Vitamin D serum levels and allergic rhinitis

In addition to its role in the regulation of calcium metabolism, vitamin D has a number of immunological effects. Several studies in children found an effect of oral supplementation on allergic sensitization but so far there are no population-based studies of vitamin D serum levels. We therefore examined 25(OH)-D(3) status in 18,224 adults of the Third National Health and Nutrition Examination Survey. There was no effect on sensitization to a single allergen while the prevalence of allergic rhinitis increased across quartile groups of current vitamin D serum levels. The association could be due to unrecognized confounding, however, could also point towards an altered metabolism or an increased sensitivity to vitamin D in allergic patients.     

An efficient integrative resampling method for gene–trait association analysis

Genetic association studies are popular for identifying genetic variants, such as single nucleotide polymorphisms (SNPs), that are associated with complex traits. Statistical tests are commonly performed one SNP at a time with an assumed mode of inheritance such as recessive, additive, or dominant genetic model. Such analysis can result in inadequate power when the employed model deviates from the underlying true genetic model. We propose an integrative association test procedure under a generalized linear model framework to flexibly model the data from the above three common genetic models and beyond. A computationally efficient resampling procedure is adopted to estimate the null distribution of the proposed test statistic. Simulation results show that our methods maintain the Type I error rate irrespective of the existence of confounding covariates and achieve adequate power compared to the methods with the true genetic model. The new methods are applied to two genetic studies on the resistance of severe malaria and sarcoidosis.     

Propensity scores using missingness pattern information: a practical guide

Electronic health records are a valuable data source for investigating health-related questions, and propensity score analysis has become an increasingly popular approach to address confounding bias in such investigations. However, because electronic health records are typically routinely recorded as part of standard clinical care, there are often missing values, particularly for potential confounders. In our motivating study—using electronic health records to investigate the effect of renin-angiotensin system blockers on the risk of acute kidney injury—two key confounders, ethnicity and chronic kidney disease stage, have 59% and 53% missing data, respectively. The missingness pattern approach (MPA), a variant of the missing indicator approach, has been proposed as a method for handling partially observed confounders in propensity score analysis. In the MPA, propensity scores are estimated separately for each missingness pattern present in the data. Although the assumptions underlying the validity of the MPA are stated in the literature, it can be difficult in practice to assess their plausibility. In this article, we explore the MPA's underlying assumptions by using causal diagrams to assess their plausibility in a range of simple scenarios, drawing general conclusions about situations in which they are likely to be violated. We present a framework providing practical guidance for assessing whether the MPA's assumptions are plausible in a particular setting and thus deciding when the MPA is appropriate. We apply our framework to our motivating study, showing that the MPA's underlying assumptions appear reasonable, and we demonstrate the application of MPA to this study.     

Quantifying the bias due to observed individual confounders in causal treatment effect estimates

It is often of interest to use observational data to estimate the causal effect of a target exposure or treatment on an outcome. When estimating the treatment effect, it is essential to appropriately adjust for selection bias due to observed confounders using, for example, propensity score weighting. Selection bias due to confounders occurs when individuals who are treated are substantially different from those who are untreated with respect to covariates that are also associated with the outcome. A comparison of the unadjusted, naive treatment effect estimate with the propensity score adjusted treatment effect estimate provides an estimate of the selection bias due to these observed confounders. In this article, we propose methods to identify the observed covariate that explains the largest proportion of the estimated selection bias. Identification of the most influential observed covariate or covariates is important in resource-sensitive settings where the number of covariates obtained from individuals needs to be minimized due to cost and/or patient burden and in settings where this covariate can provide actionable information to healthcare agencies, providers, and stakeholders. We propose straightforward parametric and nonparametric procedures to examine the role of observed covariates and quantify the proportion of the observed selection bias explained by each covariate. We demonstrate good finite sample performance of our proposed estimates using a simulation study and use our procedures to identify the most influential covariates that explain the observed selection bias in estimating the causal effect of alcohol use on progression of Huntington's disease, a rare neurological disease.     

Impact of Pattern A Behavior on Ischemic Heart Disease when Controlling for Conventional Risk Indicators

Abstract

The presence of Pattern A behavior was assessed by means of the Structured Interview in three groups of Swedish men, 50 with manifest ischemic heart disease (IHD), 50 with risk indicators for IHD and fifty healthy men. They were also examined for presence of hypertension, hyperlipidemia, hyperglycemia, obesity, impaired pulmonary function, smoking and alcohol consumption.

The relative risk of having developed clinical IHD, associated with the presence of Pattern A behavior was found to be four times greater with than without such behavior. When conventional risk indicators were controlled for, by means of a multivariate confounder score, this relative risk was reduced to 2.7.     

Tracheostomy and mortality in patients with severe burns: A nationwide observational study

Background

Tracheostomy is often performed in patients with severe burns who are undergoing prolonged mechanical ventilation. However, the appropriate timing of tracheostomy and its effect on mortality remain unknown. The aim of this study was to determine whether tracheostomy can reduce mortality in patients with severe burns.

Ultrasonographic measurements of the ulnar nerve at the elbow: role of confounders.

OBJECTIVE: The purpose of this study was to identify factors confounding high-resolution ultrasonographic measurements of the ulnar nerve to test their influence when discriminating between limbs affected and unaffected by ulnar nerve entrapment (UNE) at the elbow. METHODS: High-resolution ultrasonographic measurements of ulnar nerve dimensions at the elbow were compared between 2 groups of subjects: symptomatic and asymptomatic for UNE. Rank analysis of covariance regression tests were performed to determine whether significant differences existed between the 2 groups. The changing coefficient method (using rank analysis of covariance tests) was used to test for potential confounding effects of age, weight, height, body mass index, sex, limb sidedness, limb handedness, and nerve mobility. These tests were repeated for each measurement while controlling for the identified confounders. Exact 2-tailed Wilcoxon signed rank tests were performed to test for significant differences between measurements of the diameter of the ulnar nerve with the elbow in full extension and full flexion. RESULTS: Age, weight, body mass index, sex, and elbow position were shown to have confounding influences on high-resolution ultrasonographic measurements of the ulnar nerve. No confounding effect was apparent for limb sidedness or dominance. Cross-sectional area and long-axis diameter measurements demonstrated significant differences between nerves with and without UNE after controlling for confounders. CONCLUSIONS: Two cross-sectional measurements (area and maximum cross-sectional diameter) of the ulnar nerve, made at the level of the medial epicondyle, were found to be robust discriminators between nerves with and without UNE. In the absence of normative reference values of the ulnar nerve, the contralateral limb may be used as the comparative control.