Dimensionality reduction and ensemble of LSTMs for antimicrobial resistance prediction

Bacterial resistance to antibiotics has been rapidly increasing, resulting in a low antibiotic effectiveness even treating common infections. The presence of resistant pathogens in environments such as a hospital Intensive Care Unit (ICU) exacerbates the critical admission-acquired infections. This work focuses on the prediction of antibiotic resistance in Pseudomonas aeruginosa nosocomial infections at the ICU, using Long Short-Term Memory (LSTM) artificial neural networks as predictive method. The analyzed data were extracted from the Electronic Health Records (EHR) of patients admitted in the University Hospital of Fuenlabrada from 2004 to 2019, and were modeled as Multivariate Time Series. A data-driven dimensionality reduction method is built by adapting three feature importance techniques from the literature to the considered data, and proposing an algorithm for selecting the most appropriate number of features. This is done using LSTM sequential capabilities so that the temporal aspect of features is taken into account. Furthermore, an ensemble of LSTMs is used to reduce the performance variance. Our results indicate that the patient's admission information, the antibiotics administered during the ICU stay, and the previous antimicrobial resistance are the most important features. The proposed dimensionality reduction method dramatically reduces the number of features while considerably increasing the prediction performance. The variance in the performance is reduced by considering the ensemble of classifiers. In essence, the proposed framework achieve, in a computationally cost efficient manner, promising results for supporting decisions in this clinical task, characterized by high dimensionality, data scarcity and concept drift.This work has been partly supported by the Spanish Research Agency, grant numbers PID2019-106623RB-C41, AEI/10.13039/501100011033 (BigTheory), PID2019-107768RA-I00 (AAVis-BMR), by funding action by the Community of Madrid in the framework of the Multiannual Agreement with Rey Juan Carlos University in line of action 1 ‘‘Encouragement of Young Phd students investigation’’ Project Mapping-UCI (Ref F661), by the IDEAI-UPC Consolidated Research Group Grant from Catalan Agency of University and Research Grants (AGAUR, Generalitat de Catalunya) (2017 SGR 574) and by the Secretariat for Universities and Research of the Ministry of Research and Universities of the Government of Catalonia and the European Social Fund (2021 FI-B 00965).Peer ReviewedPostprint (published version

Antimicrobial Resistance Prediction in Intensive Care Unit for Pseudomonas Aeruginosa using Temporal Data-Driven Models

One threatening medical problem for human beings is the increasing antimicrobial resistance of some microorganisms. This problem is especially difficult in Intensive Care Units (ICUs) of hospitals due to the vulnerable state of patients. Knowing in advance whether a concrete bacterium is resistant or susceptible to an antibiotic is a crux step for clinicians to determine an effective antibiotic treatment. This usual clinical procedure takes approximately 48 hours and it is named antibiogram. It tests the bacterium resistance to one or more antimicrobial families (six of them considered in this work). This article focuses on cultures of the Pseudomonas Aeruginosa bacterium because is one of the most dangerous in the ICU. Several temporal data-driven models are proposed and analyzed to predict the resistance or susceptibility to a determined antibiotic family previously to know the antibiogram result and only using the available past information from a data set. This data set is formed by anonymized electronic health records data from more than 3300 ICU patients during 15 years. Several data-driven classifier methods are used in combination with several temporal modeling approaches. The results show that our predictions are reasonably accurate for some antimicrobial families, and could be used by clinicians to determine the best antibiotic therapy in advance. This early prediction can save valuable time to start the adequate treatment for an ICU patient. This study corroborates the results of a previous work pointing that the antimicrobial resistance of bacteria in the ICU is related to other recent resistance tests of ICU patients. This information is very valuable for making accurate antimicrobial resistance predictions

Evaluation of Different Compatibilization Strategies to Improve the Performance of Injection-Molded Green Composite Pieces Made of Polylactide Reinforced with Short Flaxseed Fibers

[EN] Green composites made of polylactide (PLA) and short flaxseed fibers (FFs) at 20 wt % were successfully compounded by twin-screw extrusion (TSE) and subsequently shaped into pieces by injection molding. The linen waste derived FFs were subjected to an alkalization pretreatment to remove impurities, improve the fiber surface quality, and make the fibers more hydrophobic. The alkali-pretreated FFs successfully reinforced PLA, leading to green composite pieces with higher mechanical strength. However, the pieces also showed lower ductility and toughness and the lignocellulosic fibers easily detached during fracture due to the absence or low interfacial adhesion with the biopolyester matrix. Therefore, four different compatibilization strategies were carried out to enhance the fiber-matrix interfacial adhesion. These routes consisted on the silanization of the alkalized FFs with a glycidyl silane, namely (3-glycidyloxypropyl) trimethoxysilane (GPTMS), and the reactive extrusion (REX) with three compatibilizers, namely a multi-functional epoxy-based styrene-acrylic oligomer (ESAO), a random copolymer of poly(styrene-co-glycidyl methacrylate) (PS-co-GMA), and maleinized linseed oil (MLO). The results showed that all the here-tested compatibilizers improved mechanical strength, ductility, and toughness as well as the thermal stability and thermomechanical properties of the green composite pieces. The highest interfacial adhesion was observed in the green composite pieces containing the silanized fibers. Interestingly, PS-co-GMA and, more intensely, ESAO yielded the pieces with the highest mechanical performance due to the higher reactivity of these additives with both composite components and their chain-extension action, whereas MLO led to the most ductile pieces due to its secondary role as plasticizer for PLA.This research work was funded by the Spanish Ministry of Science and Innovation (MICI) project numbers RTI2018-097249-B-C21 and MAT2017-84909-C2-2-R. D.L. and J.I.-M. thanks UPV for the grant received through the PAID-01-18 and PAID-01-19 (SP2019001) programs, respectively. S.T.-G. is recipient of a Juan de la Cierva contract (IJCI-2016-29675) from MICIU while S.R.J. is funded through the Santiago Gisolía contract (GRISOLIAP/2019/132) from Generalitat Valenciana (GVA). The microscopy services of UPV are also acknowledged for their help in collecting and analyzing the FESEM images.Agüero, Á.; Garcia-Sanoguera, D.; Lascano-Aimacaña, DS.; Rojas-Lema, SP.; Ivorra-Martínez, J.; Fenollar, O.; Torres Giner, S. (2020). Evaluation of Different Compatibilization Strategies to Improve the Performance of Injection-Molded Green Composite Pieces Made of Polylactide Reinforced with Short Flaxseed Fibers. Polymers. 12(4):1-22. https://doi.org/10.3390/polym12040821S12212

Violencia institucional en materia de salud sexual y reproductiva: Una mirada del ejercicio del derecho de las/los adolescentes en Posadas y Gran Posadas. 16H304

En este proyecto se aborda la problemática de la violencia institucional en relación a las oportunidades y posibilidades reales de ejercicio de los derechos de las/los adolescentes en materia de salud sexual y reproductiva. La investigación se focaliza en adolescentes de la ciudad de Posadas y de zonas aledañas, a las cuales se considera formando parte del complejo que puede denominarse Gran Posadas. Como dimensiones de análisis, se explora el régimen jurídico, los dispositivos organizacionales, las condiciones materiales y las prácticas sociales, en relación con el ejercicio efectivo de los derechos de las/los adolescentes en materia de salud sexual y reproductiva. Mediante el relevamiento y análisis de la información que pueda obtenerse de fuentes secundarias y de los propios actores, se interpretará teóricamente el problema de investigación y se buscará identificar, describir e interpretar los factores más relevantes que intervienen en relación a las oportunidades y posibilidades reales de ejercicio efectivo de los derechos en materia de salud sexual y reproductiva. Se buscará construir no sólo una interpretación crítica de la situación de las/los adolescentes en relación a tales derechos, sino, además, se buscará plantear una propuesta de líneas de acción que persigan como logro la transformación de dicha situación

Relaciones de género y poder en la política. La configuración de las prácticas políticas en la Unión Cívica Radical y el Partido Justicialista de Misiones entre 1983 y 2003. 16H260

Se trata de las actividades efectivamente realizadas durante el período de referencia. Pueden ser las mismas que las incluidas en el Proyecto, pero también pueden aparecer nuevas actividades que no hayan sido previstas originalmente. Esta sección puede ser publicada en la página de la Facultad y de la Universidad

Violencia institucional en materia de salud sexual y reproductiva: Una mirada del ejercicio del derecho de las/los adolescentes en Posadas y Gran Posadas. 16H304

Actividades desarrolladas durante el período: relevamiento de información secundaria; Consulta bibliográfica; Elaboración de guías de entrevistas; Selección de informantes claves; Desarrollo de entrevistas con responsables y trabajadores de la salud; Análisis de las entrevistas con responsables y trabajadores de la salud; Elaboración del informe de avance

Relaciones de género y poder en la política.La configuración de las prácticas políticas en la Unión Cívica Radical y el Partido Justicialista de Misiones entre 1983 Y 2003. 16H260

Actividades desarrolladas durante el período: se trata de las actividades efectivamente realizadas durante el período de referencia. Consulta bibliográfica; Recopilación de documentos; Selección de unidades de análisis; Desarrollo de entrevistas; Análisis de datos; Producción de documentos

C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein

Clinical Presentation and Outcome of COVID-19 in a Latin American Versus Spanish Population: Matched Case-Control Study

Introduction: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic. Methods: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes. Results: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups). Conclusion: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio