Clinical Features and Outcomes Differ between Skeletal and Extraskeletal Osteosarcoma.

Background. Extraskeletal osteosarcoma (ESOS) is a rare subtype of osteosarcoma. We investigated patient characteristics, overall survival, and prognostic factors in ESOS. Methods. We identified cases of high-grade osteosarcoma with known tissue of origin in the Surveillance, Epidemiology, and End Results database from 1973 to 2009. Demographics were compared using univariate tests. Overall survival was compared with log-rank tests and multivariate analysis using Cox proportional hazards methods. Results. 256/4,173 (6%) patients with high-grade osteosarcoma had ESOS. Patients with ESOS were older, were more likely to have an axial tumor and regional lymph node involvement, and were female. Multivariate analysis showed ESOS to be favorable after controlling for stage, age, tumor site, gender, and year of diagnosis [hazard ratio 0.75 (95% CI 0.62 to 0.90); p = 0.002]. There was an interaction between age and tissue of origin such that older patients with ESOS had superior outcomes compared to older patients with skeletal osteosarcoma. Adverse prognostic factors in ESOS included metastatic disease, larger tumor size, older age, and axial tumor site. Conclusion. Patients with ESOS have distinct clinical features but similar prognostic factors compared to skeletal osteosarcoma. Older patients with ESOS have superior outcomes compared to older patients with skeletal osteosarcoma

Holonomy observables in Ponzano-Regge type state sum models

We study observables on group elements in the Ponzano-Regge model. We show that these observables have a natural interpretation in terms of Feynman diagrams on a sphere and contrast them to the well studied observables on the spin labels. We elucidate this interpretation by showing how they arise from the no-gravity limit of the Turaev-Viro model and Chern-Simons theory.Comment: 15 pages, 2 figure

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Appropriateness of Upper Gastrointestinal Endoscopy: Comparison of American and Swiss Criteria

Objective: Examine the reproducibility of the RAND method for developing criteria for the appropriateness of medical procedures. Design: Comparison of two sets of explicit criteria for appropriateness of upper gastrointestinal (UGI) endoscopy, developed by separate expert panels from two countries.Setting: United States, Switzerland. Study participants: National experts from different medical specialties involved in the referral or application of UGI endoscopy.Interventions: Each panel was presented with about 500clinical scenarios (indications)that were rated on a nine-point scale as to the appropriateness of performing UGI endoscopy for a patient with that clinical presentation. Main outcome measurer: (1) distribution of appropriateness ratings and intrapanel agreement categories between the two panels, (2)between-panel agreement of assigning appropriateness for comparable indications and, (3) percentage of indications with major between-panel differences. Results: Ratings for 2/3 of indications could be compared. The Swiss panel showed higher intrapanel agreement (54.6% versus 46.2% p=0.002). Seventy-eight percent of comparable Indications were assigned to indentical categories of appropriateness by both panels (kappa=0.76,P <0.001). For 93% of the 376 comparable indications, there were no major interpanel differences. Conclusion: Separate expert panels in different countries, using a standardized methodology, produce criteria for appropriatenesof medical procedures that are similar. Given the resources being invested throught the world in devilping criteria and guidelines, international collaboration in seeking optimal use of limited health care resources should be intensifled. © 1997 Elsevier Science Ltd. All rights reserve

Drug development in Alzheimer’s disease: The path to 2025

The global impact of Alzheimer’s disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025. If pipeline attrition rates remain high, only a few compounds at best will meet this time frame. There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts to help with more rapid enrollment of appropriate study populations; validated biomarkers to better detect disease, determine risk and monitor disease progression as well as predict disease response; more sensitive clinical assessment tools; and faster regulatory review. To implement change requires efforts to build awareness, educate and foster engagement; increase funding for both basic and clinical research; reduce fragmented environments and systems; increase learning from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development. Improved mechanistic understanding of disease onset and progression is central to more efficient AD drug development and will lead to improved therapeutic approaches and targets. The opportunity for more than a few new therapies by 2025 is small. Accelerating research and clinical development efforts and bringing DMTs to market sooner would have a significant impact on the future societal burden of AD. As these steps are put in place and plans come to fruition, e.g., approval of a DMT, it can be predicted that momentum will build, the process will be self-sustaining, and the path to 2025, and beyond, becomes clearer

Clinical Features and Outcomes Differ between Skeletal and Extraskeletal Osteosarcoma

Background. Extraskeletal osteosarcoma (ESOS) is a rare subtype of osteosarcoma. We investigated patient characteristics, overall survival, and prognostic factors in ESOS. Methods. We identified cases of high-grade osteosarcoma with known tissue of origin in the Surveillance, Epidemiology, and End Results database from 1973 to 2009. Demographics were compared using univariate tests. Overall survival was compared with log-rank tests and multivariate analysis using Cox proportional hazards methods. Results. 256/4,173 (6%) patients with high-grade osteosarcoma had ESOS. Patients with ESOS were older, were more likely to have an axial tumor and regional lymph node involvement, and were female. Multivariate analysis showed ESOS to be favorable after controlling for stage, age, tumor site, gender, and year of diagnosis [hazard ratio 0.75 (95% CI 0.62 to 0.90); p=0.002]. There was an interaction between age and tissue of origin such that older patients with ESOS had superior outcomes compared to older patients with skeletal osteosarcoma. Adverse prognostic factors in ESOS included metastatic disease, larger tumor size, older age, and axial tumor site. Conclusion. Patients with ESOS have distinct clinical features but similar prognostic factors compared to skeletal osteosarcoma. Older patients with ESOS have superior outcomes compared to older patients with skeletal osteosarcoma

When is it appropriate to prescribe postmenopausal hormone therapy?

OBJECTIVE: To develop evidence and consensus-based recommendations for the use of hormone therapy (HT) in postmenopausal women. DESIGN: Using evidence from clinical trials and other publications, a multidisciplinary group of women's health experts developed consensus-based recommendations for HT use in more than 300 clinical scenarios. These panelists utilized the RAND Appropriateness Method and a quantitative scale to rate the appropriateness of treatment options for women with various risk factors and clinical scenarios. RESULTS: The panel judged it appropriate to prescribe all forms of HT to women with intolerable menopause symptoms and usual (age-expected) risks of cardiovascular disease (CVD), venous thromboembolism (VTE), or stroke. Use of HT was judged not appropriate for the clinical scenarios of bone preservation, cosmetic appearance, current memory loss, loss of libido, or CVD protection. For a woman still using HT after 5 or more years, it was considered appropriate to recommend the options of stopping or lowering the dose even if stopping was previously attempted. In treating intolerable symptoms in the presence of some elevated risk for diseases related to HT, route of administration may affect appropriateness but prior stroke or TIA# risk is a contraindication. CONCLUSIONS: Standard HT is appropriate for women with intolerable menopausal symptoms in the absence of HT-related risk factors (eg, CVD, stroke, VTE, breast cancer). Panelists judged it appropriate to repeatedly present the option of stopping or reducing the dose. In most cases, presence of risk factors makes standard-dose oral HT not appropriate; however, some women may be candidates for a different dose or route of administration. [Authors]]]> Estrogen Replacement Therapy ; Gynecology ; Menopause ; Physician's Practice Patterns ; Practice Guidelines as Topic oai:serval.unil.ch:BIB_F6BBBCACCC3A 2022-05-07T01:30:17Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_F6BBBCACCC3A Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes. info:doi:10.1093/eurheartj/ehv289 info:eu-repo/semantics/altIdentifier/doi/10.1093/eurheartj/ehv289 info:eu-repo/semantics/altIdentifier/pmid/26142466 Nanchen, D. Gencer, B. Auer, R. Räber, L. Stefanini, G.G. Klingenberg, R. Schmied, C.M. Cornuz, J. Muller, O. Vogt, P. Jüni, P. Matter, C.M. Windecker, S. Lüscher, T.F. Mach, F. Rodondi, N. info:eu-repo/semantics/article article 2015 European Heart Journal, vol. 36, no. 36, pp. 2438-2445 info:eu-repo/semantics/altIdentifier/eissn/1522-9645 urn:issn:0195-668X <![CDATA[AIMS: We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (&gt;5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION: A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required

Hotspots of Large Rare Deletions in the Human Genome

Background: We have examined the genomic distribution of large rare autosomal deletions in a sample of 440 parentparent-child trios from the Quebec founder population (QFP) which was recruited for a study of Attention Deficit Hyperactivity Disorder. Methodology/Principal Findings: DNA isolated from blood was genotyped on Illumina Hap300 arrays. PennCNV combined with visual evaluation of images generated by the Beadstudio program was used to determine deletion boundary definition of sufficient precision to discern independent events, with near-perfect concordance between parent and child in about 98 % of the 399 events detected in the offspring; the remaining 7 deletions were considered de novo. We defined several genomic regions of very high deletion frequency (‘hotspots’), usually of 0.4–0.6 Mb in length where independent rare deletions were found at frequencies of up to 100 fold higher than the average for the genome as a whole. Five of the 7 de novo deletions were in these hotspots. The same hotspots were also observed in three other studies on members of the QFP, those with schizophrenia, with endometriosis and those from a longevity cohort. Conclusions/Significance: Nine of the 13 hotspots carry one gene (7 of which are very long), while the rest contain no known genes. All nine genes have been implicated in disease. The patterns of exon deletions support the proposed roles for some of these genes in human disease, such as NRXN1 and PARKIN, and suggest limited roles or no role at all, for others