Inconsistent treatment estimates from mis‐specified logistic regression analyses of randomized trials

When the difference between treatments in a clinical trial is estimated by a difference in means, then it is well known that randomization ensures unbiassed estimation, even if no account is taken of important baseline covariates. However, when the treatment effect is assessed by other summaries, for example by an odds ratio if the outcome is binary, then bias can arise if some covariates are omitted, regardless of the use of randomization for treatment allocation or the size of the trial. We present accurate closed‐form approximations for this asymptotic bias when important normally distributed covariates are omitted from a logistic regression. We compare this approximation with ones in the literature and derive more convenient forms for some of these existing results. The expressions give insight into the form of the bias, which simulations show is usable for distributions other than the normal. The key result applies even when there are additional binary covariates in the model. Copyright © 2015 John Wiley & Sons, Ltd.     

Circulating interleukin-6 is associated with disease progression,but not cachexia in pancreatic cancer

Background

Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression.

Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease

BackgroundObesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown.ObjectivesThe aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes.MethodsA screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n = 48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints.ResultsBecause ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles. High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with ThAT ceramides, dysregulated vascular redox signaling, and increased systemic inflammation in 633 patients with atherosclerosis. Exogenous C16:0-ceramide directly increased superoxide via tetrahydrobiopterin-mediated endothelial nitric oxide synthase uncoupling and dysregulated protein phosphatase 2 in human aortic endothelial cells. High plasma C16:0-ceramide and its glycosylated derivative were independently related with increased risk for cardiac mortality (adjusted hazard ratios: 1.394; 95% confidence interval: 1.030 to 1.886; p = 0.031 for C16:0-ceramide and 1.595; 95% confidence interval: 1.042 to 2.442; p = 0.032 for C16:0-glycosylceramide per 1 SD). In a randomized controlled clinical trial, 1-year treatment of obese patients with the glucagon-like peptide-1 analog liraglutide suppressed plasma C16:0-ceramide and C16:0-glycosylceramide changes compared with control subjects.ConclusionsThese results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183)     

Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats

The purpose of this study was to examine the hypoglycaemic effect of the lyophilised aqueous extract of the whole plant of Ajuga iva (L.) Schreber (Labiatae) in normal and streptozotocin-induced diabetic rats. Single and repeated oral administration of the extract of Ajuga iva L (AI) at a dose of 10 mg/kg produced a slight and significant decrease in plasma glucose levels in normal rats 6 h after administration and after 3 weeks of treatment. AI reduced plasma glucose levels of streptozotocin diabetic rats from 337±9.3 to 102.2±17.7 mg/dl after 6 h of oral administration (P<0.001). Repeated oral administration of AI to streptozotocin diabetic rats significantly decreased the plasma glucose levels after 1 week of treatment (112±14.4 mg/dl at 1 week vs 337±9.3 mg/dl at the baseline values, (P<0.001). It continuously decreased thereafter and showed a rapid normalisation after 1 week of AI treatment. It is concluded that these results demonstrated that the water extract of the whole plant of AI possess a strong hypoglycaemic effect in diabetic rats, and support therefore, its traditional use in diabetes mellitus control.     

Metabolic syndrome: treatment of hypertensive patients

Metabolic syndrome (MetSyndr), a constellation of abnormalities [obesity, glucose intolerance, insulin resistance (IR), dyslipidemia (low HDL-cholesterol, high LDL-cholesterol and triglycerides (TG)], and elevated blood pressure (BP)], increases the risk of cardiovascular (CV) disease and premature death. From 10% to 30% of the adult population in industrialized countries has MetSyndr, which effectively predicts the development of type 2 diabetes mellitus (T2D) and CV disease. Because of the complex etiology of MetSyndr, a multi-targeted, integrated therapeutic approach is required to simultaneously treat high BP, obesity, lipid disorders and T2D (if present), to fully protect CV, cerebrovascular and renal systems. If lifestyle modification (weight control, diet, exercise, smoking cessation, moderation of alcohol intake) is ineffective, pharmaco-theraphy should be added to treat simultaneously the lipid- and non-lipid CV risk factors.Patients with HTN and MetSyndr should be started on angiotensin-converting enzyme (ACE) inhibitors, unless contraindicated. The ACE inhibitors and angiotensin receptor blockers (ARBs) reduce the odds of developing new onset T2D and also decrease albuminuria. The ACE inhibitors provide cardioprotective and renoprotective benefits beyond their effect on BP; they also improve IR. The ARBs are renoprotective in addition to being cardioprotective. Long-acting calcium channel blockers are also recommended in hypertensive patients with MetSyndr; these drugs also improve IR. Thiazides (at low doses) and selected ss-blockers can be given to patients with HTN and MetSyndr. Celiprolol in combination with diuretics has a favorable effect on glucose tolerance and IR in patients with HTN and MetSyndr, and spironolactone added to ACE inhibitor or ARB therapy provides additional reno- and CV protective benefits in patients with diabetic nephropathy. Carvedilol, a ss-blocker with vasodilating properties, added to ACE inhibitor or ARB therapy, is effective in preventing worsening of microalbuminuria in patients with HTN and MetSyndr; it also improves IR and glycemic control. Most patients eventually require two or more antihypertensive drugs to reach BP goal. It is recommended that therapy in patients whose BP is more than 20/10 mm Hg above target at diagnosis be initiated with a combination of antihypertensive drugs, administered either as individual drugs or as fixed-dose formulations. Treatment with fixed-dose combinations, such as irbesartan + hydrochlorothiazide provides good BP control in more than two-thirds of hypertensive patients with MetSyndr. Lipid and BP targets are reached in a high percent of patients with HTN and CV disease treated with a combination of amlodipine + atorvastatin.In conclusion, hypertensive patients with the MetSyndr be treated aggressively for each component of the syndrome to provide CV, cerebrovascular and renal protection.     

Testing for sphericity in a fixed effects panel data model

Summary This paper proposes a test for the null of sphericity in a fixed effects panel data model. It uses the Random Matrix Theory based approach of Ledoit and Wolf to test for the null of sphericity of the error terms in a fixed effects panel model with a large number of cross‐sectional units and time series observations. Because the errors are unobservable, the residuals from the fixed effects regression are used. The limiting distribution of the proposed test statistic is derived. In addition, its finite sample properties are examined using Monte Carlo simulations.     

Health Care Expenditure and Income: A Global Perspective

This paper investigates the long‐run economic relationship between healthcare expenditure and income in the world using data on 167 countries over the period 1995–2012, collected from the World Bank data set. The analysis is carried using panel data methods that allow one to account for unobserved heterogeneity, temporal persistence, and cross‐section dependence in the form of either a common factor model or a spatial process. We estimate a global measure of income elasticity using all countries in the sample, and for sub‐groups of countries, depending on their geo‐political area and income. Our findings suggest that at the global level, health care is a necessity rather than a luxury. However, results vary greatly depending on the sub‐sample analysed. Our findings seem to suggest that size of income elasticity depends on the position of different countries in the global income distribution, with poorer countries showing higher elasticity. Copyright © 2016 John Wiley & Sons, Ltd.     

Design and development of highly sensitive PEDOT-PSS/AuNP hybrid nanocomposite-based sensor towards room temperature detection of greenhouse methane gas at ppb level

Herein, we present fabrication of a novel methane sensor based on poly (3,4-ethylenedioxythiophene:poly (styrene sulfonic acid)) (p-PEDOT-PSS) and gold nanoparticles (AuNPs) treated with dimethyl sulfoxide (DMSO) and Zonyl using a spin coating technique. The nanocomposite films were further post treated with H₂SO₄ to improve the charge transport mechanism. The structural and morphological features of the composites were analyzed through scanning electronic microscopy, transmission electron microscopy, Fourier transform infra-red spectroscopy, UV-Vis spectroscopy and thermogravimetric analysis. Treatment with organic solvents and post treatment of H₂SO₄ significantly enhances the conductivity of the composite to 1800 S cm⁻¹. The fabricated sensor shows an excellent sensing response, fast response and recovery time along with acceptable selectivity towards methane gas at ppb concentrations. Due to a simple fabrication technique, excellent conductivity, superior sensing performance and improved mechanical properties, the sensor fabricated in this study could potentially be used to detect greenhouse methane gas at low concentrations.

Fabrication of novel methane sensor based on PEDOT-PSS:AuNPs composite treated with DMSO and Zonyl using spin coating technique.