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

Failure of central venous catheter insertion and care bundles in a high central line–associated bloodstream infection rate, high bed occupancy hospital

Background: Our hospital has several characteristics different from the settings in which the central venous catheter (CVC) care bundle has been implemented so far, that is, care bundles or protocols are not systematically used, and the prevalence of central line–associated bloodstream infections (CLABSI) is high, as is bed occupancy rate. We examined the effectiveness of CVC care bundles. Methods: Modified CVC bundles were implemented across all settings of our hospital. During both phases of the study, we collected data on CLABSI, and we monitored CVC insertion and management practices with direct observation audits. Results: We have studied 913 CVC insertions (454 in PRE and 459 in POST) for 11,871 catheter-days. The incidence of CLABSI was 8.3 per 1,000 catheter-days PRE, and 7.6 per 1,000 catheter-days POST (incidence rate ratio, 0.92; 95% confidence interval, 0.60-1.40). Compliance with the CVC insertion bundle increased from 8.4%-74.3% (P <.0001). The CVC management bundle compliance also increased from 11.4%-57.7% (P <.0001). Conclusions: Despite improved compliance after the intervention, implementation of a modified CVC bundle failed to decrease CLABSI incidence. Higher bundle compliance rates may be necessary for a significant decrease in the incidence of CLABSI, along with the appropriate organizational culture and levels of staffing. © 2019 Association for Professionals in Infection Control and Epidemiology, Inc

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers

Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial oxyhemoglobin saturation (SaO2), is a common phenomenon in endurance athletes. Acute intensive exercise is associated with the generation of reactive species that may result in redox status disturbances and oxidation of cell macromolecules. The purpose of the present study was to investigate whether EIAH augments oxidative stress as determined in blood plasma and erythrocytes in well-trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes were assigned into either the normoxemic (n = 9, SaO 2 [92%, V O2max: 62.0 ± 1.9 ml kg-1 min-1) or hypoxemic (n = 12, SaO2\92%, V O2max: 60.5 ± 2.2 ml kg-1 min-1, mean ± SEM) group, following an incremental V O2max test on a wind resistance braked rowing ergometer. On aseparate day the rowers performed a 2,000-m all-out effort on the same rowing ergometer. Following an overnight fast, blood samples were drawn from an antecubital vein before and immediately after the termination of the 2,000-mall-out effort and analyzed for selective oxidative stress markers. In both the normoxemic (SaO2: 94.1 ± 0.9%) and hypoxemic (SaO2: 88.6 ± 2.4%) rowers similar and significant exercise increase in serum thiobarbituric acidreactive substances, protein carbonyls, catalase and total antioxidant capacity concentration were observed post-2,000 m all-out effort. Exercise significantly increased the oxidized glutathione concentration and decreased the ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group only, whereas the reduced form of glutathione remained unaffected in either groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic individuals suggest that erythrocyte redox status may be affected by the oxygen saturation degree of hemoglobin. Our findings indicate that exercise-induced hypoxemia did not further affect the increased blood oxidative damage of lipids and proteins observed after a2,000-m rowing ergometer race in highly-trained male rowers. The present data do not support any potential link between exercise-induced hypoxemia, oxidative stress increase and exercise performance. © 2011 Springer-Verlag

Retained surgical sponges: What the practicing clinician should know

Retained surgical sponges (RSS) are an avoidable complication following surgical operations. RSS can elicit either an early exudative-type reaction or a late aseptic fibrous tissue reaction. They may remain asymptomatic for long time; when present, symptomatology varies substantially and includes septic complications (abscess formation, peritonitis) or fibrous reaction resulting in adhesion formation or fistulation into adjacent hollow organs or externally. Plain radiograph may be useful for the diagnosis; however, computed tomography is the method of choice to establish correct diagnosis preoperatively. Removal of RSS is always indicated to prevent further complications. This is usually accomplished by open surgery; rarely, endoscopic or laparoscopic removal may be successful. Prevention is of key importance to avoid not only morbidity and even mortality but also medicolegal consequences. Preventive measures include careful counting, use of sponges marked with a radiopaque marker, avoidance of use of small sponges during abdominal procedures, careful examination of the abdomen by the operating surgeon before closure, radiograph in the operating theater (either routinely or selectively), and recently, usage of barcode and radiofrequency identification technology. © Springer-Verlag 2010

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers

Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial oxyhemoglobin saturation (SaO(2)), is a common phenomenon in endurance athletes. Acute intensive exercise is associated with the generation of reactive species that may result in redox status disturbances and oxidation of cell macromolecules. The purpose of the present study was to investigate whether EIAH augments oxidative stress as determined in blood plasma and erythrocytes in well-trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes were assigned into either the normoxemic ( = 9, SaO(2) > 92%, : 62.0 +/- A 1.9 ml kg(-1) min(-1)) or hypoxemic ( = 12, SaO(2) < 92%, : 60.5 +/- A 2.2 ml kg(-1) min(-1), mean +/- A SEM) group, following an incremental test on a wind resistance braked rowing ergometer. On a separate day the rowers performed a 2,000-m all-out effort on the same rowing ergometer. Following an overnight fast, blood samples were drawn from an antecubital vein before and immediately after the termination of the 2,000-m all-out effort and analyzed for selective oxidative stress markers. In both the normoxemic (SaO(2): 94.1 +/- A 0.9%) and hypoxemic (SaO(2): 88.6 +/- A 2.4%) rowers similar and significant exercise increase in serum thiobarbituric acid-reactive substances, protein carbonyls, catalase and total antioxidant capacity concentration were observed post-2,000 m all-out effort. Exercise significantly increased the oxidized glutathione concentration and decreased the ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group only, whereas the reduced form of glutathione remained unaffected in either groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic individuals suggest that erythrocyte redox status may be affected by the oxygen saturation degree of hemoglobin. Our findings indicate that exercise-induced hypoxemia did not further affect the increased blood oxidative damage of lipids and proteins observed after a 2,000-m rowing ergometer race in highly-trained male rowers. The present data do not support any potential link between exercise-induced hypoxemia, oxidative stress increase and exercise performance

No adverse effects of statins on muscle function and health-related parameters in the elderly: An exercise study

The aim of the present study was to investigate the effects of a repeated bout of eccentric exercise on health-related parameters and muscle performance on subjects undergoing atorvastatin therapy. Twenty-eight elderly men participated in the investigation and were assigned either in a control (n=14) or in a statin therapy group (n=14). All participants performed two isokinetic eccentric exercise bouts separated by 3 weeks. Muscle damage indices, resting energy expenditure, substrate metabolism, lipid and lipoprotein profile, as well as insulin sensitivity, were evaluated before and after eccentric. No differences in muscle function were observed between the two groups either at rest or after exercise. Eccentric exercise increased resting energy expenditure, increased fat oxidation, improved lipid profile, and increased insulin resistance 2 days after both eccentric exercise bouts. However, these changes appeared to lesser extent after the second bout. No differences were observed in the responses in the health-related parameters in the control and in the statin therapy group. Eccentric exercise affected similarly the control and the atorvastatin-treated individuals. The present results indicate that atorvastatin-treated elderly individuals may participate in various physical activities, even high-intensity muscle-damaging activities, without negative impact on muscle function and adaptation

Glycaemic control of Type1 diabetes in clinical practice early in the 21st century: an international comparison

AimsImproving glycaemic control in people with Type1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type1 diabetes using data gathered in regional or national registries. MethodsData were obtained for children and/or adults with Type1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173880. Proportions with HbA(1c) We present HbA(1c) data from registries in 19 different countries describing control in 324501 people with Type1 diabetes, across all age groups. These data are the best representation of diabetes care available and therefore describe the state of the art'. We show clearly that Type1 diabetes control is not as good as suggested in guidelines, but that some healthcare systems appear to result in better control than others. These data present a challenge to diabetes services. Leaders in diabetes units/service can compare their local data to our data and encourage improvement

A Greek registry of current type 2 diabetes management, aiming to determine core clinical approaches, patterns and strategies

Background: To analyze data in terms of the glycaemic control and therapeutic regimens used for Type-2 Diabetes Mellitus (T2DM) management in Greece, identify factors that influence clinical decisions and determine the level of compliance of T2DM management with the latest international and local guidelines. Methods: &apos;AGREEMENT&apos; was a national-multicenter, non-interventional, cross-sectional disease registry. A total of 1191 adult T2DM patients were enrolled consecutively from 59 sites of the National Health System (NHS) or University Hospitals, representing the majority of Diabetes centers or Diabetes outpatient clinics in Greece with a broad geographic distribution. Patients were stratified by gender and analysis was done according to 3 treatment strategies: A (lifestyle changes or use of one oral antidiabetic agent), B (up to 3 antidiabetic agents including injectables but not insulin) and C (any regimens with insulin). Results: Mean (±SD) HbA1c % of the total population was 7.1 (±1.2) while mean (±SD) FPG (mg/dl) was measured at 136 (±42). The proportion of patients who achieved HbA1c &lt; 7% was 53% and ranged from 74.2% for group A, to 60.6% for group B and 35.5% for group C. Median age of the studied population was 65.0 year old (Interquartile Range-IQR 14.0) with an equal distribution of genders between groups. Patients on insulin therapy (treatment strategy C) were older (median age: 67 years vs 63 or 65 for A and B, respectively) with longer diabetes duration (mean duration: 15.3 years vs 5.2 and 10.1 for A and B, respectively). Patients who received insulin presented poor compliance. There was a consensus for a series of decision criteria and factors that potentially influence clinical decisions, used by physicians for selection of the therapeutic strategy among the three groups. Compliance with international and Greek guidelines received a high score among groups A, B and C. No significant differences were presented as per sites&apos; geographic areas, NHS or University centers and physicians&apos; specialty (endocrinologists, diabetologists and internists). Conclusions: The presented findings suggest the need for improvement of the glycaemic control rate, especially among insulin treated patients as this group seems to achieve low glycaemic control, by setting appropriate HbA1c targets along with timely and individualised intensification of treatment as well as post-therapy evaluation of the compliance with the proposed treatment. © 2019 The Author(s)