Classification of skin blemishes with cell phone images using deep learning techniques.

Skin blemishes can be caused by multiple events or diseases and, in some cases, it is difficult to distinguish where they come from. Therefore, there may be cases with a dangerous origin that go unnoticed or the opposite case (which can lead to overcrowding of health services). To avoid this, the use of artificial intelligence-based classifiers using images taken with mobile devices is proposed; this would help in the initial screening process and provide some information to the patient prior to their final diagnosis. To this end, this work proposes an optimization mechanism based on two phases in which a global search for the best classifiers (from among more than 150 combinations) is carried out, and, in the second phase, the best candidates are subjected to a phase of evaluation of the robustness of the system by applying the cross-validation technique. The results obtained reach 99.95% accuracy for the best case and 99.75% AUC. Comparing the developed classifier with previous works, an improvement in terms of classification rate is appreciated, as well as in the reduction of the classifier complexity, which allows our classifier to be integrated in a specific purpose system with few computational resources.

Stability of individualized neonatal parenteral nutrition admixtures with fish oil and high calcium content.

Introduction: Introduction: the stability of total parenteral nutrition admixtures for neonates (TPNAn) has been questioned in relation to the interaction between calcium and fish oil emulsions. Aim: the aim of this study was to check the stability (particle size < 1 µm) of different individualized TPNAn prepared with fish-oil emulsion and containing calcium at concentrations ranging from 10 to 20 mmol/L. Methods: admixtures analyzed: twelve different formulations with SMOFlipid® 20 % (conserved for 24 h and for 96 h), three formulations with Lipoplus® 20 % (conserved for 96 h) and three formulations with SMOFlipid® 20 % with Multi-12K1® Pediatric (conserved for 96 h). Two bags were compounded for each formulation and conservation period. Measurements on each admixture bag: particle standardized diameter by laser diffraction technique and pH by a calibrated pH-meter. Data analysis with mixed linear regression models. Results: maximum particle size was < 0.8 µm for all investigated admixtures. Lipid concentration of 5 g/L and sodium and potassium concentration of 100 mmol/L slightly increased the proportion of particles > 0.6 µm. Ninety six hours storage also increased the percentage of particles > 0.6 µm (+0.143 ± 0.07; p = 0.038) but did not influence other parameters. No association with calcium composition was observed. Amino acid content was inversely correlated with pH (-0.83; p < 0.0001). Conclusions: the studied individualized parenteral nutrition admixtures for newborns that contain fish oil emulsions and meet cation requirements are stable for at least 96 hours.

Introducción: Introducción: existe controversia sobre la estabilidad de las mezclas de nutrición parenteral total para recién nacidos (TPNAn) con emulsiones de omega-3 y alto contenido en calcio. Objetivo: estudiar la estabilidad (tamaño de partículas < 1 µm) de diferentes TPNAn individualizadas preparados con una emulsión lipídica que contiene w3 y concentraciones de calcio entre 10 y 20 mmol/L. Métodos: se analizaron doce formulaciones diferentes con SMOFlipid® 20 % (conservadas durante 24 h y por 96 h), tres formulaciones con Lipoplus® 20 % (conservadas durante 96 h) y tres formulaciones con SMOFlipid® 20 % con Multi-12K1® Pediatric (conservadas durante 96 h). Se prepararon dos bolsas por cada formulación y período de conservación. Se midieron el diámetro de partícula estandarizado mediante técnica de difracción láser y el pH con un pH-metro calibrado. Análisis de datos con modelos de regresión lineal mixta. Resultados: el tamaño máximo de partícula fue < 0,8 µm para todas las mezclas investigadas. La concentración de lípidos de 5 g/L y la concentración de sodio y potasio de 100 mmol/L aumentaron ligeramente la proporción de partículas > 0,6 µm. El almacenamiento de noventa y seis horas también aumentó el porcentaje de partículas > 0,6 µm (+0,143 ± 0,07; p = 0,038) pero no influyó en otros parámetros. No se observó asociación con la concentración de calcio. El contenido de aminoácidos se correlacionó inversamente con el pH (-0,83; p < 0,0001). Conclusiones: las TPNAn individualizadas estudiadas con emulsiones de omega-3 que incluyen los requerimientos de cationes son estables durante al menos 96 horas.

Performance of a pilot-scale BDD reactor by numerical analysis of reaction rate parameters and additional numbers for mass transfers.

The performance of a pilot-scale boron-doped diamond (BDD) reactor through a numerical analysis of reaction rate parameters and enhanced mass transfer has been investigated. The main objective of this research is to evaluate the efficiency of the reactor in mineralizing and degrading caffeine as an emerging contaminant. Based on the kinetic mechanisms and mass transport correlations reported in the literature, two reaction rate kinetic models for caffeine degradation are proposed and analyzed. The models consider different electrolytes (NaCl and Na2SO4) and applied current densities. The kinetic fitting process utilizes the gradient-maximal electrochemical approach, together with orthogonal placement methods, fourth-order Runge-Kutta (RK4) methods, and Nelder & Mead methods for optimization of kinetic parameters and spatial discretization of the material balance. Experimental data obtained from a factorial design with four factors and two levels (24) validate the proposed kinetic models. Caffeine degradation is achieved with NaCl and Na2SO4 electrolytes at concentrations of 60 ppm and 100 ppm, respectively. The corresponding applied loads are 1.5 AhL-1 and 3 AhL-1. Na2SO4 exhibits superior performance with a total organic carbon (TOC) removal efficiency of 99.13%, while NaCl achieves 31.47% mineralization. The behavior of caffeine degradation under the operational and scale conditions demonstrates that NaCl, as a support electrolyte, enables controlled charge transfer (current density) during the degradation process. In contrast, Na2SO4 as a support electrolyte introduces a mixed control of charge and mass transfer. The pilot-scale kinetic parameters obtained in this study provide valuable insights into the support electrolyte dynamics and current density dynamics in BDD-based Electrooxidation (EO) systems, particularly in complex matrix applications. Furthermore, the observed electrical consumption supports the potential application of EO as a viable technology for industrial-scale tertiary wastewater treatment, specifically for caffeine removal.

[Translated article] Influence of augmented renal clearance in the lower incidence of linezolid-related haematological toxicity.

OBJECTIVES: Linezolid is an oxazolidin commonly related to the development of haematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced haematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. MATERIAL AND METHODS: A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014-2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60-90 mL/min) were compared. Haematological toxicity was defined as a decrease of 25% in platelets, of 25% in haemoglobin, and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of haematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentage diminution of all 3 parameters was calculated and compared by Mann-Whitney test and treatment interruption and transfusion requirements were registered. RESULTS: 30 ARC patients and 38 reference patients were included. Haematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (P=.014); thrombocytopenia in 13.33% vs 36.84% (P=.051), anaemia in 3.3% vs 10.52% (P=.374) and neutropenia in 10% vs 23.68% (P=.204). Median percentage of platelets decrease in ARC patients was -10.36 (-193.33-62.03) vs 2.68 (-163.16-82.71) in reference patients (P=.333), while haemoglobin decrease was 2.50 (-12.12-25.93) vs 9.09 (-17.72-30.63) (P=.047) and neutrophils decrease was 9.14 (-73.91-76.47) vs 27.33 (-86.66-90.90) (P=.093). 10.5% of normal renal function patients reported at least 1 adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had transfusion requirements. No major events or interruptions were reported in ARC patients. CONCLUSION: Our findings suggest a lower incidence and clinical relevance of haematological toxicity in augmented renal clearance patients. Thrombocytopenia was the major event in both populations. This might be related to a lower exposure to the drug due to the higher clearance and likely lower therapeutic efficiency. These results suggest a potential benefit of therapeutic drug monitoring on high risk patients.

Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid / Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity

Objetivos linezolid es una oxazolidina frecuentemente implicada en el desarrollo de toxicidad hematológica, siendo el aclaramiento renal el mecanismo mayoritario en su eliminación. Se evaluó la influencia de la hiperfiltración glomerular en la toxicidad hematológica inducida por linezolid en pacientes con aclaramiento incrementado frente a pacientes con función renal normal. Material y métodos se diseñó un estudio observacional y retrospectivo en pacientes hospitalizados, tratados al menos 5 días con linezolid entre 2014 y 2019. Se compararon pacientes con aclaramiento de creatinina incrementado (≥130 mL/min) y normal (60–90 mL/min). Se definió la toxicidad hematológica como el descenso en plaquetas y hemoglobina del 25% y en neutrófilos del 50% frente a los valores basales. Se clasificó el grado de toxicidad según Common Terminology Criteria for Adverse Events v5 y se comparó la incidencia entre ambos grupos mediante Chi-cuadrado y Fisher. Así mismo, se calculó el porcentaje de disminución de los 3 parámetros y su asociación mediante el test de Mann–Whitney y se registraron las interrupciones y transfusiones asociadas.Resultados se evaluaron 30 pacientes hiperfiltradores y 38 normofiltradores. El 16,66% de hiperfiltradores presentó toxicidad hematológica frente al 44,74% (p = 0,014). La trombocitopenia fue del 13,33 vs. 36,84% (p = 0,051), la anemia del 3,3 vs. 10,52% (p = 0,374) y la neutropenia del 10 vs. 23,68% (p = 0,204). La mediana del porcentaje de descenso plaquetario en hiperfiltradores frente a normofiltradores fue del −10,36 (−193,33–62,03) vs. 2,68 (−163,16–82,71) (p = 0,333), de hemoglobina 2,50 (−12,12–25,93) vs. 9,09 (−17,72–30,63) (p = 0,047) y de neutrófilos 9,14 (−73,91–76,47) vs. 27,33 (−86,66–90,90) (p = 0,093). El 10,5% con filtrado normal presentó toxicidad grado 3 o superior, el 2,6% interrumpió el tratamiento y el 5,2% requirieron transfusiones... (AU)

Objectives Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. Material and methods A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014–2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60–90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann–Whitney test and treatment interruption and tranfusion requirements were registered. Results 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was −10.36 (−193.33–62.03) vs 2.68 (−163.16–82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (−12.12–25.93) vs 9.09 (−17.72–30.63) (p = 0.047) and neutrophils decrease was 9.14 (−73.91–76.47) vs 27.33 (−86.66–90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements... (AU)

Influence of augmented renal clearance on the lower incidence of linezolid-related hematological toxicity. / Influencia de la hiperfiltración glomerular en la menor toxicidad hematológica inducida por linezolid.

OBJECTIVES: Linezolid is an oxazolidin commonly related to the development of hematological toxicity, being renal clearance the major factor involved in the drug clearance. The aim of this study is to evaluate the influence of increased filtration rates in the incidence of linezolid-induced hematological toxicity by comparing augmented renal clearance (ARC) patients versus normal renal function patients. MATERIAL AND METHODS: A retrospective, observational study was conducted on hospitalized patients treated with linezolid for 5 days or more during 2014-2019 period. Patients with a filtration rate of ≥130 mL/min versus reference patients (60-90 mL/min) were compared. Hematological toxicity was defined as a decrease of 25% in platelets, of 25% in hemoglobin and/or 50% in neutrophils from baseline. Toxicity relevance was classified according to Common Terminology Criteria for Adverse Events v5. Incidence of hematological toxicity between groups was studied by chi-square and Fisher test. Furthermore, percentaje disminution of all three parameters was calculated and compared by Mann-Whitney test and treatment interruption and tranfusion requirements were registered. RESULTS: 30 ARC patients and 38 reference patients were included. Hematological toxicity was observed in 16.66% of ARC patients vs 44.74% of reference patients (p = 0.014); thrombocytopenia in 13.33% vs 36.84% (p = 0.051), anemia in 3.3% vs 10.52% (p = 0.374) and neutropenia in 10% vs 23.68% (p = 0.204). Median percentaje of platelets decrease in ARC patients was -10.36 (-193.33-62.03) vs 2.68 (-163.16-82.71) in reference patients (p = 0.333), while hemoglobin decrease was 2.50 (-12.12-25.93) vs 9.09 (-17.72-30.63) (p = 0.047) and neutrophils decrease was 9.14 (-73.91-76.47) vs 27.33 (-86.66-90.90) (p = 0.093). 10.5% of normal renal function patients reported at least one adverse event grade 3 or superior while 2.6% of them interrupted treatment and 5.2% had tranfusion requirements. No major events or interruptions were reported in ARC patients. CONCLUSION: Our findings suggest a lower incidence and clinical relevance of hematological toxicity in augmented renal clearance patients. Thrombocytopenia was the major event in both populations. This might be related to a lower exposure to the drug due to the higher clearance and likely lower therapeutic efficiency. These results suggest a potential benefit of therapeutic drug monitoring on high risk patients.

Rivaroxabán e inhibidores selectivosde la recaptación de serotonina: Análisis comparativo del riesgo de sangrado / Rivaroxaban and selective serotonin reuptake inhibitors: Bleeding risk resulting from their concomitant use

Objetivo: La combinación de rivaroxabán e inhibidores selectivos de larecaptación de serotonina presenta un riesgo de interacción farmacodinámicay farmacocinética que depende del tipo de inhibidor selectivo dela recaptación de serotonina empleado, ya que algunos son inhibidoresdel citocromo p450, mientras que otros no lo son. El objetivo del presenteestudio fue evaluar con datos de vida real si el tipo de inhibidor selectivode la recaptación de serotonina utilizado influye en la frecuencia y en lagravedad de sangrado en pacientes anticoagulados con rivaroxabán.Método: Estudio observacional, longitudinal, retrospectivo y unicéntrico,realizado entre enero de 2016 y febrero de 2020 en pacientes ≥ 18 añosque recibían rivaroxabán, en indicaciones autorizadas y financiadas, y queestaban siendo tratados concomitantemente con inhibidores selectivos dela recaptación de serotonina. Se establecieron dos cohortes en funcióndel inhibidor selectivo de la recaptación de serotonina coadministrado:inhibidores del CYP3A4 (grupo 1) —sertralina, fluoxetina y paroxetina—,y no inhibidores del CYP3A4 (grupo 2) —citalopram y escitalopram—. Seanalizaron los eventos hemorrágicos, la gravedad del sangrado, la dosisdiaria de rivaroxabán y la medicación concomitante que pudiese influir enel riesgo de sangrado.Resultados: Se incluyeron 146 pacientes (89 en el grupo 1 y 57 en elgrupo 2) y se identificaron un total de 35 eventos hemorrágicos (24% delos pacientes), de los que 12 fueron eventos mayores y 23 menores. Lafrecuencia de sangrado fue ligeramente mayor en el grupo 1 que en el 2(25,8% versus 21%), pero no se encontraron diferencias significativas entre ambos grupos, ni tampoco en la frecuencia de sangrados mayores (10,1%versus 5,3%; p = 0,235) o menores (13,5% versus 15,8%; p = 0,496).

Objective: The combination of selective serotonin reuptake inhibitorswith rivaroxaban may result in a dual interaction (pharmacokinetic andpharmacodynamic) depending on the type of selective serotonin reuptakeinhibitor employed (CYP3A4-inhibiting vs. non-CYP3A4 inhibiting). Thepurpose of this study was to use real world data to determine if the typeof selective serotonin reuptake inhibitor used plays a role in the risk andseverity of bleeding in patients receiving rivaroxaban.Method: This was a single-center retrospective longitudinal observationalstudy carried out between January 2016 and February 2020 inpatients aged 18 years or older treated concurrently with rivaroxaban(prescribed for treatments) and a selective serotonin reuptake inhibitor. Patients were divided into two groups according to the selective serotoninreuptake inhibitor they received, i.e., a CYP3A4 inhibitor (group 1): sertraline,fluoxetine and paroxetine, or a non-CYP3A4 inhibitor (group 2):citalopram and escitalopram. We analyzed the bleeding events and severity,the daily dose of rivaroxaban used and the medication administeredconcomitantly.Results: A total of 146 patients were included (89 in group 1 and 57in group 2) and 35 bleeding events (24% of patients) were identified, of which 12 were major and 23 were minor. The bleeding rate was higherin group 1 (25.8% vs 21.0%) but there were no differences in major bleeding(10.1% vs 5.3%; p = 0.235) or minor bleeding (13.5% vs 15.8%;p = 0.496).

Evaluation of Spanish Health System during the COVID-19 Pandemic: Accountability and Wellbeing Results.

The COVID-19 pandemic poses a challenge for health systems. For this reason, it is essential to evaluate the management of health systems in the face of the pandemic, identifying the factors that may contribute to its failure or success. This management is more difficult in decentralized countries, since in them, health competencies are distributed among different levels of government. This is the case in Spain, one of the countries most affected by the pandemic. Therefore, the aim of this article is to evaluate how the Spanish health system has managed the COVID-19 pandemic. Four factors related to health management are analyzed: transparency, communication, reputation and well-being generated. For this purpose, a quantitative analysis is used with the contrast of secondary sources, such as the Merco rankings or survey data from the Centro de Investigaciones Sociológicas (Sociological Research Center). The results show that although the flow of communication about the health system increases considerably, such information comes mainly from the media, with a deficit in the transparency of health management. Likewise, although the reputation of the health system increases at the beginning of the pandemic, as it progresses, there is a deterioration in citizen satisfaction with the healthcare management and the services provided, as well as in the well-being generated by them. This study may have implications for decision making by public authorities regarding the different factors of health management.

Interacción entre ácido valproico con meropenemo ertapenem en pacientes con epilepsia: relevancia clínica y resultados de la intervención farmacéutica / Interaction between valproic acid and meropenem or ertapenem in patients with epilepsy: clinical relevance and results from pharmaceutical intervention

Objetivo: La interacción entre ácido valproico y carbapenems está descrita en la literatura y conlleva una disminución de los niveles plasmáticosde ácido valproico. Los objetivos son evaluar su relevancia en la prácticaclínica, conocer las variables que se asocian a un incremento de crisisepilépticas y analizar el impacto de la intervención farmacéutica paraevitar las consecuencias de dicha interacción.Método: En este estudio observacional retrospectivo se estudiaronpacientes con epilepsia hospitalizados entre 2016 y 2020. Se registróel tratamiento farmacológico prescrito en el ingreso y se revisó la presencia de otras interacciones que redujeran la concentración plasmática deácido valproico. La frecuencia de crisis epilépticas durante el año previo alingreso se comparó con la correspondiente al periodo de interacción. Serealizó una intervención en todos los episodios con la interacción detectada informando al prescriptor sobre la interacción y proponiendo sustitución de la antibioterapia, así como monitorización farmacocinética deácido valproico.Resultados: Se incluyeron 37 episodios. El 58,1% eran varones y lamediana de edad fue de 70 años. El 56,8% de los pacientes recibiómeropenem y el 43,2% restante, ertapenem. Para la duración del tratamiento concomitante entre ácido valproico y el carbapenem prescrito se obtuvo una mediana de 4 días. Se halló una razón de tasas de incidencia de 2,60 (intervalo de confianza del 95%: 1,61-4,21), por lo queesta interacción se asocia a una mayor frecuencia de crisis epilépticas.Se asoció una mayor frecuencia de crisis estadísticamente significativaen los pacientes tratados con más de un fármaco antiepiléptico. Los farmacéuticos hospitalarios detectaron 24 episodios (64,9%). (AU)

Objective: The literature has described the interaction between valproicacid and carbapenems. This interaction leads to decreases in plasmaconcentrations of valproic acid. The main objectives of this study were toassess its relevance in clinical practice, to identify variables associatedwith increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction.Method: An observational retrospective study of inpatients withepilepsy admitted between 2016 and 2020. Their pharmacologicaltreatment throughout admission was recorded, and the presence of otherinteractions leading to decreased plasma concentrations of valproicacid was reviewed. The seizure rate during the year prior to admissionwas compared to that during the interaction period. For every episodein which the interaction was detected, an intervention was conducted byproviding the prescriber with information on the interaction and suggesting a change of antibiotherapy as well as the pharmacokinetic monitoring of valproic acid.Results: 37 episodes were included. 58.1% of the patients were maleand median age was 70 years. In total, 56.8% of the patients receivedmeropenem and 43.2% received ertapenem. The median duration of concomitant treatment with valproic acid and carbapenem was 4 days. The incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus,this interaction was associated with a higher seizure rate. A statistically significant association was found between higher seizure rates andpatients treated with more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes (64.9%). In total, 17 interventions (70.8%)were accepted and 13 combinations were discontinued. Pharmacokineticmonitoring was conducted in 13 episodes (35.1%) and infratherapeuticlevels were found in all of them. (AU)

Interaction between valproic acid and meropenem or ertapenem in patients with epilepsy: clinical relevance and results from pharmaceutical intervention.

OBJECTIVE: The literature has described the interaction between valproic acid  and carbapenems. This interaction leads to decreases in plasma concentrations  of valproic acid. The main objectives of this study were  to assess its relevance in clinical practice, to identify variables associated with  increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction. METHOD: An observational retrospective study of inpatients with epilepsy  admitted between 2016 and 2020. Their pharmacological treatment throughout  admission was recorded, and the presence of other interactions  leading to decreased plasma concentrations of valproic acid was reviewed. The  seizure rate during the year prior to admission was compared to that during  the interaction period. For every episode in which the interaction was detected, an intervention was conducted by providing the prescriber with information on  the interaction and suggesting a change of antibiotherapy as well as the  pharmacokinetic monitoring of valproic acid. RESULTS: 37 episodes were included. 58.1% of the patients were male and  median age was 70 years. In total, 56.8% of the patients received meropenem  and 43.2% received ertapenem. The median duration of  concomitant treatment with valproic acid and carbapenem was 4 days. The  incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus, this  interaction was associated with a higher seizure rate. A statistically significant  association was found between higher seizure rates and patients treated with  more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes  (64.9%). In total, 17 interventions (70.8%) were accepted and 13  combinations were discontinued. Pharmacokinetic monitoring was conducted in  13 episodes (35.1%) and infratherapeutic levels were found in all of them. CONCLUSIONS: The interaction between valproic acid and meropenem or ertapenem is clinically relevant. It is recommended that this combination should be avoided provided that a viable alternative is available.  Pharmaceutical intervention may contribute to preventing seizures associated with this combination.

Objetivo: La interacción entre ácido valproico y carbapenems está descrita en  la literatura y conlleva una disminución de los niveles plasmáticos de ácido  valproico. Los objetivos son evaluar su relevancia en la práctica clínica, conocer  las variables que se asocian a un incremento de crisis epilépticas y  analizar el impacto de la intervención farmacéutica para evitar las  consecuencias de dicha interacción.Método: En este estudio observacional retrospectivo se estudiaron pacientes  con epilepsia hospitalizados entre 2016 y 2020. Se registró el tratamiento  farmacológico prescrito en el ingreso y se revisó la presencia de otras  interacciones que redujeran la concentración plasmática de ácido valproico. La  frecuencia de crisis epilépticas durante el año previo al ingreso se comparó con  la correspondiente al periodo de interacción. Se realizó una intervención  en todos los episodios con la interacción detectada informando al prescriptor  sobre la interacción y proponiendo sustitución de la antibioterapia, así como  monitorización farmacocinética de ácido valproico.Resultados: Se incluyeron 37 episodios. El 58,1% eran varones y la mediana  de edad fue de 70 años. El 56,8% de los pacientes recibió meropenem y el  43,2% restante, ertapenem. Para la duración del tratamiento concomitante  entre ácido valproico y el carbapenem prescrito  se obtuvo una mediana de 4  días. Se halló una razón de tasas de incidencia de 2,60 (intervalo de confianza  del 95%: 1,61-4,21), por lo que esta interacción se asocia a una mayor  frecuencia de crisis epilépticas. Se asoció una mayor frecuencia de crisis  estadísticamente significativa en los pacientes tratados con más de un fármaco  antiepiléptico. Los farmacéuticos hospitalarios detectaron 24  episodios (64,9%). Se aceptaron 17 intervenciones farmacéuticas (70,8%) y  se suprimieron 13 combinaciones. Se realizó monitorización farmacocinética en  13 episodios (35,1%) y en todos se hallaron niveles infraterapéuticos. Conclusiones: La interacción entre ácido valproico y meropenem o ertapenem  es clínicamente relevante y se recomienda evitarla siempre que  existan alternativas viables. La intervención farmacéutica puede contribuir a  prevenir las crisis epilépticas favorecidas por esta combinación.

Formalization of gene regulation knowledge using ontologies and gene ontology causal activity models.

Gene regulation computational research requires handling and integrating large amounts of heterogeneous data. The Gene Ontology has demonstrated that ontologies play a fundamental role in biological data interoperability and integration. Ontologies help to express data and knowledge in a machine processable way, which enables complex querying and advanced exploitation of distributed data. Contributing to improve data interoperability in gene regulation is a major objective of the GREEKC Consortium, which aims to develop a standardized gene regulation knowledge commons. GREEKC proposes the use of ontologies and semantic tools for developing interoperable gene regulation knowledge models, which should support data annotation. In this work, we study how such knowledge models can be generated from cartoons of gene regulation scenarios. The proposed method consists of generating descriptions in natural language of the cartoons; extracting the entities from the texts; finding those entities in existing ontologies to reuse as much content as possible, especially from well known and maintained ontologies such as the Gene Ontology, the Sequence Ontology, the Relations Ontology and ChEBI; and implementation of the knowledge models. The models have been implemented using Protégé, a general ontology editor, and Noctua, the tool developed by the Gene Ontology Consortium for the development of causal activity models to capture more comprehensive annotations of genes and link their activities in a causal framework for Gene Ontology Annotations. We applied the method to two gene regulation scenarios and illustrate how to apply the models generated to support the annotation of data from research articles.

COVID-19 and the Political Economy of Mass Hysteria.

In this article, we aim to develop a political economy of mass hysteria. Using the background of COVID-19, we study past mass hysteria. Negative information which is spread through mass media repetitively can affect public health negatively in the form of nocebo effects and mass hysteria. We argue that mass and digital media in connection with the state may have had adverse consequences during the COVID-19 crisis. The resulting collective hysteria may have contributed to policy errors by governments not in line with health recommendations. While mass hysteria can occur in societies with a minimal state, we show that there exist certain self-corrective mechanisms and limits to the harm inflicted, such as sacrosanct private property rights. However, mass hysteria can be exacerbated and self-reinforcing when the negative information comes from an authoritative source, when the media are politicized, and social networks make the negative information omnipresent. We conclude that the negative long-term effects of mass hysteria are exacerbated by the size of the state.

A novel high rotation bubble reactor for the treatment of a model pollutant in ozone/goethite/H2O2 and UV/goethite coupled processes.

This work proposes a novel approach for the coupling of ozonation and Fenton processes using a new prototype of a high rotation bubble reactor (HRBR), which improves utilization of the ozone and hydrogen peroxide through bubble generation and axial and radial dispersion of the flow. The HRBR integrates the rotor and the diffuser in the same device facilitating the generation and dispersion of the ozone bubbles inside the reaction tank. Thus, the mass transfer to the liquid phase is enhanced. Most of the experiments were carried out under neutral pH and 1580 rpm of agitation during the 20 min of reaction. Total ibuprofen degradation was achieved within 20 min of operation for most of the couplings and individual processes evaluated. It was successfully demonstrated that the HRBR can be used as a reactive system for heterogeneous Fenton and ozonation coupling because it presents a high synergy. For the ozonation process, the reactor also displayed a good performance because the residual ozone in the gas is lower than 0.4 mg/L, which indicates that there is a suitable ozone utilization. Ibuprofen degradation by other processes like oxidation direct by H2O2 and heterogeneous Fenton was 28.0% and 73.1%, respectively. It was determined that the reaction rate, synergy, OUI (ozone utilized index), and consumption of electrical energy (EE/O) of the coupled processes could be improved by using the HRBR depending on the experimental conditions.

Rivaroxaban and selective serotonin reuptake inhibitors: Bleeding risk resulting from their concomitant use.

OBJECTIVE: The combination of selective serotonin reuptake inhibitors with  rivaroxaban may result in a dual interaction (pharmacokinetic and pharmacodynamic) depending on the type of selective serotonin reuptake inhibitor employed (CYP3A4-inhibiting vs. non-CYP3A4 inhibiting).  The purpose of this study was to use real world data to determine if the type of  selective serotonin reuptake inhibitor used plays a role in the risk and severity of bleeding in patients receiving rivaroxaban. Method: This was a single-center retrospective longitudinal observational study carried out between January 2016 and February 2020 in patients aged 18 years or older treated concurrently with rivaroxaban (prescribed for treatments) and a selective serotonin reuptake  nhibitor. Patients were divided into two groups according to the selective  serotonin reuptake inhibitor they received, i.e., a CYP3A4 inhibitor (group 1):  sertraline, fluoxetine and paroxetine, or a non-CYP3A4 inhibitor (group 2): citalopram and escitalopram. We analyzed the bleeding events and  everity, the daily dose of rivaroxaban used and the medication administered concomitantly. RESULTS: A total of 146 patients were included (89 in group 1 and 57 in group  2) and 35 bleeding events (24% of patients) were identified, of  which 12 were  major and 23 were minor. The bleeding rate was higher in group 1  (25.8% vs 21.0%) but there were no differences in major bleeding (10.1% vs  5.3%; p = 0.235) or minor bleeding (13.5% vs 15.8%; p = 0.496). The  bleeding rate with a daily rivaroxaban dose of 20 mg was 9% (8/89) in group 1  and 14% (8/57) in group 2 (p = 0.2137), as compared with 16.9% (15/89)  in group 1 versus 7% (4/57) in group 2 (p = 0.042) for a daily 15 mg dose. CONCLUSIONS: Although the type of selective serotonin reuptake inhibitor used  concurrently with rivaroxaban was not found to influence the patients' bleeding  risk, a significant increase in the risk of bleeding was  bserved based on the dose of rivaroxaban used.

OBJETIVO: La combinación de rivaroxabán e inhibidores selectivos de la recaptación de serotonina presenta un riesgo de interacción  farmacodinámica y farmacocinética que depende del tipo de inhibidor selectivo  de la recaptación de serotonina empleado, ya que algunos son inhibidores del  citocromo p450, mientras que otros no lo son. El objetivo del presente estudio  fue evaluar con datos de vida real si el tipo de inhibidor selectivo de la  recaptación de serotonina utilizado influye en la frecuencia y en la gravedad de  sangrado en pacientes anticoagulados con rivaroxabán. Método: Estudio observacional, longitudinal, retrospectivo y unicéntrico, realizado entre enero de 2016 y febrero de 2020 en pacientes ≥  18 años que recibían rivaroxabán, en indicaciones autorizadas y financiadas, y  que estaban siendo tratados concomitantemente con inhibidores selectivos de  la recaptación de serotonina. Se establecieron dos cohortes en función del  inhibidor selectivo de la recaptación de serotonina coadministrado: inhibidores  del CYP3A4 (grupo 1) ­sertralina, fluoxetina y paroxetina­, y no inhibidores  del CYP3A4 (grupo 2) ­citalopram y escitalopram­. Se analizaron los eventos  hemorrágicos, la gravedad del sangrado, la dosis diaria de rivaroxabán y la  medicación concomitante que pudiese influir en el riesgo de sangrado. RESULTADOS: Se incluyeron 146 pacientes (89 en el grupo 1 y 57 en el grupo  2) y se identificaron un total de 35 eventos hemorrágicos (24% de los  pacientes), de los que 12 fueron eventos mayores y 23 menores. La frecuencia  de sangrado fue ligeramente mayor en el grupo 1 que en el 2 (25,8% versus 21%), pero no se encontraron diferencias significativas entre  ambos grupos, ni tampoco en la frecuencia de sangrados mayores  (10,1% versus 5,3%; p = 0,235) o menores (13,5% versus 15,8%; p =  0,496). La frecuencia de eventos hemorrágicos con la dosis de 20 mg fue del  9% (8/89) en el grupo 1 y del 14% (8/57) en el grupo 2 (p = 0,2137), mientras que con una dosis de 15 mg la frecuencia de eventos fue del 16,9% (15/89) en el grupo 1 y del 7% (4/57) en el grupo 2 (p = 0,042). CONCLUSIONES: No se han hallado diferencias significativas en el riesgo de  sangrado según el tipo de inhibidor selectivo de la recaptación de serotonina  que se administre de forma concomitante al rivaroxabán. Sí se han observado  diferencias significativas en función de la dosis de rivaroxabán utilizada.

Parâmetros morfométricos e quantitativos de tecidos adiposos de ratos alimentados com resíduos de lichia / Morphometric and quantitative parameters of adipose tissues of rats fed lychee residues

Objetivo: avaliar os parâmetros morfométricos e a quantidade de tecidos adiposos de ratos alimentados com resíduos da lichia. Métodos: na etapa 1, os animais foram divididos em grupo C (controle) e grupo H (dieta hipercalórica); enquanto, na etapa 2, os animais do grupo C permaneceram neste grupo, e os demais foram divididos no grupo H, grupo HCL (10% de farinha da casca de lichia), e o grupo HSL (10% de farinha da semente de lichia). Avaliaram-se os Índices de Massa Corporal (IMC) e de Lee; o consumo alimentar, o Coeficiente de Eficiência Alimentar e a Digestibilidade Aparente; os Índices Hepato-Somático, de Gordura Visceral e de Gordura Epididimal. Compararam-se os dados pelo Teste de Tukey a 5%. Resultados: não houve diferença estatística quanto o peso corporal, o IMC, o consumo alimentar, e o Índice Hepato-Somático. O grupo HCL não diferiu do grupo C quanto ao Coeficiente de Eficiência Alimentar e à quantidade dos tecidos adiposos (visceral e epididimal). Os grupos que receberam as farinhas de lichia não diferiram do grupo C quanto ao ganho de peso e ao Índice de Lee; entretanto, apresentaram menor Índice de Gordura Epididimal que o grupo H e maior que o grupo C, embora o grupo controle (C) apresentasse menor Digestibilidade Aparente das dietas nas duas avaliações. Conclusão: a farinha da casca de lichia apresentou os melhores resultados, uma vez que não diferiu do grupo controle (C) para alguns parâmetros morfométricos e a quantidade dos tecidos adiposos, sugerindo que as fibras e os polifenóis dessa farinha promoveram os efeitos identificados neste estudo.

Objective: to evaluate the morphometric parameters and the amount of adipose tissue of rats fed lychee residues. Methods: in stage 1, the animals were divided into group C (control) and group H (hypercaloric diet); while in stage 2, the animals from group C remained in this group, and the others were divided into group H, group LPF (10% lychee peel flour), and group LSF (10% lychee seed flour). Body Mass Index (BMI) and Lee Index; dietary intake, Food Efficiency Coefficient and Apparent Digestibility; Hepato-Somatic, Visceral Fat (VFI) and Epididymal Fat Indexes (EFI) were evaluated. The data were compared by the Tukey Test at 5%. Results: there was no statistical difference regarding body weight, BMI, food intake, and Hepato-Somatic Index. The LPF group did not differ from group C (p>0.05) regarding the Food Efficiency Coefficient and the amount of adipose tissues (visceral and epididymal). The groups that received the lychee flours did not differ from group C regarding weight gain and Lee Index, however they presented lower Epididymal Fat Index than group H and higher than group C, and the control group (C) presented lower Apparent Dietary Digestibility in both evaluations. Conclusion: lychee peel flour showed the best results, since it did not differ from the control group (C) for some morphometric parameters and the amount of adipose tissues, suggesting that the fibers and polyphenols of this flour promoted the effects identified in this study.

Experimental data on synthesis and characterization of WO3/TiO2 as catalyst.

WO3/TiO2 is a composite photocatalyst that is being widely used in heterogeneous photocatalysis because it presents better photocatalytic properties than TiO2. For example, the probability of recombination of the electron/hole pairs is diminished and a more range of the solar spectrum is used for its excitation. However, this depend of variables such as tungsten oxide concentration, calcination temperature and synthesis method. This work is focused in establish the effect of WO3 on the morphological and structural characteristics of TiO2. WO3/TiO2 was synthesized by sol-gel method at different calcination temperatures and at different concentrations of tungsten oxide. The surface area, the possible transition between valence band and conduction band, particle size, elemental analysis and crystallography were examined through the BET, DRS, SEM-EDS and XRD analysis.

EHR problem list clustering for improved topic-space navigation.

BACKGROUND: The amount of patient-related information within clinical information systems accumulates over time, especially in cases where patients suffer from chronic diseases with many hospitalizations and consultations. The diagnosis or problem list is an important feature of the electronic health record, which provides a dynamic account of a patient's current illness and past history. In the case of an Austrian hospital network, problem list entries are limited to fifty characters and are potentially linked to ICD-10. The requirement of producing ICD codes at each hospital stay, together with the length limitation of list items leads to highly redundant problem lists, which conflicts with the physicians' need of getting a good overview of a patient in short time. This paper investigates a method, by which problem list items can be semantically grouped, in order to allow for fast navigation through patient-related topic spaces. METHODS: We applied a minimal language-dependent preprocessing strategy and mapped problem list entries as tf-idf weighted character 3-grams into a numerical vector space. Based on this representation we used the unweighted pair group method with arithmetic mean (UPGMA) clustering algorithm with cosine distances and inferred an optimal boundary in order to form semantically consistent topic spaces, taking into consideration different levels of dimensionality reduction via latent semantic analysis (LSA). RESULTS: With the proposed clustering approach, evaluated via an intra- and inter-patient scenario in combination with a natural language pipeline, we achieved an average compression rate of 80% of the initial list items forming consistent semantic topic spaces with an F-measure greater than 0.80 in both cases. The average number of identified topics in the intra-patient case (µIntra = 78.4) was slightly lower than in the inter-patient case (µInter = 83.4). LSA-based feature space reduction had no significant positive performance impact in our investigations. CONCLUSIONS: The investigation presented here is centered on a data-driven solution to the known problem of information overload, which causes ineffective human-computer interactions at clinicians' work places. This problem is addressed by navigable disease topic spaces where related items are grouped and the topics can be more easily accessed.

Supervised ICD Code Assignment to Short Clinical Problem List Entries.

Clinical information systems contain free-text entries in different contexts to be used in a variety of application scenarios. In this study we investigate to what extent diagnosis codes using the disease classification system ICD-10 can be automatically post-assigned to patient-based short problem list entries, (50 characters maximum). Classifiers using random forest and Adaboost performed best with an F-measure of 0.87 and 0.85 running against an unbalanced data set, and an F-measure of 0.88 and 0.94 using a balanced data set, respectively.

ATLANTIS: a Phase III study of lurbinectedin/doxorubicin versus topotecan or cyclophosphamide/doxorubicin/vincristine in patients with small-cell lung cancer who have failed one prior platinum-containing line.

Lurbinectedin is an inhibitor of active transcription of protein-coding genes, causing DNA-break accumulation, apoptosis and modulation of the tumor microenvironment. Early-phase clinical trials indicate promising activity of lurbinectedin in small-cell lung cancer. Here, we describe the rationale and design of ATLANTIS (NCT02566993), an open-label, randomized, multicenter Phase III study to compare the efficacy of lurbinectedin and doxorubicin combination with standard-of-care chemotherapy, investigator's choice of cyclophosphamide/doxorubicin/vincristine or topotecan, in patients with small-cell lung cancer that has progressed following one line of platinum-based chemotherapy. Patients are randomized in a 1:1 ratio. The primary end point is overall survival and key secondary end points include progression-free survival, best tumor response and duration of response, each assessed by independent review committee.

EHR Text Categorization for Enhanced Patient-Based Document Navigation.

Patients with multiple disorders usually have long diagnosis lists, constitute by ICD-10 codes together with individual free-text descriptions. These text snippets are produced by overwriting standardized ICD-Code topics by the physicians at the point of care. They provide highly compact expert descriptions within a 50-character long text field frequently not assigned to a specific ICD-10 code. The high redundancy of these lists would benefit from content-based categorization within different hospital-based application scenarios. This work demonstrates how to accurately group diagnosis lists via a combination of natural language processing and hierarchical clustering with an overall F-measure value of 0.87. In addition, it compresses the initial diagnosis list up to 89%. The manuscript discusses pitfall and challenges as well as the potential of a large-scale approach for tackling this problem.