European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin

We aimed to provide practical recommendations for the screening of subclinical atrial fibrillation (AF) in patients with ischaemic stroke or transient ischaemic attack (TIA) of undetermined origin. These guidelines are based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Five relevant Population, Intervention, Comparator, Outcome questions were defined by a multidisciplinary module working group (MWG). Longer duration of cardiac rhythm monitoring increases the detection of subclinical AF, but the optimal monitoring length is yet to be defined. We advise longer monitoring to increase the rate of anticoagulation, but whether longer monitoring improves clinical outcomes needs to be addressed. AF detection does not differ from in- or out-patient ECG-monitoring with similar monitoring duration, so we consider it reasonable to initiate in-hospital monitoring as soon as possible and continue with outpatient monitoring for more than 48 h. Although insertable loop recorders (ILR) increase AF detection based on their longer monitoring duration, comparison with non-implantable ECG devices for similar monitoring time is lacking. We suggest the use of implantable devices, if feasible, for AF detection instead of non-implantable devices to increase the detection of subclinical AF. There is weak evidence of a useful role for blood, ECG and brain imaging biomarkers for the identification of patients at high risk of AF. In patients with patent foramen ovale, we found insufficient evidence from RCT, but prolonged cardiac monitoring in patients >55 years is advisable for subclinical AF detection. To conclude, in adult patients with ischaemic stroke or TIA of undetermined origin, we recommend longer duration of cardiac rhythm monitoring of more than 48 h and if feasible with IRL to increase the detection of subclinical AF

The Atrial Fibrillation Risk Score for Hyperthyroidism Patients

Thyrotoxicosis (TT) is associated with an increase in both total and cardiovascu-lar mortality. One of the main thyrotoxicosis risks is Atrial Fibrillation (AF). Right AF predicts help medical personal prescribe the correct medicaments and correct surgical or radioiodine therapy. The main goal of this study is creating a method for practical treatment and diagnostic AF. This study proposes a new method for assessing the risk of occurrence atrial fibrillation for patients with TT. This method considers both the features of the complication and the specifics of the chronic disease. A model is created based on case histories of patients with thyrotoxicosis. We used Machine Learning methods for creating several models. Each model has advantages and disadvantages depending on the diagnostic and medical purposes. The resulting models show high results in the different metrics of the prediction of AF. These models interpreted and simple for use. Therefore, models can be used as part of the support and decision-making system (DSS) by medical specialists in the treatment and diagnostic of AF

The Effectiveness of Co-Determination Laws in Cooperative and Adversarial Employment Relations: When Does Regulation Have Bite?

The German Codetermination Law grants workers of establishments with 200 or more employees the right to have a works councillor who is fully exempted from his or her regular job duties while still paid a regular salary. This article analyses theoretically and empirically how this de jure right to exemption translates into de facto practice, and explicitly takes into account the nature of the employment relations participation regime. It is found that the right of exemption has no effect in cooperative employment relations because exemptions are granted even in the absence of legal rights, but does make a difference in adversarial relations when exemptions are only granted above the threshold where legal rights force employers to do so, i.e. legal rights do make a decisive difference in exactly those situations where the legislators’ intent would not be realized without the right to legal enforcemen

Wage effects of works councils and opening clauses: the German case

"German employment relations are characterized by a distinct dual system. First, working conditions and wages are determined by industry-level collective bargaining agreements. Second, on the establishment-level, the works council is responsible for employer - employee negotiations. However, since the mid-1980s, an increasing number of areas of regulation have been transferred from the industry- to the establishment-level using so-called opening clauses. The analysis in this article relies on rich German establishment data and reveals new insights into the institutional machinery of wage bargaining. While the existence of such clauses is related to higher wages, their application results in wage cuts of roughly the same size. The results also suggest that works councils, on average, are able to prevent the negative wage effects of opening clauses." (Author's abstract, IAB-Doku) ((en)

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine

Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide poly-morphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach.Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N= 6669), B-type natriuretic peptide (BNP) (N= 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N= 6813) were measured in the FINRISK 1997 cohort. N=30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely.Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms

Combination of scoring schemes for protein docking

<p>Abstract</p> <p>Background</p> <p>Docking algorithms are developed to predict in which orientation two proteins are likely to bind under natural conditions. The currently used methods usually consist of a sampling step followed by a scoring step. We developed a weighted geometric correlation based on optimised atom specific weighting factors and combined them with our previously published amino acid specific scoring and with a comprehensive SVM-based scoring function.</p> <p>Results</p> <p>The scoring with the atom specific weighting factors yields better results than the amino acid specific scoring. In combination with SVM-based scoring functions the percentage of complexes for which a near native structure can be predicted within the top 100 ranks increased from 14% with the geometric scoring to 54% with the combination of all scoring functions. Especially for the enzyme-inhibitor complexes the results of the ranking are excellent. For half of these complexes a near-native structure can be predicted within the first 10 proposed structures and for more than 86% of all enzyme-inhibitor complexes within the first 50 predicted structures.</p> <p>Conclusion</p> <p>We were able to develop a combination of different scoring schemes which considers a series of previously described and some new scoring criteria yielding a remarkable improvement of prediction quality.</p

World Heart Federation Roadmap on Atrial Fibrillation - A 2020 Update

The World Heart Federation (WHF) commenced a Roadmap initiative in 2015 to reduce the global burden of cardiovascular disease and resultant burgeoning of healthcare costs. Roadmaps provide a blueprint for implementation of priority solutions for the principal cardiovascular diseases leading to death and disability. Atrial fibrillation (AF) is one of these conditions and is an increasing problem due to ageing of the world’s population and an increase in cardiovascular risk factors that predispose to AF. The goal of the AF roadmap was to provide guidance on priority interventions that are feasible in multiple countries, and to identify roadblocks and potential strategies to overcome them. Since publication of the AF Roadmap in 2017, there have been many technological advances including devices and artificial intelligence for identification and prediction of unknown AF, better methods to achieve rhythm control, and widespread uptake of smartphones and apps that could facilitate new approaches to healthcare delivery and increasing community AF awareness. In addition, the World Health Organisation added the non-vitamin K antagonist oral anticoagulants (NOACs) to the Essential Medicines List, making it possible to increase advocacy for their widespread adoption as therapy to prevent stroke. These advances motivated the WHF to commission a 2020 AF Roadmap update. Three years after the original Roadmap publication, the identified barriers and solutions were judged still relevant, and progress has been slow. This 2020 Roadmap update reviews the significant changes since 2017 and identifies priority areas for achieving the goals of reducing death and disability related to AF, particularly targeted at low-middle income countries. These include advocacy to increase appreciation of the scope of the problem; plugging gaps in guideline management and prevention through physician education, increasing patient health literacy, and novel ways to increase access to integrated healthcare including mHealth and digital transformations; and greater emphasis on achieving practical solutions to national and regional entrenched barriers. Despite the advances reviewed in this update, the task will not be easy, but the health rewards of implementing solutions that are both innovative and practical will be great