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G Molenberghs

Publications and source records attributed to G Molenberghs.

At least 19 recordsLinked to original sources
PubMed2006

Approaches to handling incomplete data in family-based association testing.

The high throughput of data arising from the complete sequence of the human genome has left statistical geneticists with a rich and extensive information source. The wide availability of software and the increase in computing power has improved the possibilities to access and process such data. One problem is incompleteness of the data: unobserved or partially observed data points due to technical reasons or reasons associated with the patient's status or erroneous measurements of phenotype or genotype, to name a few. When not properly accounted for, these sources of incompleteness may seriously jeopardize the credibility of results from analyses. In this paper we provide some perspectives on the occurrence and analysis of different forms of incomplete data in family-based genetic association testing.

Data Interpretation, Statistical↗
PubMed2006

Model selection for incomplete and design-based samples.

The Akaike information criterion, AIC, is one of the most frequently used methods to select one or a few good, optimal regression models from a set of candidate models. In case the sample is incomplete, the naive use of this criterion on the so-called complete cases can lead to the selection of poor or inappropriate models. A similar problem occurs when a sample based on a design with unequal selection probabilities, is treated as a simple random sample. In this paper, we consider a modification of AIC, based on reweighing the sample in analogy with the weighted Horvitz-Thompson estimates. It is shown that this weighted AIC-criterion provides better model choices for both incomplete and design-based samples. The use of the weighted AIC-criterion is illustrated on data from the Belgian Health Interview Survey, which motivated this research. Simulations show its performance in a variety of settings.

Adult↗
PubMed2006

Modelling age-dependent force of infection from prevalence data using fractional polynomials.

The force of infection is one of the primary epidemiological parameters of infectious diseases. For many infectious diseases it is assumed that the force of infection is age-dependent. Although the force of infection can be estimated directly from a follow up study, it is much more common to have cross-sectional seroprevalence data from which the prevalence and the force of infection can be estimated. In this paper, we propose to model the force of infection within the framework of fractional polynomials. We discuss several parametric examples from the literature and show that all of these examples can be expressed as special cases of fractional polynomial models. We illustrate the method on five seroprevalence samples, two of Hepatitis A, and one of Rubella, Mumps and Varicella.

Adolescent↗
PubMed2006

Evidence for a substantial role of sharing of injecting paraphernalia other than syringes/needles to the spread of hepatitis C among injecting drug users.

In industrialized countries, transmission of hepatitis C occurs primarily through injecting drug use. Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of other injecting paraphernalia is increasing. In this paper, the independent effects of sharing paraphernalia other than syringes/needles have been estimated. The prevalence and force of infection were modelled using three serological data sets from drug users in three centres in Belgium as a function of the sharing behaviour. It was found that sharing of materials other than syringes/needles indeed seemed to contribute substantially to the spread of hepatitis C among injecting drug users.

Adolescent↗
PubMed2005

Risk factors for bovine herpesvirus-1 seropositivity.

This paper reports the investigation of risk factors for bovine herpesvirus-1-seropositivity, based on a cluster-sample survey of the Belgian cattle population. This serosurvey was carried out in 1998 in 309 randomly selected unvaccinated herds of all types (dairy, mixed and beef) were all bovids (N = 11,284) were sampled. Older and male cattle had higher seroprevalence. Origin (homebred or purchased) and herd size interacted; for smaller herds (< or = 50 cattle on the premises), purchase status and larger herd size were risk factors, whereas these effects were not observed for larger herds.

Age Factors↗
PubMed2005

The effects of foot disease on quality of life: results of the Achilles Project.

BACKGROUND: Foot diseases have a high prevalence in the general population, but their impact on quality of life has not been assessed in large-scale studies. The Achilles Project surveyed foot disease in patients visiting their primary care physician or dermatologist. METHODS: A total of 43 593 patients were asked about the impact of their condition on their quality of life: pain, discomfort in walking, limitations in daily activities, and embarrassment. RESULTS: Overall, 52.5% of patients had some aspect of their quality of life affected by their foot disease. More specifically, 30.7% of patients experienced pain, 40.3% had discomfort in walking, 19.6% had their daily activities limited, and 27.3% were embarrassed. The survey indicated a larger impact of foot disease on the quality of life of women vs. men in all categories, except for daily activities. Similarly, the elderly (> or = 65 years) were more affected by their foot disease, although they suffered no more embarrassment than other age groups. Participation in sports seemed to lower the proportion of patients who had their quality of life adversely affected. Non-fungal foot diseases, particularly ulcer and gangrene, are more likely to cause pain, discomfort in walking and limit daily activities, than fungal diseases. CONCLUSIONS: In general, non-fungal foot diseases caused pain, discomfort in walking and limitations in daily activities in more patients than fungal foot diseases, but a higher proportion of patients with fungal foot diseases were embarrassed by their condition than patients with non-fungal foot diseases. The study found that the impact of foot disease on quality of life may be greater than previously suggested. Given that effective treatments are available, routine examination of patients' feet by dermatologists and primary care physicians may help to reduce the burden of these foot conditions.

Activities of Daily Living↗
PubMed2003

Geographical differences in cancer incidence in the Belgian province of Limburg.

Correctly addressing the questions of worried citizens with respect to possible clusters of cancer occurrence requires a risk communication strategy that is informed by a previously established analytical procedure. The aim of this study was to analyse cancer registration data in order to identify municipalities or clusters of municipalities with an increased incidence of one or more cancer types, adjusted for background characteristics at the same level. Ideally, the approach is proactive, straightforward, and easy for untrained citizens to follow and imprecision effects are taken into account. For all municipalities and most cancers, all relevant calculations were performed proactively and all methods and decision thresholds were defined beforehand. For each municipality, standardised incidence ratios (SIRs) were calculated and smoothed using a Poisson-gamma (PG) and a conditional autoregressive (CAR) model. Clusters were confirmed using the Spatial scan statistic of Kulldorff. Identified clusters were tested for possible confounders using all information that was available for each municipality. The Limburg Cancer Registry, serving the population of the Belgian province of Limburg (n=781 759) was used. We identified a possible cluster of increased prostate cancer incidence (smoothed SIRs around 1.2) and a cluster of increased bladder cancer incidence in males that included seven municipalities with CAR-smoothed SIRs between 1.5 and 2.1. SIRs followed a more or less circular decrease around the centre that was situated in Alken and Hasselt, the provincial capital. Bladder cancer incidence was positively related to an index of socio-economic status (SES) per municipality. No relationship was found with the other indexes that were available. 82% of all bladder cancers were transitional cell carcinomas (TCC). A repeated analysis based on TCCs only resulted in similar results with CAR-smoothed relative risks that tended to be even higher in the cluster zone. A pre-emptive analysis of possible cancer incidence clustering on the municipality level proved to be feasible.

Belgium↗
PubMed2003

Design-based analysis of surveys: a bovine herpesvirus 1 case study.

This paper critically assesses the design implications for the analysis of surveys of infections. It indicates the danger of not accounting for the study design in the statistical investigation of risk factors. A stratified design often implies an increased precision while clustering of infection results in a decreased precision. Through pseudo-likelihood estimation and linearisation of the variance estimator, the design effects can be taken into account in the analysis. The intra-cluster-correlation can be investigated through a logistic random effect model and a generalised estimating equation (GEE), allowing the investigation of the extent of spread of infections in a herd (cluster). The advantage of using adaptive Gaussian quadrature in a logistic random effect model is discussed. Applicable software is briefly reviewed. The methods are illustrated with data from a bovine herpesvirus 1 (BHV-1) serosurvey of Belgian cattle.

Animals↗
PubMed2003

High prevalence of foot diseases in Europe: results of the Achilles Project.

OBJECTIVE: To provide an insight into the prevalence of foot disease in Europe, and to include an assessment of the prevalence of predisposing factors and their correlation with foot disease. DESIGN: Large population-based survey conducted in 16 European countries. SETTING: The project consisted of two parts (study I and study II), in which all patients presenting to general practitioners and dermatologists over a defined time period were invited to participate. Patients. In study I, 70,497 patients presenting to dermatologists or general practitioners were recruited, and in study II 19,588 patients presenting to dermatologists were recruited. MAIN OUTCOME MEASURE: The feet of all participants were examined for signs of foot disease. The assessors also recorded relevant details such as the age and sex of patients, and the presence of predisposing factors for foot disease. In addition, patients in study II were offered a free mycological examination of the toenails and skin on the feet. RESULTS: In study I, 57.0% of patients had at least one foot disease. In study II, 61.3% had at least one foot disease. The proportions of patients with fungal foot disease and non-fungal foot disease in study I were 34.9% and 38.4%, respectively, and in study II were 40.6% and 41.7%, respectively. Orthopedic conditions and metatarsal corns were the most frequently reported non-fungal foot diseases, and onychomycosis and tinea pedis were the most frequently observed fungal infections. CONCLUSIONS: This large-scale survey suggests that the prevalence of fungal and non-fungal foot disease is higher than previously estimated.

Adult↗
PubMed2003

Hepatitis B in St Petersburg, Russia (1994-1999): incidence, prevalence and force of infection.

Hepatitis B (HB) is thought to be an expanding health problem in Russia. The incidence of infection was estimated from mandatorily reported HB cases in St Petersburg. The two-sided t-test for independent samples and the LOESS (locally-weighted regression) smoother were used to compare the age at infection for symptomatic, asymptomatic and chronic infections, by gender. The force of infection was estimated from seroprevalence data (907 sera taken in 1999) using a newly developed nonparametric method based on local polynomials, as well as an earlier method based on isotonic regression and kernel smoothers. With the local polynomial method, pointwise confidence intervals (95%) were constructed by bootstrapping. On average, men contracted HB infection at a significantly younger age than women (in 1999, 21.8 vs 22.7 years, respectively). The overall male to female ratio was 1.92. In 1999 the overall incidence almost doubled compared with the preceding years and tripled among the age groups with highest incidence (15-29-year olds: 85% of cases in 1999). The incidence increase was associated with a lower average age at infection (24.1 years in 1994 vs 22.1 years in 1999). The age and gender-specific force of infection estimates generally confirmed the incidence estimates and emphasized the usefulness of local polynomials to do this. Hence HB transmission in St Petersburg occurs mainly in young adults. The dramatic increase of infections in 1999 was probably due to injecting drug use. Without intervention, HB virus is expected to continue to spread rapidly with a greater proportion of female infections caused by sexual transmission. These trends may also provide an indication for HIV transmission.

Adolescent↗
PubMed2002

Prostate-specific antigen screening coverage and prostate cancer incidence rates in the Belgian province of Limburg in 1996-1998.

According to the 1996-1998 cancer incidence report of the cancer registry of the Belgian province of Limburg (LIKAR), prostate cancer is the most common cancer in men with a crude invasive cancer incidence rate of 123.7 per 100000 person-years (125.4 and 81.8 after standardization for the European and the world standard population). In a study on geographical differences between the occurrence of cancers in municipalities, prostate cancer standardized incidence rates (SIRs) were significantly higher in a number of municipalities, with mean relative risks of 1.2 and 1.3 after full Bayesian smoothing. We hypothesized that prostate cancer incidence rates are largely influenced by the prostate-specific antigen (PSA) screening policy of local physicians and that differences between municipalities are more informative about local screening habits then about real differences in cancer occurrence. The aim of this study was to test this hypothesis by relating local prostate cancer SIRs to the PSA screening coverage of the population of men in each municipality. The SIRs of prostate cancer in 1996-1998 for each municipality were provided by LIKAR. They related to all histologically or cytologically proven new invasive prostate cancers during these years. For each municipality, PSA coverage data were provided by the largest sick fund of the region. Coverage was defined as the proportion of men above the age of 40 that was tested at least once within the registration period. The SIR of each municipality (dependent variable) was related to the age-standardized corresponding coverage (independent variable) by linear regression and was adjusted for the number of inhabitants per municipality: log (standardized incidence rate) = 164 + 602 * (standardized PSA coverage), = 0.12. The model explained 6% of the variance in incidence. In conclusion, in this study no statistically significant relationship was identified between PSA coverage and prostate cancer incidence rate per municipality. This could result from no such relationship existing or from low statistical power.

Adult↗
PubMed2002

Analysing longitudinal continuous quality of life data with dropout.

Quality of Life (QL) is becoming an increasingly popular endpoint in phase III cancer clinical trials. However, there is still no agreement as to what is the optimal approach to analysis. In this paper we review some concepts which should be considered during a QL analysis. We present two modelling approaches that have been substantively developed in other research fields: selection models and pattern-mixture models. These models are compared using data from an EORTC clinical trial in poor-prognosis prostate cancer patients. It is illustrated that, although selection models and pattern mixture are probabilistically equivalent, they may shed completely different light on data from a modeller's point of view.

Clinical Trials, Phase III as Topic↗
PubMed2001

Sensitivity analysis of longitudinal binary quality of life data with drop-out: an example using the EORTC QLQ-C30.

Analysing quality of life data (QOL) may be complicated for several reasons. Quality of life data not only involves repeated measures but is also usually collected on ordered categorical responses. In addition, it is evident that not all patients provide the same number of assessments, due to attrition caused by death or other medical reasons. In the recent statistical literature, increasing attention is given to methods which can handle non-continuous outcomes in the presence of missing data. The aim of this paper is to investigate the effect on statistical conclusions of applying different modelling techniques to QOL data generated from an EORTC phase III trial. Treatment effects and treatment differences are of major concern. First, a random-effects model is fitted, relating a binary longitudinal response (derived from the physical functioning scale of the QLQ-C30) to several covariates. In a second approach, marginal models are fitted, retaining the response variable and the mean structure used before. The fitted marginal models only differ with respect to the considered estimation procedure: generalized estimating equations (GEE); weighted generalized estimating equations (WGEE), and maximum likelihood (ML).

Antibiotics, Antineoplastic↗
PubMed2001

Evaluation of surrogate endpoints in randomized experiments with mixed discrete and continuous outcomes.

A statistical definition of surrogate endpoints as well as validation criteria was first presented by Prentice. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs pointed to inadequacies of these criteria and suggested a new definition of surrogacy based on (i) the relative effect linking the overall effect of treatment on both endpoints and (ii) an individual-level measure of agreement between both endpoints. Using data from a randomized trial, they showed how a potential surrogate endpoint can be studied using a joint model for the surrogate and the true endpoint. Whereas Buyse and Molenberghs restricted themselves to the fairly simple cases of jointly normal and jointly binary outcomes, we treat the situation where the surrogate is binary and the true endpoint is continuous, or vice versa. In addition, we consider the case of ordinal endpoints. Further, Buyse et al. extended the approach of Buyse and Molenberghs to a meta-analytic context. We will adopt a similar approach for responses of a mixed data type.

Anticholesteremic Agents↗
PubMed2001

Modelling bivariate ordinal responses smoothly with examples from ophthalmology and genetics.

A non-parametric implementation of the bivariate Dale model (BDM) is presented as an extension of the generalized additive model (GAM) of Hastie and Tibshirani. The original BDM is an example of a bivariate generalized linear model. In this paper smoothing is introduced on the marginal as well as on the association level. Our non-parametric procedure can be used as a diagnostic tool for identifying parametric transformations of the covariates in the linear BDM, hence it also provides a kind of goodness-of-fit test for a bivariate generalized linear model. Cubic smoothing spline functions for the covariates are estimated by maximizing a penalized version of the log-likelihood. The method is applied to two studies. The first study is the classical Wisconsin Epidemiologic Study of Diabetic Retinopathy. The second study is a twin study, where the association between the elements of twin pairs is of primary interest. The results show that smoothing on the association level can give a significant improvement to the model fit.

Adolescent↗
PubMed2001

Sexual dysfunction associated with protease inhibitor containing highly active antiretroviral treatment.

BACKGROUND: A high proportion of individuals receiving highly active antiretroviral treatment (HAART) complain of sexual dysfunction (SD), encompassing a lack of desire or erectile dysfunction. OBJECTIVE: To determine whether SD was associated with particular components of the HAART regimens and to identify risk factors for the development of SD in patients on HAART. METHODS: A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. A total of 904 individuals currently receiving antiretroviral agents were included in the analyses. RESULTS: A decrease in sexual interest was significantly more frequently reported by subjects (men and women) using HAART containing protease inhibitors (PI) (308/766, 40%), compared with PI-naive patients (22/138, 16%; OR 3.55; 95% CI 2.15--5.89). In addition, a significantly larger number of PI-experienced men reported a decrease in sexual potency (216/628, 34%) compared with PI-naive men (12/99, 12%; OR 2.56; 95% CI 1.33--5.03). In multivariate analyses the following factors were associated with a decrease in sexual interest: a current PI-containing regimen, a history of a PI regimen, symptomatic HIV infection, age and homosexual contact as HIV transmission mode. Factors associated with a decrease in sexual potency were: current use of a PI-containing regimen, symptomatic HIV disease, age and the use of tranquillisers. CONCLUSION: SD appears to be a common side-effect of HAART regimens containing a PI. The potential association between SD and other side-effects of HAART, such as lipodystrophy syndrome and neuropathy, should be investigated further.

Adult↗
PubMed2001

Repeated-measures models to evaluate a hepatitis B vaccination programme.

In 1985-1986, a hepatitis B vaccination programme was conducted in a Belgian institution for the mentally handicapped. A group of 97 residents was followed up for 11 years in order to characterize the long-term persistence of hepatitis B antibodies after vaccination. This paper proposes the use of linear mixed-effects models to account for serial correlation and between-individual heterogeneity in the data, while adjusting the analysis for various individual characteristics and important risk factors in the response to vaccination. We propose several model building strategies and focus on the prediction of future levels of antibodies.

Belgium↗