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PubMed1999

Tuberculin sensitivity: conversions and reversions in a rural African population.

SETTING: Karonga District, northern Malawi, 1980-1989. OBJECTIVE: To measure and interpret incidence and prevalence of tuberculin sensitivity. DESIGN: Tuberculin testing carried out within two total population surveys. Tuberculin 'positivity' and 'conversion' were defined using criteria recommended by the Tuberculosis Surveillance Research Unit and the American Thoracic Society, respectively. RESULTS: Data on 64,225 tests were available for analysis, including paired results on 6991 individuals tested in both surveys. Frequency distributions of induration varied by age, sex, BCG scar status and zone within the district. The prevalence of 'positivity' was similar in males and females until age 15, then higher among males, and was consistently higher among individuals with than among those without a BCG scar. Tuberculin 'conversion' rates estimated from cross-sectional data ranged from 0.34 to 1.15 per cent per annum. Conversion rates derived from longitudinal data were found to increase linearly with age, and the reversion rates declined rapidly with age among younger individuals. Such trends, which have been reported in other populations, are shown here to arise as an artefact of test instability. Prospective follow-up of observed converters showed greatly increased risks of tuberculosis, in particular during the two years following the second ('converted') test (relative risk > 10). CONCLUSION: Estimation of a convincing 'true' annual risk of infection from tuberculin survey data is not possible from either cross-sectional or longitudinal data, due to misclassifications and the instability of delayed type hypersensitivity over time. An apparent increase in infection risk with age can arise as an artefact of test instability. BCG-induced tuberculin sensitivity declines rapidly in this population in most individuals. It is necessary to consider tuberculin reversions, whether real or apparent, when interpreting tuberculin data on individuals or populations.

Adolescent↗
PubMed1990

Analysis and presentation of data on the natural course of otitis media with effusion in children.

Methods of analysing and presenting longitudinal data on health characteristics that have a fluctuating course are by no means standard. Several possibilities are discussed and tried out on longitudinal data on Otitis Media with Effusion (OME) in Dutch children. If the purpose of a study is descriptive, a graphical presentation based on an idea from Fiellau-Nikolajsen is preferred. For estimation purposes on the other hand, hazard functions are the most suitable. Further reduction of the data does not lead to a clear view into the complex nature of the course of a disease such as OME.

Acoustic Impedance Tests↗
PubMed2006

Analysis of incomplete longitudinal binary data using multiple imputation.

We propose a propensity score-based multiple imputation (MI) method to tackle incomplete missing data resulting from drop-outs and/or intermittent skipped visits in longitudinal clinical trials with binary responses. The estimation and inferential properties of the proposed method are contrasted via simulation with those of the commonly used complete-case (CC) and generalized estimating equations (GEE) methods. Three key results are noted. First, if data are missing completely at random, MI can be notably more efficient than the CC and GEE methods. Second, with small samples, GEE often fails due to 'convergence problems', but MI is free of that problem. Finally, if the data are missing at random, while the CC and GEE methods yield results with moderate to large bias, MI generally yields results with negligible bias. A numerical example with real data is provided for illustration.

Clinical Trials as Topic↗
PubMedDate not supplied

Patterns of physical symptoms and relationships with psychosocial factors in adolescents.

OBJECTIVES: Physical symptoms are common in otherwise healthy adolescents. This study sought to identify meaningful patterns of multiple physical symptoms and to examine relationships between the patterns and psychosocial factors. One-year stability of symptom patterns and factors contributing to stability were also examined. METHODS: This secondary data analysis used longitudinal data from a nationally representative sample of adolescents in grades 7 through 12 (n = 9,141) who participated in the National Longitudinal Study of Adolescent Health during 1994 to 1996. Ten selected physical symptoms (i.e., headache, stomachaches, fatigue) were used to construct clusters. Each cluster was compared in regard to demographic factors, psychological adjustment and interpersonal relationships. RESULTS: K-means in combination with Ward method clustered the sample into 4 groups according to the overall patterns of the 10 symptoms: nonsymptom (41%), moderate symptom (38%), high symptom (19%) and extreme symptom (2%). Adolescents in higher symptom clusters were more likely to be girls, nonwhites, or from families on welfare and reported high depressive symptoms, low self-esteem, and poor perceptions of parental affection and friendship quality. About 16% in clusters with lower symptom patterns develop somatizing patterns in Wave II; new onset was predicted by gender, younger age, and depressive symptoms. CONCLUSION: Symptom patterns characterized by overall high frequencies of multiple symptoms may indicate somatization. This study also suggests that adolescents with a somatizing tendency are more likely to experience psychological and interpersonal difficulties, and girls and younger adolescents are more vulnerable. Targeted prevention programs are needed for these vulnerable individuals by addressing their psychosocial functioning.

Adaptation, Psychological↗
PubMed2006

Longitudinal patterns of alcohol, drug, and mental health need and care in a national sample of U.S. adults.

OBJECTIVE: Use of longitudinal data can help clarify the extent of persistent need for services or persistent problems in gaining access to services. This study examined the level of transient and persistent need and unmet need over time among respondents to a national survey and whether need was met by provision of mental health services or resolved without treatment. METHODS: Data from the longitudinal Health Care for Communities (HCC) household telephone survey were used to produce joint distributions of need status and care for two periods (wave 1 data collected in 1997 to 1998 and wave 2 data collected in 2000 to 2001; N=6,659). Perceived need was measured as self-report of need for help with a mental or substance use problem. Probable clinical need was assessed with the Composite International Diagnostic Interview, the Alcohol Use Disorders Identification Test, and the 12-item Short Form Health Survey. RESULTS: High levels of persistent unmet need for care (44 to 52 percent) were found among respondents who had probable clinical need in wave 1. Although a majority of those with need received some care, an equal proportion (about 30 percent) of those with perceived need only or probable clinical need in wave 1 did not receive any care. A substantial portion of need (22 to 26 percent) appears to have resolved without treatment, which may suggest high levels of transient need. CONCLUSIONS: Persistent patterns of unmet need represent important targets for policy and programs that can improve utilization, including outreach, education, and improved insurance coverage.

Adolescent↗
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↗
PubMed2005

Racial differences in rate of decline in bone mass in older men: the Baltimore men's osteoporosis study.

UNLABELLED: Older black men have higher adjusted BMD than older white men. Using data from a longitudinal cohort study of older men followed for a mean of 18.8 +/- 6.5 (SD) months, we found that older black men have a higher rate of decline in femoral neck and total hip BMD and femoral neck BMAD than older white men. INTRODUCTION: Older black men have higher adjusted BMD compared with older white men. The difference in BMD may be caused by having attained higher peak bone mass as young adults and/or having a slower rate of decline in bone mass as adults. There are few published longitudinal data on change in bone mass in older white men and no published data for older black men. MATERIALS AND METHODS: Three hundred forty-nine white men and 119 black men 65 of age (mean age, 75 +/- 5.7 and 72 +/- 5.6 years, respectively) who participated in the longitudinal component of the Baltimore Men's Osteoporosis Study returned for a second visit after a mean of 18.8 +/- 6.5 (SD) months and were not taking medications used to treat low bone mass at either visit. BMD was measured at the femoral neck and total hip by Hologic-certified technicians using a QDR 2000 at the baseline visit (V1) and QDR 4500 at the first follow-up visit (V2). Participants also completed self-administered and interviewer-administered questionnaires and underwent standardized clinic examinations. Bone mineral apparent density (BMAD) at the femoral neck was calculated as an estimate of volumetric BMD. Annual crude and multiple variable adjusted percent changes in BMD and BMAD were calculated. RESULTS: In univariate analyses, black men had lower percent decline in femoral neck and total hip BMD and femoral neck BMAD than white men. In addition, older age at baseline, lower baseline weight, current smoking, and lower baseline BMD were associated with greater percent decline per year in femoral neck BMD; older age at baseline, current smoking, and lower baseline BMD were associated with greater percent decline per year in total hip BMD; and older age at baseline and lower baseline femoral neck BMAD were associated with greater percent decline per year in femoral neck BMAD. Racial differences in bone loss persisted in multiple variable models that controlled for other factors associated with change in BMD and BMAD. CONCLUSIONS: Older black men seem to lose bone mass at a slower rate than older white men. These differences in the rate of bone loss may account, in part, for the racial disparities in BMD and BMAD and risk of osteoporotic fractures among older men.

Black or African American↗
PubMed2004

The application of multilevel modeling in the analysis of longitudinal periodontal data--part II: changes in disease levels over time.

BACKGROUND: The aim of this study was to investigate the longitudinal relationships between the outcome measurements of changes in lifetime cumulative attachment loss (cLCAL) and changes in probing depth (cPD) in relation to potential risk factors or other risk markers for periodontal disease progression from a cohort of 100 young males. In order to account for the hierarchical data structure, and to explore explicitly the site, tooth, and subject levels simultaneously, multilevel modeling was undertaken. METHODS: The analyses were undertaken in two parts. Within a previous article, the absolute levels of disease were analyzed in relation to potential risk factors; within this article, changes in disease are analyzed in relation to these factors. Each analytical approach yielded substantively different insights. RESULTS: Subject-level risk factors had limited predictive value for cLCAL/cPD throughout the 30-month observation period. Tooth position demonstrated a near linear relationship for both outcomes, with disease increasing from anterior to posterior teeth. Supragingival plaque had no significant effect on cLCAL/cPD, while subgingival calculus and bleeding on probing were negatively associated with cLCAL/cPD. In contrast to the outcomes LCAL/PD, supragingival calculus had no significant protective effect on cLCAL/cPD. There was no significant influence of smoking in this cohort. CONCLUSIONS: This study provides, for a relatively young cohort, considerable insights into the factors associated with longitudinal patterns of early-life periodontal disease at all levels of the natural hierarchy of sites within teeth within subjects. Furthermore, it is demonstrated how multilevel modeling can provide considerable insight into some of the inconsistencies and controversies found in the previous periodontal literature.

Adolescent↗
PubMed2024

Free-water: A promising structural biomarker for cognitive decline in aging and mild cognitive impairment.

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 ± 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 ± 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-ε4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (ΔRadj 2 = 3.47 ± 1.65%) and executive function (ΔRadj 2 = 2.43 ± 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (ΔRadj 2 = 8.13 ± 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

Alzheimer’s disease (AD)↗
PubMed1999

Risk-adjusted capitation based on the Diagnostic Cost Group Model: an empirical evaluation with health survey information.

OBJECTIVE: To evaluate the predictive accuracy of the Diagnostic Cost Group (DCG) model using health survey information. DATA SOURCES/STUDY SETTING: Longitudinal data collected for a sample of members of a Dutch sickness fund. In the Netherlands the sickness funds provide compulsory health insurance coverage for the 60 percent of the population in the lowest income brackets. STUDY DESIGN: A demographic model and DCG capitation models are estimated by means of ordinary least squares, with an individual's annual healthcare expenditures in 1994 as the dependent variable. For subgroups based on health survey information, costs predicted by the models are compared with actual costs. Using stepwise regression procedures a subset of relevant survey variables that could improve the predictive accuracy of the three-year DCG model was identified. Capitation models were extended with these variables. DATA COLLECTION/EXTRACTION METHODS: For the empirical analysis, panel data of sickness fund members were used that contained demographic information, annual healthcare expenditures, and diagnostic information from hospitalizations for each member. In 1993, a mailed health survey was conducted among a random sample of 15,000 persons in the panel data set, with a 70 percent response rate. PRINCIPAL FINDINGS: The predictive accuracy of the demographic model improves when it is extended with diagnostic information from prior hospitalizations (DCGs). A subset of survey variables further improves the predictive accuracy of the DCG capitation models. The predictable profits and losses based on survey information for the DCG models are smaller than for the demographic model. Most persons with predictable losses based on health survey information were not hospitalized in the preceding year. CONCLUSIONS: The use of diagnostic information from prior hospitalizations is a promising option for improving the demographic capitation payment formula. This study suggests that diagnostic information from outpatient utilization is complementary to DCGs in predicting future costs.

Adolescent↗
PubMed1993

Factors affecting conversion rates to Medicaid among new admissions to nursing homes.

OBJECTIVE: This study examines conversion to Medicaid as a payment source among a cohort of newly admitted nursing home residents. DATA SOURCE: The longitudinal data used came from regular assessments of residents in the National Health Corporation's 43 for-profit nursing homes in Missouri, Kentucky, South Carolina, and Tennessee. This information system tracked all residents who were discharged, providing a comprehensive record that may have spanned multiple admissions. STUDY DESIGN: Using survival analysis methods, Cox regression, and survival trees, we contrasted the effect of state, initial payment source, education, age, and functional status on the rate of spend-down to Medicaid. DATA EXTRACTION METHODS: New-admission cohorts were created by linking an admission record for a newly admitted resident with all subsequent assessments and follow-up records to ascertain the precise dates of any payment source changes and other discharge transitions. PRINCIPAL FINDINGS: For the 1,849 individuals who were admitted as self-payers and who were still in the nursing home at the end of one year, there is a 19 percent probability of converting to Medicaid. All analytic methods revealed that education, age, and state of residence were predictive of spend-down among residents who were admitted as self-payers. CONCLUSIONS: Our results confirm the effect of education as an SES indicator and state as a proxy for Medicaid policy on spend-down. Future research should model the effects and duration of intervening hospitalizations and other transitions on Medicaid spend-down among new admissions.

Activities of Daily Living↗
PubMed2004

A longitudinal study of Alzheimer's disease: rates of cognitive and functional decline.

OBJECTIVE: To measure rates of decline in cognition and function in patients with Alzheimer's disease (AD) and to investigate their accelerating risk factors in Korea. METHODS: This study presents longitudinal data on a community-based sample of 107 patients with AD, followed at 6 months and 12 months. The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini Mental State Examination (MMSE) and the Disability Assessment for Dementia Scale (DAD) were given. Mixed model analyses were conducted using the following independent variables: times of repeated assessment (0, 6 or 12 months), severity of dementia assessed by the Functional Assessment Staging (FAST) and individual indicators as covariates. RESULTS: Average annual rates of decline in the MMSE, the ADAS-cog and the DAD were 2.3, 11.4 and 15.1 points, respectively. Neither gender, duration of formal education, nor duration of AD since onset was significant predictors of cognitive and functional decline. Patterns of functional decline in total DAD, instrumental ADLs, planning and organization and performance subscale are linear as MMSE score declines, while those of the basic ADLs and the initiation are curvilinear. CONCLUSION: This naturalistic observational study measured rates of cognitive and functional decline in AD, and can provide reference data for further longitudinal studies or clinical trials. Further study will be necessary to determine whether linear or curvilinear pattern in functional decline is due to progression of AD itself or statistical artifact.

Activities of Daily Living↗
PubMed1991

A bibliography and comments on the use of statistical models in epidemiology in the 1980s.

This paper reviews developments in statistical modelling in epidemiology in the 1980's, with emphasis on cohort and case-control studies. The central roles of the logistic and proportional hazard models are highlighted, and it is shown how these models lead to a deeper understanding of classical designs and methods of analysis as well as to efficient new designs and analytical procedures. The important area of model misspecification is discussed, including the problems of omitted latent structure, mis-modelling of available measurements, missing data and errors in measurements. Various designs motivated by the logistic model are illustrated numerically, and designs based on the proportional hazards model are discussed, as are papers on sample size determination. There are brief introductions to the literature on other topics, including attributable risk, disease clustering, family studies and genetics, analysis of disease incidence data, infectious disease, longitudinal data, screening and miscellaneous related topics in statistics. An extensive bibliography is indexed according to the outline of the paper.

Data Interpretation, Statistical↗
PubMed1994

Progression of chronic renal failure in a historical group of patients with nephropathic cystinosis. European Collaborative Study on Cystinosis.

In a historical group of 205 patients with infantile or adolescent cystinosis treated without cysteamine, the rate of deterioration of renal function was analysed retrospectively. Patient survival curves and renal survival data are presented. Longitudinal data of serum creatinine values (n = 3280) in 157 patients were plotted for each patient, smoothed by the method of the running medians and grouped into 12 serum creatinine classes. In every patient the age at the last smoothed serum creatinine value observed in each serum creatinine class was determined. These virtual age values were then summarized per serum creatinine class, expressed as median and centiles and plotted, thus describing the "natural" course of the disease. In 9 pairs of affected siblings the rate of progression showed a median difference of about 12 months. Our data describe the "natural" course of nephropathic cystinosis and can be used as a prognostic aid for recently detected patients. The data can also be applied for the assessment of the influence of new therapeutic strategies on the rate of progression of renal failure in cystinotic patients.

Child, Preschool↗
PubMed2002

Strategies to fit pattern-mixture models.

Whereas most models for incomplete longitudinal data are formulated within the selection model framework, pattern-mixture models have gained considerable interest in recent years (Little, 1993, 1994). In this paper, we outline several strategies to fit pattern-mixture models, including the so-called identifying restrictions strategy. Multiple imputation is used to apply this strategy to realistic settings, such as quality-of-life data from a longitudinal study on metastatic breast cancer patients.

Journal Article↗
PubMed1997

Age-associated loss of power and strength in the upper extremities in women and men.

Cross-sectional and longitudinal age-associated reductions in power and isometric strength are described for the upper extremities. Over a 25-year period, repeated measures were taken approximately every 2 years from men and women in the Baltimore Longitudinal Study of Aging (BLSA). The longitudinal measures covered an average 9.6 years, range 1-25 years for men and an average 4.6 years, range 1-8 years for women. Strength and power declined beginning by age 40 in both women and men. Thereafter, power declined about 10% more than strength in men, while no significant differences were found in women. Age had a statistically independent influence on strength and power measures after adjusting for gender, height, weight, caloric expenditure, and muscle mass. Twenty-five-year longitudinal analyses in men confirmed the declines observed cross-sectionally, while no changes were observed in women over the 4-5 years of longitudinal data available. Further longitudinal studies are needed to understand the relationships between strength and power losses with age in women. The differences between power and strength changes with age in men argue for the importance of factors other than strength affecting power.

Adult↗
PubMedDate not supplied

Systematic review of the optimal frequency of follow-up in persons with mild dementia who continue to drive.

Fitness-to-drive guidelines commonly indicate that persons with mild dementia may be safe to drive but that periodic reevaluation is required. This paper presents the findings of a systematic review of primary evidence regarding the optimal timing of follow-up in persons with mild dementia who continue to drive. A search of Medline, CINAHL, PsychInfo, AARP Ageline, and Sociofile from 1984 to 2005 was performed. No published studies focus primarily on the timing of follow-up of drivers with mild dementia. Three studies present longitudinal data that the authors reference when recommending periodicity of follow-up. This study identifies a concerning research gap in the field of dementia and driving. To provide better evidence to guide recommendations for periodicity of follow-up, 3 recommendations are proposed: (1) that prospective cohort driving research be undertaken to follow patients with mild dementia who continue to drive, (2) that data from such longitudinal research be presented as survival analyses, and (3) that existing research on the progression rates of Alzheimer disease be employed as a default until the first 2 recommendations are realized.

Aged↗