS, las áreas sanitarias de residencia de los pacientes explicaron un 33% de la variación en las HPE. Sobre estos resultados generales, se observaron diferencias específicas en función de la condición clínica, edad y sexo. Conclusiones La amplia variación sistemática en HPE indica la existencia de un problema de calidad en la atención prestada a pacientes crónicos por el conjunto de proveedores de las áreas sanitarias. La identificación y análisis de aquellas zonas y áreas sanitarias con mejores resultados podría servir de referencia para la mejora de los cuidados en otros proveedores con peor desempeño (AU)

Background and objective Potentially avoidable hospitalisations (PAHs) due to chronic conditions are a healthcare problem that could reflect healthcare of insufficient quality. This study reports the systematic variations in PAHs for the collection of providers of the Spanish National Health System. Materials and methods We conducted an ecological study on government data, analysing the systematic variation in PAHs for 6 chronic conditions during 2013–2015. To determine the variation, we performed a small area analysis using Bayesian methodology. Results Between 2013 and 2015, 439,878 admissions for PAHs were recorded in the Spanish National Health System. There was an up to 4-fold difference in PAH rates between certain basic health areas (BHA), with highly variable differences depending on the analysed condition. Forty percent of the BHAs showed a greater than expected risk of PAH. Beyond the systematic variation observed between BHAs, the healthcare areas of the patients’ residence explained 33% of the variation in PAHs. We observed specific differences in these general results according to clinical condition, age and sex. Conclusions The wide systematic variation in PAHs suggests a problem of quality in the care provided to chronically ill patients by the providers of healthcare areas in Spain. Identifying and analysing these areas and other healthcare areas with better results could provide a reference for improving the care of other suppliers with poorer performance (AU)

Arrhythmic risk biomarkers for the assessment of drug cardiotoxicity: from experiments to computer simulations.

In this paper, we illustrate how advanced computational modelling and simulation can be used to investigate drug-induced effects on cardiac electrophysiology and on specific biomarkers of pro-arrhythmic risk. To do so, we first perform a thorough literature review of proposed arrhythmic risk biomarkers from the ionic to the electrocardiogram levels. The review highlights the variety of proposed biomarkers, the complexity of the mechanisms of drug-induced pro-arrhythmia and the existence of significant animal species differences in drug-induced effects on cardiac electrophysiology. Predicting drug-induced pro-arrhythmic risk solely using experiments is challenging both preclinically and clinically, as attested by the rise in the cost of releasing new compounds to the market. Computational modelling and simulation has significantly contributed to the understanding of cardiac electrophysiology and arrhythmias over the last 40 years. In the second part of this paper, we illustrate how state-of-the-art open source computational modelling and simulation tools can be used to simulate multi-scale effects of drug-induced ion channel block in ventricular electrophysiology at the cellular, tissue and whole ventricular levels for different animal species. We believe that the use of computational modelling and simulation in combination with experimental techniques could be a powerful tool for the assessment of drug safety pharmacology.

High-throughput cardiac science on the Grid.

Cardiac electrophysiology is a mature discipline, with the first model of a cardiac cell action potential having been developed in 1962. Current models range from single ion channels, through very complex models of individual cardiac cells, to geometrically and anatomically detailed models of the electrical activity in whole ventricles. A critical issue for model developers is how to choose parameters that allow the model to faithfully reproduce observed physiological effects without over-fitting. In this paper, we discuss the use of a parametric modelling toolkit, called Nimrod, that makes it possible both to explore model behaviour as parameters are changed and also to tune parameters by optimizing model output. Importantly, Nimrod leverages computers on the Grid, accelerating experiments by using available high-performance platforms. We illustrate the use of Nimrod with two case studies, one at the cardiac tissue level and one at the cellular level.

Bioactive peptides released from Saccharomyces cerevisiae under accelerated autolysis in a wine model system.

The ACE inhibitory activity (IACE) and the oxygen radical absorbance capacity (ORAC-FL) values of yeast peptides isolated from a model wine during accelerated autolysis of Saccharomyces cerevisiae have been studied. Samples were taken at 6, 24, 48, 121, and 144 h of autolysis. Peptide concentration increased throughout autolysis process. Peptides were fractionated into 2 fractions: F1, constituted by hydrophilic peptides, and F2, containing hydrophobic peptides. Both IACE activity and ORAC-FL values increased during 121 h of autolysis, then decreased afterward. Peptide fraction F2 was the main fraction involved in IACE activity and ORAC-FL.

Análisis del exceso de consumo de recursos en pacientes con enfermedad tromboembólica tras cirugía, infección por uso de dispositivo vascular postoperatorio o sepsis post-quirúrgica en el Sistema Nacional de Salud / Analysis of excess resources in patients with catheter-related infection (bacteremia), postoperative pulmonary embolism or deep vein (DVT-PTE) or postoperative sepsis in the National Health System

Objetivo: Estimar el exceso de estancia atribuible a la presencia de eventos adversos en pacientes que han sido sometidos a una intervención quirúrgica en el mismo episodio. Población y métodos: Estudio observacional, transversal, sobre bases de datos clínico-administrativos al alta hospitalaria. Las altas elegidas fueron producidas en los años 2009 y 2010 en los centros hospitalarios de agudos de las 17 comunidades autónomas del SNS español, las cuales forman parte del proyecto Atlas de Variabilidad de la Práctica Médica en el Sistema Nacional de Salud (Atlas VPM). Resultados: El exceso de estancia fue de 28, 10 y 14 días en las altas con infección debida a uso de dispositivo vascular, altas con tromboembolismo o trombosis venosa profunda tras la cirugía y altas con sepsis post-quirúrgica, respectivamente. Las variables predictoras del paciente (edad, sexo, Elixhauser) influyen en el exceso de estancia. Conclusión: Los eventos adversos están asociados a un incremento significativo de exceso de estancia. El CMBD (Conjunto Mínimo Básico de Datos hospitalario) permite hacer una estimación del impacto que esto tiene en los hospitales españoles (AU)

Objective: To estimate the excess of length of stay (LOS) attributable to the presence of adverse events in patients who were operated. Methodology: Observational, cross-sectional study on the basis of clinical and administrative hospital discharge data. Discharge chosen were produced in 2009 and 2010 in acute hospitals of the 17 Spanish autonomous communities of the National Health System, which are part of the project Atlas of Variability in Medical Practice in the National Health System (Atlas VPM Group). Results: Excess of LOS was 28 days, 10 days and 14 days in the catheter-related infection (bacteremia), postoperative pulmonary embolism or deep vein (DVT-PTE) or postoperative sepsis stays. The predictor variables of the patient (age, sex and Elixhauser) influence in the excess of LOS. Conclusion: Adverse events are associated with a significant increase of excess of LOS. The discharge minimum basic dataset (CMBD) allows to estimate the impact of adverse events in the Spanish hospitals (AU)

Changes in the Amino Acid Composition of Dehydrated Orange Juice during Accelerated Nonenzymatic Browning.

Maillard reaction in dehydrated orange juice stored at 30 or 50 degrees C and a(w) = 0.44 was studied. The decreases of the total amino acids were 30 and 65% of initial concentration after 14 days of storage at 30 and 50 degrees C, respectively. Storage at 50 degrees C for 14 days caused a decrease of 11.8 g/L of carbohydrates, and glucose was more reactive than fructose. Loss of sucrose due to hydrolysis was also observed. Presence of 1-(N-substituted)amino-1-deoxy-D-fructose compounds in stored dehydrated orange juice was detected by thin-layer chromatography.