What's the Risk? A Simple Approach for Estimating Adjusted Risk Measures from Nonlinear Models Including Logistic Regression

To develop and validate a general method (called regression risk analysis) to estimate adjusted risk measures from logistic and other nonlinear multiple regression models. We show how to estimate standard errors for these estimates. These measures could supplant various approximations (e.g., adjusted odds ratio [AOR]) that may diverge, especially when outcomes are common. Study Design . Regression risk analysis estimates were compared with internal standards as well as with Mantel–Haenszel estimates, Poisson and log-binomial regressions, and a widely used (but flawed) equation to calculate adjusted risk ratios (ARR) from AOR. Data Collection . Data sets produced using Monte Carlo simulations. Principal Findings . Regression risk analysis accurately estimates ARR and differences directly from multiple regression models, even when confounders are continuous, distributions are skewed, outcomes are common, and effect size is large. It is statistically sound and intuitive, and has properties favoring it over other methods in many cases. Conclusions . Regression risk analysis should be the new standard for presenting findings from multiple regression analysis of dichotomous outcomes for cross-sectional, cohort, and population-based case–control studies, particularly when outcomes are common or effect size is large.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74652/1/j.1475-6773.2008.00900.x.pd

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required