Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to ...describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated.
The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults (≥18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with ≥1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean±SD CHADS2 score was 1.9±1.2, and 57.2% had a score ≥2. Mean CHA2DS2-VASc score was 3.2±1.6, and 8,957 (84.4%) had a score ≥2. Overall, 38.0% of patients with a CHADS2 score ≥2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy.
These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.
ClinicalTrials.gov TRI08888.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Po River delta is characterized by a large system of shallow lagoons, wetlands, and reclaimed lands. Like many other deltaic regions, the Po Delta has largely subsided due to natural processes ...and anthropogenic activities, with a strong impact on its geomorphological evolution and significant socio- economic consequences. This paper aimed at highlighting the evolution of the study area over the last 120 years, analysing the land-uses changes in relation to the land subsidence, and using these findings to discuss the main management issues of this fragile low lying area in the decades to come. The analysis of the land use evolution from 1892 to 2015 and the information derived from the metrics measurement suggest a simplification of the land use with a decrease of the saltmarsh extent and an enlargement of the agricultural cover. The analysis of land subsidence, mainly due to gas-bearing groundwater withdrawal, confirms a strong impact on the delta territory, and in particular on its geomorphological asset. In the early 1900s the elevation of the delta plain ranged between −1.0 and +1.6 m above msl, while in 2007 it reduced between −2.8 to +0.3 m above msl. The land reclamation projects have largely increased the farmland usable for crop production but the concurrent loss of land elevation has resulted in a territory extremely difficult to be managed. Because of its elevation, the delta is particularly vulnerable to weather and marine events. As a consequence, the present management of the area is mainly aimed at maintaining the agricultural productivity. Unfortunately, if the human impacts will continue with the actual trend, the stability of the natural ecosystems, such as the wetlands, which represent important socioeconomic realities, will be further undermined. Surely, the conservation of these natural environments should be a priority in the future land use management.
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•The paper analyses the long term evolution of the land use in the Po delta.•We assess the relation between land use change and subsidence.•Land cover changes were a consequence of the loss of land elevation relative to MSL.•The study has implications for land use and territorial management.
We present an analysis of a sample of Seyfert 1 galaxies observed with Suzaku. The aim of this work is to examine critically the evidence for a relativistic Fe Kα line in the X-ray spectra of these ...active galactic nuclei. The sample was compiled from those sources in which a relativistic component was missing in at least one XMM–Newton observation. We analysed the Suzaku spectra of these objects in order to have more constraints on the high-energy emission, including the Compton reflection hump. The results show that the relativistic Fe Kα line is detected (at >95 per cent confidence) in all sources observed with high-signal-to-noise ratio (e.g. where the counts in the 5–7 keV energy band are ≳4 × 104). This is in agreement with the idea that relativistic lines are a ubiquitous feature in the spectra of Seyfert galaxies, but are often difficult to detect without very high-quality data. We also investigate the relation between the Fe Kα line and the reflection continuum at high energies. For most of the sample, the strength of the reflection component is consistent with that of the line. There are exceptions in both senses, however i.e. where the reflection continuum is strong but with weak line emission, and vice versa. These observations present a challenge for standard reflection models.
The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data ...about rivaroxaban use in routine clinical practice are needed.
XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007.
Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 95% CI 0·54-1·54, p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 95% CI 0·24-1·07, p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 36·0% of 2619 in the rivaroxaban group vs 805 37·5% of 2149 in the standard anticoagulation group).
In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings.
Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
Nonadherence to antihypertensive treatment is a common problem in cardiovascular prevention and may influence prognosis. We explored predictors of adherence to antihypertensive treatment and the ...association of adherence with acute cardiovascular events.
Using data obtained from 400 Italian primary care physicians providing information to the Health Search/Thales Database, we selected 18,806 newly diagnosed hypertensive patients >or=35 years of age during the years 2000 to 2001. Subjects included were newly treated for hypertension and initially free of cardiovascular diseases. Patient adherence was subdivided a priori into 3 categories-high (proportion of days covered, >or=80%), intermediate (proportion of days covered, 40% to 79%), and low (proportion of days covered, <or=40%)-and compared with the long-term occurrence of acute cardiovascular events through the use of multivariable models adjusted for demographic factors, comorbidities, and concomitant drug use. At baseline (ie, 6 months after index diagnosis), 8.1%, 40.5%, and 51.4% of patients were classified as having high, intermediate, and low adherence levels, respectively. Multiple drug treatment (odds ratio, 1.62; 95% CI, 1.43 to 1.83), dyslipidemia (odds ratio, 1.52; 95% CI, 1.24 to 1.87), diabetes mellitus (odds ratio, 1.40; 95% CI, 1.15 to 1.71), obesity (odds ratio, 1.50; 95% CI, 1.26 to 1.78), and antihypertensive combination therapy (odds ratio, 1.29; 95% CI, 1.15 to 1.45) were significantly (P<0.001) associated with high adherence to antihypertensive treatment. Compared with their low-adherence counterparts, only high adherers reported a significantly decreased risk of acute cardiovascular events (hazard ratio, 0.62; 95% CI, 0.40 to 0.96; P=0.032).
The long-term reduction of acute cardiovascular events associated with high adherence to antihypertensive treatment underscores its importance in assessments of the beneficial effects of evidence-based therapies in the population. An effort focused on early antihypertensive treatment initiation and adherence is likely to provide major benefits.
Pulmonary delivery offers a non-invasive route for the administration of biotherapeutics. In this context, understanding and control of a transport into, and across cellular barriers is central to ...the design of delivery systems. Here, we report our study on receptor mediated delivery of protein cargo by a formulation comprising sub-300 nm sized non-covalent protein complexes with biotin-conjugated PEG-poly(glutamic acid) (biotin-PEG2k-b-GA10) and PEG2k-b-GA30 copolymers blend as targeting and complexing functionalities. Designed complexes achieve intracellular delivery of the cargo in lung derived A549 epithelial cells in vitro via sodium-dependent multivitamin transporter (biotin receptor). We further show that biotin receptor driven endocytosis preferentially involves dynamin- and caveolae-dependent vesicular internalization, switching the transport pathway away from predominantly clathrin-dependent entry of free protein. Significantly for a protective intracellular delivery of biotherapeutics based on non-covalent complexation with polymeric excipients, the study provides evidence of intracellular presence of the complexing copolymer; demonstrated exploiting biotin in biotin-PEG2k-b-GA10 copolymer as a tag for binding with fluorescently labelled avidin. Moreover, analysis of intracellular localization of constitutive species shortly following cellular internalization suggests a co-localization of biotin-PEG2k-b-GA10 copolymer and protein constitutive species. The study demonstrates intracellular delivery of biotin targeted non-covalent complexes with a protein cargo, the result with important implications in a design of enabling technology platforms for protective, receptor mediated intracellular delivery of biotherapeutics.
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Hypercholesterolemia is a clinically relevant condition with an ascertained role in atherogenesis. In particular, its presence directly correlates to the risk of atherosclerotic cardiovascular ...disease (ASCVD). As known, cardiovascular diseases pose a significant economic burden worldwide; however, a clear picture of the economic impact of ASCVD secondary to hypercholesterolemia is lacking. This study aiming at conducting a systematic review of the current literature to assess the economic impact of familial hypercholesterolemia (FH), non-familial hypercholesterolemia (non-FH) or mixed dyslipidemia. A literature search was performed in Medline/PubMed and Embase database up to September 1st, 2020, exploring evidence published from 2010. The literature review was conducted in accordance with PRISMA guidelines. To be included the studies must be conducted on people who have been diagnosed with familial hypercholesterolemia, non-familial hypercholesterolemia or mixed dyslipidemia, and report data/information on costs attributable to these conditions and their sequelae. A total of 1260 studies were retrieved. After reading the titles and abstract, 103 studies were selected for full reading and eight met the criteria for inclusion. All but one studies were published in the American continent, with the majority conducted in US. An observational design with a prevalence approach were used and all estimated the economic burden of CVD. Direct cost estimates as annual average health expenditure on all population, ranging from $17 to $259 million. Few studies assessing the economic impact of hypercholesterolemia are available in the literature and new researches are needed to provide a more updated and reliable picture. Despite this scarceness of evidence, this review adds important data for future discussion on the knowledge of the economic impact of hypercholesterolemia and costs of care associated to this condition, with important implication for public health researches and novel therapies implementation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Olive samples were subjected to the salting process in brine containing 1196 mol m-3 of NaCl and 402 mol m-3 of KCl. Samples were collected during 60 h and salt concentration values were determined. ...With the finite element method (FEM) and the minimization of the errors percentage between the simulated and experimental values, the mass transfer coefficients in the film (hm) were obtained, being 1.0072 × 10-8 and 1.2499 × 10-8 for NaCl and KCl, respectively. The salts concentration at the olive/brine interface was simulated by FEM and analyzed via SOFM. A network with 4 × 4 topology and 10000 training epochs was used. It was observed that the influence of the stationary film formed on the surface of the olives during the salting process depends on the position, the salt involved in the diffusion and that the concentration of the salts, at each point, varies according to the immersion time.
Background
Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are ...increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications.
Purpose
We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.
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