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PubMedDate not supplied

Statistical vector field analysis applied to mixed cross-sectional and longitudinal data.

Combined cross-sectional and longitudinal data often present complex patterns of change. Growth functions representing the change in some measure as a function of chronological age can be a function of initial values of the measurement. Individual differences in developmental age with respect to chronological age tend to distort attempts to fit a single growth curve through combined cross-sectional and longitudinal data. We present a method by which these data can be visualized along with several examples from a data set comprising measurements of intellectual abilities with respect to aging. We call this new method a statistical vector field (svf) plot. An svf plot simultaneously allows the visualization of cross-sectional information summarizing sampling densities and longitudinal information summarizing how individuals at each particular age and ability are likely to change over time. The C source code for the svf software described in this paper may be obtained free from the University of Virginia anonymous ftp archive server (ftp. Virginia.EDU), or from the authors.

Adult↗
PubMedDate not supplied

Approaches to the nonparametric analysis of limited longitudinal data sets.

The traditional goals of longitudinal studies are many: consideration of stability and change; description of patterns of development and behavior; and understanding of the processes involved in disease, including disease onset, recovery, response to treatment, natural history of the aging process, and identification of factors that predict age-related outcomes. Researchers in aging seek to unravel the impact and interaction of physical and psychological processes on human development, health, and disease. From the point of view of statistical analysis, the critical aspect of data obtained from longitudinal studies is the inherent correlational structure of multiple measurements made on a single subject or other experimental unit, which must be appropriately treated in the analysis of the data. We discuss a series of nonparametric approaches that are both analytically accessible and particularly well suited to the analysis of sparse or otherwise limited longitudinal data.

Humans↗
PubMed2000

Effects of iron intake on iron stores in elderly men and women: longitudinal and cross-sectional results.

OBJECTIVE: For middle aged and elderly subjects there is a concern that increased iron intake, especially heme iron associated with consumption of red meat, leads to increased iron stores resulting in disturbed glucose homeostasis and risk for cardiovascular disease and certain types of cancer. The aim of this study was to investigate the influence of heme, non-heme and iron supplementation on iron stores in healthy elderly men and women. METHOD: We conducted a 10 year longitudinal study (48 men and 77 women) and a one year cross-sectional study (165 men and 226 women) in healthy elderly men and women enrolled in the New Mexico Aging Process Study. Iron stores were estimated by serum ferritin concentrations and iron intake was determined by three-day food records in the longitudinal study and by a food frequency questionnaire in the cross-sectional study. RESULTS: We found no association between heme iron intake and iron stores in either the longitudinal or cross sectional study. In the cross-sectional study we found in women, but not in men, that age and supplemental iron intake were significantly and positively associated with increased iron stores. CONCLUSION: Iron stores in elderly men are thought to reach steady state levels where iron absorption is adjusted to a level just sufficient to cover basal iron losses. In elderly women, we speculate that not enough time has elapsed for postmenopausal women to reach steady state levels of iron stores resulting in increases in iron absorption with age. Another factor is that use of hormone replacement therapy could further delay some women in reaching steady state iron levels due to continued menstrual blood losses.

Aged↗
PubMed2005

Longitudinal characterization of course types of functional limitations.

PURPOSE: Longitudinal data have provided evidence on factors that increase the risk of incidence of functional limitations. However, little insight exists in course types of functional limitations other than simple incidence or recovery. METHODS: This contribution examines the variety of course types across the first three cycles of the Longitudinal Aging Study Amsterdam (n = 3107, initial ages 55 - 85 years, 6-year period covered). Using cluster analysis, course types were determined among both the survivors and the deceased. Multinomial analyses were performed to determine the predictive ability of baseline physical and mental chronic conditions for each course type. RESULTS: Eight course types were distinguished: (1) stable not limited (53%) (2) stable mild (8%) (3) stable severe (3%) (4) gradual increase (4%) (5) delayed increase (5%) (6) not limited, died t3 (8%) (7) increase t1-t2, died t3 (4%) (8) died t2 (15%). Socio-demographic and chronic conditions differentially predicted the course types. Arthritis was predictive mainly of course types not ending in death, cancer of course types ending in death. The other physical and mental conditions were predictive of both. CONCLUSION: These longitudinal data show the usefulness of distinguishing between course types of functional limitations beyond incidence and recovery.

Activities of Daily Living↗
PubMed1998

A comparison of the random-effects pattern mixture model with last-observation-carried-forward (LOCF) analysis in longitudinal clinical trials with dropouts.

The last-observation-carried-forward imputation method is commonly used for imputting data missing due to dropouts in longitudinal clinical trials. The method assumes that outcome remains constant at the last observed value after dropout, which is unlikely in many clinical trials. Recently, random-effects regression models have become popular for analysis of longitudinal clinical trial data with dropouts. However, inference obtained from random-effects regression models is valid when the missing-at-random dropout process is present. The random-effects pattern-mixture model, on the other hand, provides an approach that is valid under more general missingness mechanisms. In this article we describe the use of random-effects pattern-mixture models under different patterns for dropouts. First, subjects are divided into groups depending on their missing-data patterns, and then model parameters are estimated for each pattern. Finally, overall estimates are obtained by averaging over the missing-data patterns and corresponding standard errors are obtained using the delta method. A typical longitudinal clinical trial data set is used to illustrate and compare the above methods of data analyses in the presence of missing data due to dropouts.

Clinical Trials as Topic↗
PubMed2004

Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

OBJECTIVES: After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. METHODS: Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. RESULTS: In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.

Aged↗
PubMed2003

A longitudinal approach for constructing beta-expectation tolerance intervals.

A new method is presented for constructing beta-expectation tolerance limits (TLs) for longitudinal data with error components regression structure. The TLs are mainly intended for small samples where the variation between and within subjects is large. In such cases the new method is superior to existing methods, which are based on a cross-sectional approach and which do not utilize the longitudinal structure of the data. Simulation studies show that the mean length of the TLs can be much reduced by using the new approach, while at the same time the beta-expectation property is maintained. The gain from using the longitudinal approach furthermore increases with the beta-expectation level. The results are demonstrated on data consisting of measurements of glutamate concentrations in brains from rats. Here, the cross-sectional approach due to Wilks give 90-99% TLs, which are up to 101-230% wider than are those obtained with the new approach.

Animals↗
PubMed2006

Chronic versus episodic irritability in youth: a community-based, longitudinal study of clinical and diagnostic associations.

OBJECTIVE: Irritability is both a normal developmental phenomenon and a common psychiatric symptom in children. In psychiatric nosology, a distinction is made between chronic and episodic irritability. This study examines the validity of this distinction. METHODS: A sample of 776 youths received Diagnostic and Statistical Manual of Mental Disorders (DSM)-based structured interviews at three time points. Questions regarding episodic and chronic irritability were used to create scales measuring these constructs; associations with age, gender, and diagnosis were examined. RESULTS: Episodic and chronic irritability differed in their associations with age. The longitudinal stability within irritability type was stronger than between types. In longitudinal analyses, chronic irritability at time 1 (mean age 13.8 +/- 2.6 years) predicted attention deficit/ hyperactivity disorder at time 2 (mean age 16.2 +/- 2.8 years) and major depression at time 3 (mean age 22.1 +/- 2.7 years). Episodic irritability at time 1 predicted simple phobia and mania at time 2. CONCLUSIONS: Episodic and chronic irritability in adolescents appear to be stable, distinct constructs. Further research is needed to elucidate the longitudinal associations of each with specific psychiatric diagnoses.

Adolescent↗
PubMed1998

Gender and longitudinal changes in physical activities in later life.

OBJECTIVES: to describe gender differences in levels of, and longitudinal changes in, habitual physical activity among older people. DESIGN: longitudinal study. PARTICIPANTS: sub-groups of survivors (with sample sizes dependent on the availability of complete datasets, ranging from 303-344) assessed on three occasions: 1985, 1989 and 1993 in Nottingham, UK. All were 65 years and over in 1985. METHODS: descriptive presentation (median and range values) of quantitative longitudinal data by gender across five activity categories assessed in a recall-based questionnaire. MAIN OUTCOME MEASURES: participation in walking, shopping, indoor, outdoor and leisure activities. RESULTS: while levels of indoor and outdoor activities were marked by decline for both sexes, gender differentials were maintained over the 8 years of the study, with women showing higher levels of activity participation indoors and men showing higher levels of activity participation outdoors. In levels of walking/shopping activity, however, there was evidence of gender differentials reducing over time. CONCLUSIONS: within these cohorts of older people traditional gender roles continue to exert a strong influence on levels and types of habitual physical activity well into later life. In some areas of activity, however, temporal changes provide some evidence of gender convergence consistent with late-life transitions in marital status and dependency.

Activities of Daily Living↗
PubMed2006

Longitudinal examination of 24-h urinary iodine excretion in schoolchildren as a sensitive, hydration status-independent research tool for studying iodine status.

BACKGROUND: Because worldwide iodine status (IS) depends on continuous fortification, the adequacy of IS needs to be regularly monitored. OBJECTIVE: Our study aimed to evaluate IS in a longitudinal sample of healthy schoolchildren who regularly used table salt iodized with 20 microg I/g. DESIGN: Urine osmolality (Uosm) and 24-h urinary excretion rates of iodine (24-h UI), sodium, creatinine, and total urine volume (24-h Uvol) were measured in 1046 specimens that were collected at repeated intervals from 1996 to 2003 in a sample of 358 German children aged 6-12 y. Energy intake and food consumption were calculated from 3-d weighed dietary records that were collected in parallel to the urine samples. RESULTS: During the 4-y period from 1996 to 1999, the median 24-h UI increased from 87 to 93 microg I/d (P = 0.017), whereas urinary iodine concentration (UIC), Uosm, and 24-h Uvol did not change significantly. Thereafter (from 2000 to 2003), UIC stagnated and Uosm decreased (P = 0.004), whereas 24-h Uvol (P = 0.008) and 24-h UI (P = 0.002) increased. The final median 24-h UI reached 120 microg I/d. Milk, fish, egg, and meat intakes and 24-h sodium excretion were all significant predictors of IS, with an almost doubled contribution from milk intake during the second 4-y period. CONCLUSIONS: Our study shows a continuous improvement of IS in a longitudinal sample of German schoolchildren. This improvement was masked when UIC was used as an IS index, especially from 2000 to 2003 because of changes in hydration status. Thus, in research-oriented studies that focus on UIC measurements, hydration status can be a relevant confounder. Longitudinal analyses of 24-h UI in cohort studies may represent an alternative hydration status-independent tool to examine trends in IS and the contribution of relevant foods to IS.

Child↗
PubMed2004

Five-year obesity incidence in the transition period between adolescence and adulthood: the National Longitudinal Study of Adolescent Health.

BACKGROUND: No nationally representative longitudinal data have been analyzed to evaluate the incidence of obesity in the transition between adolescence and adulthood. OBJECTIVE: The objective was to examine dynamic patterns of change in obesity among white, black, Hispanic, and Asian US teens as they transitioned to young adulthood. DESIGN: We used nationally representative, longitudinally measured height and weight data collected from US adolescents enrolled in wave II (1996; ages 13-20 y) and wave III (2001; 19-26 y) of the National Longitudinal Study of Adolescent Health (n = 9795). Obesity incidence was defined on the basis of International Obesity Task Force (IOTF) cutoffs (wave II), which link childhood body mass index (BMI) centiles to adult cutoffs (BMI > or = 30; wave III), for comparability between adolescence and adulthood. In addition, the more commonly used cutoff of BMI > or = 95th percentile for age- and sex-specific cutoffs from the 2000 Centers for Disease Control and Prevention growth charts for adolescents (wave II) were compared with adult cutoffs (BMI > or = 30; wave III). RESULTS: On the basis of the IOTF cutoffs, obesity incidence over the 5-y study period was 12.7%; 9.4% of the population remained obese and 1.6% shifted from obese to nonobese. Obesity incidence was especially high in non-Hispanic black (18.4%) females relative to white females. The prevalence of obesity increased from 10.9% in wave II to 22.1% in wave III, and extreme obesity was 4.3% at wave III on the basis of a BMI > or = 40. CONCLUSIONS: During a 5-y transitional period between adolescence and young adulthood, the proportion of adolescents becoming and remaining obese into adulthood was very high. This upward trend is likely to continue. Effective preventive and treatment efforts are critically needed.

Adolescent↗
PubMed2005

Quality of reporting of observational longitudinal research.

Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making. However, there are no structured reporting requirements for studies of this design to assist authors, editors, and readers. The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies. The checklist criteria concerned recruitment, data collection, biases, and data analysis and descriptive issues relevant to study rationale, study population, and generalizability. Two raters independently assessed 49 randomly selected articles describing stroke research published from 1999 to 2003 in six journals: American Journal of Epidemiology, Journal of Epidemiology and Community Health, Stroke, Annals of Neurology, Archives of Physical Medicine and Rehabilitation, and American Journal of Physical Medicine and Rehabilitation. On average, 17 of the 33 checklist criteria were reported. Criteria describing the study design were better reported than those related to internal validity. No relation was found between study type (etiologic or prognostic) or word count and quality of reporting. A flow diagram for summarizing participant flow through a study was developed. Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research.

Epidemiology↗
PubMed2025

PROLONG: penalized regression for outcome guided longitudinal omics analysis with network and group constraints.

MOTIVATION: There is a growing interest in longitudinal omics data paired with some longitudinal clinical outcome. Given a large set of continuous omics variables and some continuous clinical outcome, each measured for a few subjects at only a few time points, we seek to identify those variables that co-vary over time with the outcome. To motivate this problem we study a dataset with hundreds of urinary metabolites along with Tuberculosis mycobacterial load as our clinical outcome, with the objective of identifying potential biomarkers for disease progression. For such data clinicians usually apply simple linear mixed effects models which often lack power given the low number of replicates and time points. We propose a penalized regression approach on the first differences of the data that extends the lasso + Laplacian method [Li and Li (Network-constrained regularization and variable selection for analysis of genomic data. Bioinformatics 2008;24:1175-82.)] to a longitudinal group lasso + Laplacian approach. Our method, PROLONG, leverages the first differences of the data to increase power by pairing the consecutive time points. The Laplacian penalty incorporates the dependence structure of the variables, and the group lasso penalty induces sparsity while grouping together all contemporaneous and lag terms for each omic variable in the model. RESULTS: With an automated selection of model hyper-parameters, PROLONG correctly selects target metabolites with high specificity and sensitivity across a wide range of scenarios. PROLONG selects a set of metabolites from the real data that includes interesting targets identified during EDA. AVAILABILITY AND IMPLEMENTATION: An R package implementing described methods called "prolong" is available at https://github.com/stevebroll/prolong. Code snapshot available at 10.5281/zenodo.14804245.

Humans↗
PubMed2003

A parametric empirical Bayes method for cancer screening using longitudinal observations of a biomarker.

A revolution in molecular technology is leading to the discovery of many biomarkers of disease. Monitoring these biomarkers in a population may lead to earlier disease detection, and may prevent death from diseases like cancer that are more curable if found early. For markers whose concentration is associated with disease progression the earliest detection is achieved by monitoring the marker with an algorithm able to detect very small changes. One strategy is to monitor the biomarkers using a longitudinal algorithm that incorporates a subject's screening history into screening decisions. Longitudinal algorithms that have been proposed thus far rely on modeling the behavior of a biomarker from the moment of disease onset until its clinical presentation. Because the data needed to observe the early pre-clinical behavior of the biomarker may take years to accumulate, those algorithms are not appropriate for timely development using new biomarker discoveries. This manuscript presents a computationally simple longitudinal screening algorithm that can be implemented with data that is obtainable in a short period of time. For biomarkers meeting only a few modest assumptions our algorithm uniformly improves the sensitivity compared with simpler screening algorithms but maintains the same specificity. It is unclear what performance advantage more complex methods may have compared with our method, especially when there is doubt about the correct model for describing the behavior of the biomarker early in the disease process. Our method was specifically developed for use in screening for cancer with a new biomarker, but it is appropriate whenever the pre-clinical behavior of the disease and/or biomarker is uncertain.

Algorithms↗
PubMed2004

Semiparametric regression analysis on longitudinal pattern of recurrent gap times.

In longitudinal studies, individual subject may experience recurrent events of the same type over a relatively long period of time. The longitudinal pattern of gaps between successive recurrent events is often of great research interest. In this article, the probability structure of the recurrent gap times is first explored in the presence of censoring. According to the discovered structure, we introduce the stratified proportional reverse-time hazards models with unspecified baseline functions to accommodate individual heterogeneity, when the longitudinal pattern parameter is of main interest. Inference procedures are proposed and studied by way of proper riskset construction. The proposed methodology is demonstrated by the Monte Carlo simulations and an application to a well-known Denmark schizophrenia cohort study data set.

Age of Onset↗
PubMed2004

Semiparametric estimation of time-dependent ROC curves for longitudinal marker data.

One approach to evaluating the strength of association between a longitudinal marker process and a key clinical event time is through predictive regression methods such as a time-dependent covariate hazard model. For example, a Cox model with time-varying covariates specifies the instantaneous risk of the event as a function of the time-varying marker and additional covariates. In this manuscript we explore a second complementary approach which characterizes the distribution of the marker as a function of both the measurement time and the ultimate event time. Our goal is to extend the standard diagnostic accuracy concepts of sensitivity and specificity so as to recognize explicitly both the timing of the marker measurement and the timing of disease. The accuracy of a longitudinal marker can be fully characterized using time-dependent receiver operating characteristic (ROC) curves. We detail a semiparametric estimation method for time-dependent ROC curves that adopts a regression quantile approach for longitudinal data introduced by Heagerty and Pepe (1999, Applied Statistics, 48, 533-551). We extend the work of Heagerty and Pepe (1999, Applied Statistics, 48, 533-551) by developing asymptotic distribution theory for the ROC estimators where the distributional shape for the marker is allowed to depend on covariates. To illustrate our method, we analyze pulmonary function measurements among cystic fibrosis subjects and estimate ROC curves that assess how well the pulmonary function measurement can distinguish subjects that progress to death from subjects that remain alive. Comparing the results from our semiparametric analysis to a fully parametric method discussed by Etzioni et al. (1999, Medical Decision Making, 19, 242-251) suggests that the ability to relax distributional assumptions may be important in practice.

Adolescent↗
PubMed2005

Exploratory analysis of longitudinal trials with staggered intervention times.

Longitudinal trials involving surgical interventions commonly have subject-specific intervention times, due to constraints on the availability of surgeons and operating theatres. Moreover, the intervention often effects a discontinuous change in the mean response. We propose a nonparametric estimator for the mean response profile of longitudinal data with staggered intervention times and a discontinuity at the times of intervention, as an exploratory tool to assist the formulation of a suitable parametric model. We use an adaptation of the standard generalized additive model algorithm for estimation, with smoothing constants chosen by a cross-validation criterion. We illustrate the method using longitudinal data from a trial to assess the effect of lung resection surgery in the treatment of emphysema patients.

Algorithms↗
PubMed1996

Longitudinal changes in smell identification.

BACKGROUND: Cross-sectional studies have demonstrated that olfactory function diminishes with increasing age, which may impact on the safety and quality of life of older persons. To date, however, there have been no published longitudinal studies on olfaction. The purpose of this study was to examine the influence of age and gender on smell identification over a 3-year period in a group of generally healthy men and women. METHODS: Males (n = 85) and females (n = 76) between the ages of 19 and 95 years were administered the University of Pennsylvania Smell Identification Test (SIT) over a 3-year span as part of the oral physiology component of the Baltimore Longitudinal Study of Aging. A linear mixed-effects regression model was used to determine how longitudinal changes in SIT scores differ with respect to gender, history of medical problems, and use of prescription medications. RESULTS: Over the 3-year period, SIT scores diminished progressively with increased age. Women and men in the eighth decade of life experienced a decline of greater than one SIT point per year. Females consistently performed better than males in smell identification. Similar results were obtained regardless of medical problems or medication usage. CONCLUSIONS: These results extend the conclusions of previous cross-sectional olfactory studies and indicate that smell identification deteriorates progressively with greater age. Furthermore, age-related declines in olfaction occur even in the absence of overt medical problems.

Adult↗