Risk and Clinical Significance of Idiopathic Preterm Birth in Microvillus Inclusion Disease

Microvillus inclusion disease (MVID) is a rare enteropathy caused by mutations in the MYO5B or STX3 gene. MVID is a disease that is difficult to manage with clinical heterogeneity. Therefore, knowledge about factors influencing MVID morbidity and mortality is urgently needed. Triggered by a recent study that reported a high percentage of preterm births in twelve cases of MVID, we have conducted a comprehensive retrospective study involving 88 cases of MVID with reported gestational ages. We found that moderate to late preterm birth occurred in more than half of all cases, and this was particularly prominent in MYO5B-associated MVID. Preterm birth in MVID counterintuitively correlated with higher birth weight percentiles, and correlated with higher stool outputs and a significantly shorter average survival time. Data from this study thus demonstrate an increased risk of preterm birth in MYO5B-associated MVID, with a clinical impact on morbidity and mortality. Adverse effects associated with preterm birth should be taken into account in the care of children diagnosed with MVID. Documentation of gestational age may contribute to a better prognostic risk assessment in MVID.

Correlated gamma frailty models for bivariate survival time data

Frailty models have been developed to quantify both heterogeneity as well as association in multivariate time-to-event data. In recent years, numerous shared and correlated frailty models have been proposed in the survival literature allowing for different association structures and frailty distributions. A bivariate correlated gamma frailty model with an additive decomposition of the frailty variables into a sum of independent gamma components was introduced before. Although this model has a very convenient closed-form representation for the bivariate survival function, the correlation among event- or subject-specific frailties is bounded above which becomes a severe limitation when the values of the two frailty variances differ substantially. In this article, we review existing correlated gamma frailty models and propose novel ones based on bivariate gamma frailty distributions. Such models are found to be useful for the analysis of bivariate survival time data regardless of the censoring type involved. The frailty methodology was applied to right-censored and left-truncated Danish twins mortality data and serological survey current status data on varicella zoster virus and parvovirus B19 infections in Belgium. From our analyses, it has been shown that fitting more flexible correlated gamma frailty models in terms of the imposed association and correlation structure outperforms existing frailty models including the one with an additive decomposition.

ROC Estimation from Clustered Data with an Application to Liver Cancer Data

In this article, we propose a regression model to compare the performances of different diagnostic methods having clustered ordinal test outcomes. The proposed model treats ordinal test outcomes (an ordinal categorical variable) as grouped-survival time data and uses random effects to explain correlation among outcomes from the same cluster. To compare different diagnostic methods, we introduce a set of covariates indicating diagnostic methods and compare their coefficients. We find that the proposed model defines a Lehmann family and can also introduce a location-scale family of a receiver operating characteristic (ROC) curve. The proposed model can easily be estimated using standard statistical software such as SAS and SPSS. We illustrate its practical usefulness by applying it to testing different magnetic resonance imaging (MRI) methods to detect abnormal lesions in a liver.