The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia

Hypertriglyceridemia (triglycerides > 150 mg/dL) affects ~25 % of the United States (US) population and is associated with increased cardiovascular risk. Severe hypertriglyceridemia (≥ 500 mg/dL) is also a risk factor for pancreatitis. Three omega-3 fatty acid (OM3FA) prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia: (1) OM3FA ethyl esters (OM3EE), a mixture of OM3FA ethyl esters, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lovaza®, Omtryg™, and generics); (2) icosapent ethyl (IPE), EPA ethyl esters (Vascepa®); and (3) omega-3 carboxylic acids (OM3CA), a mixture of OM3FAs in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (Epanova®). At approved doses, all formulations substantially reduce triglyceride and very-low-density lipoprotein levels. DHA-containing formulations may also increase low-density lipoprotein cholesterol. However, this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk in this patient population. Proposed mechanisms of action of OM3FAs include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation. OM3CA bioavailability (area under the plasma concentration-time curve from zero to the last measurable concentration) is up to 4-fold greater than that of OM3FA ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis. All three formulations are well tolerated (the most common adverse events are gastrointestinal) and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs, such as statins and fibrates. OM3FAs appear to be an effective treatment option for patients with severe hypertriglyceridemia

Optimal Lipid Modification: the Rationale for Combination Therapy

This is the publisher's version, also available electronically from "http://www.dovepress.com".No abstract available

Optimal Lipid Modification: The Rationale for Combination Therapy

James M Backes1, Cheryl A Gibson2, Patricia A Howard31Department of Pharmacy Practice, Lipid, Atherosclerosis, Metabolic and LDL Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 3Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, KS, USABackground: An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence.Objective: To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations. Method: Literature was obtained from MEDLINE (1966 – June 2005) and references from selected articles.Results: A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising.Conclusion: Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.Keywords: combination therapy, coronary heart disease, hypercholesterolemia, lipid-lowering, low-density lipoprotein, statin

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. Trial registration:NCT02657044(Clinicaltrials.gov), registered January 8, 2016

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Experimental evidence that novel land management interventions inspired by history enhance biodiversity

1. To address biodiversity declines within semi-natural habitats, land-management must cater for diverse taxonomic groups. Integrating our understanding of the ecological requirements of priority (rare, scarce or threatened) species through ‘biodiversity auditing’, with that of the intensity and complexity of historical land-use, encourages novel forms of management. Experimental confirmation is needed to establish whether this enhances biodiversity conservation relative to routine management. 2. Biodiversity auditing and historical land-use of dry-open terrestrial habitats in Breckland (Eastern England) both encourage management incorporating ground-disturbance and spatio-temporal variability. To test biodiversity conservation outcomes, we developed 40 4-ha management complexes over three successive winters, of which 20 were shallow-cultivated (rotovation) and 20 deep-cultivated (ploughing), stratified across 3,850-ha of closed-sward dry grassland and lowland heathland (collectively ‘dry grassland’). Complexes comprised four 1-ha sub-treatments: repeat-cultivation, first-time-cultivation, one-year-old fallow and two-year-old fallow. We examined responses of vascular plants; spiders; true bugs; ground, rove and ‘other’ beetles; bees and wasps; ants; and true flies on treatment complexes and 21 4-ha untreated controls. Sampling gave 132,251 invertebrates from 877 species and 28,846 plant observations from 167 species. 3. Resampling and rarefaction analyses showed shallow- and deep-cultivation both doubled priority species richness (pooling sub-treatments within complexes) compared to controls. Priority spider, ground beetle, other beetle, and true bug richness were greater on both treatments than controls. Responses were strongest for those priority dry-open-habitat associated invertebrates initially predicted (by biodiversity auditing) to benefit from heavy physical-disturbance. 4. Assemblage composition (pooling non-priority and priority species) varied between sub-treatments for plants, ants, true bugs, spiders, ground, rove and other beetles; but only one-year-old fallowed deep-cultivation increased priority richness across multiple taxa. 5. Treatments produced similar biodiversity responses across various dry grassland ‘habitats’ that differed in plant composition, allowing simplified management guidance. 6. Synthesis and applications. Our landscape-scale experiment confirmed the considerable biodiversity value of interventions inspired by history and informed by systematic multi-taxa analysis of ecological requirements across priority biota. Since assemblage composition varied between sub-treatments, providing heterogeneity in management will support the widest suite of species. Crucially, the intended recipients responded most strongly, suggesting biodiversity audits could successfully inform interventions within other systems

Political masculinities, crisis tendencies, and social transition: Toward an understanding of change

This introduction to the special issue on “Political Masculinities and Social Transition” rethinks the notion of “crisis in masculinity” and points to its weaknesses, such as cyclical patterns and chronicity. Rather than viewing key moments in history as points of rupture, we understand social change as encompassing ongoing transitions marked by a “fluid nature” (Montecinos 2017, 2). In line with this, the contributions examine how political masculinities are implicated within a wide range of social transitions, such as nation building after war, the founding of a new political party in response to an economic crisis, an “authoritarian relapse” of a democracy, attempts at changing society through terrorism, rapid industrialization as well as peace building in conflict areas. Building on Starck and Sauer’s definition of “political masculinities” we suggest applying the concept to instances in which power is explicitly either being (re)produced or challenged. We distinguish between political masculinities that are more readily identified as such (e.g., professional politicians) and less readily identified political masculinities (e.g., citizens), emphasizing how these interact with each other. We ask whether there is a discernible trajectory in the characteristics of political masculinities brought about by social transition that can be confirmed across cultures. The contributors’ findings indicate that these political masculinities can contribute to different kinds of change that either maintain the status quo, are progressive, retrogressive, or a mixture of these. Revolutionary transitions, it seems, often promote the adherence to traditional forms of political masculinity, whereas more reformatory transition leaves discursive spaces for argument