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PubMed2005

Season of death and birth predict patterns of mortality in Burkina Faso.

BACKGROUND: Mortality in developing countries has multiple causes. Some of these causes are linked to climatic conditions that differ over the year. Data on season-specific mortality are sparse. METHODS: We analysed longitudinal data from a population of approximately 35,000 individuals in Burkina Faso. During the observation period 1993-2001, a total number of 4,098 deaths were recorded. The effect of season on mortality was investigated separately by age group as (i) date of death and (ii) date of birth. For (i), age-specific death rates by month of death were calculated. The relative effect of each month was assessed using the floating relative risk method and modelled continuously. For (ii), age-specific death rates by month of birth were calculated and the mean date of birth among deaths and survivors was compared. RESULTS: Overall mortality was found to be consistently higher during the dry season (November to May). The pattern was seen in all age groups except in infants where a peak was seen around the end of the rainy season. In infants we found a strong association between high mortality and being born during the time period September to February. No effect was seen for the other age groups. CONCLUSIONS: The observed excess mortality in young children at or around the end of the rainy season can be explained by the effects of infectious diseases and, in particular, malaria during this time period. In contrast, the excess mortality seen in older children and adults during the early dry season remains largely unexplained although specific infectious diseases such as meningitis and pneumonia are possible main causes. The association between high infant mortality and being born at around the end of the rainy season is probably explained by most of the malaria deaths in areas of high transmission intensity occurring in the second half of infancy.

Adolescent↗

PubMedDate not supplied

Psychometric approaches to the identification of LD: IQ and achievement scores are not sufficient.

Simulated data were used to demonstrate that groups formed by imposing cut-points based on either discrepancy or low-achievement definitions of learning disabilities (LD) are unstable over time. Similar problems were demonstrated in longitudinal data from the Connecticut Longitudinal Study, where 39% of the children designated as having LD in Grade 3 changed group placement with repeated testing in Grade 5. These results show that the practice of subdividing a normal distribution with arbitrary cut-points leads to instability in group membership. Approaches to the identification of children as having LD based solely on individual test scores not linked to specific behavioral criteria lead to invalid decisions about individual children. Low-achievement definitions are not a viable alternative to IQ-discrepancy definitions in the absence of other criteria, such as the traditional exclusions and response to quality intervention. If we accept the premise of multiple classes of low achievers, then we must develop identification systems that are valid and abandon systems whose only merits are their historical precedence and convenience.

Child↗

PubMed1997

Construction of hearing percentiles in women with non-constant variance from the linear mixed-effects model.

Current age-specific reference standards for adult hearing thresholds are primarily cross-sectional in nature and vary in the degree of screening of the reference sample for noise-induced hearing loss and other hearing problems. We develop methods to construct age-specific percentiles for longitudinal data that have been modelled using the linear mixed-effects model. We apply these methods to construct percentiles of hearing level using data from a carefully screened sample of women from the Baltimore Longitudinal Study of Aging. However, the variation in the residuals and random effects from the linear mixed-effects model does not remain constant with age and frequency of the stimulus tone. In addition, the distribution of the hearing levels is not symmetric about the mean. We develop a number of methods to use the output from the linear mixed-effects model to construct percentiles that do not have constant variance. We use a transformation of the hearing levels to provide for skewness in the final percentile curves. The change in the variation of the residuals and random effects is modelled as a function of beginning age and frequency and we use this variance function to construct the hearing percentiles. We present a number of approaches. First, we use the absolute values of the population residuals to model the total deviation about the mean as a function of beginning age and frequency. Second, we model the standard deviation in the person-specific (cluster) residuals as well as the standard deviation in the estimated random effects. Finally, we use weighted least squares with the regressions on the absolute cluster residuals and absolute estimated random effects where the weights are the reciprocal of the standard deviations of their estimates.

Adolescent↗

PubMed2005

[Who needs what? New approaches to multidisciplinary diagnostics and therapy for adipose children and youths in a multiethnic city].

Over the past two decades, obesity in children has been increasing worldwide, leading to serious complications. The treatment for childhood obesity remains largely ineffective; therefore preventive measures are crucial. The prevalence of obesity depends on the BMI-percentiles used. Recent BMI-percentiles may underestimate the problem. Currently, the only representative cross-sectional BMI-data are obtained at the school entry examination. These data reveal certain risk groups (migrants, low socioeconomic status). More representative longitudinal data are needed to study the progression of obesity during childhood. Our obesity clinic provides multidisciplinary therapy programs (group or individual) and is also focused on the diagnosis and treatment of comorbidity, especially of the metabolic syndrome. Almost 60% of our severely obese patients are already affected. The molecular diagnosis of rare monogenetic or syndromal forms of obesity may be helpful in providing additional support for these patients. In general, most obesity programs are successful only in families without severe psychosocial problems and with motivation for lifestyle changes. This can be expected in only 3% of our families. Therefore, a substantial societal effort is needed to facilitate prevention for all children, and effective therapies have to be tailored depending on biological and psychosocial risk factors.

Adolescent↗

PubMed2006

Established diabetic neuropathy seems irreversible despite improvements in metabolic and vascular risk markers--a retrospective case-control study in a hospital patient cohort.

AIMS: To gain insight into the natural history of diabetic peripheral neuropathy (DPN) and its risk factors by means of sequential quantitative testing in a hospital patient cohort. METHODS: A retrospective case-control study involving 300 diabetic patients (100 subjects with neuropathy and 200 control subjects) attending Poole Hospital diabetes clinic between 1995 and 2002. All subjects had a detailed annual clinic assessment including vibration perception threshold (VPT) and physical and metabolic assessments and were categorized according to neuropathy status. Established neuropathy was defined as a VPT > 25 V. Cross-sectional data were analysed by means of a t-test and longitudinal data by means of ANOVA. RESULTS: VPTs increased over time in neuropathy patients, with no change in control patients (P < 0.001). Glycaemic control was better over that period in control patients but the rate of improvement in HbA1c over time was similar in both groups. Triglyceride and high-density lipoprotein cholesterol levels improved in both groups, with significantly greater change in the control group. CONCLUSIONS: Data on reversibility of neuropathy are scarce and our 8-year series shows a continual deterioration in VPT in patients with a threshold > 25 V despite modest improvements in glycaemic control and lipid parameters. This work also supports a vascular association with neuropathy and identifies neuropathic patients as a high-risk cardiovascular group in whom, despite little influence on neuropathy itself, the above metabolic factors should be actively addressed.

Adult↗

PubMed2006

Measurement variability in Heidelberg Retina Tomograph imaging of neuroretinal rim area.

PURPOSE: To investigate the optimal frequency of imaging during follow-up to detect glaucoma progression by characterizing variability (noise) in neuroretinal rim area (RA) measured by Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany). METHODS: RA noise was estimated from patient data and characterized by fitting theoretical distributions to the observed data. Multilevel regression was used to determine factors that significantly affect noise. Computer simulations of disease progression were performed by adding noise generated from the distribution derived from the observed data to the average rate of loss in RA estimated from longitudinal data. Rates of detection of disease progression were investigated for various progression rates, follow-up periods, and rates of imaging. RESULTS: Noise was not normally distributed and was best characterized by the hyperbolic distribution, which fit averages well while allowing for extreme values. Noise was greatly influenced by image quality, but age did not have a significant effect. Rates of detection improved for more frequent imaging, better quality images, and faster rates of disease progression. CONCLUSIONS: Noise in HRT measurement of RA is well characterized by the hyperbolic distribution. Sensitivity of detection improves with more frequent testing, but if consistently poor-quality images are yielded for a patient, the probability of detection is low. Results from this work could be used to tailor individual follow-up patterns for patients with different rates of RA loss and image quality, especially in a clinical trial setting.

Cross-Sectional Studies↗

PubMed2026

Mortality of Individuals With PRNP Variants Associated With Prion Disease in the United States, 1998-2024.

BACKGROUND AND OBJECTIVES: To characterize the survival of individuals with pathogenic PRNP variants-including to estimate annual hazards, to judge the accuracy of previously reported survival data, and to evaluate the utility of public record searches in determining vital status. METHODS: In this single-center cohort study, we gathered data on individuals who received positive antemortem PRNP genetic tests at the US National Prion Disease Pathology Surveillance Center (NPDPSC), including both diagnostic tests in symptomatic individuals, and predictive tests in asymptomatic individuals. Genetic test and autopsy results were queried from the NPDPSC database, and public record searches were conducted using online tools. RESULTS: Four hundred four individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated 92.6% sensitivity. We evaluated the age-dependent penetrance of the reportedly highly penetrance variants D178N and E200K and the reportedly low-penetrance variant V210I. Among 99 initially asymptomatic individuals with the pathogenic E200K variant, more than 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from these longitudinal data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. For the pathogenic D178N variant, the median age at death was 57, which was numerically later, but not significantly different from, that seen in retrospective data. For V210I, just 2 deaths occurred, both after age 90, consistent with minimal penetrance. DISCUSSION: Our data support high penetrance of PRNP D178N and E200K variants and low penetrance of V210I. For E200K, the age at onset distribution appears to be shifted slightly later, and lifetime risk slightly lower, than previously reported. Autopsy data and public death records in combination were sensitive and concordant for determining long-term outcomes, but additional prospective data should be gathered to support future preventive trials.

Journal Article↗

PubMed2002

Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease.

OBJECTIVE: To examine volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). BACKGROUND: Previous cross-sectional studies examining the relationship between cognitive impairment and dementia have shown that hippocampal and cortical gray matter atrophy are the most important predictors of cognitive impairment, even in cases with SCVBI. The authors hypothesized that hippocampal and cortical gray matter volume also would best predict rate of cognitive decline in cases with and without SCVBI. METHODS: Subjects were recruited for a multicenter study of contributions to dementia of AD and SCVBI. The sample (n = 120) included cognitively normal, cognitively impaired, and demented cases with and without lacunes identified by MRI. Cases with cortical strokes were excluded. Average length of follow-up was 3.0 years. Measures of hippocampal volume, volume of cortical gray matter, presence of subcortical lacunes, and volume of white matter hyperintensity were derived from MRI. Random effects modeling of longitudinal data was used to assess effects of baseline MRI variables on longitudinal change in a measure of global cognitive ability. RESULTS: Cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present. Hippocampal atrophy predicted decline only in those without lacunes. Neither lacunes nor white matter hyperintensity independently predicted decline. CONCLUSIONS: Results suggest that cortical atrophy is an index of disease severity in both AD and subcortical cerebrovascular brain injury and consequently predicts faster progression. Hippocampal volume may index disease severity and predict progression in AD. The absence of this effect in cases with lacunes suggests that this group is etiologically heterogeneous and is not composed simply of cases of AD with incidental stroke.

Aged↗

PubMed1990

On estimating fertility using first and second order births.

"An attempt has been made to present two regression equations for estimating total fertility rate from the birth order data. While one of the equations has been derived from the longitudinal data of Malaysia another has been obtained from cross sectional data on Mother's total fertility rate...and births of orders one and two. These equations are used to estimate the [total fertility rate] for the districts of [Uttar Pradesh, India,] which are quite close to the estimates obtained by using other methods."

Asia↗

PubMed1993

Computers in total quality management. Statistical process control to expedite stats.

We developed a system of computer programs to gather and then display data on turnaround time for stat tests. The data were those generated by the testing process itself so that no additional data entry was necessary. The system provided daily as well as longitudinal data for statistical process control implemented in the laboratory. The median and 90th percentile turnaround times were calculated for high-volume tests (complete blood cell count and Chem6 [six chemical serum component concentrations, ie, sodium, potassium, chloride, carbon dioxide, glucose, and urea nitrogen]), and a graphic display was automatically generated. These parameters and visual aids permitted evaluation of stat processing in the laboratory. The impact of management decisions on the stat process could be measured. Intralaboratory processing procedures were modified, and phlebotomy personnel were repositioned. Our various measurements showed which decisions improved stat turnaround time.

Blood Chemical Analysis↗

PubMed1997

Are human subject volunteers still players in aeromedical research as we enter the 21st century?

The U.S. Air Force has enjoyed the luxury of having dedicated human volunteer subjects for sustained and impact acceleration research for over 50 yr. However, with today's world economy and budgetary cutbacks, this may no longer be a viable option. The onslaught of advanced medical technology, combined with an increasing performance envelope for aircraft and their ejection systems, have created an environment where the validity of research data and the ethics of human-use research are being challenged. Now is an opportune time to reevaluate the way human-use aeromedical research is conducted. The validity of using nonpilots in lieu of pilots in aeromedical research is discussed in light of the following: a) the increased emphasis on performance metrics within sustained acceleration; b) the matching of human subjects (nonpilots) to pilots in the appropriate attributes to ensure validity of data; c) degree of medical screening required given the ethics of human-use research and concerns of pilots; and d) the challenge of evaluating the "value added" of new technology for medical screening. It is concluded that volunteer panels should be maintained with nonpilots matched with pilots physically and psychologically such that operational performance characteristics are similar. Medical screening should be similar so that research data from subjects can be applied to the target population (pilots). Longitudinal data collection (e.g., spinal X-rays) on pilots would also be of great value as a basis for studying the occupational hazards of flying.

Acceleration↗

PubMed2006

A robust approach to t linear mixed models applied to multiple sclerosis data.

We discuss a robust extension of linear mixed models based on the multivariate t distribution. Since longitudinal data are successively collected over time and typically tend to be auto-correlated, we employ a parsimonious first-order autoregressive dependence structure for the within-subject errors. A score test statistic for testing the existence of autocorrelation among the within-subject errors is derived. Moreover, we develop an explicit scoring procedure for the maximum likelihood estimation with standard errors as a by-product. The technique for predicting future responses of a subject given past measurements is also investigated. Results are illustrated with real data from a multiple sclerosis clinical trial.

Bayes Theorem↗

PubMed2000

Modeling prevention program effects on growth in substance use: analysis of five years of data from the Adolescent Alcohol Prevention Trial.

The efficacy of prevention programs is typically determined through analysis of covariance. To date, a growth curve modeling approach is not used extensively in program evaluation. However, for longitudinal data there are several advantages to using this approach as compared to methods comparing means at two time points in a piecemeal fashion. In this study, latent growth curve models were used to evaluate the effect of a program on the average level of drug use, rate of change (growth) of drug use, and acceleration or deceleration in the rate of change of drug use. The study relied on data from the Adolescent Alcohol Prevention Trial, a randomized longitudinal drug use prevention program. The program consists of drug use information, resistance skills training, and normative education components. Data regarding cigarette and alcohol use were collected over a 5-year period, grade 7 to grade 11. Students receiving the normative education program had significantly lower average levels of reported cigarette and alcohol use, lower rates of growth for reported cigarette and alcohol use, and less deceleration of reported levels of cigarette and alcohol use as compared with the control group. Growth curve analysis is a powerful and effective tool with which to model change and program efficacy.

Adolescent↗

PubMedDate not supplied

Depending on the kindness of strangers: current national data initiatives and developmental research.

This article provides a brief review of current large-scale, longitudinal data collection initiatives focusing on children. These studies will be available for secondary data analyses in the twenty-first century. In addition to child outcome data, process-oriented information is being collected on child-parent interactions, quality of child care, elementary school teacher reports and classroom observations, accessibility and use of health, educational and social services, parental mental health, family violence, fathering, parental residence patterns, income and income sources, child support, employment patterns, and community characteristics. Several of these studies are randomized trials of the efficacy of early childhood intervention services and housing mobility programs. The usefulness of these efforts for exploring policy-relevant issues (child support enforcement, work requirements for welfare recipients, antipoverty strategies, housing subsidies and relocation, availability of child care, child-care subsidies) are discussed.

Child↗

PubMed1999

A discriminant analysis extension to mixed models.

Discriminant analysis is commonly used to classify an observation into one of two (or more) populations on the basis of correlated measurements. Classical discriminant analysis approaches require complete data for all observations. Our extension enables the use of all available longitudinal data, regardless of completeness. Traditionally a linear discriminant function assumes a common unstructured covariance matrix for both populations, which may be taken from a multivariate model. Here, we can model the correlated measurements and use a structured covariance in the discriminant function. We illustrate cases in which the estimated covariance structure is either compound symmetric, heterogeneous compound symmetric or heterogeneous autoregressive. Thus a structured covariance is incorporated into the discrimination process in contrast to standard discriminant analysis methodology. Simulations are performed to obtain a true measure of the effect of structure on the error rate. In addition, the usual multivariate expected value structure is altered. The impact on the discrimination process is contrasted when using the multivariate and random-effects covariance structures and expected values. The random-effects covariance structure leads to an improvement in the error rate in small samples. To illustrate the procedure we consider repeated measurements data from a clinical trial comparing two active treatments; the goal is to determine if the treatment could be unblinded based on repeated anxiety score measurements.

Anti-Anxiety Agents↗

PubMed2006

Some frontiers in social science.

The fundamental challenge in the social sciences is moving from complicated correlations to useful prediction. Progress usually reflects an interplay between theory, data, and tools. Six areas of innovation, principally data and tools, are now pushing at the frontiers of these sciences: longitudinal data, laboratory experimentation, improved statistical methods, geographic information tools, biosocial science, and international replication. These innovations are gaining power as they cross disciplinary boundaries, helping to attribute causality to observed relationships, to understand their nature, and thereby to improve the accuracy and usefulness of predictions.

Animals↗

PubMed2001

The relationship of APOE genotype to cognitive functioning in older African-American and Caucasian community residents.

OBJECTIVES: To determine whether cognitive decline associated with the apolipoprotein E (APOE) epsilon4 allele is different in older African Americans than it is in Caucasians. DESIGN: Performance on a brief screen of cognitive functioning was examined at baseline (N = 1,891) and 4 years later (N = 1,389) to determine the extent to which the presence of APOE epsilon4 affected level of and change in performance, and whether this differed as a function of race, age, initial score, and change in score. SETTING: Five adjacent counties in the Piedmont area of North Carolina. PARTICIPANTS: In 1986, a stratified random household sample of community residents age 65 and older (n = 4,162; 54% African-American, 45% Caucasian, 1% other race) formed the Duke Established Populations for Epidemiologic Studies of the Elderly. Of those available at the sixth annual wave, 76% were genotyped, with 1,891 providing baseline data on this wave, and the available survivors (n = 1,389) providing longitudinal data 4 years later. MEASUREMENTS: The Short Portable Mental Status Questionnaire (SPMSQ), a brief screen of cognitive functioning, was administered to all subjects on both occasions. We examined score at baseline and cognitive decline (i.e., increase of 2+ errors) at follow-up. Control measures included demographic characteristics, health behaviors, health and functional status, and medication use. APOE status was coded as epsilon4 present versus absent. RESULTS: APOE epsilon4 was significantly and uniquely related to lower score at baseline and significantly increased the odds of cognitive decline by 59%. There was no statistically significant interaction between APOE epsilon4 and age, race, initial SPMSQ score, or SPMSQ score at follow-up. CONCLUSION: APOE epsilon4 is modestly, if significantly, related to poorer cognitive functioning and to decline in cognitive functioning. No differences were found by age or race in this community representative sample.

Aged↗

PubMed2004

The effect of correlation structure on treatment contrasts estimated from incomplete clinical trial data with likelihood-based repeated measures compared with last observation carried forward ANOVA.

Valid analyses of longitudinal data can be problematic, particularly when subjects dropout prior to completing the trial for reasons related to the outcome. Regulatory agencies often favor the last observation carried forward (LOCF) approach for imputing missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood-based analyses developed under the missing at random framework provide viable alternatives. The within-subject error correlation structure is often the means by which such methods account for the bias from missing data. The objective of this study was to extend previous work that used only one correlation structure by including several common correlation structures in order to assess the effect of the correlation structure in the data, and how it is modeled, on Type I error rates and power from a likelihood-based repeated measures analysis (MMRM), using LOCF for comparison. Data from four realistic clinical trial scenarios were simulated using autoregressive, compound symmetric and unstructured correlation structures. When the correct correlation structure was fit, MMRM provided better control of Type I error and power than LOCF. Although misfitting the correlation structure in MMRM inflated Type I error and altered power, misfitting the structure was typically less deleterious than using LOCF. In fact, simply specifying an unstructured matrix for use in MMRM, regardless of the true correlation structure, yielded superior control of Type I error than LOCF in every scenario. The present and previous investigations have shown that the bias in LOCF is influenced by several factors and interactions between them. Hence, it is difficult to precisely anticipate the direction and magnitude of bias from LOCF in practical situations. However, in scenarios where the overall tendency is for patient improvement, LOCF tends to: 1) overestimate a drug's advantage when dropout is higher in the comparator and underestimate the advantage when dropout is lower in the comparator; 2) overestimate a drug's advantage when the advantage is maximum at intermediate time points and underestimate the advantage when the advantage increases over time; and 3) have a greater likelihood of overestimating a drug's advantage when the advantage is small. In scenarios in which the overall tendency is for patient worsening, the above biases are reversed. In the simulation scenarios considered in this study, which were patterned after acute phase neuropsychiatric clinical trials, the likelihood-based repeated measures approach, implemented with standard software, was more robust to the bias from missing data than LOCF, and choice of correlation structure was not an impediment to its implementation.

Analysis of Variance↗