Bias in trials comparing paired continuous tests can cause researchers to choose the wrong screening modality

<p>Abstract</p> <p>Background</p> <p>To compare the diagnostic accuracy of two continuous screening tests, a common approach is to test the difference between the areas under the receiver operating characteristic (ROC) curves. After study participants are screened with both screening tests, the disease status is determined as accurately as possible, either by an invasive, sensitive and specific secondary test, or by a less invasive, but less sensitive approach. For most participants, disease status is approximated through the less sensitive approach. The invasive test must be limited to the fraction of the participants whose results on either or both screening tests exceed a threshold of suspicion, or who develop signs and symptoms of the disease after the initial screening tests.</p> <p>The limitations of this study design lead to a bias in the ROC curves we call <it>paired screening trial bias</it>. This bias reflects the synergistic effects of inappropriate reference standard bias, differential verification bias, and partial verification bias. The absence of a gold reference standard leads to inappropriate reference standard bias. When different reference standards are used to ascertain disease status, it creates differential verification bias. When only suspicious screening test scores trigger a sensitive and specific secondary test, the result is a form of partial verification bias.</p> <p>Methods</p> <p>For paired screening tests with bivariate normally distributed scores, we give formulae and programs to quantify the effect of <it>paired screening trial bias </it>on a paired comparison of area under the curves. We fix the prevalence of disease, and the chance a diseased subject manifests signs and symptoms. We derive the formulas for true sensitivity and specificity, and those for the sensitivity and specificity observed by the study investigator.</p> <p>Results</p> <p>The observed area under the ROC curves is quite different from the true area under the ROC curves. The typical direction of the bias is a strong inflation in sensitivity, paired with a concomitant slight deflation of specificity.</p> <p>Conclusion</p> <p>In paired trials of screening tests, when area under the ROC curve is used as the metric, bias may lead researchers to make the wrong decision as to which screening test is better.</p

Eating disorders in sport : current status and future directions in the study of the psychological factors

Este trabalho procura atingir dois objetivos. Em primeiro lugar, apresenta-se a situação atual da investigação sobre desordens alimentares no desporto. Neste caso, salientam-se as linhas de investigação dedicadas ao estudo da prevalência destes problemas no desporto e analisam-se as diferenças entre atletas e modalidades desportivas. Dadas as dificuldades destas linhas de investigação na compreensão dos comportamentos alimentares de risco nos atletas, são avançadas outras possibilidades de desenvolvimento da investigação. Assim, e enquanto segundo objetivo deste artigo, salientamos a necessidade dos estudos se dirigirem para a compreensão dos fatores psicológicos associados aos comportamentos alimentares de risco e implicados no desenvolvimento das desordens alimentares. Esta abordagem tem como vantagem adicional ajudar a prevenir estes problemas através da promoção das competências mentais dos atletas no sentido de resistirem melhor aos possíveis efeitos nocivos da prática desportiva, onde se inserem os problemas com a alimentação.This paper focuses on two main goals. In first place, we present the current status on the research about eating disorders in sport contexts. In this case, we point out studies dedicated to the analysis of the incidence of eating disorders in sport and studies that observe the differences between athletes and different sports in the tendency for these problems. Second, we proposed new research directions on this subject, namely the need of analysing the psychological factors that are related with the development of eating disorders on athletes. This research approach has the advantage of helping the prevention of eating disorders on athletes through the promotion of psychological skills that protect athletes from the negative effects of sport practicing, where are included maladaptive eating behaviors.(undefined

GLIMMPSE: Online Power Computation for Linear Models with and without a Baseline Covariate

GLIMMPSE is a free, web-based software tool that calculates power and sample size for the general linear multivariate model with Gaussian errors (http://glimmpse.SampleSizeShop.org/). GLIMMPSE provides a user-friendly interface for the computation of power and sample size. We consider models with fixed predictors, and models with fixed predictors and a single Gaussian covariate. Validation experiments demonstrate that GLIMMPSE matches the accuracy of previously published results, and performs well against simulations. We provide several online tutorials based on research in head and neck cancer. The tutorials demonstrate the use of GLIMMPSE to calculate power and sample size

Prenatal Vitamin D Intake, Cord Blood 25-Hydroxyvitamin D, and Offspring Body Composition: The Healthy Start Study

Vitamin D deficiency in pregnancy may be associated with increased offspring adiposity, but evidence from human studies is inconclusive. We examined associations between prenatal vitamin D intake, 25-hydroxyvitamin D (25(OH)D) in cord blood, and offspring size and body composition at birth and 5 months. Participants included 605 mother-offspring dyads from the Healthy Start study, an ongoing, pre-birth prospective cohort study in Denver, Colorado, USA. Prenatal vitamin D intake was assessed with diet recalls and questionnaires, and offspring body composition was measured via air displacement plethysmography at birth and 5 months. General linear univariate models were used for analysis, adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index (BMI), offspring sex, and gestational age at birth. Non-Hispanic white race, lower pre-pregnancy BMI, higher prenatal vitamin D intake, and summer births were associated with higher cord blood 25(OH)D. Higher 25(OH)D was associated with lower birthweight (β = –6.22, p = 0.02), but as maternal BMI increased, this association became increasingly positive in direction and magnitude (β = 1.05, p = 0.04). Higher 25(OH)D was also associated with lower neonatal adiposity (β = –0.02, p &lt; 0.05) but not after adjustment for maternal BMI (β = –0.01, p = 0.25). Cord blood 25(OH)D was not associated with offspring size or body composition at 5 months. Our data confirm the hypothesis that vitamin D exposure in early life is associated with neonatal body size and composition. Future research is needed to understand the implications of these associations as infants grow

Nicotinamide Promotes Adipogenesis in Umbilical Cord-Derived Mesenchymal Stem Cells and Is Associated with Neonatal Adiposity: The Healthy Start BabyBUMP Project

<div><p>The cellular mechanisms whereby excess maternal nutrition during pregnancy increases adiposity of the offspring are not well understood. However, nicotinamide (NAM), a fundamental micronutrient that is important in energy metabolism, has been shown to regulate adipogenesis through inhibition of SIRT1. Here we tested three novel hypotheses: 1) NAM increases the adipogenic response of human umbilical cord tissue-derived mesenchymal stem cells (MSCs) through a SIRT1 and PPARγ pathway; 2) lipid potentiates the NAM-enhanced adipogenic response; and 3) the adipogenic response to NAM is associated with increased percent fat mass (%FM) among neonates. MSCs were derived from the umbilical cord of 46 neonates born to non-obese mothers enrolled in the Healthy Start study. Neonatal %FM was measured using air displacement plethysmography (Pea Pod) shortly after birth. Adipogenic differentiation was induced for 21 days in the 46 MSC sets under four conditions, +NAM (3mM)/–lipid (200 μM oleate/palmitate mix), +NAM/+lipid, –NAM/+lipid, and vehicle-control (–NAM/–lipid). Cells incubated in the presence of NAM had significantly higher PPARγ protein (+24%, p <0.01), FABP4 protein (+57%, p <0.01), and intracellular lipid content (+51%, p <0.01). Lipid did not significantly increase either PPARγ protein (p = 0.98) or FABP4 protein content (p = 0.82). There was no evidence of an interaction between NAM and lipid on adipogenic response of PPARγ or FABP4 protein (p = 0.99 and p = 0.09). In a subset of 9 MSC, SIRT1 activity was measured in the +NAM/-lipid and vehicle control conditions. SIRT1 enzymatic activity was significantly lower (-70%, p <0.05) in the +NAM/-lipid condition than in vehicle-control. In a linear model with neonatal %FM as the outcome, the percent increase in PPARγ protein in the +NAM/-lipid condition compared to vehicle-control was a significant predictor (β = 0.04, 95% CI 0.01–0.06, p <0.001). These are the first data to support that chronic NAM exposure potentiates adipogenesis in human MSCs <i>in-vitro</i>, and that this process involves PPARγ and SIRT1.</p></div