Uncertainty exists regarding the relative performance of drug-eluting stents DES versus bare-metal stents BMS in octogenarians undergoing percutaneous coronary intervention PCI.
A total of one RCT and six observational studies were included and analyzed in this meta-analysis. All trials were of acceptable quality. The OR for mortality 1. Octogenarians constitute the fastest growing segment of the population in the Western world. Firstly, very elderly patients were not adequately represented in these studies.
There is a paucity of data on long-term safety and efficacy of DES pertaining specifically to octogenarians undergoing PCI. Additionally, the greater co-morbidity in octogenarians might make them more susceptible to complications due to the dual antiplatelet therapy required and the more frequent need for interruptions of this treatment.
These concerns about safety may explain the reason why DES are used relatively less frequently in the very elderly population. The references of the retrieved articles were also confirmed.
Language restrictions were not imposed in our search. The major reasons for exclusion from the study were: 1 Studies investigated either coronary DES or BMS but not both in octogenarians; 2 Data were duplicated; 3 Demographic background of the patients and preoperative conditions were not similar; and 4 No useful data on relevant clinical outcomes were reported.
Aspects of the BMS/CFT correspondence
Inconsistencies were resolved by consensus among all authors. The following information was extracted from each study: year of publication, study design, number of patients, stent type, average length of follow-up, all-cause death, myocardial infarction MIstent thrombosis STtarget vessel revascularization TVRmajor bleeding, and major adverse cardiac events.
Included studies were assessed for the following characteristics: design prospective or retrospectiverandomization yes or nomulti-center enrollment yes or nocharacteristics of participants and personnel performance biasoutcome assessment detection biasincomplete outcome data addressed attrition bias and consideration of multivariate adjustment s for possible confounders.Everything About Circle Theorems - In 3 minutes!
Two independent reviewers assessed the risk of bias. Agreement between the two reviewers was assessed using kappa statistics for full text screening, and rating of relevance and risk of bias. When there was disagreement concerning the risk of bias, a third reviewer the first author checked the data and determined the final decision on the differing controversial opinions.
For the meta-analysis, both the fixed-effects model and the random-effects model were considered. To assess the inter-study heterogeneity more precisely, both the chi-square based Q statistic test-to-test for heterogeneity and the I 2 statistic to quantify the proportion of the total variation attributable to heterogeneity were calculated. For P values less than 0. Additionally, to validate the credibility of outcomes in this meta-analysis, a sensitivity analysis was performed by sequential omission of individual studies.
Publication bias in this meta-analysis was assessed using funnel plot, and an asymmetric plot suggested the possiblility of publication bias. Consequently, funnel plot asymmetry was further assessed by linear regression test method of Egger. All P values were two-sided and a P value of less than 0. As shown in Figure 1potentially eligible studies were identified.
A total of of these records were excluded, leaving 20 potentially relevant studies. We then excluded seven duplicate articles and six studies for no lacking available data. Thus, seven studies one randomized, controlled trial RCT and six observational studies from 20 full-text articles met our selection criteria and were included in this meta-analysis, involving a total of 2, octogenarians receiving coronary DES or BMS implantation.
Table 1 summarized the main characteristics of the analyzed studies. However, there was incomplete reporting of baseline demographics across studies. Medication profiles, including duration of antiplatelet drug therapy, were inconsistently reported. RCT: randomized, controlled trials.
Data are presented as nunless otherwise noted. To assess the impact of heterogeneity on the pooled effect estimates, we performed a sensitivity analysis. Eliminating the RCT study did not substantially change the pooled point estimate Table 4. The present study was designed to analyze the safety and efficacy of DES in an unselected population of octogenarian patients with an indication for revascularization.
There are limited data available concerning DES benefits specifically in octogenarians. Recently, Wang et al.BMS is a novel oral tyrosine kinase inhibitor of ErbB and vascular endothelial growth factor receptor. This open-label phase I dose-escalation study ClinicalTrials. Patients with advanced or metastatic solid tumors received oral BMS once daily continuously until disease progression or intolerable toxicity occurred. Dose-limiting toxicity DLT was evaluated from the first dose to Day Assessments included adverse events, tumor response, pharmacokinetics, pharmacodynamics, 2 [18F] fluorodeoxyglucose positron-emitting tomography, and epidermal growth factor receptor and K-ras mutations.
No treatment-related serious adverse events or DLTs were reported. Frequently observed treatment-related AEs were acne, diarrhea, dry skin, hypertension, stomatitis, blood fibrinogen increased, hemoglobin decreased, pruritus, and hypoalbuminemia.
These were generally reported as Grade 1 and 2. Angiogenesis and tumorigenesis are complex processes in which tumors utilize multiple pathways to promote growth. Targeted inhibition of the vascular endothelial growth factor receptor VEGFR and other key signaling pathways such as the epidermal growth factor receptor EGFR and HER2 pathways has been clinically validated in the treatment for several solid tumor types [ 1 — 5 ]. Because inhibition of multiple pathways may provide synergistic antitumor effects, agents that target multiple pathways may be more effective than single-targeted agents.
The dose-limiting toxicity DLT was diarrhea [ 10 ]. This is the first study to assess the safety profile of BMS in Japanese patients. All patients provided written informed consent to participate in this study. The primary objective was to identify the MTD of BMS administered orally, once daily to Japanese patients with advanced or metastatic solid tumors.
Secondary objectives were to assess the safety of BMS, to determine the antitumor activity observed with BMS, to characterize the pharmacokinetic profile of BMS, and to explore the pharmacodynamic profile of biologic response to BMS DLTs were evaluated from the initial dose until assessment on Day Tumor response was determined for all patients with measurable lesions according to modified World Health Organization WHO tumor response criteria.
The relative percent change from baseline Day 1 for each protein concentration was calculated for each on-treatment specimen. All patients who received study medication were included in the analysis of safety and efficacy. All statistical analyses were performed using SAS Version 8. All patients had metastatic lesions. Tumor types included 5 NSCLC adenocarcinoma2 leiomyosarcoma, 1 colon cancer, and 1 thymic carcinoma.
All patients had received previous treatment for their cancer median number of chemotherapy regimens range was 2. No DLTs were reported in this study. Most AEs were mild in severity. Frequently observed treatment-related AEs n were acne 9diarrhea 8dry skin 7hypertension 7stomatitis 4blood fibrinogen increased 4hemoglobin decreased 4pruritus 4and hypoalbuminemia 4.
No treatment-related serious adverse events SAEs were reported in this study. AE profiles were similar between the DLT evaluation period and the entire treatment period. Following repeated-dose administration, the pharmacokinetics did not change and the accumulation index values were 1. Among the 9 patients evaluated in this study, 5 had stable disease SD and 4 had progressive disease PD. No changes in collagen IV concentration were detected.
This was a phase I dose-escalation study in Japanese patients with advanced or metastatic solid tumors. The study was originally planned to determine MTD as the highest dose at which no more than one patient experience DLT out of 6 patients. The safety, efficacy, pharmacodynamics, and pharmacokinetics of BMS were explored.Metrics details. With the shift of drug development from cytotoxic to targeted mechanisms of action, new and exciting drug classes are being created; over 10 different classes with first-in-human results were identified from this year's meeting alone.
These targeted agents, as compared to traditional cytotoxic therapies, may have decreased toxicity and unique pharmacokinetic profiles. Furthermore, armed with pharmacodynamic assays that measure successful inhibition of designated targets, these phase I trial results suggest potential for using biomarkers to help predict and monitor clinical response. We have limited our discussion to systemic therapies, although phase 1 results for two virus-vector drugs that are injected directly into tumors, OBP and JX, were presented at ASCO as well [ 12 ].
The drugs discussed below are grouped by the cellular location of their intended targets — cell surface, intra-cytoplasmic, or intra-nuclear. Some of these drugs inhibit well-known targets by a novel mechanism, such as the anti-angiogenic adnectins. Other drugs seek to alter the milieu surrounding cancer cells and enhance anti-tumor immunity, such as the antibody to CD BMS and the antioxidant inflammation modulator RTA And finally, small-molecule drugs targeting telomerase GRNLsurvivin LY and vaccineand the hedgehog pathway GDC were presented at ASCO this year, marking the culmination of intense pre-clinical research over the past one to two decades for these agents.
All of the drugs under discussion entered phase I trials because of demonstration of anti-tumor effect in vitro and in xenograft animal models. Patient characteristics were typical for phase I clinical trials-all patients had good performance status ECOG 1 or betterand most patients were heavily pre-treated with standard drug regimens before enrollment. The anti-angiogenic drug trials also excluded patients with intracranial masses, uncontrolled hypertension, and other factors that increased bleeding risk.
Dose-limiting toxicities DLT were typically defined as grade 3 or worse non-hematological, or grade 4 or worse hematological adverse events, at least possibly related to study drug, occurring within a specified time period after drug delivery, although variations of DLT definitions may exist based on anticipated toxicity from preclinical data. Finally, although evaluation of clinical efficacy is not the purpose of phase I trials, the clinical outcomes for patients enrolled in these trials is of major interest and was presented for most drugs discussed below.
BMS is a fully humanized monoclonal antibody agonist of CD, a tumor necrosis factor TNF -receptor that is expressed on the surfaces of activated white blood cells. Stimulation of CD enhances immune response, specifically an anti-tumor immune response, by a variety of mechanisms [ 4 ].
Phase I and II data presented by M. Sznol et al. Toxicity was not related to dose level of drug ranging from 0. Pharmacodynamic studies of blood showed increased levels of activated CD8 cells on day 8 post-treatment, however the increase in CD8 levels, as well as blood levels of other immunologic biomarkers, did not correlate with clinical outcomes. A phase II clinical trial using BMS as 2nd line treatment for patients with metastatic melanoma has opened [ 6 ].
Lewis et al. Toxicity in the form of liver enzyme elevation, abdominal discomfort, and diarrhea was dose-limiting at the highest dose initially tested 1. Pharmacokinetic profiling prompted a change from once-weekly dosing to twice and three-times weekly dosing, to minimize peak serum concentrations without compromising steady state levels. Out of 41 patients evaluated, 7 patients showed some evidence of stable disease, 1 additional patient with pancreatic cancer had stable disease lasting greater than 5 months, and 1 other patient with colorectal cancer had partial response lasting greater than 8 months.
A phase II study in combination with chemotherapy, at a dose of 0. TSP-1 is a known inhibitor of angiogenesis [ 9 ], and attaching the small TSP-1 peptide to an antibody not only preserves anti-angiogenic properties but greatly extends the half-life [ 10 ]. Mendelson et al.However, not only does AACR have nothing on tiragolumab, there are no presentations obviously highlighting any Tigit-targeting projects.
The instalment of AACR was to have started on Friday, but the Covid pandemic has caused the organisers to turn the meeting into two virtual events. The first, next Monday and Tuesday, will feature most of the clinical presentations, which AACR says it wanted to get out in a timely manner, and it is this meeting for which abstract titles have been made available. The focus on Ox40 will come as a surprise to those who had already written off this approach. Kras data should be of interest to Mirati, which slumped yesterday on a short report from Kerrisdale Capital.
Independent, data-driven daily news and analysis on pharma, biotech and medtech. Sign up. Related Articles September 11, June 03, April 27, June 05, June 04, Editor's Picks September 11, September 11, September 30, August 27, September 16, We note the fundamental obstacle at 4 space time dimensions, and continue with discussion of renormalization group ideas. Here we find analogies to fluid turbulence useful. Turbulence, as with Quantum Chromodynamics, has the simplifying property of asymptotic freedom.
We assume a Kolmogorov style bound and prove as a result existence of solutions to the Euler equation. The Euler equation solutions are not unique and in need of an admissibility condition. Here a major scientific controversy occurs.
We comment on the solution of the deflagration to detonation transition in SN Ia, and its relation to this controversy.
The subfactors in the two cases appear to be the same up to a type III factor. As is the question of which subfactors arise in CFT. I will explain a perspective on them that is based on a discrete anomaly.
It also gives a geometric realization of all stabilizer codes, which represents both the stabilizer group and stabilizer states in a geometric way simultaneously. I will discuss the issue of constructing models with specific modular data, including the double of the Haagerup subfactor. This is joint work with Terry Gannon. Finally we discuss current concepts of consciousness in the brain.
Titles & Abstracts
Bas Janssens. In this context, we give sufficient and, under extra assumptions, necessary conditions for reflection positivity. The main novelty here is that the systems under consideration can be not only bosonic or fermionic, but also parafermionic. Joint work with Arthur Jaffe.
Abstract: This talk will survey methods of recovering information about a Lie algebra from the quiver representation theory of its finite or affine ADE Dynkin diagram.
The discrete differentiation of functions across hyperplanes equips the linear span of permutohedral cones with the structure of a combinatorial Lie coalgebra. Using this Lie structure, we show that permutohedral cones satisfy the Steinmann relations of axiomatic quantum field theory, and we give an algorithm for expressing any function which satisfies the Steinmann relations in terms of permutohedral cones. We show that the universal enveloping coalgebra is the dual Hopf algebra of the braid arrangement, which is a combinatorial analog of the shuffle algebra.
In this talk, we introduce locally compact planar algebras with reflection positivity. Within this framework, we can generalize the two monodical categories for locally compact groups.
Moreover, we formalize and prove their Morita equivalence for compact groups. Abstract: It is well-known that a finite depth subfactor is associated to a fusion category and a planar algebra.
Skip to main content. Main Menu Utility Menu Search. Levin Schedule: Jefferson Bas Janssens Delft University of Technology. William Norledge Penn State University. Title: Algebraic and Topological Structures of Subfactors Abstract: It is well-known that a finite depth subfactor is associated to a fusion category and a planar algebra.Study record managers: refer to the Data Element Definitions if submitting registration or results information.
Placebo matching with BMS 0 mg solution single dose subcutaneously once. BMS 3 mg solution single dose subcutaneously once. BMS 10 mg solution single dose subcutaneously once. BMS 30 mg solution single dose subcutaneously once. And Keyhole limpet hemocyanin KLH 1 mg solution single intramuscular dose once.
BMS mg solution single dose subcutaneously once. BMS mg solution single dose intravenously once. Placebo matching with BMS 0 mg solution single dose intravenously once. BMS mg solution subcutaneously once weekly for 4 weeks. Placebo matching with BMS 0 mg solution subcutaneously once weekly for 4 weeks. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
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Federal Government. Read our disclaimer for details. Last Update Posted : May 12, Study Description. The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics PK and pharmacodynamics PD of BMS in healthy subjects.In the spirit of two dimensional conformal field theory, the symmetry algebra of asymptotically flat spacetimes at null infinity in 4 dimensions is taken to be the semi-direct sum of supertranslations with infinitesimal local conformal transformations and not, as usually done, with the Lorentz algebra.
As a first application, we derive how the symmetry algebra is realized on solution space. This is a preview of subscription content, log in to check access. Rent this article via DeepDyve. Maldacena, The large-N limit of superconformal field theories and supergravityAdv. Henneaux and C. Teitelboim, Asymptotically anti-de Sitter spacesCommun. Brown and M. Henneaux, Central charges in the canonical realization of asymptotic symmetries: an example from three-dimensional gravityCommun.
Ruffini ed. Bondi, M.
Comparison of coronary DES and BMS in octogenarians: A systematic review and meta-analysis
Metzner, Gravitational waves in general relativity. Waves from axisymmetric isolated systemsProc. Sachs, Gravitational waves in general relativity.
Waves in asymptotically flat space-timesProc. Sachs, Asymptotic symmetries in gravitational theoryPhys. Barnich and C. Troessaert, Symmetries of asymptotically flat 4 dimensional spacetimes at null infinity revisitedarXiv Barnich and G.
Compere, Classical central extension for asymptotic symmetries at null infinity in three spacetime dimensionsClass.