1,720,988 research outputs found
IMPROVE-IT: What have we learned?
No full textPurpose of review: Recent studies and dyslipidemia treatment guidelines indicate that combination lipid-lowering therapy is frequently needed and its use has increased in recent years. Ezetimibe and simvastatin as a fixed dose is an efficacious treatment choice based on positive results of the recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). In this review, we discuss recent controversies surrounding ezetimibe and provide clinical perspective on the results of the IMPROVE-IT study. Recent findings: IMPROVE-IT is the first trial that demonstrates a significant clinical benefit of a nonstatin hypolipidemic agent (ezetimibe) used in combination with statin (simvastatin) therapy in patients who have experienced an acute coronary syndrome. For almost a decade, the use of ezetimibe was limited by a relative lack of definitive evidence. However, the most recent Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound study showed greater coronary plaque regression by statin/ezetimibe combination compared with statin monotherapy. The results of the IMPROVE-IT trial are fostering new debate about the value of adjunctive low-density lipoprotein cholesterol lowering over and above a statin. Summary: Ezetimibe/simvastatin combination, either as a single pill or as the combined use of the individual compounds, represents a well-tolerated and efficacious choice for dyslipidemia treatment in high-risk subjects, including patients with diabetes. Limited additional risk for adverse events compared with simvastatin monotherapy is observed, and an individualized, patient-centered approach to therapy is recommended
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Emerging therapies for raising high-density lipoprotein cholesterol (HDL-C) and augmenting HDL particle functionality
No full textHigh-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wall injury. HDL metabolism and the molecular constitution of HDL particles are highly complex and can change in response to both acute and chronic alterations in the metabolic milieu. To date, some of these interventions have been shown to positively impact rates of coronary artery disease progression. However, none of them have as yet been shown to significantly reduce risk for cardiovascular events. In the next 3-5 years a variety of pharmacologic interventions for modulating HDL metabolism and functionality will be tested in large, randomized, prospective outcomes trials. It is hoped that one or more of these therapeutic approaches will result in the ability to further reduce risk for cardiovascular events once low-density lipoprotein cholesterol and non-HDL-cholesterol targets have been attained. © 2013 Elsevier Ltd. All rights reserved
Should low high-density lipoprotein cholesterol (HDL-C) be treated?
No full textThe first observations linking a low serum level of HDL-C to increased risk for cardiovascular disease were made over 50 years ago. High serum levels of HDL-C appear to protect against the development of atherosclerotic disease, while low serum levels of this lipoprotein are among the most important predictors of atherosclerotic disease in both men and women and people of all racial and ethnic groups throughout the world. It has long been assumed that therapeutic interventions targeted at raising HDL-C levels would lower risk for such cardiovascular events as myocardial infarction, ischemic stroke, and death. Even after five decades of intensive investigation, evidence to support this assumption has been fleeting. A number of post hoc analyses of randomized controlled trials and meta-analyses suggest that HDL-C raising, particularly when coupled with aggressive LDL-C reduction, impacts risk for cardiovascular events and rates of progression of atherosclerotic disease. Unfortunately, four recent prospective trials performed with the intent of testing the "HDL hypothesis" (ILLUMINATE, dal-OUTCOMES, AIM-HIGH, and HPS2-THRIVE) failed to meet their primary composite endpoints. These results have lead many clinicians and investigators to question the validity of the assumption that HDL-C raising reduces risk for cardiovascular events. Additional trials with other drugs are underway. In the meantime, HDL-C cannot be considered a target of therapy. Given the complexity of the HDL proteome and lipidome, there is biological plausibility for how HDL particles might exert atheroprotection. We explore the evidence supporting the inverse relationship between HDL-C and cardiovascular disease risk, documented mechanisms by which HDL particles may exert atheroprotection, and the findings either supporting or negating specific therapeutic interventions in patients afflicted with low HDL-C. © 2013 Elsevier Ltd. All rights reserved
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Novel anti-obesity drugs and plasma lipids
No full textObesity is a health problem of global, epidemic proportions and a major risk factor for chronic diseases resulting in accelerated morbidity and mortality. Dyslipidemia with a predominance of small dense LDL, impaired functionality of HDL particles, and increased serum levels of remnant particles due to impaired clearance of triglyceride-rich lipoproteins significantly heightens cardiovascular events in obese subjects. Pharmacotherapy in combination with lifestyle modification is the primary approach to reduce obesity-related cardiovascular risk. Although there are several potential anti-obesity drugs, orlistat is the only agent that remains available in the market. Lorcaserin and Qsymia®, approved by the US FDA last year, and contrave with potential approval in 2014, are new anti-obesity drugs with promising therapeutic effects. Although these drugs can be associated with adverse side-effects, these agents have favorable effects on lipid profiles. However, the need for safer anti-obesity agents is clear. © 2014 Future Medicine Ltd
Statins and new-onset diabetes
No full textStatins are highly efficacious lipid modifying agents that reduce the risk for cardiovascular (CV) events in both primary and secondary prevention settings. However, statins affect molecular mechanisms which adversely impact on insulin sensitivity and –cell function, thereby increasing risk for new onset diabetes mellitus (NOD). Defining the mechanisms involved is the focus of considerable current investigation. The statins reduce the risk for CV events in normoglycemic patients as well as in those with diabetes mellitus (DM) and their benefits outweigh the risk of inducing NOD. We review the clinical evidence for NOD with statin treatment, as well as the potential mechanisms involved. Our literature search was based on PubMed and Scopus listings. Further large studies are needed to elucidate both the association between NOD and statin use and the underlying mechanisms
Subfractions and subpopulations of HDL: An update
No full textHigh-density lipoproteins (HDL) are classified as atheroprotective because they are involved in transport of cholesterol to the liver, known as "reverse cholesterol transport (RCT)" exerting antioxidant and anti-inflammatory activities. There is also evidence for cytoprotective, vasodilatory, antithrombotic, and anti-infectious activities for these lipoproteins. HDLs are known by structural, metabolic and biologic heterogeneity. Thus, different methods are able to distinguish several subclasses of HDL. Different separation techniques appear to support different HDL fractions as being atheroprotective or related with lower cardiovascular (CV) risk. However, HDL particles are not always protective. Modification of constituents of HDL particles (primarily in proteins and lipids) can lead to the decrease in their activity and induce proatherogenic properties, especially when isolated from patients with augmented systemic inflammation. According to available studies, it seems that HDL functionality may be a better therapeutic target than HDL cholesterol quantity; however, it is still disputable which subfractions are most beneficial. There is mounting evidence supporting HDL subclasses as an important biomarker to predict and/or reduce CV risk. In this review we discuss recent notices on atheroprotective and functional characteristic of different HDL subfractions. Also, we provide a brief overview of the different methods used by clinicians and researchers to separate HDL subfractions. Ongoing and future investigations will yield important new information if any given separation method might represent a 'gold standard', and which subfractions are reliable markers of CV risk and/or potential targets of novel, more focused, and effective therapies. © 2014 Bentham Science Publishers
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