Showing papers by "James P. Howard published in 2014"
TL;DR: Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size, and in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.
Abstract: Objective To investigate whether discrepancies in trials of use of bone marrow stem cells in patients with heart disease account for the variation in reported effect size in improvement of left ventricular function.
Design Identification and counting of factual discrepancies in trial reports, and sample size weighted regression against therapeutic effect size. Meta-analysis of trials that provided sufficient information.
Data sources PubMed and Embase from inception to April 2013.
Eligibility for selecting studies Randomised controlled trials evaluating the effect of autologous bone marrow stem cells for heart disease on mean left ventricular ejection fraction.
Results There were over 600 discrepancies in 133 reports from 49 trials. There was a significant association between the number of discrepancies and the reported increment in EF with bone marrow stem cell therapy (Spearman’s r =0.4, P=0.005). Trials with no discrepancies were a small minority (five trials) and showed a mean EF effect size of −0.4%. The 24 trials with 1-10 discrepancies showed a mean effect size of 2.1%. The 12 with 11-20 discrepancies showed a mean effect of size 3.0%. The three with 21-30 discrepancies showed a mean effect size of 5.7%. The high discrepancy group, comprising five trials with over 30 discrepancies each, showed a mean effect size of 7.7%.
Conclusions Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size. The mechanism is unknown but should be explored in the design of future trials because in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.
210 citations
TL;DR: In the countries for which there are good longitudinal data, predominantly European countries, recent years have shown a continuing decline in age-standardised IHD mortality, however, the progressive aging of populations has kept crude I HD mortality high.
119 citations
TL;DR: Why, as denervation trials become increasingly bias resistant, the reported effect size may reduce, and two sources of bias are explored, which can lead to unintentional exaggeration of benefits from both drugs and device-based treatment for hypertension.
53 citations
TL;DR: Symplicity HTN-3 illustrates the importance of randomisation and blinding for exciting new treatments and shows the need to Randomise and Blindness for new treatments.
Abstract: Symplicity HTN-3 illustrates the importance of randomisation and blinding for exciting new treatments
32 citations
TL;DR: New pharmacotherapies for ACS reflect efforts to improve efficacy and minimize complications by increasing target specificity and reducing inter-individual variation in therapeutic response.
Abstract: Anti-thrombotic drugs constitute the cornerstone of therapy in the management of acute coronary syndromes (ACS) and for patients undergoing percutaneous coronary intervention. Anti-thrombotic therapy during percutaneous coronary intervention for ACS has evolved substantially over the past 15 years. In the original 1996 ACC/AHA guidelines for the management of acute myocardial infarction (MI), only one antiplatelet agent (aspirin) and one anticoagulant (unfractionated heparin) were recommended as class I therapies. Much has since changed and the contemporary therapeutic armoury for the treatment of ACS reflects the pharmacological advances that have taken place. Recent developments in the medical management of ACS have been based around developing drugs with more predictable efficacy and at known drug targets. However there has also been considerable development of novel agents. New pharmacotherapies for ACS reflect efforts to improve efficacy and minimize complications by increasing target specificity and reducing inter-individual variation in therapeutic response.
11 citations