A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

<p>Abstract</p> <p>Background</p> <p>Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.</p> <p>Methods/Design</p> <p>The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express²paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.</p> <p>Discussion</p> <p>The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at <url>http://www.clinicaltrials.gov</url>, identification numbers NCT00484315 and NCT00489541.</p

Relationship between treatment delay and final infarct size in STEMI patients treated with abciximab and primary PCI

Background Studies on the impact of time to treatment on myocardial infarct size have yielded   conflicting results. In this study of ST-Elevation Myocardial Infarction (STEMI) treated   with primary percutaneous coronary intervention (PCI), we set out to investigate the   relationship between the time from First Medical Contact (FMC) to the demonstration   of an open infarct related artery (IRA) and final scar size. Between February 2006 and September 2007, 89 STEMI patients treated with primary PCI   were studied with contrast enhanced magnetic resonance imaging (ceMRI) 4 to 8 weeks   after the infarction. Spearman correlation was computed for health care delay time   (defined as time from FMC to PCI) and myocardial injury. Multiple linear regression   was used to determine covariates independently associated with infarct size. Results An occluded artery (Thrombolysis In Myocardial Infarction, TIMI flow 0-1 at initial   angiogram) was seen in 56 patients (63%). The median FMC-to-patent artery was 89 minutes.   There was a weak correlation between time from FMC-to-patent IRA and infarct size,   r = 0.27, p = 0.01. In multiple regression analyses, LAD as the IRA, smoking and an occluded vessel   at the first angiogram, but not delay time, correlated with infarct size. Conclusions In patients with STEMI treated with primary PCI we found a weak correlation between   health care delay time and infarct size. Other factors like anterior infarction, a   patent artery pre-PCI and effects of reperfusion injury may have had greater influence   on infarct size than time-to-treatment per se

Effect of Food Residues on Norovirus Survival on Stainless Steel Surfaces

Background: In households and food processing plants, minute food residues left behind from improper cleaning may influence the survivability of human norovirus on surfaces. In this study, the survivability of norovirus on desiccated food residue-attached stainless steel coupons was investigated. Methodology/Principal Findings: Using murine norovirus-1 (MNV-1) as a surrogate of human norovirus, the survivability of norovirus was investigated on lettuce, cabbage, or ground pork-attached stainless steel coupons. A 6.2 log MPN/ml of MNV-1 infectivity was completely lost at day 30 in residue-free coupons, whereas only a 1.4 log MPN/ml reduction was observed in coupons with residues. Moreover, the disinfective effect of sodium hypochlorite was reduced when residues were present on the coupons. Conclusions/Significance: This study revealed that the food residues increased the survivability and the resistance to chemicals of norovirus, indicating the need of thorough cleaning in food processing plants and household settings

The Identification of Lymphocyte-Like Cells and Lymphoid-Related Genes in Amphioxus Indicates the Twilight for the Emergency of Adaptive Immune System

To seek evidence of a primitive adaptive immune system (AIS) before vertebrate, we examined whether lymphocytes or lymphocyte-like cells and the related molecules participating in the lymphocyte function existed in amphioxus. Anatomical analysis by electron microscopy revealed the presence of lymphocyte-like cells in gills, and these cells underwent morphological changes in response to microbial pathogens that are reminiscent of those of mammalian lymphocytes executing immune response to microbial challenge. In addition, a systematic comparative analysis of our cDNA database of amphioxus identified a large number of genes whose vertebrate counterparts are involved in lymphocyte function. Among these genes, several genes were found to be expressed in the vicinity of the lymphocyte-like cells by in situ hybridization and up-regulated after exposure to microbial pathogens. Our findings in the amphioxus indicate the twilight for the emergency of AIS before the invertebrate-vertebrate transition during evolution

The Optokinetic Reflex as a Tool for Quantitative Analyses of Nervous System Function in Mice: Application to Genetic and Drug-Induced Variation

The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable

Analysis of in vitro bioactivity data extracted from drug discovery literature and patents: Ranking 1654 human protein targets by assayed compounds and molecular scaffolds

<p>Abstract</p> <p>Background</p> <p>Since the classic Hopkins and Groom druggable genome review in 2002, there have been a number of publications updating both the hypothetical and successful human drug target statistics. However, listings of research targets that define the area between these two extremes are sparse because of the challenges of collating published information at the necessary scale. We have addressed this by interrogating databases, populated by expert curation, of bioactivity data extracted from patents and journal papers over the last 30 years.</p> <p>Results</p> <p>From a subset of just over 27,000 documents we have extracted a set of compound-to-target relationships for biochemical <it>in vitro </it>binding-type assay data for 1,736 human proteins and 1,654 gene identifiers. These are linked to 1,671,951 compound records derived from 823,179 unique chemical structures. The distribution showed a compounds-per-target average of 964 with a maximum of 42,869 (Factor Xa). The list includes non-targets, failed targets and cross-screening targets. The top-278 most actively pursued targets cover 90% of the compounds. We further investigated target ranking by determining the number of molecular frameworks and scaffolds. These were compared to the compound counts as alternative measures of chemical diversity on a per-target basis.</p> <p>Conclusions</p> <p>The compounds-per-protein listing generated in this work (provided as a supplementary file) represents the major proportion of the human drug target landscape defined by published data. We supplemented the simple ranking by the number of compounds assayed with additional rankings by molecular topology. These showed significant differences and provide complementary assessments of chemical tractability.</p

Acute ischemic heart disease and interventional cardiology: a time for pause

BACKGROUND: A major change has occurred in the last few years in the therapeutic approach to patients presenting with all forms of acute coronary syndromes. Whether or not these patients present initially to tertiary cardiac care centers, they are now routinely referred for early coronary angiography and increasingly undergo percutaneous revascularization. This practice is driven primarily by the angiographic image and technical feasibility. Concomitantly, there has been a decline in expectant or ischemia-guided medical management based on specific clinical presentation, response to initial treatment, and results of noninvasive stratification. This 'tertiarization' of acute coronary care has been fuelled by the increasing sophistication of the cardiac armamentarium, the peer-reviewed publication of clinical studies purporting to show the superiority of invasive cardiac interventions, and predominantly supporting (non-peer-reviewed) editorials, newsletters, and opinion pieces. DISCUSSION: This review presents another perspective, based on a critical reexamination of the evidence. The topics addressed are: reperfusion treatment of ST-elevation myocardial infarction; the indications for invasive intervention following thrombolysis; the role of invasive management in non-ST-elevation myocardial infarction and unstable angina; and cost-effectiveness and real world considerations. A few cases encountered in recent practice in community and tertiary hospitals are presented for illustrative purposes The numerous and far-reaching scientific, economic, and philosophical implications that are a consequence of this marked change in clinical practice as well as healthcare, decisional and conflict of interest issues are explored. SUMMARY: The weight of evidence does not support the contemporary unfocused broad use of invasive interventional procedures across the spectrum of acute coronary clinical presentations. Excessive and unselective recourse to these procedures has deleterious implications for the organization of cardiac health care and undesirable economic, scientific and intellectual consequences. It is suggested that there is need for a new equilibrium based on more refined clinical risk stratification in the treatment of patients who present with acute coronary syndromes