Estimating marginal treatment effects from observational studies and indirect treatment comparisons: When are standardization-based methods preferable to those based on propensity score weighting?

In light of newly developed standardization methods, we evaluate, via simulation study, how propensity score weighting and standardization -based approaches compare for obtaining estimates of the marginal odds ratio and the marginal hazard ratio. Specifically, we consider how the two approaches compare in two different scenarios: (1) in a single observational study, and (2) in an anchored indirect treatment comparison (ITC) of randomized controlled trials. We present the material in such a way so that the matching-adjusted indirect comparison (MAIC) and the (novel) simulated treatment comparison (STC) methods in the ITC setting may be viewed as analogous to the propensity score weighting and standardization methods in the single observational study setting. Our results suggest that current recommendations for conducting ITCs can be improved and underscore the importance of adjusting for purely prognostic factors.Comment: 33 page

Generation of folk song melodies using Bayes transforms

The paper introduces the `Bayes transform', a mathematical procedure for putting data into a hierarchical representation. Applicable to any type of data, the procedure yields interesting results when applied to sequences. In this case, the representation obtained implicitly models the repetition hierarchy of the source. There are then natural applications to music. Derivation of Bayes transforms can be the means of determining the repetition hierarchy of note sequences (melodies) in an empirical and domain-general way. The paper investigates application of this approach to Folk Song, examining the results that can be obtained by treating such transforms as generative models

Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

Objective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC)-formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).Methods: Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 mu g (n = 5 studies), indacaterol 300 mu g (n = 4), FOR/BUD 9/160 mu g (n = 2), FOR/BUD 9/320 mu g (n = 3), SAL/FP 50/500 mu g (n = 5), and SAL/FP 50/250 mu g (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St. George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.Results: Indacaterol 150 mu g resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 mu g (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 mu g (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 mu g (0.02 L [-0.04, 0.08]) and SAL/FP 50/500 mu g (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 mu g at 12 weeks and indacaterol 150/300 mu g at 6 months. Indacaterol 150 mu g demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 mu g (-2.16 point improvement [-4.96, 0.95]). Indacaterol 150 and 300 mu g demonstrated comparable TDI scores versus SAL/FP 50/250 mu g (0.21 points (-0.57, 0.99); 0.39 [-0.39, 1.17], respectively) and SAL/FP 50/500 mu g at 6 months.Conclusion: Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 mu g) and comparable to SAL/FP (50/250 and 50/500 mu g) in terms of lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 mu g) and SAL/FP 50/500 mu g in terms of health status and to SAL/FP (50/250 and 50/500 mu g) in terms of breathlessness.Novartis Pharma AGMapi Values, Boston, MA 02114 USANovartis Pharma AG, Hlth Econ & Outcomes Res, Basel, SwitzerlandNovartis Horsham Res Ctr, Horsham, W Sussex, EnglandUniversidade Federal de São Paulo, Div Resp, São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp, São Paulo, BrazilWeb of Scienc

Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: A network meta-analysis

Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction

Development of strategies for effective communication of food risks and benefits across Europe: Design and conceptual framework of the FoodRisC project

The FoodRisC project is funded under the Seventh Framework Programme (CORDIS FP7) of the European Commission; Grant agreement no.: 245124. Copyright @ 2011 Barnett et al.BACKGROUND: European consumers are faced with a myriad of food related risk and benefit information and it is regularly left up to the consumer to interpret these, often conflicting, pieces of information as a coherent message. This conflict is especially apparent in times of food crises and can have major public health implications. Scientific results and risk assessments cannot always be easily communicated into simple guidelines and advice that non-scientists like the public or the media can easily understand especially when there is conflicting, uncertain or complex information about a particular food or aspects thereof. The need for improved strategies and tools for communication about food risks and benefits is therefore paramount. The FoodRisC project ("Food Risk Communication - Perceptions and communication of food risks/benefits across Europe: development of effective communication strategies") aims to address this issue. The FoodRisC project will examine consumer perceptions and investigate how people acquire and use information in food domains in order to develop targeted strategies for food communication across Europe.METHODS/DESIGN: This project consists of 6 research work packages which, using qualitative and quantitative methodologies, are focused on development of a framework for investigating food risk/benefit issues across Europe, exploration of the role of new and traditional media in food communication and testing of the framework in order to develop evidence based communication strategies and tools. The main outcome of the FoodRisC project will be a toolkit to enable coherent communication of food risk/benefit messages in Europe. The toolkit will integrate theoretical models and new measurement paradigms as well as building on social marketing approaches around consumer segmentation. Use of the toolkit and guides will assist policy makers, food authorities and other end users in developing common approaches to communicating coherent messages to consumers in Europe.DISCUSSION: The FoodRisC project offers a unique approach to the investigation of food risk/benefit communication. The effective spread of food risk/benefit information will assist initiatives aimed at reducing the burden of food-related illness and disease, reducing the economic impact of food crises and ensuring that confidence in safe and nutritious food is fostered and maintained in Europe.This article is available through the Brunel Open Access Publishing Fund

CHARACTERISTICS OF THE INCREASED ADRENOCORTICAL FUNCTION OBSERVED IN MANY OBESE PATIENTS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75360/1/j.1749-6632.1965.tb34805.x.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment