Leonardi S.,Pratt Institute |
Thomas L.,Pratt Institute |
Neely M.L.,Pratt Institute |
Tricoci P.,Pratt Institute |
And 8 more authors.
Journal of the American College of Cardiology | Year: 2012
Objectives: This study compared prognoses of myocardial infarction related to percutaneous coronary intervention (PCI, procedural MI) using increasing creatine kinase-myocardial band (CK-MB) thresholds with spontaneous MI. Background: Procedural MI usually is defined by a CK-MB elevation of more than 3 times the upper limit of normal (ULN), but higher thresholds have been proposed. Methods: Patients from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome) study and the SYNERGY (Superior Yield of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa inhibitors) study treated with PCI were included. The primary end point was 1-year all-cause mortality from 24 h after PCI. To determine an enzymatic threshold for procedural MI with a prognosis similar to that of spontaneous MI, we redefined procedural MI using increasing CK-MB thresholds and compared corresponding hazard ratios with those of spontaneous MI (CK-MB more than twice the ULN). Hazard ratios for mortality for procedural and spontaneous MI were calculated using Cox proportional hazards regression and Global Registry of Acute Cardiac Events covariates for risk adjustment. Results: Nine thousand eighty-seven patients who underwent PCI (46.8%) were included; 773 procedural MI and 239 spontaneous MI occurred within 30 days. Adjusted hazard ratios for 1-year death were 1.39 (95% confidence interval [CI]: 1.01 to 1.89) for procedural MI and 5.37 (95% CI: 3.90 to 7.38) for spontaneous MI. The CK-MB threshold for procedural MI that achieved the same prognosis as spontaneous MI was 27.7 times the ULN (95% CI: 13.9 to 58.4), but this differed between the SYNERGY study (57.9 times the ULN, 95% CI: 17.9 to 63.6) and the EARLY-ACS study (20.4 times the ULN, 95% CI: 5.16 to 24.2). Of all procedural MI, 49 (6%) had CK-MB elevations of 27.7 or more times the ULN. Conclusions: The current enzymatic definition of procedural MI (CK-MB more than 3 times the ULN) used in clinical trials is less strongly associated with death than that of spontaneous MI. Procedural MI achieves similar prognosis for 1-year mortality when much higher CK-MB thresholds are applied. © 2012 American College of Cardiology Foundation.
Hirsch B.R.,Duke Cancer Institute |
Hirsch B.R.,Duke Clinical Research Institute |
Califf R.M.,Duke Translational Medicine Institute |
Cheng S.K.,Oregon Health And Science University |
And 7 more authors.
JAMA Internal Medicine | Year: 2013
Importance: Clinical trials are essential to cancer care, and data about the current state of research in oncology are needed to develop benchmarks and set the stage for improvement. Objective: To perform a comprehensive analysis of the national oncology clinical research portfolio. Design: All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. Results: Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P =.04] and 0.77 [P =.001], respectively). More than one-third of all oncology trials were conducted solely outside North America. Conclusions and Relevance : There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources. ©2013 American Medical Association. All rights reserved.
Vickery B.P.,University of North Carolina at Chapel Hill |
Scurlock A.M.,University of Arkansas for Medical Sciences |
Kulis M.,University of North Carolina at Chapel Hill |
Steele P.H.,University of North Carolina at Chapel Hill |
And 15 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014
Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness after withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at 2 US centers. Subjects age 1 to 16 years were recruited and treated for up to 5 years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg/d peanut protein. Blood was collected at multiple time points. Clinical end points were measured with 5000-mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. Twelve (50%) of 24 successfully passed a challenge 1 month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin test results, as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2 and lower ratios of peanut-specific IgE/total IgE compared with subjects not passing. There were no differences in peanut IgG4 levels or functional activity at the end of the study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated for up to 5 years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin test results and lower allergen-specific IgE levels were predictive of successful outcome. © 2013 American Academy of Allergy, Asthma & Immunology.
Fiuzat M.,Duke University |
Califf R.M.,Duke University |
Califf R.M.,Duke Translational Medicine Institute
Heart Failure Clinics | Year: 2011
Clinical trials are often conducted globally. Differences in standard of care, patient populations including genetic and phenotypic differences, disease etiologies, rates of comorbidities, ascertainment of endpoints, and differences in concomitant therapies and medical culture may influence subsequent outcomes. There has been little consensus on how clinical trial results should be evaluated. This article reviews the differences in cardiovascular trial results by geographic region, offers potential explanations for these differences, and suggests methods for standardization of trial results. © 2011 Elsevier Inc.
Syed A.,Stanford University |
Garcia M.A.,Stanford University |
Lyu S.-C.,Stanford University |
Bucayu R.,Stanford University |
And 8 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014
Background The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance. Objective Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy. Methods In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13). Results Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells. Conclusion In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT. © 2013 American Academy of Allergy, Asthma & Immunology.