Meta-Analysis Design and Results in Real Life: Problem Solvers or Detour to Maze. A Critical Review of Meta-Analysis of DAPT Randomized Controlled Trials.

Therapeutic strategies - such as duration of dual antiplatelet therapy after coronary artery stenting - usually generate a large quantity of meta-analyses. The meta-analyses that include the same randomized clinical trials should produce similar results. Our aim in the study is to analyze the quality and to compare the results of meta-analyses focused on a controversial topic such as dual antiplatelet therapy after percutaneous coronary intervention. We searched all published meta-analyses published up to November 2015 (near DAPT trial publication) selecting those that included the same randomized clinical trials comparing patterns of briefer versus longer-term double antiplatelet therapy. Seventeen meta-analyses achieved our selection criteria. Of the seventeen analyzed, we identified seven (41.1%) based on the same ten randomized clinical trials (RCTs), yet their results varied widely. Many of the meta-analyses differed in only some minor aspect of the design (i.e. eligible studies, length of comparators and statistical methods used). Some authors differed in the number of patients participating in RCTs and even, despite reviewing the same underlying trials, only 2 of the 7 meta-analyses included the same number of patients. Meta-analyses around cardiovascular, all-cause or non-cardiovascular death differ frequently. In the DAPT duration setting, several meta-analyses have been recently published based on the same data, presenting several issues making it difficult to determine clear recommendations on certain points.IN receives research funding from Astrazeneca; has received minor consulting fees from Boston, Medtronic, Astrazeneca; and speaking fees or support for attending scientificmeetings fromBoehringer, Daiichi-Sankyo, Lilly, AstraZeneca and Pfizer. AE is Astrazeneca employee. HB receives research funding from the Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, BMS, Janssen and Novartis; has received consulting fees from Abbott, AstraZeneca, Bayer, BMS-Pfizer, Novartis; and speaking fees or support for attending scientificmeetings from AstraZeneca, Bayer, BMS-Pfizer, Ferrer, Novartis, Servier and MEDSCAPE-the heart.og. The other authors pose no relevant disclosures regarding this manuscript.S

Electroactive biofilms: new means for electrochemistry

This work demonstrates that electrochemical reactions can be catalysed by the natural biofilms that form on electrode surfaces dipping into drinking water or compost. In drinking water, oxygen reduction was monitored with stainless steel ultra-microelectrodes under constant potential electrolysis at )0.30 V/SCE for 13 days. 16 independent experiments were conducted in drinking water, either pure or with the addition of acetate or dextrose. In most cases, the current increased and reached 1.5–9.5 times the initial current. The current increase was attributed to biofilm forming on the electrode in a similar way to that has been observed in seawater. Epifluorescence microscopy showed that the bacteria size and the biofilm morphology depended on the nutrients added, but no quantitative correlation between biofilm morphology and current was established. In compost, the oxidation process was investigated using a titanium based electrode under constant polarisation in the range 0.10–0.70 V/SCE. It was demonstrated that the indigenous micro-organisms were responsible for the current increase observed after a few days, up to 60 mA m)2. Adding 10 mM acetate to the compost amplified the current density to 145 mA m)2 at 0.50 V/SCE. The study suggests that many natural environments, other than marine sediments, waste waters and seawaters that have been predominantly investigated until now, may be able to produce electrochemically active biofilm

Aplicación de algoritmos de optimización multiobjetivo a la mezcla de distintas fuentes de minerales en el largo plazo

Se presentan en este trabajo estrategias basadas en optimización multiobjetivo y supervisión predictiva destinadas a lograr una mezcla óptima de las distintas fuentes de mineral que ingresan a una planta de tratamiento, para las minas Cerro Vanguardia (Santa Cruz) y Casposo (Calingasta, San Juan). El planteo tiene una concepción Multiobjetivo, debido a las diversas variables que influyen en este caso de problemas y una concepción predictiva debido a que se desea modelar el comportamiento de las variables a lo largo del tiempo. Este algoritmo se plantea con la suficiente flexibilidad como para ser adaptados fácilmente a otras situaciones semejantes.Eje: Agentes y Sistemas Inteligentes.Red de Universidades con Carreras en Informátic

Aplicación de algoritmos de optimización multiobjetivo a la mezcla de distintas fuentes de minerales en el largo plazo

Se presentan en este trabajo estrategias basadas en optimización multiobjetivo y supervisión predictiva destinadas a lograr una mezcla óptima de las distintas fuentes de mineral que ingresan a una planta de tratamiento, para las minas Cerro Vanguardia (Santa Cruz) y Casposo (Calingasta, San Juan). El planteo tiene una concepción Multiobjetivo, debido a las diversas variables que influyen en este caso de problemas y una concepción predictiva debido a que se desea modelar el comportamiento de las variables a lo largo del tiempo. Este algoritmo se plantea con la suficiente flexibilidad como para ser adaptados fácilmente a otras situaciones semejantes.Eje: Agentes y Sistemas Inteligentes.Red de Universidades con Carreras en Informátic

Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults

Background: Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for infammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. Methods: Cross-sectional study in 100 (65% women) individuals aged 18–25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory ftness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample. Results: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+42.5%), tri‑ glycerides (+63.9%), C-reactive protein (+124.2%), diastolic blood pressure (+5.5%), and pro-infammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity. Conclusions: Plasma succinate levels are linked to a specifc pro-infammatory omega-6 signature pattern and higher VAT levels, and seem to refect the cardiovascular status of young adults.Spanish Ministry of Economy and Competitiveness via Retos de la Sociedad (DEP2016-79512-R to JRR and RTI2018-093919-B to SFV)European Regional Development Funds (ERDF)Spanish Ministry of Education (FPU16/02828, FPU16/05159, FPU17/01523 and FPU19/01609)University of Granada Plan Propio de Investigación 2016-Excellence actions–Unit of Excellence on Exercise and Health (UCEES)Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: ref. SOMM17/6107/UGR)The Spanish Ministry of Science and Innovation (PI20/00095 to VCM and PI20/00338 to JV) co-fnanced by the European Regional Development Fund (ERDF)Ramón y Cajal program (RYC2019026490-I) from the Spanish Ministry of Science and Innovation, co-fnanced by the ERDFy Fundación Bancaria Caixa d’Estalvis i Pensions de Barcelona (HR20-00051 to S.F.-V.)The Netherlands CardioVascular Research Initiative: ‘the Dutch Heart Foundation, Dutch Federation of University Medical Centers, The Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences’ (CVON2017-20 GENIUS-2) to PCNRChinese Scholarship Council (CSC, No. 201707060012) to XDMiguel Servet tenure-track program (CP10/00438 and CPII16/00008) from the Fondo de Investigación Sanitaria, co-fnanced by the ERDFFundación Alfonso Martin Escuder

Sex differences in treatment strategy for coronary artery aneurysms: Insights from the international Coronary Artery Aneurysm Registry

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up

El estudio PROPRESE: resultados de un nuevo modelo organizativo en atención primaria para pacientes con cardiopatía isquémica crónica basado en una intervención multifactorial

ResumenObjetivoComparando los resultados obtenidos en los estudios EUROASPIRE I y EUROASPIRE III en pacientes con cardiopatía isquémica se muestra que el grado de control de los factores de riesgo mayores es mejorable. El objetivo de este estudio es evaluar la eficacia de una intervención multifactorial orientada a la mejora del grado de control en estos pacientes en el ámbito de la atención primaria.MétodosEn este estudio de intervención aleatorizado, con 1 año de seguimiento, se reclutó a pacientes con diagnóstico de cardiopatía isquémica (145 en el grupo de intervención y 1.461 en el grupo control). Se aplicó una intervención organizativa mixta basada en la mejora de la relación profesional sanitario-paciente (de acuerdo a los modelos del Chronic Care, el Stanford Expert Patient Programme y el Kaiser Permanente) y en la formación profesional continuada. Los principales resultados fueron el efecto sobre el tabaquismo, el colesterol unido a lipoproteínas de baja densidad (cLDL), la presión arterial sistólica (PAS) y la presión arterial diastólica (PAD) a través de un análisis multivariable.ResultadosLas características de los pacientes fueron: edad (68,4±11,8 años), varones (71,6%), diabetes mellitus (51,3%), dislipemia (68,5%), hipertensión arterial (76,7%), no fumadores (76,1%); cLDL < 100mg/dl (46,9%); PAS < 140mmHg (64,5%); PAD < 90 (91,2%). El análisis multivariable mostró que el riesgo para el buen control en el grupo de intervención fue tabaquismo, riesgo relativo ajustado (RRa): 15,7 (intervalo de confianza del 95% [IC95%], 4,2–58,7); p < 0,001; cLDL, RRa: 2,98 (IC95%, 1,48–6,02); p < 0,002; PAS, RRa: 1.97 (IC95%, 1,21–3,23); p < 0,007, y PAD; RRa: 1,51 (IC95%, 0,65–3,50); p < 0,342.ConclusionesUna intervención multifactorial basada en el modelo de paciente crónico centrada en atención primaria y que facilite la toma de decisiones compartidas con los pacientes y la formación de los profesionales mejora el grado de control de los factores de riesgo cardiovascular (tabaquismo, cLDL y PAS). Las estrategias de mejora en la atención de la cronicidad pueden ser una herramienta eficaz para conseguir mejores resultados.AbstractObjectiveComparison of the results from the EUROASPIRE I to the EUROASPIRE III, in patients with coronary heart disease, shows that the prevalence of uncontrolled risk factors remains high. The aim of the study was to evaluate the effectiveness of a new multifactorial intervention in order to improve health care for chronic coronary heart disease patients in primary care.MethodsIn this randomized clinical trial with a 1-year follow-up period, we recruited patients with a diagnosis of coronary heart disease (145 for the intervention group and 1461 for the control group). An organizational intervention on the patient-professional relationship (centered on the Chronic Care Model, the Stanford Expert Patient Programme and the Kaiser Permanente model) and formative strategy for professionals were carried out. The main outcomes were smoking control, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). A multivariate analysis was performed.ResultsThe characteristics of patients were: age (68.4±11.8 years), male (71.6%), having diabetes mellitus (51.3%), dyslipidemia (68.5%), arterial hypertension (76.7%), non-smokers (76.1%); LDL-C < 100mg/dL (46.9%); SBP < 140mmHg (64.5%); DBP < 90 (91.2%). The multivariable analysis showed the risk of good control for intervention group to be: smoking, adjusted relative risk (aRR): 15.70 (95% confidence interval [95%CI], 4.2–58.7); P < .001; LDL-C, aRR: 2.98 (95%CI, 1.48–6.02); P < .002; SPB, aRR: 1.97 (95%CI, 1.21–3.23); P < .007, and DBP: aRR: 1.51 (95%CI, 0.65–3.50); P < .342.ConclusionsAn intervention based on models for chronic patients focused in primary care and involving patients in medical decision making improves cardiovascular risk factors control (smoking, LDL-C and SBP). Chronic care strategies may be an efficacy tool to help clinicians to involve the patients with a diagnosis of CHD to reach better outcomes

Short- and Long-Term Prognosis of Patients With Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature

Background Takotsubo syndrome (TTS) is an acute reversible heart condition initially believed to represent a benign pathology attributable to its self-limiting clinical course; however, little is known about its prognosis based on different triggers. This study compared short- and long-term outcomes between TTS based on different triggers, focusing on various physical triggering events. Methods and Results We analyzed patients with a definitive TTS diagnosis recruited for the Spanish National Registry on TTS (RETAKO [Registry on Takotsubo Syndrome]). Short- and long-term outcomes were compared between different groups according to triggering factors. A total of 939 patients were included. An emotional trigger was detected in 340 patients (36.2%), a physical trigger in 293 patients (31.2%), and none could be identified in 306 patients (32.6%). The main physical triggers observed were infections (30.7%), followed by surgical procedures (22.5%), physical activities (18.4%), episodes of severe hypoxia (18.4%), and neurological events (9.9%). TTS triggered by physical factors showed higher mortality in the short and long term, and within this group, patients whose physical trigger was hypoxia were those who had a worse prognosis, in addition to being triggered by physical factors, including age >70 years, diabetes mellitus, left ventricular eyection fraction <30% and shock on admission, and increased long-term mortality risk. Conclusions TTS triggered by physical factors could present a worse prognosis in terms of mortality. Under the TTS label, there could be as yet undiscovered very different clinical profiles, whose differentiation could lead to individual better management, and therefore the perception of TTS as having a benign prognosis should be generally ruled out

Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics. © 2022 The Author(s