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PubMed2001

Two families with phenotypically different hereditary low frequency hearing impairment: longitudinal data and linkage analysis.

Two families with low frequency hearing impairment have been described previously. Family A (Danish) presented a sensorineural hearing impairment most pronounced for frequencies below 2 kHz and a pedigree typical for an autosomal dominant trait with complete penetrance (Königsmark type). Family B, originating from the Faroe Islands, showed conflicting audiological test results, making a valid classification impossible. The pedigree suggested autosomal dominant inheritance with incomplete penetrance. The objectives of the present study are to acquire longitudinal audiometric data, to clarify the mode of transmission, and to localize the mutant gene by reevaluation of the two families. The methods used are evaluation of the family history, audiological examination and linkage analysis. In family A, update of the pedigree fitted the assumption of an autosomal dominant mode of transmission. In six examined subjects audiological data were available from the previous study. The median progression over a 13-21-year period was 13.8 dB HL for the thresholds, averaged across 0.5, 1, 2 and 4 kHz and 17.5 dB HL for the thresholds, averaged across 2 and 4kHz. In family B, the probable mode of transmission is autosomal dominant with reduced penetrance. In this family no progression of the hearing impairment was found. Linkage analysis of family A showed a lod score of 3.53, indicating significant linkage to the loci DFNA6 and DFNA14 on chromosome 4, previously found to be involved in low frequency hearing impairment. Family B was not linked to the region on chromosome 4, further adding to the genetic heterogeneity in low frequency sensorineural hearing impairment.

Adult↗
PubMed2006

Analysis of longitudinal data: the integration of theoretical model, temporal design, and statistical model.

This article argues that ideal longitudinal research is characterized by the seamless integration of three elements: (a) a well-articulated theoretical model of change observed using (b) a temporal design that affords a clear and detailed view of the process, with the resulting data analyzed by means of (c) a statistical model that is an operationalization of the theoretical model. Two general varieties of theoretical models are considered: models in which the time-related change of primary interest is continuous, and those in which it is characterized by movement between discrete states. In addition, two general types of temporal designs are considered: the longitudinal panel design and the intensive longitudinal design. For each general category of theoretical models, some of the analytic possibilities available for longitudinal panel designs and for intensive longitudinal designs are discussed. The article concludes with brief discussions of two issues particularly relevant to longitudinal research--missing data and measurement--and a few words about exploratory research.

Humans↗
PubMed2004

Associations of the IL12B promoter polymorphism in longitudinal data from asthmatic patients 7 to 42 years of age.

BACKGROUND: The IL12B gene encodes the p40 chain of IL-12, a proinflammatory cytokine that antagonizes TH2 expression and hence may play a critical role in the pathogenesis of airway inflammation observed in asthma. A promoter polymorphism of the gene was recently shown to be associated with asthma severity in children but only in heterozygotes. OBJECTIVE: The aim of the present study was to test the hypothesis that the IL12B promoter polymorphism is associated with asthma susceptibility, severity, and related phenotypes in a cohort with longitudinal phenotypic data, from childhood to adulthood. METHODS: Four hundred one 7-year-old children (106 control children, 295 asthmatic children) and 83 10-year-old children with severe asthma were recruited from a 1957 birth cohort. Atopic status and respiratory functions were determined at ages 7, 10, 14, 21, 28, 35, and 42 years. At age 42 years, blood samples were taken from 244 individuals for genotyping and the determination of plasma IgE levels and PHA- and house dust mite-induced IFN-gamma responses. Genotyping was done by the PCR restriction fragment length polymorphism method, using Alu I, and confirmed in 10% of the samples by direct sequencing. RESULTS: The IL12B genotypes were not associated with asthma susceptibility, severity, or atopy at ages 7 and 42 years. Total serum IgE levels at age 42 of men with at least one CTCTAA allele were higher than those homozygous for the GC allele (P = .042), whereas no difference was observed for women. At all ages, female subjects with at least 1 copy of the CTCTAA allele had lower mean percent predicted levels of FEV1 and FVC compared with those without this allele; these differences were significant at ages 10 and 14 years (P < .05) and in the asthmatic subgroup at age 7 years (P = .001). CONCLUSIONS: In this long-term study of asthmatic subjects with comprehensive data on asthma severity, we found no evidence to support the presence of a heterozygote effect of the IL12B promoter polymorphism on the level of asthma in early childhood or adulthood. The polymorphism was also not associated with asthma susceptibility, but the CTCTAA allele may have been associated with elevated serum IgE levels in male subjects and reduced pulmonary function in female subjects in early childhood.

Adolescent↗
PubMed2003

Semiparametric regression analysis of longitudinal data with informative drop-outs.

Informative drop-out arises in longitudinal studies when the subject's follow-up time depends on the unobserved values of the response variable. We specify a semiparametric linear regression model for the repeatedly measured response variable and an accelerated failure time model for the time to informative drop-out. The error terms from the two models are assumed to have a common, but completely arbitrary joint distribution. Using a rank-based estimator for the accelerated failure time model and an artificial censoring device, we construct an asymptotically unbiased estimating function for the linear regression model. The resultant estimator is shown to be consistent and asymptotically normal. A resampling scheme is developed to estimate the limiting covariance matrix. Extensive simulation studies demonstrate that the proposed methods are suitable for practical use. Illustrations with data taken from two AIDS clinical trials are provided.

Child↗
PubMed1994

Interval censoring in longitudinal data of respiratory symptoms in aluminium potroom workers: a comparison of methods.

In a longitudinal study of workers in seven Norwegian aluminium plants, the time to development of asthmatic symptoms could only be determined to lie in the interval between two consecutive health examinations. In a previous paper we analysed the data by survival techniques for interval censored data. In the present paper the data are reanalysed in two ways and compared to the previous analyses. First, it is assumed that occurrence of symptoms coincided with reporting, in which case the data can be analysed as right censored. Secondly, the follow-up times are completely disregarded and the effects of covariates are analysed on the binary outcomes of symptoms. Comparing the estimated effects of the covariates between the three approaches, only minor differences were found. However, the estimates on incidence were strongly influenced by whether the data were analysed as right or interval censored.

Adult↗
PubMedDate not supplied

Autoregressive modelling for the analysis of longitudinal data with unequally spaced examinations.

Missing and/or unequally spaced examinations are often present in longitudinal studies. An autoregressive model is presented for the analysis of such data for continuous outcome variables. The fitting of the model can be accomplished by weighted non-linear regression methods available in standard statistical packages. Some features of the model include consideration of both time-dependent and fixed covariates, assessment of the relationships between changes in outcome and exposure over short periods of time, and use of all available person-time for an individual. An illustration looking at the role of personal cigarette smoking on changes in pulmonary function in children is included.

Adolescent↗
PubMed1999

Empirical power for distribution-free tests of incomplete longitudinal data with applications to AIDS clinical trials.

The design of AIDS clinical trials is of growing importance. These studies tend to be longitudinal and typically involve missing data. HIV-1 RNA is a common endpoint for these studies and is inherently non-normal, although viral load can be measured only within certain bounds, resulting in censored data. We compared several analysis methods, both univariate and multivariate, on the basis of empirical power and provide an illustrative example of data from a controlled clinical trial. Simulated viral load data demonstrate that methods adjusting for baseline data have power increasing with increasing positive intrasubject correlation expected with this type of data. Several summary measures considered have power compatible with multivariate tests.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Structural modeling of dynamic changes in memory and brain structure using longitudinal data from the normative aging study.

This is an application of new longitudinal structural equation modeling techniques to time-dependent associations of memory and brain structure measurements. There were 225 participants aged 30-80 years at baseline who were measured again after a 7-year interval on both the lateral ventricular size and Wechsler memory score. Multiple regression analyses show nonlinear associations with age but no relationships among longitudinal changes. Mixed-effects latent growth curve analyses and analyses based on latent difference scores indicate that longitudinal changes in both variables are reasonably well described by an exponential or dual change model. Bivariate dynamic structural equation modeling analyses indicate age-lagged changes operate in a coupled-over-time fashion, with the brain measure (lateral ventricular size) as a leading indicator in time of memory (Wechsler memory score) declines.

Adult↗
PubMed2007

A nonlinear latent class model for joint analysis of multivariate longitudinal data and a binary outcome.

We consider a joint model for exploring association between several correlated longitudinal markers and a clinical event. A nonlinear growth mixture model exhibits the different latent classes of evolution of the latent quantity underlying the correlated longitudinal markers and a logistic regression models the probability of occurence of the clinical event according to the latent classes. By introducing a flexible nonlinear transformation including parameters to be estimated between each marker and the latent process, the model also deals with non-Gaussian continuous markers. Through an application on cognitive ageing, the two advantages of the model are underlined: (1) the latent profiles of evolution associated with the clinical event are described including covariate effects in the longitudinal model but also in the probability of class membership and in the probability of occurence of the event, and (2) a diagnostic and a prognostic tools are derived from the model for early detection of the clinical event using any available information about the longitudinal markers.

Data Interpretation, Statistical↗
PubMed2006

Joint modeling of survival and longitudinal data: likelihood approach revisited.

The maximum likelihood approach to jointly model the survival time and its longitudinal covariates has been successful to model both processes in longitudinal studies. Random effects in the longitudinal process are often used to model the survival times through a proportional hazards model, and this invokes an EM algorithm to search for the maximum likelihood estimates (MLEs). Several intriguing issues are examined here, including the robustness of the MLEs against departure from the normal random effects assumption, and difficulties with the profile likelihood approach to provide reliable estimates for the standard error of the MLEs. We provide insights into the robustness property and suggest to overcome the difficulty of reliable estimates for the standard errors by using bootstrap procedures. Numerical studies and data analysis illustrate our points.

Algorithms↗
PubMed2005

The use of electronic debit cards in longitudinal data collection with geographically mobile drug users.

OBJECTIVE: To assess the use of electronic debit (ATM) cards in conducting longitudinal research with geographically mobile ("urban nomad") drug users. METHODS: Young illicit drug users with recent travel history were street-recruited from the Lower East Side area of New York City. Multiple efforts were made to develop positive relationships between participants and the study. Honoraria were paid through electronic debit cards usable at ATMs countrywide. Participants were encouraged to complete follow-up interviews in person if they were in New York, or by telephone if elsewhere. Follow-up rates from two other recent cohort studies of young drug users in New York are used to illustrate use of the electronic debit card method. RESULTS: One hundred and thirty-nine participants were recruited during 2001-2002. They had traveled extensively, averaging 31 trips per participant to different cities during the previous 3 years. Telephone follow-up interviews were obtained from participants in over 200 different cities/towns. Follow-up interview rates were 81% at 6 months and 71% at 12 months - substantially higher than corresponding rates in the comparison studies. CONCLUSIONS: The use of electronic debit cards, combined with other efforts to develop positive relationships with participants, led to high rates of continued study participation. Debit cards may be very useful in conducting longitudinal research with geographically mobile populations.

Adolescent↗
PubMed2005

Estimating heterogeneity in random effects models for longitudinal data.

In this paper, we are interested in estimating parameters entering nonlinear mixed effects models using a likelihood maximization approach. As the accuracy of the likelihood approximation is likely to govern the quality of the derived estimates of both the distribution of the random effects and the fixed parameters, we propose a methodological approach based on the adaptive Gauss Hermite quadrature to better approximate the likelihood function. This work presents improvements of this quadrature that render it accurate and computationally efficient in the problem of likelihood approximation with, an application to mixture models, models which allow the description of coexistence of several different homogeneous subpopulations specifying the distribution of random effects as a mixture of Gaussian distributions. These improvements are based on a new choice of the scaling matrix followed by its optimisation. An application to a phase III clinical trial of an anticoagulant molecule is proposed and estimation results are compared to those obtained with the most frequently used method in population pharmacokinetic analysis. Moreover, in order to evaluate the accuracy of the estimations, an analysis of simulated pharmacokinetic data derived from the model and the a priori values of population parameters of the previous study are presented.

Algorithms↗
PubMed2005

Robust estimating functions and bias correction for longitudinal data analysis.

Robust methods are useful in making reliable statistical inferences when there are small deviations from the model assumptions. The widely used method of the generalized estimating equations can be "robustified" by replacing the standardized residuals with the M-residuals. If the Pearson residuals are assumed to be unbiased from zero, parameter estimators from the robust approach are asymptotically biased when error distributions are not symmetric. We propose a distribution-free method for correcting this bias. Our extensive numerical studies show that the proposed method can reduce the bias substantially. Examples are given for illustration.

Age Factors↗