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 Once-Weekly Insulin Data Published; It Could Alter Treatments Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine. "Insulin Icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin," said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual meeting of the EASD. Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual's basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its

 BACKGROUND Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin–kexin type  9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial)  and patients with atherosclerotic cardiovascular disease or an atherosclerotic car- diovascular disease risk equivalent (ORION-11 trial) who had elevated LDL choles- terol levels despite receiving statin therapy at the maximum tolerated dose. Patients  were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or pla- cebo, administered by subcutaneous injection on day 1, day 90, and every 6 months  thereafter over a period of 540 days. The coprimary end points in each trial were  the placebo-corrected percentage change in LDL cholesterol level from baseline to  day 510 and the time-adjusted percentage change in LDL cholesterol lev

 Experts Call for Immediate Suspension of ECT, Others Push Back Michael Vlesside Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression. A new review by investigators led by John Read, PhD, University of East London, United Kingdom, concludes there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective. However, the review's conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions. "We've concluded there is no adequate research on which to base an answer to the question, 'Does ECT work?,' " Read told Medscape

 BACKGROUND Patients with highly drug-resistant forms of tuberculosis have limited treatment  options and historically have had poor outcomes. METHODS In an open-label, single-group study in which follow-up is ongoing at three South  African sites, we investigated treatment with three oral drugs — bedaquiline,  pretomanid, and linezolid — that have bactericidal activity against tuberculosis and  to which there is little preexisting resistance. We evaluated the safety and efficacy  of the drug combination for 26 weeks in patients with extensively drug-resistant  tuberculosis and patients with multidrug-resistant tuberculosis that was not respon- sive to treatment or for which a second-line regimen had been discontinued because  of side effects. The primary end point was the incidence of an unfavorable outcome,  defined as treatment failure (bacteriologic or clinical) or relapse during follow-up,  which continued until 6 months after the end of treatment. Patients were classified  as hav

 General considerations in rabies  Post-Exposure Prophylaxis (PEP) • WHO strongly recommends discontinuation of the nerve tissue vaccine, and replacement with modern concentrated and purified cell culture derived vaccines (CCDV) and embryonated egg-based rabies vaccines • These vaccines must comply with WHO criteria for potency and innocuity following satisfactory assessment in humans during well-designed field trials  Top 10 General Considerations in Rabies PEP 1. Wounds must be immediately washed/flushed for 15 minutes and disinfected 2. Rabies PEP should be instituted immediately. PEP consists of a course of potent, effective rabies vaccine that meets WHO recommendations and administration of rabies immunoglobulin 3. PEP must be applied using vaccine regimens and administration routes that have been proven to be safe and effective 4. PEP does not have contraindications if purified rabies immunoglobulin and vaccine are used. Pregnancy and infancy are not contraindications to PEP  5.

 THE LIPOPROTEINS Introduction The French physician-scientist Michel Macheboeuf is acknowledged as the father of plasma lipoproteins. His seminal 1928 discovery fi ts the adage that science usually precedes tech- nology, in this case by several de- cades. In his doctoral thesis, Recher- ches sur les lipides, les stérols et les protéides du sérum et du plasma san- guinis, Macheboeuf described horse serum lipoproteins, demonstrating the association of lipids and proteins, ìlipido-protéidiquesî, in plasma.1 It is now recognized that plasma lipids are transported by lipoproteins, which are defi ned by the densities at which they are isolated, that is, as the high-, low-, intermediate-, and very- low-density lipoproteins (HDLs, LDLs, IDLs, and VLDLs, respectively); chy- lomicrons, which are intestinally de- rived, are composed mainly of dietary lipids and small amounts of protein. HDL appears in two subclasses, HDL2 and HDL3. Through a simple veni- puncture, plasma lipoprote

 1. ATHEROSCLEROSIS Atherosclerotic diseases, particularly coronary artery disease and stroke, are  leading causes of death (Mozaffarian et al., 2015). Atherosclerosis is a chronic  process that progresses in a clinically silent manner for decades. The devas- tating consequence of lesion evolution is the abrupt formation of thrombi,  due to lesion rupture or erosion that occludes blood flow, with the attendant  overt clinical symptoms (Bentzon et al., 2014) (Figure 1). The slow progres- sion of human atherosclerosis, combined with tissue inaccessibility and the  absence of effective imaging techniques, provides challenges for characteri- sation of lesion evolution. Hence, the understanding of mechanisms underly- ing the evolution of human atherosclerotic lesion progression is incomplete. FIGURE 1 A section of a human atherosclerotic coronary artery. The lesion contains a large lipid-rich core, containing cholesterol crystals, derived from apoptotic and/or necrotic foam cells. A thin