1Design of the Primary Prevention Parameters Evaluation (PREPARE) trial of implantablecardioverter defibrillators to reduce patient morbidity [NCT00279279]

BACKGROUND: Implantable Cardioverter Defibrillator (ICD) therapy has been proven to be beneficial and efficacious for the treatment of serious ventricular tachyarrhythmias in primary prevention patients. However, primary prevention patients appear to have a lower incidence of ventricular arrhythmias in comparison to secondary prevention patients and consequently likely experience a higher proportion of detections due to supraventricular arrhythmias. Recent trials have demonstrated that strategic and specific programming choices reduce the number of inappropriate shocks and that anti-tachycardia pacing (ATP) is an effective alternative to shock therapy for many sustained ventricular arrhythmias. METHODS: The Primary Prevention Parameters Evaluation (PREPARE) study is a multi-center cohort study, evaluating the efficacy of a pre-specified strategic profile of VT/VF detection and therapy settings in 700 primary prevention patients in an effort to safely reduce the number of shock therapies delivered. The patients, both with and without cardiac resynchronization therapy, are compared to a well-qualified set (n = 691) of historical controls derived from the MIRACLE ICD and EMPIRIC trials. This manuscript describes the design of the PREPARE study. The study results, to be presented separately, will characterize the efficacy of this programming set (PREPARE) compared with physician-tailored programming (MIRACLE ICD and EMPIRIC)

A straightforward multiallelic significance test for the Hardy-Weinberg equilibrium law

Much forensic inference based upon DNA evidence is made assuming Hardy-Weinberg Equilibrium (HWE) for the genetic loci being used. Several statistical tests to detect and measure deviation from HWE have been devised, and their limitations become more obvious when testing for deviation within multiallelic DNA loci. The most popular methods-Chi-square and Likelihood-ratio tests-are based on asymptotic results and cannot guarantee a good performance in the presence of low frequency genotypes. Since the parameter space dimension increases at a quadratic rate on the number of alleles, some authors suggest applying sequential methods, where the multiallelic case is reformulated as a sequence of “biallelic” tests. However, in this approach it is not obvious how to assess the general evidence of the original hypothesis; nor is it clear how to establish the significance level for its acceptance/rejection. In this work, we introduce a straightforward method for the multiallelic HWE test, which overcomes the aforementioned issues of sequential methods. The core theory for the proposed method is given by the Full Bayesian Significance Test (FBST), an intuitive Bayesian approach which does not assign positive probabilities to zero measure sets when testing sharp hypotheses. We compare FBST performance to Chi-square, Likelihood-ratio and Markov chain tests, in three numerical experiments. The results suggest that FBST is a robust and high performance method for the HWE test, even in the presence of several alleles and small sample sizes

Routine DFT

Defibrillation threshold (DFT) testing has been an integral part of implantable cardioverter-defibrillator (ICD) implantation to confirm appropriate sensing of ventricular fibrillation and to establish an adequate safety margin for defibrillation. However, there is a lack of evidence regarding benefits of routine DFT testing. Therefore, we performed a meta-analysis to assess its mortality benefit. We searched MEDLINE for studies comparing mortality outcomes in ICD recipients who underwent DFT testing to those who did not. For the second analysis, studies comparing outcomes in patients with high- vs low-energy DFT were included. Odds ratio and standard errors were calculated, and inverse variance method in a random-effect model was used to combine effect sizes. Fifteen studies with 10,975 subjects comparing outcomes in patients who underwent routine DFT testing during ICD implantation and those who did not were included. There was no difference in the group that did not undergo DFT testing with regards to all-cause mortality (OR 0.935; CI 0.725-1.207; = 0.606), cardiac mortality (OR 0.709; CI 0.385-1.307; = 0.271), noncardiac mortality (OR 0.921; CI 0.701-1.210; = 0.554), and arrhythmic mortality (OR 1.152; CI 0.831-1.596; = 0.396). Percentage of successful appropriate first shocks among the two groups showed no difference. Five studies with 2278 subjects were included in the second analysis comparing patients with low DFT vs high DFT. Patients with high DFT had no significant increase in all-cause mortality compared to patients with low DFT (OR 0.527; CI 0.034-8.107; = 0.646). Patients requiring higher DFT had no increased all-cause mortality compared to patients with lower DFT. Routine DFT testing during ICD implantation does not confer any significant benefit