Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Effect of Ionising Irradiation on Wheat Flour

Radiation processing suppresses the development of microorganisms and pests in food products. This method is safe and does not affect nutritional value; however, it may change the properties of starch and proteins. The research objective was to define the effect of ionization on the baking properties and safety indicators of wheat flour. The study featured wheat flour subjected to gamma irradiation at 0–47.52 kGy, as well as dough and bread made from this flour. The flour samples were tested for the radioactivity of radionuclides; a set of experiments revealed their microbiological indicators and falling-number values. The dough samples were studied on an Alveograph and a Mixolab analyzer to define their structural and mechanical properties. The quality of bread was evaluated by its specific volume, shape stability, and sensory profile. The flour proved safe in terms of residual gamma radiation after 24 and 72 h. At the maximal dose of gamma radiation, the total viable count of mesophyll aerobic and optional-anaerobic microorganisms decreased by fifteen times, whereas the amount of mold decreased by five times. The total strain energy, elastic properties, and elasticity index of the dough declined by more than 50%. The dough had a lower stability during kneading. Its gelatinization onset started earlier by 2.3–3.3°C. The falling number decreased by more than four times, probably, due to the changes in the state of wheat starch. The bread samples had a smaller specific volume and a lower dimensional stability. They also demonstrated signs of darkening, stickiness, and crumb crushing at the maximal irradiation dose (47.52 kGy). The microbiological safety indicators of wheat flour increased at the maximal irradiation dose. However, the baking properties of flour decreased. The sensory and physicochemical parameters of bread quality started to deteriorate at ≥ 23 kGy. Therefore, ionization cannot be recommended as a disinfection method for baking wheat flour production

Correlation between Myocardial Function and Electric Current Pulsatility of the Sputnik Left Ventricular Assist Device: In-Vitro Study

This study assesses the electric current parameters and reports on the analysis of the associated degree of myocardial function during left ventricular assist device (LVAD) support. An assumption is made that there is a correlation between cardiac output and the pulsatility index of the pump electric current. The experimental study is carried out using the ViVitro Pulse Duplicator System with Sputnik LVAD connected. Cardiac output and cardiac power output are used as a measure of myocardial function. Different heart rates (59, 73, 86 bpm) and pump speeds (7600–8400 rpm in 200 rpm steps) are investigated. In our methodology, ventricular stroke volumes in the range of 30–80 mL for each heart rate at a certain pump speed were used to simulate different levels of contractility. The correlation of the two measures of myocardial function and proposed pulsatility index was confirmed using different correlation coefficients (values ≥ 0.91). Linear and quadratic models for cardiac output and cardiac power output versus pulsatility index were obtained using regression analysis of measured data. Coefficients of determination for CO and CPO models were in the ranges of 0.914–0.982 and 0.817–0.993, respectively. Study findings suggest that appropriate interpretation of parameters could potentially serve as a valuable clinical tool to assess myocardial therapy using LVAD infrastructure

Wearable Light-and-Motion Dataloggers for Sleep/Wake Research: A Review

Long-term recording of a person’s activity (actimetry or actigraphy) using devices typically worn on the wrist is increasingly applied in sleep/wake, chronobiological, and clinical research to estimate parameters of sleep and sleep-wake cycles. With the recognition of the importance of light in influencing these parameters and with the development of technological capabilities, light sensors have been introduced into devices to correlate physiological and environmental changes. Over the past two decades, many such new devices have appeared from different manufacturers. One of the aims of this review is to help researchers and clinicians choose the data logger that best fits their research goals. Seventeen currently available light-and-motion recorders entered the analysis. They were reviewed for appearance, dimensions, weight, mounting, battery, sensors, features, communication interface, and software. We found that all devices differed from each other in several features. In particular, six devices are equipped with a light sensor that can measure blue light. It is noteworthy that blue light most profoundly influences the physiology and behavior of mammals. As the wearables market is growing rapidly, this review helps guide future developments and needs to be updated every few years

Wearable Light-and-Motion Dataloggers for Sleep/Wake Research: A Review

Long-term recording of a person’s activity (actimetry or actigraphy) using devices typically worn on the wrist is increasingly applied in sleep/wake, chronobiological, and clinical research to estimate parameters of sleep and sleep-wake cycles. With the recognition of the importance of light in influencing these parameters and with the development of technological capabilities, light sensors have been introduced into devices to correlate physiological and environmental changes. Over the past two decades, many such new devices have appeared from different manufacturers. One of the aims of this review is to help researchers and clinicians choose the data logger that best fits their research goals. Seventeen currently available light-and-motion recorders entered the analysis. They were reviewed for appearance, dimensions, weight, mounting, battery, sensors, features, communication interface, and software. We found that all devices differed from each other in several features. In particular, six devices are equipped with a light sensor that can measure blue light. It is noteworthy that blue light most profoundly influences the physiology and behavior of mammals. As the wearables market is growing rapidly, this review helps guide future developments and needs to be updated every few years

Structural changes of erythrocyte membrane revealed by 3D confocal optical profilometer

We examined hematological changes influenced by the experimental hypervitaminosis A. The 3D confocal optical profilometer was applied for assessment of the erythrocytes’ membrane structural changes influenced by an overdose of vitamin A. The blood smears were evaluated in terms of alterations of geometrical and optical parameters of erythrocytes for two groups of animals: oil base and retinol palmitate (n=9 animals for each group). The results demonstrate that an overdose of retinol palmitate causes changes in the torus curvature and pallor of discocytes, their surface area and volume. The observed structural malformations of the shape of red blood cells become visible at the earlier pre-clinical stage of changes in animal state and behaviour. With this in mind, the results of the study open a new area of research in the certain dysfunction diagnosis of red blood cells and has a great potential in the further development of new curative protocols