VER THE PAST DECADE, SEVeral studies have suggested that blood transfusions depress immune function in recipients. 1,2 Evidence of transfusion-associated immune suppression emerged following observations that blood transfusions improved renal allograft survival 3 and accelerated 4 and increased postoperative infections. 5 A recent randomized controlled trial undertaken to examine infections in cardiovascular surgical patients found an approximately 4.2% absolute decrease in mortality but no decrease in
Purpose: Hereditary long QT syndrome is named for a prolonged QT interval reflecting predisposition to ventricular arrhythmias and sudden death. A high rate in a remote, northern Canadian First Nations community was brought to attention. Methods: Two severely affected index cases and 122 relatives were ascertained using communitybased participatory research principles. Genetic sequencing of five known genes responsible for long QT syndrome was carried out on the index cases, leading to the identification of a novel missense mutation. Functional properties of the identified mutation were studied in transfected mouse ltk-cells using whole cell patch clamp techniques. Corrected QT interval measurements were obtained from participants and subsequent genotyping of relatives was carried out. Results: In the two index cases, a novel missense mutation (V205M) was identified in the S3 transmembrane helix of KvLQT1, the pore forming domain of the I Ks channel complex. In transfected mouse ltk-cells the V205M mutation suppressed I Ks by causing a dramatic depolarizing shift in activation voltage coupled with acceleration of channel deactivation. Twenty-two mutation carriers had a significantly higher mean corrected QT interval than noncarriers (465 Ϯ 28 milliseconds vs. 434 Ϯ 26 milliseconds, P Ͻ 0.0001); however, 30% of carriers had a corrected QT interval below 440 milliseconds. Conclusion: A novel KCNQ1 mutation in this founder population likely confers increased susceptibility to arrhythmias because of decreased I Ks current. Even with a common mutation within a relatively homogenous population, clinical expression remains variable, exemplifying the multifactorial nature of long QT syndrome, and supporting the difficulty of definitive diagnosis without genetic testing. A community participatory approach enabled a comprehensive evaluation of the impact. Genet Med 2008:10(7):545-550.
Recently developed disease mapping and ecological regression methods have become important techniques in studies of disease epidemiology and in health services research. This increase in importance is partially a result of the development of Bayesian statistical methodologies that make it possible to study associations between health problems and risk factors at an aggregate (i.e. areal) level while taking into account such matters as unmeasured confounding and spatial relationships. In this paper we present a demonstration of the joint use of empirical Bayes (EB) and full Bayesian inferential techniques in a small area study of adverse medical events (also known as 'iatrogenic injury') in British Columbia, Canada. In particular, we illustrate a unified Bayesian hierarchical spatial modelling framework that enables simultaneous examinations of potential associations between adverse medical event occurrence and regional characteristics, age effects, residual variation and spatial autocorrelation. We propose an analytic strategy for complementary use of EB and FB inferential techniques for risk assessment and model selection, presenting an EB-FB combined approach that draws on the strengths of each method while minimizing inherent weaknesses. The work was motivated by the need to explore relatively efficient ways to analyse regional variations of health services outcomes and resource utilization when a considerable amount of statistical modelling and inference are required.
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