A population-based study of cholinesterase inhibitor use for dementia.

Objectives: To examine current utilization patterns of cholinesterase inhibitor (ChEI) therapy for dementia to determine treatment duration, use in long-term care, how often patients receive these drugs until death, and frequency of switching between the available ChEIs.

Design: A population-based healthcare administrative database study.

Setting: Patients aged 66 and older from the Canadian province of Ontario who received a new prescription for a ChEI between June 1, 2000, and December 31, 2002.

Intracerebral hemorrhage: outcomes and eligibility for factor VIIa treatment in a National Stroke Registry.

Background: Intracerebral hemorrhage (ICH) is a devastating form of stroke for which the lack of treatment options, high mortality rate, and the tendency to severely disable result in high social and economic burden.

Methods: We analyzed data in the Registry of the Canadian Stroke Network (RCSN). We sought to: (1) provide a descriptive analysis of ICH; (2) determine the proportion of ICH patients that might have been eligible for treatment with recombinant activated factor VII (rFVIIa) using criteria from a recent phase II trial; (3) compare 6-month outcomes of ICH patients with those of ischemic stroke patients, matched for gender, age, and stroke severity.

Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals.

We use the Genetic Analysis Workshop 14 simulated data to explore the effectiveness of a two-stage strategy for mapping complex disease loci consisting of an initial genome scan with confidence interval construction for gene location, followed by fine mapping with family-based tests of association on a dense set of single-nucleotide polymorphisms. We considered four types of intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval based on the position of the maximum Zlr score, and asymptotic and bootstrap confidence intervals based on a generalized estimating equations method. For fine mapping we considered two family-based tests of association: a test based on a likelihood ratio statistic and a transmission-disequilibrium-type test implemented in the software FBAT.

Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans.

Using the simulated data of Problem 2 for Genetic Analysis Workshop 14 (GAW14), we investigated the ability of three bootstrap-based resampling estimators (a shrinkage, an out-of-sample, and a weighted estimator) to reduce the selection bias for genetic effect estimation in genome-wide linkage scans. For the given marker density in the preliminary genome scans (7 cM for microsatellite and 3 cM for SNP), we found that the two sets of markers produce comparable results in terms of power to detect linkage, localization accuracy, and magnitude of test statistic at the peak location. At the locations detected in the scan, application of the three bootstrap-based estimators substantially reduced the upward selection bias in genetic effect estimation for both true and false positives.