Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial

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Portion control for the treatment of obesity in the primary care setting

<p>Abstract</p> <p>Background</p> <p>The increasing prevalence of obesity is a significant health threat and a major public health challenge. A critical need exists to develop and evaluate practical methods for the treatment of obesity in the clinical setting. One of the factors contributing to the obesity epidemic is food portion sizes. Limited data are available on the efficacy of visual or tactile devices designed to enhance patient understanding and control of portion sizes. A portion control plate is a commercially-available product that can provide visual cues of portion size and potentially contribute to weight loss by enhancing portion size control among obese patients. This tool holds promise as a useful adjunct to dietary counseling. Our objective was to evaluate a portion control intervention including dietary counseling and a portion control plate to facilitate weight loss among obese patients in a primary care practice.</p> <p>Findings</p> <p>We randomized 65 obese patients [body mass index (BMI) ≥ 30 and < 40] to an intervention including counseling by a dietitian incorporating a portion control plate or to usual care. Following initial consultation, patients in the intervention arm were contacted at 1, 3, and 5 months by the dietician for brief follow-up counseling. Usual care subjects received instructional handouts on diet and exercise. Forty-two (65%) subjects returned to have weight assessed at 6 months. Subjects in the portion control intervention had a greater percentage change (± SD) in weight from baseline at 3 months (-2.4% ± 3.7% <it>vs</it>. -0.5% ± 2.2%; p = 0.041) and a non significant trend in weight change from baseline at 6 months (-2.1% ± 3.8% vs. -0.7% ± 3.7%; p = 0.232) compared with usual care. Nearly one-half of patients assigned to the portion control intervention who completed the study reported the overall intervention was helpful and the majority would recommend it to others.</p> <p>Conclusions</p> <p>Our findings suggest that a portion control intervention incorporating dietary counseling and a portion control plate may be effective for enhancing weight loss among obese subjects. A portion control intervention deserves further evaluation as a weight control strategy in the primary care setting.</p> <p>Trial registration</p> <p>Current controlled trials <a href="http://clinicaltrials.gov/ct2/show/NCT01451554">NCT01451554</a></p

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-013-2416-2) contains supplementary material, which is available to authorized users

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Heritable symbionts in a world of varying temperature

Heritable microbes represent an important component of the biology, ecology and evolution of many plants, animals and fungi, acting as both parasites and partners. In this review, we examine how heritable symbiont–host interactions may alter host thermal tolerance, and how the dynamics of these interactions may more generally be altered by thermal environment. Obligate symbionts, those required by their host, are considered to represent a thermally sensitive weak point for their host, associated with accumulation of deleterious mutations. As such, these symbionts may represent an important determinant of host thermal envelope and spatial distribution. We then examine the varied relationship between thermal environment and the frequency of facultative symbionts that provide ecologically contingent benefits or act as parasites. We note that some facultative symbionts directly alter host thermotolerance. We outline how thermal environment will alter the benefits/costs of infection more widely, and additionally modulate vertical transmission efficiency. Multiple patterns are observed, with symbionts being cold sensitive in some species and heat sensitive in others, with varying and non-coincident thresholds at which phenotype and transmission are ablated. Nevertheless, it is clear that studies aiming to predict ecological and evolutionary dynamics of symbiont–host interactions need to examine the interaction across a range of thermal environments. Finally, we discuss the importance of thermal sensitivity in predicting the success/failure of symbionts to spread into novel species following natural/engineered introduction

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

Clouds as Turbulent Density Fluctuations. Implications for pressure confinement and spectral line data interpretation

We examine the idea that diffuse and giant molecular clouds and their substructure form as density fluctuations induced by large scale interstellar turbulence. We do this by investigating the topology of various fields in realistic simulations of the ISM. We find that a) the velocity field is continuous across threshold-defined cloud boundaries; b) such cloud boundaries are rather arbitrary, with no correspondence to any actual physical boundary, such as a density discontinuity; c) abrupt velocity jumps are coincident with the density maxima; d) the volume and surface kinetic terms in the Eulerian Virial Theorem for a cloud ensemble are comparable in general; e) the magnetic field exhibits bends and reversals highly correlated with similar density features. These results suggest that clouds are formed by colliding gas streams. Within this framework, we argue that thermal pressure equilibrium is irrelevant for cloud confinement in a turbulent medium, since inertial motions can still distort or disrupt a cloud. Turbulent pressure confinement appears self-defeating, because turbulence contains large-scale motions which necessarily distort cloud boundaries. Density-weighted velocity histograms show similar FWHMs and similar multi-component structure to those of observational line profiles, though the histogram features do not correspond to isolated "clumps", but rather to extended regions throughout a cloud. We argue that the results presented here may be also applicable to small scales with larger densities (molecular clouds and cores) and suggest that quasi- hydrostatic configurations cannot be produced from turbulent fluctuations unless the thermodynamic behavior of the flow becomes nearly adiabatic at late stages of collapse. We expect this to occur only at protostellar densities.Comment: 20 pages, 11 PostScript figures, LaTex, ApJ submitted. Added reference to Chandrasekhar & Munch (1952) and corresponding discussio