Technical Note: mzML and imzML Libraries for Processing Mass Spectrometry Data with the High-Performance Programming Language Julia.

Julia combines the virtues of high-level and low-level programming languages: The code is human-readable, and the performance of the created binaries competes with machine-orientated compilers. Thus, Julia is popular in "Big Data" sciences. Reading mass spectrometry (MS) data with Julia was impossible until now due to missing libraries. Here, we present a Julia library for importing mass spectrometry (MS) data in HUPO standard mzML and imzML formats and demonstrate its function with direct and ambient ionization MS, liquid chromatography-MS, and MS imaging data on standard platforms (Windows, Linux, and Mac OS). The processing speed of Julia for reading imzML MS imaging files was up to 214 times faster than the comparable code in R. Julia can remove bottlenecks for computationally demanding tasks in large-scale MS-Omics and MS imaging data processing workflows and supports their agile development. In addition, time-critical and complex data evaluation tasks become possible, such as following the real-time monitoring of biological processes and pattern recognition in large MS imaging projects. Our mzML/imzML libraries and code examples are available under the terms of the MIT license from https://github.com/CINVESTAV-LABI/julia_mzML_imzML.

Use of digoxin in the emergency department to treat patients with acute heart failure and its impact on short-term outcomes. / Uso de digoxina endovenosa en urgencias para tratar pacientes con insuficiencia cardiaca aguda y su impacto en la evolución a corto plazo.

OBJECTIVES: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. MATERIAL AND METHODS: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. RESULTS: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. CONCLUSION: Digoxin continues to be used in one out of ten ED patients who are not already on long-term treatment with the drug. Digoxin use is associated with cardiac decompensation triggered by atrial fibrillation with rapid ventricular response, younger age, women, and patients with better initial NYHA function status but possibly more severe decompensation. Digoxin use leads to a longer ED stay but is safe, as it is not associated with need for admission, prolonged hospitalization, or short-term mortality.

OBJETIVO: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. METODO: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. RESULTADOS: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. CONCLUSIONES: La digoxina continúa utilizándose en uno de cada 10 pacientes con ICA atendidos en urgencias que no utilizaban este fármaco de manera habitual. Su uso se relaciona con un paciente cuya ICA ha sido descompensada por una FA con respuesta ventricular rápida, más joven y más frecuentemente mujer, en mejor clase funcional de la NYHA basal y con una descompensación posiblemente más grave. El uso de digoxina conlleva una estancia en urgencias más prolongada, pero su uso es seguro, pues no se asocia a la necesidad de ingreso, hospitalización prolongada o mortalidad a corto plazo.

Decisions to admit vs. discharge patients with acute heart failure from the emergency department: consistency with a measure of severity of decompensation and the impact on prognosis. / Decisión de hospitalización o alta en pacientes con insuficiencia cardiaca aguda en urgencias, su adecuación con la gravedad de la descompensación e impacto pronóstico.

OBJECTIVES: To analyze the consistency between decisions to discharge or admit patients with acute heart failure (AHF) treated in emergency departments (EDs) and the level of risk of adverse events, and to analyze the impact of decisions to discharge patients. MATERIAL AND METHODS: Prospective study of baseline clinical data collected from patients diagnosed with AHF in 16 Spanish emergency departments. Patients were stratified by severity of decompensated AHF based on MEESSI assessment (Multiple Estimation of Risk Based on the Spanish Emergency Department Score). The distribution of severity was described for patients who were hospitalized (overall and for departments receiving the largest number of admissions) and for discharged patients. We analyzed the data for discharged patients for associations with the following quality-of-care indicators: all-cause mortality of less than 2% at 30 days, revisits to the ED for AHF in less than 10% of patients within 7 days of discharge, and revisits to the ED or admission for AHF in less than 20% within 30 days of discharge. RESULTS: We included 2855 patients with a median (interquartile range) age of 84 (76-88) years. Fifty-four percent were women, 1042 (36.5%) were classified as low risk, 1239 (43.4%) as intermediate risk, 301 (10.5%) as high risk, and 273 (9.6%) as very high risk. Thirty-day mortality rates by level of low to very high risk were 1.9%, 9.3%, 15.3%, and 38.4%, respectively. One-year mortality rates by risk level were 15.4%, 35.6%, 52.0%, and 74.2%. Admission rates by risk level were 62.2%, 77.4%, 87.0%, and 88.3%. Overall, 47.1% o patients discharged from the ED were in the 3 higher-risk categories (intermediate to very high), and 30.7% were in the lowest risk category. The 5 hospital areas receiving the most admissions, in order of lowest-to-highest risk classification, were internal medicine, the short-stay unit, cardiology, intensive care, and geriatrics. Rates and 95% CIs for quality-of-care indicators in patients discharged from EDs were as follows: 30-day mortality, 4.3% (3.0%-6.1%); ED revisits within 7 days, 11.4% (9.2%-14.0%), and ED revisits or admissions within 30 days, 31.5% (28.0%-35.1%). In patients classified as low risk on ED discharge, these percentages were lower, as follows, respectively: 0.5% (0.1%-1.8%), 10.5% (7.6%-14.0%), and 29.5% (26.6%-32.6%). CONCLUSION: We detected disparity between severity of AHF decompensation and the decision to discharge or admit patients. Outcomes in patients discharged from EDs do not reach the recommended quality-of-care standards. Reducing inconsistencies between severity of decompensation and ED decisions could help to improve quality targets.

OBJETIVO: Analizar cómo se ajusta la decisión de ingreso o alta del paciente con insuficiencia cardiaca aguda (ICA) atendido en urgencias a su riesgo de evento adverso, así como su impacto en el pronóstico en aquellos dados de alta desde urgencias. METODO: Se recogieron datos basales y clínicos de pacientes diagnosticados de ICA en 16 servicios de urgencias españoles. Los pacientes se estratificaron según la gravedad de la descompensación mediante la escala MEESSI y se analizó la distribución de dicha gravedad en hospitalizados (en conjunto, e individualmente para los servicios con mayor número de hospitalizaciones) y dados de alta desde urgencias. En este último grupo, se analizó el cumplimiento de los siguientes indicadores de calidad: mortalidad por cualquier causa a 30 días ( 2%), reconsulta a urgencias por ICA a 7 días posalta ( 10%), y reconsulta a urgencias u hospitalización por ICA a 30 días posalta ( 20%). RESULTADOS: Se incluyeron 2.855 pacientes (edad mediana = 84 años, RIC = 76-88; mujeres = 54%): 1.042 pacientes (36,5%) de riesgo bajo, 1.239 (43,4%) intermedio, 301 (10,5%) alto y 273 (9,6%) muy alto. La mortalidad a 30 días por categorías de riesgo fue 1,9%, 9,3%, 15,3% y 38,4%, respectivamente; la mortalidad al año 15,4%, 35,6%, 52,0% y 74,2%; y la hospitalización 62,2%, 77,4%, 87,0% y 88,3%. El 47,1% de pacientes dados de alta de urgencias tenía un riesgo incrementado (intermedio, alto o muy alto) y el 30,7% de hospitalizados eran de bajo riesgo. La gravedad de la descompensación según el servicio de hospitalización se incrementaba en el siguiente orden: medicina interna, corta estancia, cardiología, intensivos y geriatría. El 4,3% de pacientes dados de alta de urgencias (IC 95%: 3,0-6,1) falleció a los 30 días, el 11,4% (9,2-14,0) reconsultó en urgencias a los 7 días, y el 31,5% (28,0-35,1) reconsultó en urgencias o se hospitalizó a los 30 días. Si sólo se consideran los pacientes dados de alta de bajo riesgo, estos porcentajes descienden al 0,5% (0,1-1,8), 10,5% (7,6-14,0) y 29,5% (26,6-32,6), respectivamente. CONCLUSIONES: Existe disparidad entre la gravedad de la descompensación y la decisión en urgencias de hospitalizar o dar de alta a los pacientes con ICA. Los resultados que se obtienen en los pacientes dados de alta desde urgencias no alcanzan los estándares de calidad recomendados. Disminuir las incongruencias entre gravedad de la descompensación y toma de decisión podría contribuir a cumplir con estos estándares.

Guided analysis of ambient ionization mass spectrometry data with the MQ_Assistant.

RATIONALE: Ambient ionization mass spectrometry (AIMS) delivers realistic data from samples in their native state. In addition, AIMS methods reduce time and costs for sample preparation and have less environmental impact. However, AIMS data are often complex and require substantial processing before interpretation. METHODS: We developed an interactive R script for guided mass spectrometry (MS) data processing. The "MQ_Assistant" is based on MALDIquant, a popular R package for MS data processing. In each step, the user can try and preview the effect of chosen parameters before deciding on the values with the best result and proceeding to the next stage. The outcome of the MQ_Assistant is a feature matrix that can be further analyzed in R and statistics tools such as MetaboAnalyst. RESULTS: Using 360 AIMS example spectra, we demonstrate the step-by-step processing for creating a feature matrix. In addition, we show how to visualize the results of three biological replicates of a plant-microbe interaction between Arabidopsis and Trichoderma as a heatmap using R and upload them to MetaboAnalyst. The final parameter set can be saved for reuse in MALDIquant workflows of similar data. CONCLUSIONS: The MQ_Assistant helps novices and experienced users to develop workflows for (AI)MS data processing. The interactive procedure supports the quick finding of appropriate settings. These parameters can be exported and reused in future projects. The stepwise operation with visual feedback also suggests the use of the MQ_Assistant in education.

Hyperkalemia in acute heart failure: Short term outcomes from the EAHFE registry.

OBJECTIVE: Both hyperkalemia (HK) and Acute Heart Failure (AHF) are associated with increased short-term mortality, and the management of either may exacerbate the other. As the relationship between HK and AHF is poorly described, our purpose was to determine the relationship between HK and short-term outcomes in Emergency Department (ED) AHF. METHODS: The EAHFE Registry enrolls all ED AHF patients from 45 Spanish ED and records in-hospital and post-discharge outcomes. Our primary outcome was all-cause in-hospital death, with secondary outcomes of prolonged hospitalization (>7 days) and 7-day post-discharge adverse events (ED revisit, hospitalization, or death). Associations between serum potassium (sK) and outcomes were explored using logistic regression by restricted cubic spline (RCS) curves, with sK =4.0 mEq/L as the reference, adjusting by age, sex, comorbidities, patient baseline status and chronic treatments. Interaction analyses were performed for the primary outcome. RESULTS: Of 13,606 ED AHF patients, the median (IQR) age was 83 (76-88) years, 54% were women, and the median (IQR) sK was 4.5 mEq/L (4.3-4.9) with a range of 4.0-9.9 mEq/L. In-hospital mortality was 7.7%, with prolonged hospitalization in 35.9%, and a 7-day post-discharge adverse event rate of 8.7%. Adjusted in-hospital mortality increased steadily from sK ≥4.8 (OR = 1.35, 95% CI = 1.01-1.80) to sK = 9.9 (8.41, 3.60-19.6). Non-diabetics with elevated sK had higher odds of death, while chronic treatment with mineralocorticoid-receptor antagonists exhibited a mixed effect. Neither prolonged hospitalization nor post-discharge adverse events was associated with sK. CONCLUSION: In ED AHF, initial sK >4.8 mEq/L was independently associated with in-hospital mortality, suggesting that this cohort may benefit from aggressive HK treatment.

A continuous in silico learning strategy to identify safety liabilities in compounds used in the leather and textile industry.

There is a widely recognized need to reduce human activity's impact on the environment. Many industries of the leather and textile sector (LTI), being aware of producing a significant amount of residues (Keßler et al. 2021; Liu et al. 2021), are adopting measures to reduce the impact of their processes on the environment, starting with a more comprehensive characterization of the chemical risk associated with the substances commonly used in LTI. The present work contributes to these efforts by compiling and toxicologically annotating the substances used in LTI, supporting a continuous learning strategy for characterizing their chemical safety. This strategy combines data collection from public sources, experimental methods and in silico predictions for characterizing four different endpoints: CMR, ED, PBT, and vPvB. We present the results of a prospective validation exercise in which we confirm that in silico methods can produce reasonably good hazard estimations and fill knowledge gaps in the LTI chemical space. The proposed protocol can speed the process and optimize the use of resources including the lives of experimental animals, contributing to identifying potentially harmful substances and their possible replacement by safer alternatives, thus reducing the environmental footprint and impact on human health.

In Vivo Low-Temperature Plasma Ionization Mass Spectrometry (LTP-MS) Reveals Regulation of 6-Pentyl-2H-Pyran-2-One (6-PP) as a Physiological Variable during Plant-Fungal Interaction.

Volatile organic compounds (VOCs) comprises a broad class of small molecules (up to ~300 g/mol) produced by biological and non-biological sources. VOCs play a vital role in an organism's metabolism during its growth, defense, and reproduction. The well-known 6-pentyl-α-pyrone (6-PP) molecule is an example of a major volatile biosynthesized by Trichoderma atroviride that modulates the expression of PIN auxin-transport proteins in primary roots of Arabidopsis thaliana during their relationship. Their beneficial relation includes lateral root formation, defense induction, and increased plant biomass production. The role of 6-PP has been widely studied due to its relevance in this cross-kingdom relationship. Conventional VOCs measurements are often destructive; samples require further preparation, and the time resolution is low (around hours). Some techniques enable at-line or real-time analyses but are highly selective to defined compounds. Due to these technical constraints, it is difficult to acquire relevant information about the dynamics of VOCs in biological systems. Low-temperature plasma (LTP) ionization allows the analysis of a wide range of VOCs by mass spectrometry (MS). In addition, LTP-MS requires no sample preparation, is solvent-free, and enables the detection of 6-PP faster than conventional analytical methods. Applying static statistical methods such as Principal Component Analysis (PCA) and Discriminant Factorial Analysis (DFA) leads to a loss of information since the biological systems are dynamic. Thus, we applied a time series analysis to find patterns in the signal changes. Our results indicate that the 6-PP signal is constitutively emitted by T. atroviride only; the signal shows high skewness and kurtosis. In A. thaliana grown alone, no signal corresponding to 6-PP is detected above the white noise level. However, during T. atroviride-A. thaliana interaction, the signal performance showed reduced skewness and kurtosis with high autocorrelation. These results suggest that 6-PP is a physiological variable that promotes homeostasis during the plant-fungal relationship. Although the molecular mechanism of this cross-kingdom control is still unknown, our study indicates that 6-PP has to be regulated by A. thaliana during their interaction.

Circadian oscillations in Trichoderma atroviride and the role of core clock components in secondary metabolism, development, and mycoparasitism against the phytopathogen Botrytis cinerea.

Circadian clocks are important for an individual's fitness, and recent studies have underlined their role in the outcome of biological interactions. However, the relevance of circadian clocks in fungal-fungal interactions remains largely unexplored. We sought to characterize a functional clock in the biocontrol agent Trichoderma atroviride to assess its importance in the mycoparasitic interaction against the phytopathogen Botrytis cinerea. Thus, we confirmed the existence of circadian rhythms in T. atroviride, which are temperature-compensated and modulated by environmental cues such as light and temperature. Nevertheless, the presence of such molecular rhythms appears to be highly dependent on the nutritional composition of the media. Complementation of a clock null (Δfrq) Neurospora crassa strain with the T. atroviride-negative clock component (tafrq) restored core clock function, with the same period observed in the latter fungus, confirming the role of tafrq as a bona fide core clock component. Confrontation assays between wild-type and clock mutant strains of T. atroviride and B. cinerea, in constant light or darkness, revealed an inhibitory effect of light on T. atroviride's mycoparasitic capabilities. Interestingly, when confrontation assays were performed under light/dark cycles, T. atroviride's overgrowth capacity was enhanced when inoculations were at dawn compared to dusk. Deleting the core clock-negative element FRQ in B. cinerea, but not in T. atroviride, was vital for the daily differential phenotype, suggesting that the B. cinerea clock has a more significant influence on the result of this interaction. Additionally, we observed that T. atroviride clock components largely modulate development and secondary metabolism in this fungus, including the rhythmic production of distinct volatile organic compounds (VOCs). Thus, this study provides evidence on how clock components impact diverse aspects of T. atroviride lifestyle and how daily changes modulate fungal interactions and dynamics.

Build, Share and Remix: 3D Printing for Speeding Up the Innovation Cycles in Ambient Ionisation Mass Spectrometry (AIMS).

Ambient ionisation mass spectrometry (AIMS) enables studying biological systems in their native state and direct high-throughput analyses. The ionisation occurs in the physical conditions of the surrounding environment. Simple spray or plasma-based AIMS devices allow the desorption and ionisation of molecules from solid, liquid and gaseous samples. 3D printing helps to implement new ideas and concepts in AIMS quickly. Here, we present examples of 3D printed AIMS sources and devices for ion transfer and manipulation. Further, we show the use of 3D printer parts for building custom AIMS sampling robots and imaging systems. Using 3D printing technology allows upgrading existing mass spectrometers with relatively low cost and effort.

Las compañías militares y de seguridad privadas: hacia una definición operativa para el derecho internacional humanitario / Private military and security companies: towards an operational definition for international humanitarian law / Empresas privadas militares e de segurança: rumo a uma definição operacional para o direito humanitário internacional

Este artículo tiene por objeto analizar los elementos cuya ponderación podría conducir a una definición operativa de las compañías militares y de seguridad privadas para el derecho internacional humanitario. La metodología empleada para dar alcance a este objetivo consiste en el análisis de fuentes documentales comprendido en la revisión de la normatividad jurídica internacional, la doctrina y la literatura académica de otras ciencias sociales, lo que favorece un debate interdisciplinar para abordar al fenómeno de las compañías militares y de seguridad privadas con el ánimo de complementar la construcción de esta definición operativa a partir de la mayor cantidad posible de perspectivas.

The purpose of this article is to analyze the elements whose weighting could lead to an operational definition of private military and security companies for international humanitarian law. The methodology used to achieve this objective consists of the analysis of documentary sources including the review of international legal norms, doctrine and academic literature from other social sciences, which favors an interdisciplinary debate to address the phenomenon of private military and security companies with the aim of complementing the construction of this operational definition from as many perspectives as possible.

Este artigo visa analisar os elementos cuja ponderação poderia levar a uma definição operacional de empresas militares e de segurança privadas para o direito humanitário internacional. A metodologia utilizada para atingir este objetivo consiste na análise de fontes documentais, incluindo uma revisão das normas jurídicas internacionais, doutrina e literatura acadêmica de outras ciências sociais, o que favorece um debate interdisciplinar para abordar o fenômeno das empresas privadas militares e de segurança com o objetivo de complementar a construção desta definição operacional a partir do maior número possível de perspectivas.

Socio-Demographic Health Determinants Are Associated with Poor Prognosis in Spanish Patients Hospitalized with COVID-19.

INTRODUCTION: Social vulnerability is a known determinant of health in respiratory diseases. Our aim was to identify whether there are socio-demographic factors among COVID-19 patients hospitalized in Spain and their potential impact on health outcomes during the hospitalization. METHODS: A multicentric retrospective case series study based on administrative databases that included all COVID-19 cases admitted in 19 Spanish hospitals from 1 March to 15 April 2020. Socio-demographic data were collected. Outcomes were critical care admission and in-hospital mortality. RESULTS: We included 10,110 COVID-19 patients admitted to 18 Spanish hospitals (median age 68 (IQR 54-80) years old; 44.5% female; 14.8% were not born in Spain). Among these, 779 (7.7%) cases were admitted to critical care units and 1678 (16.6%) patients died during the hospitalization. Age, male gender, being immigrant, and low hospital saturation were independently associated with being admitted to an intensive care unit. Age, male gender, being immigrant, percentile of average per capita income, and hospital experience were independently associated with in-hospital mortality. CONCLUSIONS: Social determinants such as residence in low-income areas and being born in Latin American countries were associated with increased odds of being admitted to an intensive care unit and of in-hospital mortality. There was considerable variation in outcomes between different Spanish centers.

The emerging role of 3D-printing in ion mobility spectrometry and mass spectrometry.

3D-printing is revolutionizing the rapid prototyping in analytical chemistry. In the last few years, we observed the development of 3D-printed components for ion studies, such as ion sources, ion transfer and ion mobility spectrometry (IMS) devices. Often, 3D-printed gadgets add functions to existing mass spectrometry (MS) systems. Custom adapters improve the sensibility for coupling with ambient ionization and upstream chromatography methods, and sample preparation units optimize the following MS analyses. Besides, 3D-printer parts are suitable for constructing custom analytical robots and mass imaging systems. Some of those assemblies implement new concepts and are commercially not available. An essential aspect of using 3D-printing is the fast turnover of design improvements, which is motivated by permissive licenses. The easy reproducibility and exchange of ideas lead to a community-driven development, which is accompanied by economic advantages for public research and education.

Analysis of standards of quality for outcomes in acute heart failure patients directly discharged home from emergency departments and their relationship with the emergency department direct discharge rate.

OBJECTIVE: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be >40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality <2% (outcome A); 7-day ED revisit due to AHF < 10% (outcome B); and 30-day ED revisit/hospitalization due to AHF < 20% (outcome C). We investigated these outcomes in a nationwide cohort and their relationship with the ED DDWH percentage. METHODS: We analyzed the EAHFE registry (includes about 15% of Spanish EDs), calculated DDWH percentage of each ED, and A/B/C outcomes of DDWH patients, overall and in each individual ED. Relationship between ED DDWH and outcomes was assessed by linear and quadratic regression models, non-weighted and weighted by DDWH patients provided by each ED. RESULTS: Among 17,420 patients, 4488 had DDWH (25.8%, median ED stay = 0 days, IQR = 0-1). Only 12.9% EDs achieved DDWH > 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R2 = 0.184/0.322) and C (weighted R2 = 0.430/0.624), but not with outcome A (weighted R2 = 0.002/0.022). CONCLUSIONS: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge.

The CRAS-EAHFE study: Characteristics and prognosis of acute heart failure episodes with cardiorenal-anaemia syndrome at the emergency department.

BACKGROUND: The coexistence of other comorbidities confers poor outcomes in patients with acute heart failure. Our aim was to determine the characteristics of patients with acute heart failure and cardiorenal anaemia syndrome and the relationship between renal dysfunction and anaemia, alone or combined as cardiorenal anaemia syndrome, on short-term outcomes. METHODS: We analysed the Epidemiology of Acute Heart Failure in Emergency Departments registry (cohort of patients with acute heart failure in Spanish emergency departments). Renal dysfunction was defined by an estimated glomerular filtration rate <60 ml/min/m2, anaemia by haemoglobin values <12/<13 g/dl in women/men, and cardiorenal anaemia syndrome as the presence of both. Comparisons were made according to cardiorenal-anaemia syndrome positive (CRAS+) with respect to the rest of patients (CRAS-) and according the presence of renal dysfunction (RD+) and anaemia (A+), (alone, RD+/A-, RD-/A+) or in combination (RD+/A+; i.e. CRAS+) with respect to patients without renal dysfunction and anaemia (RD-/A-). The primary outcome was 30-day mortality, and the secondary outcomes were need for admission, prolonged hospitalisation (>10 days), in-hospital mortality during the index event, and reconsultation and the combination of 30-day post-discharge reconsultation/death. These short-term outcomes were compared and adjusted for differences among groups. RESULTS: Of the 13,307 patients analysed, CRAS+ (36.4%) was associated with older age, multiple comorbidities, chronic use of loop diuretics, oedemas and hypotension. The 30-day mortality in CRAS+ was greater than in CRAS- (hazard ratio = 1.46, 95% confidence interval = 1.26-1.68) and RD-/A- (hazard ratio = 1.83, 95% confidence interval = 1.46-2.28) control groups. The mortality level was also higher in RD+/A- (hazard ratio = 1.40, 95% confidence interval = 1.10-1.78) and higher, but not statistically significant, in RD-/A+ (hazard ratio = 1.28, 95% confidence interval = 0.99-1.63) with respect to RD-/A-. All of the secondary outcomes, when related to CRAS- and RD-/A- control groups, were worse for CRAS+ and to a lesser extent, RD+/A-, being more rarely observed in RD-/A+. CONCLUSIONS: Cardiorenal anaemia syndrome in acute heart failure is related to greater mortality and worse short-term outcomes, and the impact of renal dysfunction and anaemia seems to be additive.

CORT-AHF Study: Effect on Outcomes of Systemic Corticosteroid Therapy During Early Management Acute Heart Failure.

OBJECTIVES: This study investigated whether systemic corticosteroids (new onset) administered to patients with acute heart failure (AHF) have any association with outcomes, with differentiated analyses for patients with and without chronic obstructive pulmonary disease (COPD) as a comorbidity. BACKGROUND: Patients with undiagnosed dyspnea frequently receive corticosteroids in emergency departments while determining a final diagnosis, but their effect on the outcomes of patients with AHF without overt COPD exacerbation is unknown. METHODS: We selected patients with AHF from the EAHFE (Epidemiology of Acute Heart Failure in the Emergency Departments) registry, recording key data (new-onset corticosteroid therapy, COPD condition). Patients with and without COPD were analyzed separately. We calculated unadjusted and adjusted ratios for corticosteroid-treated compared with corticosteroid-untreated patients for 2 coprimary endpoints: 90-day all-cause mortality (from index episode) and 90-day post-discharge combined endpoint (all-cause mortality or readmission for AHF), with intermediate time-point estimations. Other secondary endpoints were calculated, and some sensitive and stratified analyses were performed. RESULTS: We analyzed 11,356 patients: 8,635 without COPD (841 corticosteroid-treated, 9.7%) and 2,721 with COPD (753 corticosteroid-treated, 27.7%). There were several differences between treated and untreated patients, essentially because corticosteroid-treated patients were sicker. Although unadjusted outcomes were worse in corticosteroid-treated patients, especially in patients without COPD, these differences disappeared after adjustment: hazard ratios for 90-day mortality (without/with COPD) were 0.91 (95% confidence interval (CI): 0.76 to 1.10)/0.99 (95% CI: 0.78 to 1.26), and 1.09 (95% CI: 0.93 to 1.28)/1.02 (95% CI: 0.86 to 1.21) for the post-discharge combined endpoint. Analyses of intermediate time-point coprimary endpoints and secondary outcomes rendered similar estimations. Sensitivity and stratified analysis did not significantly modify these results. CONCLUSIONS: There is no evidence of harm related to the new onset of systemic corticosteroid therapy during an episode of AHF, either in patients with or without concomitant COPD.

Recomendaciones para la vacunación frente al ROTAvirus de los recién nacidos PREMaturos (ROTAPREM) / Recommendations for vaccination against ROTAvirus in PREMature newborns (ROTAPREM)

El rotavirus (RV) es la causa principal de diarrea infantil grave en todo el mundo e infecta prácticamente a todos los niños en los primeros 5 años de vida, sobre todo en los primeros 2años. Existen dos vacunas atenuadas de administración oral frente al RV disponibles en nuestro medio que han demostrado ser seguras y eficaces frente a la enfermedad. El objetivo principal de estas vacunas ha sido reproducir la historia natural de la infección y proteger frente a la enfermedad grave en los primeros meses de vida. Los recién nacidos prematuros son especialmente vulnerables a la enfermedad por RV, no solo por tener más riesgo de adquirir la infección, sino también por sus complicaciones. La vacunación frente al RV en niños prematuros ha mostrado resultados de eficacia y seguridad similares a los comunicados en niños a término, y los datos existentes sugieren un riesgo bajo de diseminación e infección nosocomial cuando la vacunación se realiza durante la hospitalización. Dado que un porcentaje estimable de recién nacidos prematuros permanecen ingresados en las unidades neonatales más allá de las 12semanas de vida, se considera que estos, siempre que su condición clínica lo permita, deben recibir la vacunación frente al RV sin retrasos, incluso durante la hospitalización si así fuese necesario

Rotavirus (RV) is the leading cause of severe acute gastroenteritis in infants worldwide. Most children are infected by RV by the age of 5 years, and especially in the first 2 years. Two oral attenuated vaccines against RV are licensed in industrialised countries, which have proven to be safe and effective against the disease. The main objective of these vaccines has been to reproduce the natural history of infection and protect against severe disease in the first months of life. Preterm infants are at higher risk of severe RV infection compared to full-term infants and infants with normal birth weight. Data collected on RV vaccination in preterm infants demonstrated that RV vaccines are effective and safe, compared with full-term infants, with a marginal risk of horizontal viral transmission and dissemination when vaccination is performed during hospitalisation. Preterm infants frequently require admission to hospital after the beginning of the 12 th week of life, which suggests that they should receive RV vaccines during admission according to the official immunisation schedule

Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study.

OBJECTIVE: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. METHODS: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (<6/6-10/11-15/>15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH <6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units. RESULTS: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4-11): 2934 (34.3%) had a LOH <6 days, 3184 (37.2%) 6-10 days, 1287 (15.0%) 11-15 days, and 1158 (13.5%) >15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0-64.9) when LOH was 11-15 days, and by 72.0% (95%CI = 42.6-107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4-36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk. CONCLUSIONS: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments.