Development of a Novel Heart Failure Risk Tool : The Barcelona Bio-Heart Failure Risk Calculator (BCN Bio-HF Calculator)

Background: A combination of clinical and routine laboratory data with biomarkers reflecting different pathophysiological pathways may help to refine risk stratification in heart failure (HF). A novel calculator (BCN Bio-HF calculator) incorporating N-terminal pro B-type natriuretic peptide (NT-proBNP, a marker of myocardial stretch), high-sensitivity cardiac troponin T (hs-cTnT, a marker of myocyte injury), and high-sensitivity soluble ST2 (ST2), (reflective of myocardial fibrosis and remodeling) was developed. Methods: Model performance was evaluated using discrimination, calibration, and reclassification tools for 1-, 2-, and 3-year mortality. Ten-fold cross-validation with 1000 bootstrapping was used. Results: The BCN Bio-HF calculator was derived from 864 consecutive outpatients (72% men) with mean age 68.2±12 years (73%/27% New York Heart Association (NYHA) class I-II/III-IV, LVEF 36%, ischemic etiology 52.2%) and followed for a median of 3.4 years (305 deaths). After an initial evaluation of 23 variables, eight independent models were developed. The variables included in these models were age, sex, NYHA functional class, left ventricular ejection fraction, serum sodium, estimated glomerular filtration rate, hemoglobin, loop diuretic dose, β-blocker, Angiotensin converting enzyme inhibitor/Angiotensin-2 receptor blocker and statin treatments, and hs-cTnT, ST2, and NT-proBNP levels. The calculator may run with the availability of none, one, two, or the three biomarkers. The calculated risk of death was significantly changed by additive biomarker data. The average C-statistic in cross-validation analysis was 0.79. Conclusions: A new HF risk-calculator that incorporates available biomarkers reflecting different pathophysiological pathways better allowed individual prediction of death at 1, 2, and 3 years

Observational study on fluid therapy management in surgical adult patients

Background: Perioperative fluid therapy management is changing due to the incorporation of different fluids, surgical techniques, and minimally invasive monitoring systems. The objective of this study was to explore fluid therapy management during the perioperative period in our country. Methods: We designed the Fluid Day study as a cross-sectional, multicentre, observational study. The study was performed in 131 Spanish hospitals in February 2019. We included adult patients undergoing general anaesthesia for either elective or non-elective surgery. Demographic variables were recorded, as well as the type and total volume of fluid administered during the perioperative period and the monitorization used. To perform the analysis, patients were categorized by risk group. Results: We recruited 7291 patients, 6314 of which were included in the analysis; 1541 (24.4%) patients underwent high-risk surgery, 1497 (23. 7%) were high risk patients, and 554 (8.7%) were high-risk patients and underwent high-risk surgery; 98% patients received crystalloids (80% balanced solutions); intraoperative colloids were used in 466 patients (7.51%). The hourly intraoperative volume in mL/kg/h and the median [Q1; Q3] administered volume (mL/kg) were, respectively, 6.67 [3.83; 8.17] ml/Kg/h and 13.9 [9.52;5.20] ml/Kg in low-risk patients undergoing low- or intermediate-risk surgery, 6 [4.04; 9.08] ml/Kg/h and 15.7 [10.4;24.5] ml/Kg in high- risk patients undergoing low or intermediate-risk surgery, 6.41 [4.36; 9.33] ml/Kg/h and 20.2 [13.3;32.4] ml/Kg in low-risk patients undergoing high-risk surgery, and 5.46 [3.83; 8.17] ml/Kg/h and 22.7[14.1;40.9] ml/Kg in high-risk patients undergoing high- risk surgery . We used advanced fluid monitoring strategies in 5% of patients in the intraoperative period and in 10% in the postoperative period. Conclusions: The most widely used fluid was balanced crystalloids. Colloids were used in a small number of patients. Hourly surgery volume tended to be more restrictive in high-risk patients but confirms a high degree of variation in the perioperatively administered volume. Scarce monitorization was observed in fluid therapy management

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study

Objective: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. Methods: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/mu L, not starting c-ART; and group B, CD4<500 cells/mu L, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. Results: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. Conclusions: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinelnodes after neoadjuvant therapy (ADARNAT trial)

Introduction: Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. Methods and analyses: This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. Discussion: This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. Ethics and dissemination: The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results

A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)

IntroductionBreast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects.Methods and analysesThis multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival.DiscussionThis study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity.Ethics and disseminationThe Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results.Trial registrationClinicalTrials.gov, identifier number NCT04889924

Revisió de diferents mètriques per a l'avaluació de models predictius basats en la regressió logística i riscos proporcionals de Cox

Les funcions de predicció han esdevingut essencials en la medicina moderna per a l'abordatge preventiu de les malalties més prevalents. Traduint-se matemàticament en la regressió logística i en models de supervivència (com el de riscos proporcionals de Cox). Per a poder fer un ús correcte de les funcions de predicció, resulten de gran importància les mètriques que validen les seves capacitats de discriminació, de calibratge, de reclassificació i altres característiques. Aquest treball consta de dues parts: (1) la cerca bibliogràfica de les mètriques que s'utilitzen actualment, i (2) l'aplicació a dades real d'aquelles mètriques més citades o les que aporten una millora a les ja conegudes

Revisió de diferents mètriques per a l'avaluació de models predictius basats en la regressió logística i riscos proporcionals de Cox

Les funcions de predicció han esdevingut essencials en la medicina moderna per a l'abordatge preventiu de les malalties més prevalents. Traduint-se matemàticament en la regressió logística i en models de supervivència (com el de riscos proporcionals de Cox). Per a poder fer un ús correcte de les funcions de predicció, resulten de gran importància les mètriques que validen les seves capacitats de discriminació, de calibratge, de reclassificació i altres característiques. Aquest treball consta de dues parts: (1) la cerca bibliogràfica de les mètriques que s'utilitzen actualment, i (2) l'aplicació a dades real d'aquelles mètriques més citades o les que aporten una millora a les ja conegudes

Teaching English as a foreign lenguage to pre-school children, suggestions and materials of how to take advantage of their age and capacity

1. Theoretical Framework. 2. Presentation and analysis of data regarding. 3. Suggested methodology. 4. Materials. 5. ConclusionThe teaching of English as an foreign lenguage to very young children has increased in recent years. As a consequence, teachers are more interested in learning how to teach pre-school children. Also, parents want their children to receive an adequate education which will prepare them to be competitive in future years. The awakening of interest in teaching young requires teachers to be prepared for it. Many teachers do not have any knoeledge about the language acquisition capacity that children hava. Consequently, they cannot take advantage of it and also do not know which methodology is appropriate for them. Moreover, appropriate materials and activities that can be applied to teaching very young learners are not well known by teachers. For this reason, the authors have decided to work on this topic because it will be useful for theachers to know about the language acquisition capacity that children have in order to take advantage of it, and to use an appropriate teaching methodologyPontificia Universidad Católica del Ecuador, Escuela de Lenguas y LingüísticaLicenciatura en Lingüística aplicada a la enseñanza del idioma inglé