
Claes, G.; THIJS, Herbert; BRAEKERS, Roel; Orlandini, M.; Sente, F.; BULENS, Paul
Purpose/Objective(s): Currently there is no general consensus on the prevention or treatment of radiation dermatitis, a common side effect of radiation therapy. The primary objective of this retrospective study was to compare hydroactive colloid gel to dexpanthenol for the treatment of grade 1 skin erythema resulting from radiation therapy. A secondary objective was to investigate the relationship between breast size and the development of moist desquamation. Materials/methods: Patients undergoing radiation therapy for breast cancer applied dexpanthenol during the first 12 days of treatment. Acute skin toxicity was scored with a modified EORTC scoring system. Two groups of patients were studied:...

Hompes, D.; Tiek, J.; Wolthuis, A.; FIEUWS, Steffen; Penninckx, F.; Van Cutsem, E.; D'Hoore, A.
Adequate estimation of the potential benefits of 'adjuvant' hyperthermia and intraperitoneal chemotherapy (HIPEC) in T4 patients through assessment of the burden of peritoneal carcinomatosis (PC) in T4 tumors and the risk of PC as the only metastatic site. Analysis of prospectively collected data on patients who underwent surgery for colon cancer (Jan 2004Jan 2007). About 379 patients (M/F = 204/175) were included, with a median age of 71.8 years (range 35.495.0): 39 stage I, 126 stage II, 89 stage III, 116 stage IV disease (+9 with unknown stage). The median followup was 34.8months [range 0.079.4]. The 3 and 5year overall...

Dobly, Alexandre; Yzoard, Chloe; Cochez, Christel; Ducoffre, Genevieve; AERTS, Marc; Roels, Stefan; Heyman, Paul
The transmission of pathogens to susceptible hosts is dependent on the vector population dynamics. In Europe, bank voles (Myodes glareolus) carry Puumala hantavirus, which causes nephropathia epidemica (NE) in humans. Fluctuations in bank vole populations and epidemics in humans are correlated but the main factors influencing this relationship remain unclear. In Belgium, more NE cases are reported in spring than in autumn. There is also a higher incidence of human infections during years of large vole populations. This study aimed to better understand the link between virus prevalence in the vector, vole demography, habitat quality, and human infections. Three rodent...

Andraud, Mathieu; HENS, Niel; Marais, Christiaan; Beutels, Philippe
Dengue is a vectorborne disease recognized as the major arbovirose with four immunologically distant dengue serotypes coexisting in many endemic areas. Several mathematical models have been developed to understand the transmission dynamics of dengue, including the role of crossreactive antibodies for the four different dengue serotypes. We aimed to review deterministic models of dengue transmission, in order to summarize the evolution of insights for, and provided by, such models, and to identify important characteristics for future model development. We identified relevant publications using PubMed and ISI Web of Knowledge, focusing on mathematical deterministic models of dengue transmission. Model assumptions were...

Thilakarathne, Pushpike; Shkedy, Ziv; Lin, Dan
This package contains the functions that can be used to analyze the PamChip microarray data. The package is mainly useful in fitting semiparametric mixed effects models while accommodating various types of mean structures and correlation structures present in Kinase activity profiling experiments. The package can be used to visualize, cleaning Pam Chip data. And also it can be used in model fitting, velocity estimating, and testing the estimated velocities between the groups. The PamGeneMixed package is built up as a software implementation for the paper titled The Use of Semiparametric Mixed Models to Analyze PamChip Peptide Array Data: an Application...

Aregay, Mehreteab; Shkedy, Ziv; Molenberghs, Geert
In sets of count data, the sample variance is often considerably larger or smaller than the sample mean, known as a problem of over or underdispersion. The focus is on hierarchical Bayesian modeling of such longitudinal count data. Two different models are considered. The first one assumes a Poisson distribution for the count data and includes a subjectspecific intercept, which is assumed to follow a normal distribution, to account for subject heterogeneity. However, such a model does not fully address the potential problem of extraPoisson dispersion. The second model, therefore, includes also random subject and time dependent parameters, assumed to...

Doumen, Sarah; Masui, Chris; Broeckmans, Jan; Molenberghs, Geert
Alhoewel intuïtief verondersteld wordt dat meer studietijd gerelateerd is aan betere examenresultaten, blijkt dit niet altijd teruggevonden te worden in onderzoek. Aan onze universiteit werd de voorbije jaren met een nieuw meetinstrument verder onderzoek gevoerd naar a) de betekenis van studietijd voor examenresultaten van eerstejaarsstudenten (naast en bovenop andere relevante variabelen) en b) student en vakkenmerken die studietijd stimuleren. Onze belangrijkste bevindingen worden hier op een rijtje gezet.

Mallinckrodt, C. H.; Lin, Q.; Lipkovich, I.; Molenberghs, G.
An important evolution in the missing data arena has been the recognition of need for clarity in objectives. The objectives of primary focus in clinical trials can often be categorized as assessing efficacy or effectiveness. The present investigation illustrated a structured framework for choosing estimands and estimators when testing investigational drugs to treat the symptoms of chronic illnesses. Key issues were discussed and illustrated using a reanalysis of the confirmatory trials from a new drug application in depression. The primary analysis used a likelihoodbased approach to assess efficacy: mean change to the planned endpoint of the trial assuming patients stayed...

Janssens, Mark; Molenberghs, Geert; Kerstens, Rene
Missing data in clinical trials is a wellknown problem, and the classical statistical methods used can be overly simple. This case study shows how wellestablished missing data theory can be applied to efficacy data collected in a longterm openlabel trial with a discontinuation rate of almost 50%. Satisfaction with treatment in chronically constipated patients was the efficacy measure assessed at baseline and every 3?months postbaseline. The improvement in treatment satisfaction from baseline was originally analyzed with a paired ttest ignoring missing data and discarding the correlation structure of the longitudinal?data. As the original analysis started from missing completely at random...

Ghebretinsae, Aklilu Habteab; Faes, Christel; Molenberghs, Geert; Geys, Helena; Van der Leede, BasJan
Multivariate longitudinal or clustered data are commonly encountered in clinical trials and toxicological studies. Typically, there is no single standard endpoint to assess the toxicity or efficacy of the compound of interest, but coprimary endpoints are available to assess the toxic effects or the working of the compound. Modeling the responses jointly is thus appealing to draw overall inferences using all responses and to capture the association among the responses. NonGaussian outcomes are often modeled univariately using exponential family models. To accommodate both the overdispersion and hierarchical structure in the data, Molenberghs et al. A family of generalized linear models...

Iddi, Samuel; Molenberghs, Geert
The sharedparameter model and its socalled hierarchical or randomeffects extension are widely used joint modeling approaches for a combination of longitudinal continuous, binary, count, missing, and survival outcomes that naturally occurs in many clinical and other studies. A random effect is introduced and shared or allowed to differ between two or more repeated measures or longitudinal outcomes, thereby acting as a vehicle to capture association between the outcomes in these joint models. It is generally known that parameter estimates in a linear mixed model (LMM) for continuous repeated measures or longitudinal outcomes allow for a marginal interpretation, even though a...

Bilcke, J.; OGUNJIMI, Benson; Marais, C.; de Smet, F.; Callens, M.; CALLAERT, Kris; van Kerschaver, E.; Ramet, J.; van Damme, P.; Beutels, P.
Varicellazoster virus causes chickenpox (CP) and after reactivation herpes zoster (HZ). Vaccines are available against both diseases warranting an assessment of the prevaccination burden of disease. We collected data from relevant Belgian databases and performed five surveys of CP and HZ patients. The rates at which a general practitioner is visited at least once for CP and HZ are 346 and 378/100 000 personyears, respectively. The average CP and HZ hospitalization rates are 5.3 and 14.2/100 000 personyears respectively. The direct medical cost for HZ is about twice as large as the direct medical cost for CP. The qualityadjusted life...

OMELKA, Marek; VERAVERBEKE, Noel; Gijbels, Irene
This paper is concerned with inference about the dependence or association between two random variables conditionally upon the given value of a covariate. A way to describe such a conditional dependence is via a conditional copula function. Nonparametric estimators for a conditional copula then lead to nonparametric estimates of conditional association measures such as a conditional Kendall's tau. The limiting distributions of nonparametric conditional copula estimators are rather involved. In this paper we propose a bootstrap procedure for approximating these distributions and their characteristics, and establish its consistency. We apply the proposed bootstrap procedure for constructing confidence intervals for conditional...

CREEMERS, An; AERTS, Marc; HENS, Niel; MOLENBERGHS, Geert
Missing data often occur in regression analysis. Imputation, weighting, direct likelihood, and Bayesian inference are typical approaches for missing data analysis. The focus is on missing covariate data, a common complication in the analysis of sample surveys and clinical trials. A key quantity when applying weighted estimators is the mean score contribution of observations with missing covariate(s), conditional on the observed covariates. This mean score can be estimated parametrically or nonparametrically by its empirical average using the complete case data in case of repeated values of the observed covariates, typically assuming categorical or categorized covariates. A nonparametric kernel based estimator...

Vieira, Afranio M. C.; Leandro, Roseli A.; Demetrio, Clarice G. B.; MOLENBERGHS, Geert
Joint generalized linear models and double generalized linear models (DGLMs) were designed to model outcomes for which the variability can be explained using factors and/or covariates. When such factors operate, the usual normal regression models, which inherently exhibit constant variance, will underrepresent variation in the data and hence may lead to erroneous inferences. For count and proportion data, such noise factors can generate a socalled overdispersion effect, and the use of binomial and Poisson models underestimates the variability and, consequently, incorrectly indicate significant effects. In this manuscript, we propose a DGLM from a Bayesian perspective, focusing on the case of...

VeeremanWauters, G.; Staelens, S.; Van de Broek, H.; Plaskie, K.; Wesling, F.; Roger, L. C.; McCartney, A. L.; ASSAM NKOUIBERT, Pryseley
Objectives: This randomized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides (GOS), oligofructose, and longchain inulin (fructooligosaccharides, FOS) in formula. Methods: Subjects were randomized to Orafti Synergy1 (50 oligofructose: 50 FOS) 0.4 g/dL or 0.8 g/dL, GOS: FOS (90: 10) 0.8 g/dL, or a standard formula according to Good Clinical Practice guidelines. A breastfed group was included for comparison. Outcome parameters were weight, length, intake, stool characteristics, crying, regurgitation, vomiting, adverse events, and fecal bacterial population counts. Statistical analyses used nonparametric tests. Results: During the first month of life, weight, length, intake, and crying increased...

De Preter, Vicky; HABTEAB GHEBRETINSAE, Aklilu; CORTINAS ABRAHANTES, Jose; Windey, Karen; Rutgeerts, Paul; Verbeke, Kristin
Scope: Hypothesisdriven approaches have mainly focused on the quantification of SCFAs as mediators of beneficial effects of synbiotics. However, the emergence of metabolite profiling strategies allows to evaluate the colonic metabolism from a topdown approach. In the present study, we evaluated the impact of a synbiotic combination on fecal metabolite profiles. Methods and results: A synbiotic combination ( Lactobacillus casei Shirota cells+oligofructoseenriched inulin) was evaluated in nine healthy volunteers. Before the start, during and after 4wk treatment, fecal samples were obtained. GCMS technology was applied to analyze the volatile metabolites. Application of a Type III test revealed that the metabolite...

MOLENBERGHS, Geert; VERBEKE, Geert; Demetrio, Clarice G. B.; Vieira, Afranio M. C.
NonGaussian outcomes are often modeled using members of the socalled exponential family. Notorious members are the Bernoulli model for binary data, leading to logistic regression, and the Poisson model for count data, leading to Poisson regression. Two of the main reasons for extending this family are (1) the occurrence of overdispersion, meaning that the variability in the data is not adequately described by the models, which often exhibit a prescribed meanvariance link, and (2) the accommodation of hierarchical structure in the data, stemming from clustering in the data which, in turn, may result from repeatedly measuring the outcome, for various...

OGUNJIMI, Benson; Peeters, Dieter; HENS, Niel; Malfait, Ronald; Van Tendeloo, Viggo; Van Damme, Pierre; Beutels, Philippe; Smits, Evelien
Clinical and scientific work routinely relies on antecubital venipunctures for hematological, immunological or other analyses on blood. This study tested the hypothesis that antecubital veins can be considered to be a good proxy for other sampling sites. Using a hematocytometer and a flow cytometer, we analyzed the cell counts from samples coming from the radial artery, the dorsal hand veins and the antecubital veins from 18 volunteers. Most surprisingly, we identified the greatest difference not to exist between arterial and venous circulation, but between the distal (radial artery & dorsal hand veins) and proximal (antecubital veins) sampling sites. Naive T...

Nawrot, Tim S.; Vos, Robin; Jacobs, Lotte; Verleden, Stijn E.; Wauters, Shana; Mertens, Veerle; Dooms, Christophe; Hoet, Peter H.; Van Raemdonck, Dirk E.; Faes, Christel; Dupont, Lieven J.; Nemery, Benoit; Verleden, Geert M.; Vanaudenaerde, Bart M.
Background: Approximately half of all patients who underwent a lung transplantation suffer from bronchiolitis obliterans syndrome(BOS), the clinical correlate of chronic rejection, within 5 years after transplantation. This prevalence is much higher than for other solid organ transplantations, possibly due to the lung's direct contact with the environment. The authors assessed the association between proximity of the home to major roads and BOS and mortality in a cohort of patients after lung transplantation. Methods: The authors calculated hazard ratios for BOS and mortality in relation to proximity of the home to major roads, adjustng for relevant covariables, in 288 patients...