Vaclav Fidler

Hand-held myometry: reference values.

In thirteen major muscle groups of 50 healthy females and 50 males, aged 20-60 years, maximum voluntary contraction was measured with a hand-held dynamometer. The intrasession variation, the left-right variation, and the fifth and fiftieth centile values were calculated. The ratio of two observations within one session ranged from 0.85 to 1.18 and the ratio of left to right ranged from 0.82 to 1.22 (95% reference limits). In 20 volunteers the repeatability was tested after one week. The ratio of averages of three measurements in two successive weeks ranged from 0.82 to 1.23 (95% reference limits). There were only small differences between muscle groups concerning these ratios. A significant relation with age and weight/Quetelet Index could be demonstrated in some muscle groups. The mean strength of females is approximately two thirds of the strength of males. The data may be useful as reference values in the application of hand-held myometry.

The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis

Background: Acute generalized exanthematous pustulosis (AGEP) represents a severe, acute, pustular skin reaction that is most often induced by drugs. AGEP can be difficult to differentiate from generalized pustular psoriasis (GPP) both clinically and histopathologically. We present a systematic description of the histopathological spectrum of AGEP and GPP with a focus on discriminating features.

The Groningen LCPUFA study : no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years

Long-chain PUFA (LCPUFA) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy, but uncertainty exists regarding effects after 6 months. The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age. A prospective, double-blind, randomised control study was performed in two groups of healthy term infants: a control group with standard formula (n 169) and a LCPUFA-supplemented group (LF; n 146). A breast-fed group (BF; n 159) served as a reference. At age 9 years, children were neurologically assessed according to Touwen, resulting in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction (MND). Information on potential confounders was collected at enrollment and follow-up. Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders. Attrition (28 %) was selective: drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months. Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups. Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children. In conclusion, LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age. The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants.

Mental, psychomotor, neurologic, and behavioral outcomes of 2-year-old children born after preimplantation genetic screening: follow-up of a randomized controlled trial

OBJECTIVEnTo evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcomes in children.nnnDESIGNnProspective, assessor-blinded, follow-up study of children born to women randomly assigned to in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) with or without PGS.nnnSETTINGnUniversity Medical Center, Groningen, and Academic Medical Center, Amsterdam, the Netherlands.nnnPATIENT(S)nFifty-four PGS children and 77 controls.nnnINTERVENTION(S)nPGS.nnnMAIN OUTCOME MEASURE(S)nMental, psychomotor, neurologic, and behavioral outcomes in 2-year-old children as measured with the Bayley Scales of Infant Development, the Hempel neurologic examination, and the Child Behavior Check List.nnnRESULT(S)nThe mental, psychomotor, and behavioral outcomes at 2 years in children born after IVF with and without PGS were similar overall. The PGS children showed lower neurologic optimality scores than the control children. Scores on all tests were within the normal range.nnnCONCLUSION(S)nConception with PGS does not seem to be associated with impaired mental, psychomotor, or behavioral outcomes by age 2. However, the lower neurologic optimality scores found in the PGS children may signal less favorable long-term neurologic outcomes in PGS children. Our findings stress the need for safety evaluations with new assisted reproductive techniques before large-scale implementation.

Effects of Long-Chain Polyunsaturated Fatty Acid Supplementation of Infant Formula on Cognition and Behaviour at 9 Years of Age.

Aimu2002 Long‐chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9u2003years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy.

The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy

BACKGROUNDnDue to the growing number of children born following assisted reproduction technology, even subtle changes in the childrens health and development are of importance to society at large. The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4-18-month-old children.nnnMETHODSnIn this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development.nnnRESULTSnThe NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups.nnnCONCLUSIONSnWe found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4-18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.

Construct validity of the Infant Motor Profile: relation with prenatal, perinatal, and neonatal risk factors.

Aimu2002 The Infant Motor Profile (IMP) is a qualitative assessment of motor behaviour of infants aged 3 to 18u2003months. The aim of this study was to investigate construct validity of the IMP through the relation of IMP scores with prenatal, perinatal, and neonatal variables, including the presence of brain pathology indicated by neonatal ultrasound imaging of the brain.

Causal inference algorithms can be useful in life course epidemiology

OBJECTIVESnLife course epidemiology attempts to unravel causal relationships between variables observed over time. Causal relationships can be represented as directed acyclic graphs. This article explains the theoretical concepts of the search algorithms used for finding such representations, discusses various types of such algorithms, and exemplifies their use in the context of obesity and insulin resistance.nnnSTUDY DESIGN AND SETTINGnWe investigated possible causal relations between gender, birth weight, waist circumference, and blood glucose level of 4,081 adult participants of the Prevention of REnal and Vascular ENd-stage Disease study. The latter two variables were measured at three time points at intervals of about 3 years.nnnRESULTSnWe present the resulting causal graphs, estimate parameters of the corresponding structural equation models, and discuss usefulness and limitations of this methodology.nnnCONCLUSIONnAs an exploratory method, causal graphs and the associated theory can help construct possible causal models underlying observational data. In this way, the causal search algorithms provide a valuable statistical tool for life course epidemiological research.

The Mantel-Haenszel Procedure Revisited: Models and Generalizations

Several statistical methods have been developed for adjusting the Odds Ratio of the relation between two dichotomous variables X and Y for some confounders Z. With the exception of the Mantel-Haenszel method, commonly used methods, notably binary logistic regression, are not symmetrical in X and Y. The classical Mantel-Haenszel method however only works for confounders with a limited number of discrete strata, which limits its utility, and appears to have no basis in statistical models. Here we revisit the Mantel-Haenszel method and propose an extension to continuous and vector valued Z. The idea is to replace the observed cell entries in strata of the Mantel-Haenszel procedure by subject specific classification probabilities for the four possible values of (X,Y) predicted by a suitable statistical model. For situations where X and Y can be treated symmetrically we propose and explore the multinomial logistic model. Under the homogeneity hypothesis, which states that the odds ratio does not depend on Z, the logarithm of the odds ratio estimator can be expressed as a simple linear combination of three parameters of this model. Methods for testing the homogeneity hypothesis are proposed. The relationship between this method and binary logistic regression is explored. A numerical example using survey data is presented.

Estimating a Logistic Discrimination Functions When One of the Training Samples Is Subject to Misclassification: A Maximum Likelihood Approach.

The problem of discrimination and classification is central to much of epidemiology. Here we consider the estimation of a logistic regression/discrimination function from training samples, when one of the training samples is subject to misclassification or mislabeling, e.g. diseased individuals are incorrectly classified/labeled as healthy controls. We show that this leads to zero-inflated binomial model with a defective logistic regression or discrimination function, whose parameters can be estimated using standard statistical methods such as maximum likelihood. These parameters can be used to estimate the probability of true group membership among those, possibly erroneously, classified as controls. Two examples are analyzed and discussed. A simulation study explores properties of the maximum likelihood parameter estimates and the estimates of the number of mislabeled observations.