Diabetes Incidence and Glucose Tolerance after Termination of Pioglitazone Therapy: Results from ACT NOW.

Context: Thiazolidinediones have proven efficacy in preventing diabetes in high-risk individuals. However, the effect of thiazolidinediones on glucose tolerance after cessation of therapy is unclear.

Objective: To examine the effect of pioglitazone (PIO) on incidence of diabetes after discontinuing therapy in ACT NOW.

Quantifying the influence of child abuse history on the cardinal symptoms of fibromyalgia.

Objectives: To quantify the influence of abuse, particularly in childhood, with pain sensitivity and other adverse symptoms experienced by women with fibromyalgia (FM).

Methods: Subjects with FM completed a detailed abuse interview, dolorimetry, and questionnaire-based assessments of fatigue, cognitive self-appraisal, and depression. Student's t- and chi-square tests were used to analyse differences in FM symptoms between those with and without a history of childhood abuse.

Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial.

Background: Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease.

Study Design: ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.

Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial.

Background: Bromodomain and extra-terminal (BET) proteins regulate transcription of lipoprotein and inflammatory factors implicated in atherosclerosis. The impact of BET inhibition on atherosclerosis progression is unknown.

Methods: ASSURE was a double-blind, randomized, multicenter trial in which 323 patients with angiographic coronary disease and low high-density lipoprotein cholesterol (HDL-C) levels were randomized in a 3:1 fashion to treatment with the BET protein inhibitor RVX-208 200 mg or placebo for 26 weeks.

Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials.

Objective: Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes.

Methods: We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers.

Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.

Purpose: Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of US women.

Methods: In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models.

Dysfunctional HDL and atherosclerotic cardiovascular disease.

High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models.

High rate of microbleed formation following primary intracerebral hemorrhage.

Background: We sought to investigate the frequency of microbleed development following intracerebral hemorrhage in a predominantly African-American population and to identify predictors of new microbleed formation.

Aims And/or Hypothesis: To investigate the frequency and predictors of new microbleeds following intracerebral hemorrhage.

Methods: The DECIPHER study was a prospective, longitudinal, magnetic resonance-based cohort study designed to evaluate racial/ethnic differences in risk factors for microbleeds and to evaluate the prognostic impact of microbleeds in this intracerebral hemorrhage population.

Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Dyslipidaemia remains a significant risk factor for cardiovascular disease and additional lipid-modifying treatments are warranted to further decrease the cardiovascular disease burden. We assessed the safety, tolerability and efficacy of a novel cholesterol esterase transfer protein (CETP) inhibitor TA-8995 in patients with mild dyslipidaemia.

Methods: In this randomised, double-blind, placebo-controlled, parallel-group phase 2 trial, we recruited patients (aged 18-75 years) from 17 sites (hospitals and independent clinical research organisations) in the Netherlands and Denmark with fasting LDL cholesterol levels between 2·5 mmol/L and 4·5 mmol/L, HDL cholesterol levels between 0·8 and 1·8 mmol/L and triglyceride levels below 4·5 mmol/L after washout of lipid-lowering treatments.

Understanding the Association of Fatigue With Other Symptoms of Fibromyalgia: Development of a Cluster Model.

Objective: To develop a symptoms cluster model that can describe factors of fibromyalgia syndrome (FMS) associated with fatigue severity as reported by the sample and to explore FMS clinical symptom subclusters based on varying symptom intensities.

Methods: FMS individuals (n = 120, 82% ages 31-60 years, 90% women, 59% white) diagnosed with the 1990 or 2010 American College of Rheumatology diagnostic criteria were enrolled. Participants completed multiple validated self-report questionnaires to measure fatigue, pain, depression, anxiety, pain catastrophizing, daytime sleepiness, cognitive function, and FMS-related polysymptomatic distress.

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

Objective: The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal.

Research Design And Methods: Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.

Dietary antioxidant intake and its association with cognitive function in an ethnically diverse sample of US adults.

Background: Dietary antioxidants can inhibit reactions accompanying neurodegeneration and thus prevent cognitive impairment. We describe associations of dietary antioxidants with cognitive function in a large biracial population, while testing moderation by sex, race, and age and mediation by depressive symptoms.

Methods: This was a cross-sectional analysis of 1274 adults (541 men and 733 women) aged 30 to 64 years at baseline (mean [standard deviation] = 47.

Relationships between dog ownership and physical activity in postmenopausal women.

Background: Positive associations between dog ownership and physical activity in older adults have been previously reported.

Purpose: The objective of this study was to examine cross-sectional associations between dog ownership and physical activity measures in a well-characterized, diverse sample of postmenopausal women.

Methods: Analyses included 36,984 dog owners (mean age: 61.

Testing the product of slopes in related regressions.

A study was conducted of the relationships among neuroprotective factors and cytokines in brain tissue of mice at different ages that were examined on the effect of dietary restriction on protection after experimentally induced brain stroke. It was of interest to assess whether the cross-product of the slopes of pairs of variables vs. age was positive or negative.

Small hepatocellular carcinoma: MRI findings for predicting tumor growth rates.

Rationale And Objectives: Current clinical practice favors imaging rather than biopsy to diagnose hepatocellular carcinoma (HCC). There is a need to better understand tumor biology and aggressiveness of HCC. Our goal is to investigate magnetic resonance imaging (MRI) features of HCC that are associated with faster growth rates (GRs).

Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome.

The period following an acute coronary syndrome (ACS) represents a critical time frame with a high risk for recurrent events and death. The pathogenesis of this increase in clinical cardiovascular disease events after ACS is complex, with molecular mechanisms including increased thrombosis and inflammation. Dyslipoproteinemia is common in patients with ACS and predictive of recurrent cardiovascular disease events after presentation with an ACS event.

Lung function and heart disease in American Indian adults with high frequency of metabolic abnormalities (from the Strong Heart Study).

The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry.

Metabolic profiles of biological aging in American Indians: the Strong Heart Family Study.

Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study.

Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.

Objective: Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status.

Research Design And Methods: A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.

Sex-related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER Trial (Placement of Aortic Transcatheter Valve).

Objectives: This study sought to examine sex-specific differences in outcomes after surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) in high-risk patients with severe aortic stenosis.

Background: The PARTNER (Placement of Aortic Transcatheter Valve) trial demonstrated similar 2-year survival with SAVR or TAVR for high-risk patients, but sex-specific outcomes are unknown.

Methods: In all, 699 patients (300 female) were randomly assigned 1:1 to either SAVR or TAVR with a balloon expandable pericardial tissue valve.

Novel therapies focused on the high-density lipoprotein particle.

Cardiovascular disease (CVD) remains a major burden for morbidity and mortality in the general population, despite current efficacious low-density lipoprotein-cholesterol-lowering therapies. Consequently, novel therapies are required to reduce this residual risk. Prospective epidemiological studies have shown that high-density lipoprotein-cholesterol (HDL-C) levels are inversely correlated with cardiovascular disease risk, and this initiated the quest for HDL-C-increasing therapies.

Cardiometabolic risk in overweight subjects with or without relative fat-free mass deficiency: the Strong Heart Study.

Background And Aim: Sarcopenia is a condition mainly due to loss of fat-free mass (FFM) in elderly individuals. RFFMD, however, is also frequent in obese subjects due to abnormal body composition. Objective of this study was to evaluate the impact of relative fat-free mass deficiency (RFFMD) on cardiometabolic (CM) risk in obese normoglycemic individuals.

Obatoclax mesylate, a pan-bcl-2 inhibitor, in combination with docetaxel in a phase 1/2 trial in relapsed non-small-cell lung cancer.

Introduction: The proapoptotic small-molecule pan-Bcl-2 inhibitor obatoclax mesylate (GX15-070) may enhance the cytotoxicity of chemotherapy in relapsed/refractory non-small-cell lung cancer (NSCLC).

Methods: Obatoclax was administered with docetaxel in patients with relapsed or refractory NSCLC- docetaxel as a 1-hour infusion on day 1 and obatoclax as a 24-hour infusion on days 1 and 2-every 3 weeks for up to eight cycles. Four dose levels were evaluated in phase 1 (level 1: docetaxel 55 mg/m × 1 and obatoclax 30 mg × 2; levels 2-4: docetaxel 75 mg/m and obatoclax 30 mg, 45 mg, or 60 mg × 2) to identify dose-limiting toxicity and a phase 2 dose.