Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide

Objective: Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. <p/>Design: A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. <p/>Subjects: A total of 564 adults (n=90–98 per group; body mass index 30–40 kg m−2) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90–95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007–April 2009 and is registered with Clinicaltrials.gov, number NCT00480909. <p/>Results: From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7–8.0) more weight than those on placebo and 3.8 kg (1.6–6.0) more than those on orlistat (Pless than or equal to0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3–4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. <p/>Conclusion: Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Don’t make me angry, you wouldn’t like me when I’m angry: volitional choices to act or inhibit are modulated by subliminal perception of emotional faces

Volitional action and self-control—feelings of acting according to one’s own intentions and in being control of one’s own actions—are fundamental aspects of human conscious experience. However, it is unknown whether high-level cognitive control mechanisms are affected by socially salient but nonconscious emotional cues. In this study, we manipulated free choice decisions to act or withhold an action by subliminally presenting emotional faces: In a novel version of the Go/NoGo paradigm, participants made speeded button-press responses to Go targets, withheld responses to NoGo targets, and made spontaneous, free choices to execute or withhold the response for Choice targets. Before each target, we presented emotional faces, backwards masked to render them nonconscious. In Intentional trials, subliminal angry faces made participants more likely to voluntarily withhold the action, whereas fearful and happy faces had no effects. In a second experiment, the faces were made supraliminal, which eliminated the effects of angry faces on volitional choices. A third experiment measured neural correlates of the effects of subliminal angry faces on intentional choice using EEG. After replicating the behavioural results found in Experiment 1, we identified a frontal-midline theta component—associated with cognitive control processes—which is present for volitional decisions, and is modulated by subliminal angry faces. This suggests a mechanism whereby subliminally presented “threat” stimuli affect conscious control processes. In summary, nonconscious perception of angry faces increases choices to inhibit, and subliminal influences on volitional action are deep seated and ecologically embedded

The burden of breast, cervical, and colon and rectum cancer in the Balkan countries, 1990–2019 and forecast to 2030.

Background Despite effective prevention and control strategies, in countries of the Balkan region, cancers are the second leading cause of mortality, closely following circulatory system diseases. Objective To describe trends in the burden of breast, cervical, and colon and rectum cancer in the Balkan region and per country between 1990 and 2019, including a forecast to 2030. Methods We described the 2019 Global Burden of Disease (GBD) estimates for breast, cervical, and colon and rectum cancers in eleven Balkan countries over the period 1990–2019, including incidence, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALYs) rates per 100,000 population and accompanied 95% uncertainty interval. With the Autoregressive Integrated Moving Average, we forecasted these rates per country up to 2030. Results In the Balkan region, the highest incidence and DALYs rates in the study period were for colon and rectum, and breast cancers. Over the study period, the DALYs rates for breast cancer per 100,000 population were the highest in Serbia (reaching 670.84 in 2019) but the lowest in Albania (reaching 271.24 in 2019). In 2019, the highest incidence of breast cancer (85 /100,000) and highest YLD rate (64 /100,000) were observed in Greece. Romania had the highest incidence rates, YLD rates, DALY rates, and YLL rates of cervical cancer, with respective 20.59%, 23.39% 4.00%, and 3.47% increases for the 1990/2019 period, and the highest forecasted burden for cervical cancer in 2030. The highest incidence rates, YLD rates and DALY rates of colon and rectum cancers were continuously recorded in Croatia (an increase of 130.75%, 48.23%, and 63.28%, respectively), while the highest YLL rates were in Bulgaria (an increase of 63.85%). The YLL rates due to colon and rectum cancers are forecasted to progress by 2030 in all Balkan countries. Conclusion As most of the DALYs burden for breast, cervical, and colon and rectum cancer is due to premature mortality, the numerous country-specific barriers to cancer early detection and quality and care continuum should be a public priority of multi-stakeholder collaboration in the Balkan region

Assessment of insulin resistance by a 13C glucose breath test: a new tool for early diagnosis and follow-up of high-risk patients

<p>Abstract</p> <p>Background/Aims</p> <p>Insulin resistance (IR) plays an important role in the pathogenesis of diabetes and non-alcoholic fatty liver disease (NAFLD). Current methods for insulin resistance detection are cumbersome, or not sensitive enough for early detection and follow-up. The BreathID^®system can continuously analyse breath samples in real-time at the point-of-care. Here we determined the efficacy of the BreathID^®using the ¹³C-Glucose breath test (GBT) for evaluation of insulin resistance.</p> <p>Methods</p> <p>Twenty healthy volunteers were orally administered 75 mg of ¹³C-glucose 1-¹³C. An oral glucose tolerance test (OGTT) was performed immediately; followed by serum glucose and insulin level determinations using GBT. GBT and OGTT were repeated following exercise, which alters insulin resistance levels.</p> <p>Results</p> <p>Within-subject correlations of GBT parameters with serum glucose and serum insulin levels were high. Before and after exercise, between-subjects correlations were high between the relative insulin levels and the % dose recoveries at 90 min (PDR 90), and the cumulative PDRs at 60 min (CPDR 60). Pairwise correlations were identified between pre-exercise Homeostasis Model Assessment (HOMA) IR at 90 min and PDR 90; HOMA B (for beta cell function) 120 and CPDR 30; HOMA IR 60 and peak time post-exercise; and HOMA B 150 with PDR 150.</p> <p>Conclusions</p> <p>The non-invasive real-time BreathID^®GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. It may serve as a non-invasive tool for early diagnosis and follow up of patients in high-risk groups.</p

Evidence-based hydro- and balneotherapy in Hungary-a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis. © 2013 The Author(s)

Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study

Background: Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease. Methodology/Principal Findings: In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p,0.001). Three distinct telomere trajectories were observed: shortening in 45%, maintenance in 32%, and lengthening in 23 % of participants. The most powerful predictor of telomere shortening was baseline telomere length (OR per SD increase = 7.6; 95 % CI 5.5, 10.6). Other independent predictors of telomere shortening were age (OR per 10 years = 1.6; 95 % CI 1.3, 2.1), male sex (OR = 2.4; 95 % CI 1.3, 4.7), and waist-to-hip ratio (OR per 0.1 increase = 1.4; 95 % CI 1.0, 2.0). Conclusions/Significance: Leukocyte telomere length may increase as well as decrease in persons with coronary arter

The oil-dispersion bath in anthroposophic medicine – an integrative review

<p>Abstract</p> <p>Background</p> <p>Anthroposophic medicine offers a variety of treatments, among others the oil-dispersion bath, developed in the 1930s by Werner Junge. Based on the phenomenon that oil and water do not mix and on recommendations of Rudolf Steiner, Junge developed a vortex mechanism which churns water and essential oils into a fine mist. The oil-covered droplets empty into a tub, where the patient immerses for 15–30 minutes. We review the current literature on oil-dispersion baths.</p> <p>Methods</p> <p>The following databases were searched: Medline, Pubmed, Embase, AMED and CAMbase. The search terms were 'oil-dispersion bath' and 'oil bath', and their translations in German and French. An Internet search was also performed using Google Scholar, adding the search terms 'study' and 'case report' to the search terms above. Finally, we asked several experts for gray literature not listed in the above-mentioned databases. We included only articles which met the criterion of a clinical study or case report, and excluded theoretical contributions.</p> <p>Results</p> <p>Among several articles found in books, journals and other publications, we identified 1 prospective clinical study, 3 experimental studies (enrolling healthy individuals), 5 case reports, and 3 field-reports. In almost all cases, the studies described beneficial effects – although the methodological quality of most studies was weak. Main indications were internal/metabolic diseases and psychiatric/neurological disorders.</p> <p>Conclusion</p> <p>Beyond the obvious beneficial effects of warm bathes on the subjective well-being, it remains to be clarified what the unique contribution of the distinct essential oils dispersed in the water can be. There is a lack of clinical studies exploring the efficacy of oil-dispersion baths. Such studies are recommended for the future.</p

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

BACKGROUND: Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. METHODS: Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. RESULTS: HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile= 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile= 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. CONCLUSIONS: HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively