Machine learning and natural language processing (NLP) approach to predict early progression to first-line treatment in real-world hormone receptor-positive (HRþ)/HER2-negative advanced breast cancer patients.

Este artículo ha sido publicado en la revista European Journal of Cancer. Esta versión tiene Licencia Creative Commons CC-BY-NC-NDBackground: CDK4/6 inhibitors plus endocrine therapies are the current standard of care in the first-line treatment of HRþ/HER2-negative metastatic breast cancer, but there are no well-established clinical or molecular predictive factors for patient response. In the era of personalised oncology, new approaches for developing predictive models of response are needed. Materials and methods: Data derived from the electronic health records (EHRs) of real-world patients with HRþ/HER2-negative advanced breast cancer were used to develop predictive models for early and late progression to first-line treatment. Two machine learning approaches were used: a classic approach using a data set of manually extracted features from reviewed (EHR) patients, and a second approach using natural language processing (NLP) of freetext clinical notes recorded during medical visits. Results: Of the 610 patients included, there were 473 (77.5%) progressions to first-line treatment, of which 126 (20.6%) occurred within the first 6 months. There were 152 patients (24.9%) who showed no disease progression before 28 months from the onset of first-line treatment. The best predictive model for early progression using the manually extracted dataset achieved an area under the curve (AUC) of 0.734 (95% CI 0.687e0.782). Using the NLP free-text processing approach, the best model obtained an AUC of 0.758 (95% CI 0.714 e0.800). The best model to predict long responders using manually extracted data obtained an AUC of 0.669 (95% CI 0.608e0.730). With NLP free-text processing, the best model attained an AUC of 0.752 (95% CI 0.705e0.799). Conclusions: Using machine learning methods, we developed predictive models for early and late progression to first-line treatment of HRþ/HER2-negative metastatic breast cancer, also finding that NLP-based machine learning models are slightly better than predictive models based on manually obtained data

Impact of pre- and/or post-autologous stem cell transplantation exposure to brentuximab vedotin on survival outcomes in patients with high-risk Hodgkin lymphoma

The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n?=?62) or without (non-BV, n?=?94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p?=?0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p?=?0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p?=?0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p?=?0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p?=?0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

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

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Atención a alumnos con fracaso escolar en el área de Matemáticas

El proyecto pretende ofrecer una atención especial en el área de Matemáticas a tres grupos de alumnos de tercero de ESO con fracaso escolar general. Para ello, se elabora un material específico de aula para utilizar de forma sistemática en un grupo de alumnos repetidores, y de forma no sistemática en un grupo de diversificación y dos de compensatoria. En la experiencia colaboran tres profesores de otros institutos de Madrid pertenecientes al Grupo Azarquier de Matemáticas. Los objetivos son romper la secuencia fracaso-rechazo-fracaso-rechazo en Matemáticas; posibilitar el desarrollo normal de un curso de Matemáticas a la mayoría de los alumnos; facilitar a otros profesores un material de apoyo que les ayude en la misma tarea; aumentar la confianza en sí mismos y en su capacidad para afrontar situaciones con contenidos matemáticos; y que la mayoría alcancen los contenidos mínimos de la programación de Matemáticas para tercero de ESO. Se realizan actividades guiadas, a través de la utilización de hojas de trabajo con algo de teoría, casos resueltos y ejercicios, que los alumnos pegan en sus cuadernos; actividades de todo el grupo con la ayuda de un retroproyector, para presentar una situación motivadora, y los alumnos contestan a las preguntas y redactan una teoría matemática; y se trabaja con juegos matemáticos. En cuanto a la evaluación, se realiza una valoración semanal a partir de una recogida por muestreo de los cuadernos, la participación en las actividades y la actitud en clase; y controles cada quince días sobre lo trabajado en clase. También se realiza una encuesta a los alumnos. Se elaboran materiales, que se recogen en los anexos, como las unidades didácticas Números naturales, Números fraccionarios, Potencias, Raíces, Lenguaje algebraico, Sistemas de ecuaciones, y Funciones; las notas de las evaluaciones; y los resultados de la encuesta a los alumnos..Madrid (Comunidad Autónoma). Consejería de EducaciónMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Desarrollo de productos lácteos funcionales con microorganismos intestinales y extractos vegetales de mangostán.

16ª Reunión de la Red Española de Bacterias Lácticas (Red Bal), "Bacterias Lácticas en Alimentación y Salud", Madrid, 11 y 12 de mayo de 2023.El mangostán (Garcinia mangostana) es una fruta originaria del sudeste asiático, que también crece en el suroeste de la India y otras áreas tropicales. Es muy apreciada por su textura jugosa y delicada y su sabor ligeramente agridulce. La porción comestible (endocarpio o pulpa) constituye alrededor del 30% del peso de la fruta, y el pericarpio (60-65%) contiene altos niveles de polifenoles. El objetivo de este trabajo, fue desarrollar productos lácteos fermentados funcionales con cepas de origen intestinal y extractos vegetales de mangostán, ricos en polifenoles.Fuente de financiación: Proyecto RTI2018-099271-R-I00Peer reviewe

Microbiological, chemical, and sensory characteristics of Hispánico cheese manufactured using frozen high pressure treated curds made from raw ovine milk

A novel procedure to overcome the seasonal shortage of ovine milk used for cheese manufacture was investigated. Curds made from raw ovine milk in spring months were treated at 400 or 500 MPa of pressure, and frozen for 4 months. After thawing, they were added to fresh bovine curd made from pasteurized milk for the manufacture of experimental Hispánico cheeses. Experimental cheeses exhibited lower dry matter content, less firm texture and higher total free amino acid concentration than a control cheese made from a mixture of pasteurized bovine and ovine milk. Cheese obtained using curds pressurized at 400 MPa showed the highest levels of esterase activity, total free fatty acids, 2-propanol, 2-butanol, 2-pentanol and ethyl hexanoate. The use of frozen pressurized curd made from raw ovine milk for Hispánico cheese manufacture seemed not to have altered its flavour characteristics but increased the yield of the ripe cheese. © 2011 Elsevier Ltd

Microbiological, chemical, textural and sensory characteristics of Hispánico cheese manufactured using frozen ovine milk curds scalded at different temperatures

Hispánico cheese is a semi-hard variety, manufactured in Spain from a mixture of pasteurized bovine and ovine milk. To study one strategy for overcoming a seasonal shortage of ovine milk in summer and autumn, curds made from ovine milk, scalded at 32, 35 or 38 °C, were pressed for 30 min and frozen at -24 °C for 4 months. After thawing, they were added to fresh bovine milk curd for the manufacture of experimental Hispánico cheeses. Control cheese was made from a mixture of pasteurized bovine and ovine milk in the same (8020) proportion. No significant effect of the addition of frozen ovine milk curd or scalding temperature was found for lactic acid bacteria counts, dry matter content, hydrophilic and hydrophobic peptides, 45 out of 65 volatile compounds, texture, and sensory characteristics throughout a 60-day ripening period. Differences between cheeses, of low magnitude and little practical significance, were found for pH value, aminopeptidase activity, proteolysis, free amino acids, free fatty acids, and the remaining 20 volatile compounds. Thus, the addition of frozen ovine milk curd to fresh bovine milk curd does not alter the main physicochemical and sensory characteristics of Hispánico cheese. © 2009 Elsevier Ltd. All rights reserved