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PubMed1990

Longitudinal Gompertzian analysis of Parkinson's disease mortality in the U.S., 1955-1986: the dramatic increase in overall mortality since 1980 is the natural consequence of deterministic mortality dynamics.

Age-adjusted mortality rates for Parkinson's disease (PD) for men and women in the United States, from 1955 to 1986, were calculated and subjected to longitudinal Gompertzian analysis. Annual age-adjusted PD mortality rate distributions were determined by a common intersect point and a variable environmental factor. For men, the death rate at age 73.75 years was 19.15/100,000; for women, the death rate at age 78.99 years was 28.64/100,000 for each year from 1955 to 1986. The environmental factor declined (improved) 360.7-fold for men and 319.6-fold for women in 1986 compared to 1955. Despite this dramatic environmental improvement favoring survival in PD, there has been a 57.6% increase since 1980 in the annual crude PD mortality rate for men compared to the stable annual crude mortality rate from 1955 to 1979. A corresponding 37.9% increase in the annual crude PD mortality rate for women has also occurred since 1980. The increase in overall mortality is due entirely to rapidly increasing age-adjusted mortality rates at ages greater than the intersect points for men and women. The results suggest that overall mortality due to common 'degenerative' diseases may increase dramatically as has occurred in PD.

Age Factors↗
PubMed2003

Causes of stability of aggression from early childhood to adolescence: a longitudinal genetic analysis in Dutch twins.

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.

Aggression↗
PubMed1993

Longitudinal Gompertzian analysis of non-Hodgkin's lymphoma mortality in the US, 1979-1988: demonstration of the environmental basis for rising overall mortality.

Between 1979 and 1988, annual crude non-Hodgkin's lymphoma mortality rates (per 100,000) in the United States increased from 3.43 to 6.34 among men (an 85% increase in only 10 years) and, among women, increased from 2.82 to 5.71 (a 102% increase). Age-specific mortality rates for non-Hodgkin's lymphoma from 1979 through 1988 were subjected to longitudinal Gompertzian analysis, a method that may be able to identify and distinguish among genetic, environmental and competitive influences upon evolving mortality trends. The results of this analysis suggest that the basis for the dramatic rise in non-Hodgkin's lymphoma mortality is due to worsening environmental influences. The capability to distinguish between environmental and competitive influences upon evolving mortality patterns has significant public health policy implications.

Adolescent↗
PubMed2026

Lineage dynamics of invasive Escherichia coli isolates in the Netherlands from 1975 to 2021: a retrospective longitudinal genomic analysis.

BACKGROUND: Escherichia coli is a common cause of invasive infections such as bloodstream and cerebrospinal fluid infections in neonates. Strains positive for the K1 capsule are considered the most common cause of such neonatal invasive infections. This assumption of K1 dominance, and indeed the population genomics of E coli causing invasive infections in general is largely unstudied. We aimed to provide a comprehensive characterisation of this pathogen population using a longitudinal isolate collection. METHODS: In this analysis we report the findings of the SENTINEL study, a longitudinal genomic analysis of 1790 invasive E coli isolates collected mainly from newborns in the Netherlands between 1975 and 2021 by the Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam University Medical Centre, Amsterdam, Netherlands. The dataset included all bacterial strains cultured from cerebrospinal fluid or blood in cases of (clinical) bacterial meningitis (1976 to 1980). In 1981 the criteria were expanded to include neonates (aged ≤4 weeks) with E coli sepsis, and from July, 2016 all infants younger than 1 year with E coli sepsis were included. All isolates were sequenced using either the HiSeq 2500 or HiSeq 4000 platforms (Illumina, San Diego, CA, USA). We confirmed species and identified sequence types (STs), detected antimicrobial resistance genes, virulence genes, and the presence of K1 capsule, and characterised the dynamics of these factors over time. FINDINGS: Our data show a highly dynamic bacterial population that is entirely unaffected by antimicrobial resistance determinants. Key pathogen population fluctuations include the complete disappearance of the dominant lineage ST567 and the swapping of dominant ST95 clones from a single serotype O18:H7 clone to two distinct serotype O1:H7 clones, with changes in virulence factors including major fimbrial adhesins. These findings, combined with only 58·8% (1053 of 1790) prevalence in K1-expressing isolates in the entire study population, point to host-pathogen interaction and immune selection pressures as key drivers of bacterial population dynamics in this largely antimicrobial-naive population. INTERPRETATION: Our data show the vital need for ongoing genomic surveillance of microbial pathogen populations to guide appropriate intervention strategies. Additionally, genomic insights of a pathogen population from one specific disease syndrome or patient population cannot always be generalised across other cohorts. FUNDING: Wellcome Antimicrobial and Antimicrobial Resistance Doctoral Training Programme and the National Institute for Health and Care Research Birmingham Biomedical Research Centre.

Netherlands↗
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

Multivariate variance-components analysis of longitudinal blood pressure measurements from the Framingham Heart Study.

Multivariate variance-components analysis provides several advantages over univariate analysis when studying correlated traits. It can test for pleiotropy or (in the longitudinal context) gene x age interaction. It can also have more power than univariate analyses to detect a quantitative trait locus influencing several traits. We apply multivariate variance components to longitudinal systolic blood pressure data from the Framingham Heart Study. We find evidence for a polygenic influence on blood pressure (heritabilities at different ages range from 27% to 38%). Tests based on a factor-analytic parameterization of the polygenic variance find significant (p < 2 x 10(-3)) evidence that different genes affect blood pressure at different ages. Still, estimates for the proportion of polygenic variance due to shared genes ran as high as 85% for some trait pairs. Univariate and multivariate linkage analyses replicate previous linkage results on chromosome 17 (maximum LOD scores of 2.2 and 2.4, respectively). In this study, multivariate analysis provides no increase in power; this is likely due to the strong positive correlation in systolic blood pressure measured at different ages.

Adult↗
PubMed2000

[An evaluation of the impact of cardiovascular disease prevention in Portugal (1980-1996). A longitudinal Gompertzian analysis of mortality].

The behaviour of cardiovascular diseases has suffered important modifications in recent years. There have been increases in mortality and morbidity in some countries while others have seen stabilization and even reduction. In the countries where we have observed a reduction in cardiovascular mortality, the reasons are multiple: efficacy of prevention measures; improvement of environmental conditions; increase in survival; and competitiveness with other causes of death. In order to ascertain whether a certain tendency is real or fictitious, we need to use techniques that allow the evaluation of the true evolution, to study the effect of environmental factors (not genetic) and the variability of internal resistance (vitality) to disease. Based on the longitudinal Gompertzian analysis of mortality for ischemic heart disease (IHD) and cerebrovascular disease (CVD) between 1980 and 1996, it was possible to observe a reduction in mortality for both causes, which was more obvious in the case of CHD, and that the impact of the improvement in environmental conditions (not genetic) was higher in CVD versus IHD. The prevention of CVD was more efficient in men (42.8% vs 29.7%) than in women, while in IHD the most efficient prevention was 20.6% in women versus 14.9% in men, comparing the data of 1996 and 1980. During this period, the environmental influences (not genetic) were responsible for the reduction in mortality for IHD in 2.7% of men and 4.3% of women, while in CVD we observed a reduction in mortality of 7.5% in men and 4.5% in women.

Adult↗
PubMed2004

Sensitivity analysis of longitudinal normal data with drop-outs.

We propose to perform a sensitivity analysis to evaluate the extent to which results from a longitudinal study can be affected by informative drop-outs. The method is based on a selection model, where the parameter relating the dropout probability to the current observation is not estimated, but fixed to a set of values. This allows to evaluate several hypotheses for the degree of informativeness of the drop-out process. Expectation and variance of missing data, conditional on the drop-out time are computed, and a stochastic EM algorithm is used to obtain maximum likelihood estimates. Simulations show that when the drop-out parameter is correctly specified, unbiased estimates of the other parameters are obtained, and coverage percentages of their confidence intervals are close to their theoretical value. More interestingly, misspecification of the drop-out parameter does not considerably alter these results. This method was applied to a randomized clinical trial, designed to demonstrate non-inferiority of an inhaled corticosteroid in terms of bone density, compared with a reference treatment. Sensitivity analysis showed that the conclusion of non-inferiority was robust against different hypotheses for the drop-out process.

Adolescent↗
PubMed1994

The effects of family cohesiveness and peer encouragement on the development of adolescent alcohol use: a cohort-sequential approach to the analysis of longitudinal data.

This article demonstrates a latent growth curve methodology for analyzing longitudinal data for adolescent alcohol use by combining information from different overlapping age cohorts to form a single developmental trajectory. Hypotheses concerning the form of growth in alcohol use, the extent of individual differences in the common trajectory over time, and covariates influencing both initial status and the form of growth were tested. Utilizing five separate age cohorts each measured over the same 4-year period, results suggested a common trajectory existed across the 8 years represented by the cohort-sequential analysis, with alcohol use increasing more rapidly during the adolescents' transition to high school. Family cohesion and peer encouragement for alcohol use were hypothesized to influence both initial status and the trajectory of alcohol consumption during adolescence. While family cohesion served to suppress initial levels of consumption delaying the upward trajectory of alcohol use, peer encouragement was related not only to initial, and elevated, levels of use, but was predictive of those changes that occurred during adolescence. Discussion involves the importance of family and peer influences in the development of adolescent alcohol use and the utility of the cohort-sequential approach in the analysis of longitudinal data.

Adolescent↗
PubMed2003

Longitudinal familial analysis of blood pressure involving parametric (co)variance functions.

BACKGROUND: For analyzing longitudinal familial data we adopted a log-linear form to incorporate heterogeneity in genetic variance components over the time, and additionally a serial correlation term in the genetic effects at different levels of ages. Due to the availability of multiple measures on the same individual, we permitted environmental correlations that may change across time. RESULTS: Systolic blood pressure from family members from the first and second cohort was used in the current analysis. Measures of subjects receiving hypertension treatment were set as censored values and they were corrected. An initial check of the variance and covariance functions proposed for analyzing longitudinal familial data, using empirical semi-variogram plots, indicated that the observed trait dispersion pattern follows the assumptions adopted. CONCLUSION: The corrections for censored phenotypes based on ordinary linear models may be an appropriate simple model to correct the data, ensuring that the original variability in the data was retained. In addition, empirical semi-variogram plots are useful for diagnosis of the (co)variance model adopted.

Adult↗
PubMed2004

Functional data analysis in longitudinal settings using smoothing splines.

Data in many experiments arise as curves and therefore it is natural to use a curve as a basic unit in the analysis, which is termed functional data analysis (FDA). In longitudinal studies, recent developments in FDA have extended classical linear models and linear mixed effects models to functional linear models (also termed varying-coefficient models) and functional mixed effects models. In this paper we focus our review on the functional mixed effects models using smoothing splines, because functional linear models are special cases of this more general framework. Due to the connection between smoothing splines and linear mixed effects models, functional mixed effects models can be fitted using existing software such as SAS Proc Mixed. A case study is presented as an illustration.

Biomedical Research↗
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

[Analysis of longitudinal Gaussian data with missing data on the response variable].

BACKGROUND: Using an application and a simulation study we show the bias induced by missing data in the outcome in longitudinal studies and discuss suitable statistical methods according to the type of missing responses when the variable under study is gaussian. METHOD: The model used for the analysis of gaussian longitudinal data is the mixed effects linear model. When the probability of response does not depend on the missing values of the outcome and on the parameters of the linear model, missing data are ignorable, and parameters of the mixed effects linear model may be estimated by the maximum likelihood method with classical softwares. When the missing data are non ignorable, several methods have been proposed. We describe the method proposed by Diggle and Kenward (1994) (DK method) for which a software is available. This model consists in the combination of a linear mixed effects model for the outcome variable and a logistic model for the probability of response which depends on the outcome variable. RESULTS: A simulation study shows the efficacy of this method and its limits when the data are not normal. In this case, estimators obtained by the DK approach may be more biased than estimators obtained under the hypothesis of ignorable missing data even if the data are non ignorable. Data of the Paquid cohort about the evolution of the scores to a neuropsychological test among elderly subjects show the bias of a naive analysis using all available data. Although missing responses are not ignorable in this study, estimates of the linear mixed effects model are not very different using the DK approach and the hypothesis of ignorable missing data. CONCLUSION: Statistical methods for longitudinal data including non ignorable missing responses are sensitive to hypotheses difficult to verify. Thus, it will be better in practical applications to perform an analysis under the hypothesis of ignorable missing responses and compare the results obtained with several approaches for non ignorable missing data. However, such a strategy requires development of new softwares.

Data Interpretation, Statistical↗
PubMed2001

Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir.

BACKGROUND AND OBJECTIVES: To determine the factors contributing to changes in bone mineral density (BMD) over time in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Analyses of lumbar spine BMD in 183 male Caucasian participants in the Western Australian HIV Cohort study, comprising a longitudinal analysis of data from 54 patients on stable HAART regimens, and a cross-sectional analysis comparing data from 131 protease inhibitor (PI)-treated patients and 52 PI-naive (including 28 antiretroviral treatment-naive) patients. RESULTS: Average lumbar spine BMD remained stable or increased over the time frame considered. Although there was no evidence of a change of average BMD over time in patients receiving nelfinavir (P = 0.92), there was evidence of increasing bone density in the indinavir group (average increase, 0.31 z-score per year; P < 0.001). Lower initial z-scores in the longitudinal analysis were significantly associated with lower pre-HAART BMI (P = 0.003), consistent with results of the cross-sectional analysis in which lowest BMI prior to initial dual X-ray absorptiometry scan was associated with decreased BMD (P = 0.02, overall group). Although PI therapy was also associated with decreased BMD in a univariate analysis of the cross-sectional data (P = 0.04), this effect was abrogated in a multiple linear regression analysis (P = 0.11) with lowest BMI remaining significant (P = 0.04). CONCLUSIONS: We found no evidence, overall, of accelerated bone loss in patients treated with nelfinavir- or indinavir-containing HAART regimens, and propose that indinavir therapy may be associated with an increase in bone mineral density over time. Pre-HAART BMI was an independent and powerful determinant of an individual's initial z-score in the longitudinal analysis, and adjustment for this effect in a cross-sectional analysis abrogated the association between PI therapy and decreased lumbar spine z-score.

Body Mass Index↗
PubMed2000

Non-syndromic autosomal dominant progressive non-specific mid-frequency sensorineural hearing impairment with childhood to late adolescence onset (DFNA21).

An autosomal dominant trait of progressive, non-syndromic, non-specific mid-frequency sensorineural hearing impairment was identified in a Dutch family. Many affected family members (n = 21) were identified, among whom seven out of nine relatives aged < 30 years do not show pure mid-frequency hearing impairment, which suggests variable expression. Regression analysis was used to evaluate the age-related hearing threshold data in a cross-sectional analysis in 24 affected patients and in a longitudinal analysis in five of these. At all frequencies, progression in hearing impairment (i.e. the regression coefficient) was significant and fairly similar: the pooled value was about 1.0 dB/y. There was no significant (i.e. not =0 dB) offset threshold (i.e. Y intercept at age 0) found at any frequency. The regression lines could be pooled for the low frequencies (0.25-0.5 kHz) and the mid/high frequencies (1-8 kHz) and this produced apparent onset ages of about 3 and 4 years and annual threshold increases of 0.75 and 1.1 dB/y, respectively. In most patients there is a relatively late onset age (maximum in the range of at least 25-45 years). However, based on the longitudinal analysis of a patient from the age of 4 years onwards in some patients sensorineural hearing impairment might be congenital/prelingual. Oculo-vestibular function was found to be normal. Results from linkage studies tentatively position the underlying gene defect telomeric to the repositioned DFNA13 locus at chromosome 6p21-22.

Adult↗
PubMed2005

Factors affecting prognosis of patients who underwent corpectomy and fusion for treatment of cervical ossification of the posterior longitudinal ligament: analysis of 47 patients.

OBJECTIVE: Even though cervical ossification of the posterior longitudinal ligament (OPLL) has several unique clinical features compared with spondylotic myelopathy or cervical disc disease, there have been few reports about factors affecting prognosis after decompression using corpectomy. To clarify the prognostic factors for cervical OPLL, the authors analyzed the clinical and radiologic parameters of 47 patients retrospectively. METHODS: The patients were classified into a good-prognosis group and a poor-prognosis group according to the changes of Nurick grade after operation. Age at operation, gender, preoperative Nurick grade, duration of symptoms, snake-eye appearance, occupying ratio, type of OPLL, Pavlov ratio, and double-layer sign did not affect the prognosis significantly. RESULTS: Multiple logistic regression analysis revealed that diabetes mellitus (DM) was the only statistically significant factor predicting poor prognosis for the patients with cervical OPLL who underwent corpectomy and fusion. CONCLUSIONS: Surgeons do not have to be discouraged from performing anterior decompression for the patients with cervical OPLL on the basis of age, severity of disease (preoperative Nurick grade or occupying ratio), irreversible changes in gray matter of the spinal cord (snake-eye appearance), or duration of symptoms. We should direct our attention to DM as a potent risk factor for cervical OPLL and try to clarify the mechanism by which DM possibly affected the functional recovery of the patients.

Adult↗
PubMed1996

Longitudinal, prospective analysis of dietary intake in children with cystic fibrosis.

OBJECTIVES: Prospective, 3-year longitudinal dietary intakes of 25 prepubertal, pancreatic-insufficient children with cystic fibrosis (CF) and mild lung disease, and the intakes of 26 control children were compared, and relationships among energy intake, nutritional status, and pulmonary function were determined. STUDY DESIGN: Intakes from 3-day weighed food records were compared with CF recommendations, recommended dietary allowances (RDA), and the recommendations of the Third National Health and Nutrition Examination Survey (NHANES III). Energy and nutrient intakes were analyzed by repeated-measures analysis of variance. RESULTS: Children with CF consumed more energy than control children (p = 0.025) in terms of calories per day, percentage of RDA by age and by age and weight, energy adjusted for fat malabsorption, and percentage of NHANES III recommendations. Energy intake was similar between boys and girls with CF. The percentage of energy from fat was greater (p = 0.0004) in the CF group (3-year mean, 33%) than in the control group. Height and weight z scores declined in the CF group (p <0.05) with time. Vitamin and mineral intakes were generally adequate in the CF group. CONCLUSIONS: The children in this sample did not consume the CF recommended intakes of 120% RDA for energy or a high-fat (40% of energy) diet. Energy intakes may be insufficient in this group to meet requirements for optimal growth.

Child↗
PubMed2003

Longitudinal radiographic analysis of rheumatoid arthritis in the hand and wrist.

PURPOSE: To assess the longitudinal radiographic osseous changes of the wrist and hand other than interphalangeal joints in rheumatoid disease. METHODS: Serial wrist and hand x-rays in 96 patients with long-standing rheumatoid disease were reviewed. The average number of years between initial and most recent x-rays was 15.1. The Larsen scoring system was used to assess the degree and severity of joint involvement. We identified patterns of involvement in the wrist, thumb, and finger metacarpophalangeal (MCP) joints. RESULTS: The radioscaphoid and radiolunate joints had the earliest and most severe progression of all joints studied. Scaphoid erosions often were seen early (27%) and their presence was a predictor of progressive involvement. Ulnar styloid erosions commonly were seen as early isolated findings (25%). The distal radioulnar joint showed a rapid increase in Larsen score and was involved in 78% of patients on late x-rays. The thumb showed considerable late MCP joint disease that often led to boutonniere deformity and the trapeziometacarpal joint had the least rate of progression of all joints studied. The most severely and frequently involved MCP joints were the radial (index and middle), which also had the greatest increase in score over the span of the study. Finger MCP joint disease was observed to progress temporally in a predictable pattern: first radial MCP joints of the dominant hand, followed by the nondominant radial MCP joints, and last the ulnar MCP joints of the nondominant hand with small finger involvement preceding that of the ring finger. Of all MCP joints, the ring finger was least affected. CONCLUSIONS: This study clarified the longitudinal osseous radiographic changes of the wrist and hand (excluding interphalangeal joint) in rheumatoid disease.

Aged↗