COPD-Lower Respiratory Tract Infection Visual Analogue Score (c-LRTI-VAS) validation in stable and exacerbated patients with COPD

BACKGROUND: We developed the chronic obstructive pulmonary disease (COPD)-Lower Respiratory Tract Infection-Visual Analogue Score (c-LRTI-VAS) in order to easily quantify symptoms during exacerbations in patients with COPD. This study aimed to validate this score. METHODS: In our study, patients with stable COPD as well as those with an acute exacerbations of COPD (AECOPD) were included. The results of c-LRTI-VAS were compared with other markers of disease activity (lung function parameters, oxygen saturation and two health related quality of life questionnaires (St Georges Respiratory Questionnaire (SGRQ) and Clinical COPD Questionnaire (CCQ)) and validity, reliability and responsiveness were assessed. RESULTS: Eighty-eight patients with clinically stable COPD and 102 patients who had an AECOPD completed the c-LRTI-VAS questionnaire. When testing on two separate occasions for repeatability, no statistically significant difference between total scores was found 0.143 (SD 5.42) (p=0.826). Internal consistency was high across items (Cronbach's apha 0.755). Correlation with SGRQ and CCQ total scores was moderate to high. After treatment for hospitalised AECOPD, the mean c-LRTI-VAS total score improved 8.14 points (SD 9.13; p≤0.001). CONCLUSIONS: c-LRTI-VAS showed proper validity, responsiveness to change and moderate to high correlation with other questionnaires. It, therefore, appears a reliable tool for symptom measurement during AECOPD. TRIAL REGISTRATION NUMBER: NCT01232140

LEADER 3—Lipase and Amylase Activity in Subjects With Type 2 Diabetes: Baseline Data From Over 9000 Subjects in the LEADER Trial

Objectives: This report from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial describes baseline lipase and amylase activity in type 2 diabetic subjects without acute pancreatitis symptoms before randomization to the glucagonlike peptide analog liraglutide or placebo. Methods: The LEADER is an international randomized placebo-controlled trial evaluating the cardiovascular safety of liraglutide in 9340 type 2 diabetic patients at high cardiovascular risk. Fasting lipase and amylase activity was assessed at baseline, before receiving liraglutide or placebo, using a commercial assay (Roche) with upper limit of normal values of 63 U/L for lipase and 100 U/L for amylase. Results: Either or both enzymes were above the upper limit of normal in 22.7% of subjects; 16.6% (n = 1540) had an elevated lipase level (including 1.2% >3-fold elevated), and 11.8% (n = 1094) had an elevated amylase level (including 0.2% >3-fold elevated). In multivariable regression models, severely reduced kidney function was associated with the largest effect on increasing activity of both. However, even among subjects with normal kidney function, 12.2% and 7.7% had elevated lipase and amylase levels. Conclusions: In this large study of type 2 diabetic patients, nearly 25% had elevated lipase or amylase levels without symptoms of acute pancreatitis. The clinician must take these data into account when evaluating abdominal symptoms in type 2 diabetic patients

LEADER 3: Lipase and amylase activity in subjects with type 2 diabetes

Objectives: This report from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial describes baseline lipase and amylase activity in type 2 diabetic subjects without acute pancreatitis symptoms before randomization to the glucagonlike peptide analog liraglutide or placebo. Methods: The LEADER is an international randomized placebo-controlled trial evaluating the cardiovascular safety of liraglutide in 9340 type 2 diabetic patients at high cardiovascular risk. Fasting lipase and amylase activity was assessed at baseline, before receiving liraglutide or placebo, using a commercial assay (Roche) with upper limit of normal values of 63 U/L for lipase and 100 U/L for amylase. Results: Either or both enzymes were above the upper limit of normal in 22.7% of subjects; 16.6% (n = 1540) had an elevated lipase level (including 1.2% \u3e3-fold elevated), and 11.8% (n = 1094) had an elevated amylase level (including 0.2% \u3e3-fold elevated). In multivariable regression models, severely reduced kidney function was associated with the largest effect on increasing activity of both. However, even among subjects with normal kidney function, 12.2% and 7.7% had elevated lipase and amylase levels. Conclusions: In this large study of type 2 diabetic patients, nearly 25% had elevated lipase or amylase levels without symptoms of acute pancreatitis. The clinician must take these data into account when evaluating abdominal symptoms in type 2 diabetic patients

Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

BACKGROUND: Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. CONCLUSIONS: LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM

Centriole movements in mammalian epithelial cells during cytokinesis

<p>Abstract</p> <p>Background</p> <p>In cytokinesis, when the cleavage furrow has been formed, the two centrioles in each daughter cell separate. It has been suggested that the centrioles facilitate and regulate cytokinesis to some extent. It has been postulated that termination of cytokinesis (abscission) depends on the migration of a centriole to the intercellular bridge and then back to the cell center. To investigate the involvement of centrioles in cytokinesis, we monitored the movements of centrioles in three mammalian epithelial cell lines, HeLa, MCF 10A, and the p53-deficient mouse mammary tumor cell line KP-7.7, by time-lapse imaging. Centrin1-EGFP and α-Tubulin-mCherry were co-expressed in the cells to visualize respectively the centrioles and microtubules.</p> <p>Results</p> <p>Here we report that separated centrioles that migrate from the cell pole are very mobile during cytokinesis and their movements can be characterized as 1) along the nuclear envelope, 2) irregular, and 3) along microtubules forming the spindle axis. Centriole movement towards the intercellular bridge was only seen occasionally and was highly cell-line dependent.</p> <p>Conclusions</p> <p>These findings show that centrioles are highly mobile during cytokinesis and suggest that the repositioning of a centriole to the intercellular bridge is not essential for controlling abscission. We suggest that centriole movements are microtubule dependent and that abscission is more dependent on other mechanisms than positioning of centrioles.</p

Effect of Bronchoscopy on Gas Exchange and Respiratory Mechanics in Critically Ill Patients With Atelectasis: An Observational Cohort Study

Background: Atelectasis frequently develops in critically ill patients and may result in impaired gas exchange among other complications. The long-term effects of bronchoscopy on gas exchange and the effects on respiratory mechanics are largely unknown.Objective: To evaluate the effect of bronchoscopy on gas exchange and respiratory mechanics in intensive care unit (ICU) patients with atelectasis.Methods: A retrospective, single-center cohort study of patients with clinical indication for bronchoscopy because of atelectasis diagnosed on chest X-ray (CXR).Results: In total, 101 bronchoscopies were performed in 88 ICU patients. Bronchoscopy improved oxygenation (defined as an increase of PaO2/FiO2 ratio &gt; 20 mmHg) and ventilation (defined as a decrease of &gt; 2 mmHg in partial pressure of CO2 in arterial blood) in 76 and 59% of procedures, respectively, for at least 24 h. Patients with a low baseline value of PaO2/FiO2 ratio and a high baseline value of PaCO2 were most likely to benefit from bronchoscopy. In addition, in intubated and pressure control ventilated patients, respiratory mechanics improved after bronchoscopy for up to 24 h. Mild complications, and in particular desaturation between 80 and 90%, were reported in 13% of the patients.Conclusions: In selected critically ill patients with atelectasis, bronchoscopy improves oxygenation, ventilation, and respiratory mechanics for at least 24 h

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial)

Background. Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods. A randomized multicenter pragmatic clinical trial comparin

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers

Positron emission tomography and magnetic resonance imaging methods and datasets within the dominantly inherited Alzheimer network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case–control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual’s point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of ‘sporadic’ AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers