Is population screening for abdominal aortic aneurysm cost-effective?

<p>Abstract</p> <p>Background</p> <p>Ruptured abdominal aortic aneurysm (AAA) is responsible for 1–2% of all male deaths over the age of 65 years. Early detection of AAA and elective surgery can reduce the mortality risk associated with AAA. However, many patients will not be diagnosed with AAA and have therefore an increased death risk due to the untreated AAA. It has been suggested that population screening for AAA in elderly males is effective and cost-effective. The purpose of this study was to perform a systematic review of published cost-effectiveness analyses of screening elderly men for AAA.</p> <p>Methods</p> <p>We performed a systematic search for economic evaluations in NHSEED, EconLit, Medline, Cochrane, Embase, Cinahl and two Scandinavian HTA data bases (DACEHTA and SBU). All identified studies were read in full and each study was systematically assessed according to international guidelines for critical assessment of economic evaluations in health care.</p> <p>Results</p> <p>The search identified 16 cost-effectiveness studies. Most studies considered only short term cost consequences. The studies seemed to employ a number of "optimistic" assumptions in favour of AAA screening, and included only few sensitivity analyses that assessed less optimistic assumptions.</p> <p>Conclusion</p> <p>Further analyses of cost-effectiveness of AAA screening are recommended.</p

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

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

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

Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue

<p>Abstract</p> <p>Background</p> <p>Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs.</p> <p>Methods</p> <p>This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up.</p> <p>Discussion</p> <p>This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR 2159)</p

An evidence-based approach to the use of telehealth in long-term health conditions: development of an intervention and evaluation through pragmatic randomised controlled trials in patients with depression or raised cardiovascular risk

Background: Health services internationally are exploring the potential of telehealth to support the management of the growing number of people with long-term conditions (LTCs). Aim: To develop, implement and evaluate new care programmes for patients with LTCs, focusing on two common LTCs as exemplars: depression or high cardiovascular disease (CVD) risk. Methods Development: We synthesised quantitative and qualitative evidence on the effectiveness of telehealth for LTCs, conducted a qualitative study based on interviews with patients and staff and undertook a postal survey to explore which patients are interested in different forms of telehealth. Based on these studies we developed a conceptual model [TElehealth in CHronic disease (TECH) model] as a framework for the development and evaluation of the Healthlines Service for patients with LTCs. Implementation: The Healthlines Service consisted of regular telephone calls to participants from health information advisors, supporting them to make behaviour change and to use tailored online resources. Advisors sought to optimise participants’ medication and to improve adherence. Evaluation: The Healthlines Service was evaluated with linked pragmatic randomised controlled trials comparing the Healthlines Service plus usual care with usual care alone, with nested process and economic evaluations. Participants were adults with depression or raised CVD risk recruited from 43 general practices in three areas of England. The primary outcome was response to treatment and the secondary outcomes included anxiety (depression trial), individual risk factors (CVD risk trial), self-management skills, medication adherence, perceptions of support, access to health care and satisfaction with treatment. Trial results Depression trial: In total, 609 participants were randomised and the retention rate was 86%. Response to treatment [Patient Health Questionnaire 9-items (PHQ-9) reduction of ≥ 5 points and score of < 10 after 4 months] was higher in the intervention group (27%, 68/255) than in the control group (19%, 50/270) [odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.5; p = 0.02]. Anxiety also improved. Intervention participants reported better access to health support, greater satisfaction with treatment and small improvements in self-management, but not improved medication adherence. CVD risk trial: In total, 641 participants were randomised and the retention rate was 91%. Response to treatment (maintenance of/reduction in QRISK®2 score after 12 months) was higher in the intervention group (50%, 148/295) than in the control group (43%, 124/291), which does not exclude a null effect (odds ratio 1.3, 95% CI 1.0 to 1.9; p = 0.08). The intervention was associated with small improvements in blood pressure and weight, but not smoking or cholesterol. Intervention participants were more likely to adhere to medication, reported better access to health support and greater satisfaction with treatment, but few improvements in self-management. The Healthlines Service was likely to be cost-effective for CVD risk, particularly if the benefits are sustained, but not for depression. The intervention was implemented largely as planned, although initial delays and later disruption to delivery because of the closure of NHS Direct may have adversely affected participant engagement. Conclusion: The Healthlines Service, designed using an evidence-based conceptual model, provided modest health benefits and participants valued the better access to care and extra support provided. This service was cost-effective for CVD risk but not depression. These findings of small benefits at extra cost are consistent with previous pragmatic research on the implementation of comprehensive telehealth programmes for LTCs

Astrophysical magnetic fields and nonlinear dynamo theory

The current understanding of astrophysical magnetic fields is reviewed, focusing on their generation and maintenance by turbulence. In the astrophysical context this generation is usually explained by a self-excited dynamo, which involves flows that can amplify a weak 'seed' magnetic field exponentially fast. Particular emphasis is placed on the nonlinear saturation of the dynamo. Analytic and numerical results are discussed both for small scale dynamos, which are completely isotropic, and for large scale dynamos, where some form of parity breaking is crucial. Central to the discussion of large scale dynamos is the so-called alpha effect which explains the generation of a mean field if the turbulence lacks mirror symmetry, i.e. if the flow has kinetic helicity. Large scale dynamos produce small scale helical fields as a waste product that quench the large scale dynamo and hence the alpha effect. With this in mind, the microscopic theory of the alpha effect is revisited in full detail and recent results for the loss of helical magnetic fields are reviewed.Comment: 285 pages, 72 figures, accepted by Phys. Re

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies