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PubMed1999

Success and failure in periradicular surgery: a longitudinal retrospective analysis.

The objective of the present study was to compare the success rates of 2 different periapical surgical techniques, the traditional technique with rotary instruments and the ultrasonic technique, which uses ultrasonic retrotips. A longitudinal retrospective study was carried out on 302 apices (181 teeth) that had undergone periapical surgery. Surgical outcome was evaluated by 2 independent operators using standardized periapical radiographs. Each radiographic finding was classified into 1 of 4 groups: complete healing, incomplete healing, uncertain healing, and unsatisfactory outcome (failure). An SAS statistical analysis system was used for data management and analysis. Prognostic factors were determined by means of the Fisher exact test. Complete healing after 4.6 years (the average follow-up period) was observed in 68% of the teeth treated through the use of the standard technique and 85% of those treated through the use of the ultrasonic technique. The success rate increased as the follow-up period lengthened (68.4% at 2 years vs 80% at 6 years). The success rate was higher in maxillary (77.9%) than in mandibular (66.1%) teeth. A comparison between the retrofilling materials was not feasible because all teeth in the standard technique group were retrofilled with amalgam and all teeth in the ultrasonic group were retrofilled with Super-EBA.

Adult↗
PubMed1976

A regression model analysis of longitudinal dental caries data.

Longitudinal data on caries experience were derived from the reexamination and interview of a cohort of 306 subjects with an average follow-up period of 33 years after the baseline examination. Analysis of the data was accomplished by the use of contingency tables utilizing enumeration statistics compared with a multiple regression analysis. The analyses indicated a strong association of caries experience at one point in time with the caries experience of that same person earlier in life. The regression model approach offers adjustment of any given independent variable for the effect of all other independent variables, providing a powerful means of bias reduction. The model is also useful in separating out the specific effect of an independent variable over and above the contribution of other variables. The model used explained 35% of the variability in the DMFS scores recorded. Similar models could be useful adjuncts in the analyses of dental epidemiologic data.

Adolescent↗
PubMed1994

Analysis of longitudinal data: random coefficient regression modelling.

We review random coefficient regression (RCR) models and methods for fitting these models from an applications perspective. Methods for data with exponential family distributions are presented with the Gaussian distribution as a special case. Attention is given to interpretation of fixed effects and the correlation structures implied by RCR models. Estimation methods are presented wtih computational approaches. Problems associated with testing fixed effects include accurate variance estimation and robustness to misspecification of the covariance structure. Methods for model selection and assessment are presented. An example is used to demonstrate recommended approaches.

Adult↗
PubMed2005

Measurement and prediction of motor proficiency in children using Bayley infant scales and the Bruininks-Oseretsky test.

A sample of 76 Irish girls and boys of about 9 years of age, for whom neonatal (birthweight, Apgar and Neonatal Behavioural Assessment Scale) and infancy measures (Bayley Infant Scales at 18 months) were available, were administered the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). The main focus of this paper is on a longitudinal analysis of the relationships between the neonatal and infancy measures and the BOTMP administered at about 9 years. However, since the literature expresses some doubts about the basis of the division of the BOTMP subtests into fine motor and gross motor groups and about the meaningfulness of the overall battery score, an initial statistical analysis was undertaken to examine these construct validity issues with this sample of children. This analysis indicated that the division of subtests into fine motor and gross motor skills groups, as formulated by the BOTMP, is not supported. The longitudinal analysis, therefore, focused mainly on subtest scores and provided some evidence of a degree of continuity in measured motor proficiency between birth, 18 months and the prepubertal period. Continuity was more evident for female children.

Child↗
PubMed2003

Statistical significance analysis of longitudinal gene expression data.

MOTIVATION: Time-course microarray experiments are designed to study biological processes in a temporal fashion. Longitudinal gene expression data arise when biological samples taken from the same subject at different time points are used to measure the gene expression levels. It has been observed that the gene expression patterns of samples of a given tumor measured at different time points are likely to be much more similar to each other than are the expression patterns of tumor samples of the same type taken from different subjects. In statistics, this phenomenon is called the within-subject correlation of repeated measurements on the same subject, and the resulting data are called longitudinal data. It is well known in other applications that valid statistical analyses have to appropriately take account of the possible within-subject correlation in longitudinal data. RESULTS: We apply estimating equation techniques to construct a robust statistic, which is a variant of the robust Wald statistic and accounts for the potential within-subject correlation of longitudinal gene expression data, to detect genes with temporal changes in expression. We associate significance levels to the proposed statistic by either incorporating the idea of the significance analysis of microarrays method or using the mixture model method to identify significant genes. The utility of the statistic is demonstrated by applying it to an important study of osteoblast lineage-specific differentiation. Using simulated data, we also show pitfalls in drawing statistical inference when the within-subject correlation in longitudinal gene expression data is ignored.

Adaptation, Physiological↗
PubMedDate not supplied

Analysis of longitudinal data in an Alzheimer's disease clinical trial.

Evidence of delayed progression is the primary mechanism for demonstrating therapeutic efficacy in clinical trials in Alzheimer's disease. In the major trials of therapeutic treatment of AD, to date, measures based on clinical judgement and cognitive performance, instead of mortality, have been used as the primary response measures. There is good reason for this since the course of the disease is quite long, and AD trials designed around mortality would require either very large sample sizes or very long follow-up in order to have adequate power. However, the evaluation of progression in AD using clinical markers is subject to a number of challenges often found in longitudinal databases, for example, missing data, floor and ceiling effects and non-linearity. Unfortunately, few of these issues are being addressed in the typical analysis of progression data. This paper explores these analytic issues in the context of the recently completed Alzheimer's Disease Cooperative Study trial of vitamin E and Selegeline in moderate AD patients.

Aged↗
PubMed2000

The phenotype of DFNA13/COL11A2: nonsyndromic autosomal dominant mid-frequency and high-frequency sensorineural hearing impairment.

OBJECTIVE: To study nonsyndromic progressive sensorineural hearing impairment in patients with a COL11A2 mutation (DFNA13) in a Dutch kindred. STUDY DESIGN: Survey. SETTING: Department of otorhinolaryngology of a university hospital. PATIENTS: Twenty-one living members of a Dutch family (150 relatives in 5 generations; 49 were studied) with autosomal dominant nonsyndromic sensorineural hearing impairment showed linkage to the DFNA13 locus. Mutation analysis revealed a missense mutation in the COL11A2 gene. METHODS: History was taken, hearing threshold levels were measured in all affected persons, and penetrance was evaluated. Longitudinal analysis (using linear regression analysis of threshold-on-age data) was possible in only 1 case. Cross-sectional analysis comprised the comparison of threshold levels between different generations of the family. Also, hearing thresholds were corrected for median presbyacusis to find out whether the hearing impairment characteristic of this trait is stationary or progressive. Vestibular functions were evaluated with electronystagmography, by use of rotatory and caloric tests. RESULTS: Most of the affected persons dated their first hearing impairment symptoms to the second to third decade of life. A possibly reduced penetrance was found. Anamnestically, 4 affected persons had hearing impairment symptoms from early childhood onward. Longitudinal analysis in the proband (IV26) revealed the exceptional combination of congenital offset and substantial early progression. Most of the threshold levels differed significantly between the frequencies within each age group and, at the high frequencies (2-8 kHz), between the two age groups covered by generations IV and III (ages 30-38 years and 58-74 years, respectively); the latter could be attributed to presbyacusis. Various caloric abnormalities, including areflexia, were found in about half (8/17) of the tested subjects with sensorineural hearing impairment. CONCLUSIONS: Correction for age, hearing impairment-presumably present and stationary from an early age onward-showed the worst or second-worst threshold usually at 1, 2, and 6 kHz (3540 dB) or 8 kHz (50 dB), whereas the best or second-best threshold was found at 0.25 to 0.5 and 4 kHz (25 dB). Presbyacusis, presumably from the fourth decade of life onward, caused a change of the typically shaped audiogram described as midfrequency hearing impairment with additional high-frequency impairment.

Adult↗
PubMed2005

Effects of variance-function misspecification in analysis of longitudinal data.

The approach of generalized estimating equations (GEE) is based on the framework of generalized linear models but allows for specification of a working matrix for modeling within-subject correlations. The variance is often assumed to be a known function of the mean. This article investigates the impacts of misspecifying the variance function on estimators of the mean parameters for quantitative responses. Our numerical studies indicate that (1) correct specification of the variance function can improve the estimation efficiency even if the correlation structure is misspecified; (2) misspecification of the variance function impacts much more on estimators for within-cluster covariates than for cluster-level covariates; and (3) if the variance function is misspecified, correct choice of the correlation structure may not necessarily improve estimation efficiency. We illustrate impacts of different variance functions using a real data set from cow growth.

Animals↗
PubMed2004

The utility of the zero-inflated Poisson and zero-inflated negative binomial models: a case study of cross-sectional and longitudinal DMF data examining the effect of socio-economic status.

OBJECTIVES: To examine the utility of the zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) modelling approaches for modelling four sets of dental caries data from the same cohort study [with particular attention to the influence of childhood socioeconomic status (SES)]: cross-sectional data on the deciduous dentition at age 5 years; cross-sectional data on the permanent dentition at age 18 and 26 years; and longitudinal data on caries increment between ages 18 and 26 years. METHODS: Data on dental caries occurrence at ages 5, 18 and 26 years were obtained from the Dunedin Multidisciplinary Health and Development Study (DMHDS). ZIP and ZINB models were fitted to the cross-sectional (n = 745) and longitudinal (n = 809) data sets using Stata (Intercooled Stata 7.0). The dependent variables for the three cross-sectional analyses were the DMFS indices at age 5, 18, and 26 years, and net DFS increment (NETDFS) was the dependent variable for the longitudinal analysis. RESULTS: The empty ZIP model was a poor fit for all four data sets, whereas the empty ZINB model showed good fit; consequently both the cross-sectional and longitudinal analyses were conducted using ZINB modelling. Being in the high-SES group during childhood was associated with a greater probability of being caries-free by age 18 years, over and above that which would be expected from the negative binomial process. Low childhood SES also had the largest coefficient in the modelling of the negative binomial process, but at age 5 years, where the adjusted mean dmfs score in the low-SES group was 6.8 (compared with 4.7 and 2.9 in the medium- and high-SES groups, respectively). The substantial SES differences which existed at age 5 years (in the deciduous dentition) had reduced somewhat by age 18 years, and had widened again by age 26 years. In the longitudinal analysis, "baseline" caries experience (age 18-year DMFS) was a predictor both of being an extra zero and of caries severity. CONCLUSION: This investigation of the utility of the zero-inflated approach for modelling both cross-sectional and longitudinal caries data has shown that ZIP/ZINB models can provide new insight into disease patterns. It is anticipated that they will become increasingly useful in epidemiological studies that use the DMF index as the outcome measure.

Adolescent↗
PubMedDate not supplied

Analysis of longitudinal marginal deterioration of ceramic inlays.

This study quantitatively and morphologically analyzed and clarified the longitudinal marginal changes of ceramic inlays and determined the mechanism for those changes. Epoxy replicas of 15 Class II ceramic inlays in permanent premolars prepared at baseline, 6, 12, 24, 48, 72 and 96 months after placement were selected. A CCD optical laser scanner was employed to measure quantitative changes in the occlusal surfaces of restored teeth. Longitudinal cross-sections of marginal areas of a ceramic inlay were computed, and two profiles of the same location obtained at different periods were superimposed using software. The area enclosed by the two profiles obtained at different periods was defined as the quantitative marginal change, and both the area and maximum depth in the area enclosed were calculated with picture analysis software. The marginal deterioration pattern was analyzed by drawing a longitudinal curve of quantitative change for each restoration. Morphological observation was carried out by scanning electron microscopy at magnifications from 20x to 75x. Quantitative measurement and morphological observation identified a sequential three-stage pattern of marginal deterioration; initial rapid progress of wear of resin composite cement in the first stage, followed by a second stage without any remarkable visible change, then rapid progression of microfractures of ceramics and/or enamel in the third stage. Boundaries between the first and second stage were found in the six and 21-month period, and those between the second and third stage at 72 months. It was concluded that longitudinal marginal deterioration of fired ceramic inlays progressed in a sequential three-stage pattern.

Dental Porcelain↗
PubMed2004

Longitudinal transcriptional analysis of developing neointimal vascular occlusion and pulmonary hypertension in rats.

Pneumonectomized rats injected with the alkaloid toxin, monocrotaline, develop progressive neointimal pulmonary vascular obliteration and pulmonary hypertension resulting in right ventricular failure and death. The antiproliferative immunosuppressant, triptolide, attenuates neointimal formation and pulmonary hypertension in this disease model (Faul JL, Nishimura T, Berry GJ, Benson GV, Pearl RG, and Kao PN. Am J Respir Crit Care Med 162: 2252-2258, 2000). Pneumonectomized rats, injected with monocrotaline on day 7, were killed at days 14, 21, 28, and 35 for measurements of physiology and gene expression patterns. These data were compared with pneumonectomized, monocrotaline-injected animals that received triptolide from day 5 to day 35. The hypothesis was tested that a group of functionally related genes would be significantly coexpressed during the development of disease and downregulated in response to treatment. Transcriptional analysis using total lung RNA was performed on replicate animals for each experimental time point with exploratory data analysis followed by statistical significance analysis. Marked, statistically significant increases in proteases (particularly derived from mast cells) were noted that parallel the development of vascular obliteration and pulmonary hypertension. Mast-cell-derived proteases may play a role in regulating the development of neointimal pulmonary vascular occlusion and pulmonary hypertension in response to injury.

Animals↗
PubMedDate not supplied

A longitudinal cost analysis of primary and team nursing.

Cost findings from a 4-year (1984-1989) externally funded, empirical study, comparing primary and team nursing on medical units in a tertiary care teaching hospital, demonstrates that primary nursing is less costly than team nursing. An average savings of 6.5% was realized for the duration of the study. Three factors are identified as being responsible for the difference on a cost per patient per day basis. Overall, cost analysis per DRG from primary nursing suggests cost differences related to high DRG volume and average length-of-stay. An administrative review of the study's implications highlights the relevancy of these findings in relationship to nurse retention and cost savings.

Costs and Cost Analysis↗
PubMedDate not supplied

Differences in the detection of three HIV-1 protease inhibitors in non-blood compartments: clinical correlations.

PURPOSE: To study the presence of three HIV-1 protease inhibitors (PIs) in the cerebrospinal fluid (CSF), semen, and lymph nodes and to assess the correlations with residual viral replication in these compartments. METHOD: We performed a cross-sectional analysis of sanctuary samples from 41 HIV-infected patients on stable highly active antiretroviral therapy (HAART) regimens containing indinavir, nelfinavir, or lopinavir combined with ritonavir (lopinavir/r) and a longitudinal analysis of PI levels and HIV-1 RNA in plasma and CSF of 6 additional patients on nelfinavir or lopinavir/r monotherapy (3 cases each). Plasma, CSF, semen, and a lymph node (LN) biopsy were taken on the same day. Samples were assayed for PI concentrations, HIV-1 RNA levels, and, when detectable, sequencing of the reverse transcriptase and protease genes on seminal viral RNA. RESULTS: In the cross-sectional analysis, the CSF/plasma ratio was 0.14 for indinavir. Nelfinavir and lopinavir/r were consistently undetectable in CSF. The semen/plasma ratio was 1.9 for indinavir, 0.07 for nelfinavir, and 0.07 for lopinavir. The LN/plasma ratio was 2.07 for indinavir, 0.58 for nelfinavir, 0.21 for lopinavir, and 0.64 for ritonavir. Plasma HIV-1 RNA was <50 copies/mL in 28 patients and was detectable in 13 patients. HIV-1 RNA was <50 copies/mL in CSF samples when plasma RNA was undetectable. Three semen samples taken from patients with viremia <50 copies/mL showed detectable HIV-1 RNA with resistance mutations. HIV-1 RNA was detectable in all LNs, with no differences in patients on indinavir compared with those on nelfinavir or lopinavir/r. In the longitudinal analysis, HIV-1 RNA decreased in the plasma of the 6 patients on nelfinavir or lopinavir/r monotherapy, although CSF HIV-1 RNA decreased only in patients on lopinavir/r. CONCLUSION: Major differences exist between PIs in terms of detection in non-blood compartments. An undetectable PI level in CSF does not rule out drug activity in the brain for lopinavir/r, although this is not the case for nelfinavir. Poor penetration of PIs in semen in some patients can lead to double nucleoside therapy in this compartment. The persistence of HIV-1 RNA in LNs does not seem to be related to PI levels in this tissue.

Adult↗
PubMed2005

Analysis of longitudinal binary data with missing data due to dropouts.

Longitudinal binary data from clinical trials with missing observations are frequently analyzed by using the Last Observation Carry Forward (LOCF) method for imputing missing values at a visit (e.g., the prospectively defined primary visit time point for analysis at the end of treatment period). Usually, to understand time trend in treatment response, analyses are also performed separately on data at intermediate time points. The objective of such analyses is to estimate the proportion of "response" at a time point and then to compare two treatment groups (e.g., drug vs. placebo) by testing for the difference in the two proportions of response. The commonly used methods are Fisher's exact test, chi-squared test, Cochran-Mantel-Haenszel test, and logistic regression. Analyses based on the Observed Cases (OC) data are usually also performed and compared with those obtained by LOCF. Another approach that is gaining popularity (after the introduction of PROC GENMOD by the SAS Institute) is to use the method of Generalized Estimating Equations (GEE) with a view to include all repeated observations in the analysis in a more comprehensive manner. It is now well recognized, however, that results obtained by these methods are susceptible to bias, depending on the "missing data mechanism." Of particular concern is the bias introduced by NMAR dropouts. Because there is no one method to satisfactorily handle dropouts in data analysis, consensus is gathering toward doing analyses by several methods (including methods to handle NMAR dropouts) to evaluate sensitivity of results to model assumptions. In this article, we demonstrate application of the following methods for handling dropouts in longitudinal binary data: Generalized Linear Mixture Models (GLMM) (for handling NMAR dropouts), Weighted GEE (for handling MAR dropouts), and GEE (MCAR dropouts). The results are also compared with those obtained by logistic regression (univariate) on both LOCF and OC data.

Clinical Trials as Topic↗
PubMed2005

Use of total lymphocyte count for informing when to start antiretroviral therapy in HIV-infected children: a meta-analysis of longitudinal data.

BACKGROUND: Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4-cell percentage. METHODS: Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12-month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4-cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. FINDINGS: Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4-cell percentage (r=0.08-0.19 dependent on age). For children older than 2 years, the 12-month risk of death and AIDS increased sharply at values less than 1500-2000 cells per muL, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4-cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4-cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. INTERPRETATION: In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4-cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy.

Aging↗
PubMed1984

Cerebral blood flow changes in benign aging and cerebrovascular disease.

Cross-sectional analysis of CBF values was carried out among 668 volunteers and patients. Subjects were subdivided according to age, gender, and degree of cerebrovascular disease, ranging from healthy volunteers with or without risk factors for stroke to patients with multi-infarct dementia. Four-year longitudinal analysis was also carried out on 230 individuals from the original sample. Decrements in CBF values were evidenced by both cross-sectional and longitudinal analysis in relation to advancing age, progressive cerebrovascular disease, and dementia. Regional, age-related CBF declines in healthy volunteers were heterogeneous, possibly related to changes in levels of functional activity within different brain regions.

Aged↗