Nine years of comparative effectiveness research education and training: initiative supported by the PhRMA Foundation

The term comparative effectiveness research (CER) took center stage with passage of the American Recovery and Reinvestment Act (2009). The companion US$1.1 billion in funding prompted the launch of initiatives to train the scientific workforce capable of conducting and using CER. Passage of the Patient Protection and Affordable Care Act (2010) focused these initiatives on patients, coining the term ‘patient-centered outcomes research’ (PCOR). Educational and training initiatives were soon launched. This report describes the initiative of the Pharmaceutical Research and Manufacturers Association of America (PhRMA) Foundation. Through provision of grant funding to six academic Centers of Excellence, to spearheading and sponsoring three national conferences, the PhRMA Foundation has made significant contributions to creation of the scientific workforce that conducts and uses CER/PCOR

Unhousing the Urban Poor: The Reagan Legacy

The Reagan era was characterized by the popularity of individual level explanations and market based solutions for a range of social problems, including homelessness. We argue that such an approach was inadequate and may, in fact, have toorsened the housing situation. We claim that homelessness is fundamentally a housing problem linked to two key trends of the 1980s: the increasing rate of poverty and the declining supply\u27f low-income housing. Market approaches to housing policy have resulted in housing policies by default: gentrification, condo conversion and displacement as well as tax policies that explicitly favor the nonpoor. Those policies gehred towards the poor, vouchers and subsidies, were inadequate responses to increasing need. In sum, the Reagan years witnessed dramatic declines in the supply of low-cost housing, substantial increases in the poverty rate, and drastic shifts in federal policy towards housing the poor

Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (HR=2.76 [1.90-4.00]), overall survival (HR=2.36 [1.73-3.22]), and cumulative incidence of relapse (HR=3.65 [2.53-5.27]), but not non-relapse mortality (HR=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I(2)=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation

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

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

The Potential Cost-Effectiveness of HIV Vaccines: A Systematic Review

OBJECTIVE: The aim of this paper was to review and compare HIV vaccine cost-effectiveness analyses and describe the effects of uncertainty in model, methodology, and parameterization. METHODS: We systematically searched MEDLINE (1985 through May 2016), EMBASE, the Tufts Cost-Effectiveness Analysis (CEA) Registry, and the reference lists of articles following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility criteria included peer-reviewed manuscripts with economic models estimating the cost-effectiveness of preventive HIV vaccines. Two reviewers independently assessed study quality and extracted data on model assumptions, characteristics, input parameters, and outcomes. RESULTS: The search yielded 71 studies, 11 of which met the inclusion criteria. Populations included low-income (n = 7), middle-income (n = 4), and high-income countries (n = 2). Model structure varied, including decision tree (n = 1), Markov (n = 5), compartmental (n = 4), and microsimulation (n = 1). Most studies measured outcomes in quality-adjusted life-years (QALYs) gained (n = 6), whereas others used unadjusted (n = 3) or disability-adjusted life-years (n = 2). The range of HIV vaccine costs were $US1.54–75 in low-income countries,$US55–100 in middle-income countries, and $US500–1000 in the USA. Base-case incremental cost-effectiveness ratios (ICERs) ranged from dominant (cost offsetting) to$US91,000 per QALY gained. CONCLUSION: Most models predicted HIV vaccines would be cost-effective. Model assumptions about vaccine price, HIV treatment costs, epidemic context, and willingness to pay influenced results more consistently than did assumptions on HIV transmission dynamics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s41669-016-0009-9) contains supplementary material, which is available to authorized users

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

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

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

Australian consumer perceptions of regionally grown fruits and vegetables: Importance, enablers, and barriers

Fresh fruits and vegetables are a cornerstone of a balanced diet; their consumption has health, environmental, ethical, and economic implications. This pilot study aimed to: (i) measure fruit and vegetable consumption; (ii) understand consumer perceptions of the perceived importance of regionally grown fresh fruit and vegetables (RGFFV); and (iii) identify the barriers and enablers of access and consumption of RGFFV. The study took place in Tasmania (TAS) and South Western Australia (SWA). A 54-item survey included questions relating to purchasing and consumption patterns; barriers and enablers related to access and consumption of RGFFV; and sociodemographic information. Survey data were analyzed using Chi-square test and binary logistic regression. A total of n = 120 TAS and n = 123 SWA adult respondents participated. SWA respondents had higher intakes of fruit (p \u3c 0.001) and vegetables (p \u3c 0.001). Almost all respondents (97%) rated purchasing of RGFFV as important. Top enablers included produce freshness (97%), and to financially support local farmers (94%) and the local community (91%). Barriers included limited seasonal availability of the produce (26%), the belief that RGFFV were expensive (12%) and food budgetary constraints (10%). Recommendations include broader marketing and labelling of seasonal RGFFV; increasing ‘buy local’ campaigns; consumer information about how RGFFV benefits producers and communities; and pricing produce according to quality