Age differences in contemporary treatment of patients with chronic heart failure and reduced ejection fraction

Background: Elderly patients are underrepresented in clinical trials but comprise the majority of heart failure patients. Data on age-specific use of heart failure therapy are limited. The European Society of Cardiology heart failure guidelines provide no age-specific treatment recommendations. We investigated practice-based heart failure management in a large registry at heart failure outpatient clinics. Design and methods: We studied 8351 heart failure with reduced ejection fraction patients at 34 Dutch outpatient clinics between 2013 and 2016. The mean age was 72.3 11.8 years and we divided age into three categories: less than 60 years (13.9%); 60–74 years (36.0%); and 75 years and over (50.2%). Results: Elderly heart failure with reduced ejection fraction patients (75 years) received significantly fewer betablockers (77.8% vs. 84.2%), renin–angiotensin system inhibitors (75.2% vs. 89.7%), mineralocorticoid receptor antagonists (50.6% vs. 59.6%) and ivabradine (2.9% vs. 9.3%), but significantly more diuretics (88.1% vs. 72.6%) compared to patients aged less than 60 years (Pfor all trends< 0.01). Moreover, the prescribed target dosages were significantly lower in elderly patients. Also, implantable cardioverter defibrillator (18.9% vs. 44.1%) and cardiac resynchronisation therapy device (14.6% vs. 16.7%) implantation rates were significantly lower in elderly patients. A similar trend in drug prescription was observed in patients with heart failure with mid-range ejection fraction as in heart failure with reduced ejection fraction. Conclusion: With increasing age, heart failure with reduced ejection fraction patients less often received guidelinerecommended medication prescriptions and also in a lower dosage. In addition, a lower percentage of implantabl

Stratification of asthma phenotypes by airway proteomic signatures

© 2019 Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies

Western Pacific international meeting and workshop on Toga Coare : proceedings

A new reduced gravity, primitive equation model of the upper equatorial ocean has been developped by Gent and Cane (1989). It has been configured to simulate the annual cycle in the tropical Pacific ocean. It is forced by the monthly winds from Rasmusson and Carpenter (1982) and a new heat flux formulation from Seager et al. (1988). The coefficients of vertical eddy viscosity and conductivity depend upon the Ridcharson number of the flow. With this mixing a deep warm pool form in the western Pacific, increasing the west-east gradient of the thermocline and equatorial undercurrent. The model has been diagnosed as to what factors maintain this deep warm pool. (Résumé d'auteur

Synergism between the Synthetic Antibacterial and Antibiofilm Peptide (SAAP)-148 and Halicin

Recently, using a deep learning approach, the novel antibiotic halicin was discovered. We compared the antibacterial activities of two novel bactericidal antimicrobial agents, i.e., the synthetic antibacterial and antibiofilm peptide (SAAP)-148 with this antibiotic halicin. Results revealed that SAAP-148 was more effective than halicin in killing planktonic bacteria of antimicrobial-resistant (AMR) Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus, especially in biologically relevant media, such as plasma and urine, and in 3D human infection models. Surprisingly, SAAP-148 and halicin were equally effective against these bacteria residing in immature and mature biofilms. As their modes of action differ, potential favorable interactions between SAAP-148 and halicin were investigated. For some specific strains of AMR E. coli and S. aureus synergism between these agents was observed, whereas for other strains, additive interactions were noted. These favorable interactions were confirmed for AMR E. coli in a 3D human bladder infection model and AMR S. aureus in a 3D human epidermal infection model. Together, combinations of these two novel antimicrobial agents hold promise as an innovative treatment for infections not effectively treatable with current antibiotics.Immunogenetics and cellular immunology of bacterial infectious disease

Age differences in contemporary treatment of patients with chronic heart failure and reduced ejection fraction

Background: Elderly patients are underrepresented in clinical trials but comprise the majority of heart failure patients. Data on age-specific use of heart failure therapy are limited. The European Society of Cardiology heart failure guidelines provide no age-specific treatment recommendations. We investigated practice-based heart failure management in a large registry at heart failure outpatient clinics. Design and methods: We studied 8351 heart failure with reduced ejection fraction patients at 34 Dutch outpatient clinics between 2013 and 2016. The mean age was 72.3 ± 11.8 years and we divided age into three categories: less than 60 years (13.9%); 60–74 years (36.0%); and 75 years and over (50.2%). Results: Elderly heart failure with reduced ejection fraction patients (≥75 years) received significantly fewer beta-blockers (77.8% vs. 84.2%), renin–angiotensin system inhibitors (75.2% vs. 89.7%), mineralocorticoid receptor antagonists (50.6% vs. 59.6%) and ivabradine (2.9% vs. 9.3%), but significantly more diuretics (88.1% vs. 72.6%) compared to patients aged less than 60 years (Pfor all trends < 0.01). Moreover, the prescribed target dosages were significantly lower in elderly patients. Also, implantable cardioverter defibrillator (18.9% vs. 44.1%) and cardiac resynchronisation therapy device (14.6% vs. 16.7%) implantation rates were significantly lower in elderly patients. A similar trend in drug prescription was observed in patients with heart failure with mid-range ejection fraction as in heart failure with reduced ejection fraction. Conclusion: With increasing age, heart failure with reduced ejection fraction patients less often received guideline-recommended medication prescriptions and also in a lower dosage. In addition, a lower percentage of implantable cardioverter defibrillator and cardiac resynchronisation therapy device implantation in elderly patients was observed

Heart failure treatment in patients with and without obesity with an ejection fraction below 50%

BackgroundThe aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. MethodsPatients with a left ventricular ejection fraction (LVEF) = 30 kg/m(2)) was performed. ResultsSeven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI >= 30 kg/m(2), and 618 (8.1%) had a BMI >= 35 kg/m(2). Median BMI was 26.4 kg/m(2). Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving >= 100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). ConclusionsGuideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity

Sequential Open-Boundary Control by Data Assimilation in a Limited-Area Model.

The feasibility of sequential open-boundary control by data assimilation in a regional ocean model has been investigated using a barotropic wind-driven ocean circulation model. A simple open-boundary scheme has been constructed based on the idea of optimal boundary control of a diagnostic equation and illustrated with the problem of modeling the subpolar gyre subject to an open southern boundary. The results show that use of such a scheme in conjunction with traditional radiation boundary conditions allows for a longer model integration that would otherwise be unstable when only the radiation boundary conditions are imposed due to presence of dispersive waves. Copyright 1995 American Meteorological Society (AMS). Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC §108, as revised by P.L. 94-553) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form, such as on a web site or in a searchable database, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. Additional details are provided in the AMS Copyright Policy, available on the AMS Web site located at (http://www.ametsoc.org/) or from the AMS at 617-227-2425 or [email protected], Faculty ofEarth and Ocean Sciences, Department ofReviewedFacult