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Biomedical subjects

T A Louis

Publications and source records attributed to T A Louis.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lipid-lowering therapy in patients with renal disease.

A growing number of clinical trials have examined the effects of different lipid lowering strategies in patients with renal disease. We carried out a meta-analysis to compare and contrast the relative efficacy of various antilipemic therapies in different renal disease settings. Studies that investigated one or more therapies designed to lower serum lipids were combined using weighted multiple linear regression. The analysis adjusted treatment effects for differences in baseline lipid levels and possible placebo effects. The results showed that antilipemic therapies generally had similar effects on lipids in different renal disease settings. In nephrotic syndrome the greatest and most consistent reductions in low density lipoprotein cholesterol (LDL) were seen with 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (regression coefficient with 95% confidence interval in mg/dl = -63, -79 to -46). Similar results were seen for LDL in renal transplant (-51, -57 to -45), renal insufficiency (-62, -82 to -42), hemodialysis (-65, -80 to -50) and continuous ambulatory peritoneal dialysis (CAPD) patients (-84, -104 to -64). Fibric acid analogues had less effect on LDL, but caused greater reductions in triglycerides: -132, -178 to -87, in nephrotic syndrome; -69, -93 to -45 in transplant: -107, -169 to -45 in renal insufficiency; -72, -120 to -24 in hemodialysis; and -96, -162 to -30 in CAPD. In general, the effects of diet and other therapies were less consistent. Despite possible limitations of this meta-analysis, the results provide a useful framework for choosing antilipemic therapy, and point to areas for future long-term studies examining the safety and efficacy of lipid lowering strategies in patients with renal disease.

Cholesterol, HDL↗
PubMed1995

Long-term effects of reduced renal mass in humans.

The long-term risks of kidney donation have not been well defined. We carried out meta-analysis of investigations that examined the long-term effects of reduced renal mass in humans. We used multiple linear regression to combine studies and adjust for differences in the duration of follow-up, the reason for reduced renal mass, the type of controls, age and gender. We analyzed 48 studies with 3124 patients and 1703 controls. Unilateral nephrectomy caused a decrement in glomerular filtration rate (-17.1 ml/min; 95% confidence interval -20.2 to -14.0 ml/min) that tended to improve with each 10 years of follow-up (1.4 ml/min/decade; 0.3 to 2.4 ml/min/decade). Patients with single kidneys had small, progressive increases in proteinuria (76 mg/day/decade; 52 to 101 mg/day/decade), but proteinuria was negligible after nephrectomy for trauma or kidney donation. Nephrectomy did not affect the prevalence of hypertension, but there was a small increase in systolic blood pressure (2.4 mm Hg; -0.3 to 5.1 mm Hg, P > 0.05) which rose further with duration of follow-up (1.1 mm Hg/decade; 0.0 to 2.2 mm Hg/decade). Diastolic blood pressure was higher after nephrectomy (3.1 mm Hg; 1.8 to 4.4 mm Hg), but this increment did not change with duration of follow-up. Thus, in normal individuals, unilateral nephrectomy does not cause progressive renal dysfunction, but may be associated with a small increase in blood pressure.

Blood Pressure↗
PubMed1995

Healthy worker effect in a longitudinal study of one-second forced expiratory volume (FEV1) and chronic exposure to granite dust.

BACKGROUND: Low level effects of granite dust on one-second forced expiratory volume (FEV1) are estimated in 618 Vermont granite workers followed for 5 years with annual pulmonary function tests. Reduced pulmonary function has already been reported for the subset of subjects lost to follow-up (dropouts) suggesting possible bias in analyses based only on survivors. METHOD: Healthy worker selection bias is directly assessed by comparing the dose-response associations between survivors who remained in the study for the full 5-year observation period and the dropouts. RESULTS: The 353 survivors had an FEV1 of 96% of predicted at baseline and were losing FEV1 at an average rate of 44 ml/yr. No association was found in this group between the rate of FEV1 decline and lifetime dust exposure. However, the 265 workers with incomplete follow-up, 'dropouts', had a lower FEV1 at baseline (94%) and were losing FEV1 at an average rate of 69 ml/yr. The dose-response parameter in this group was estimated to be 4 ml/yr loss per mg/m3-year and was statistically significant. CONCLUSIONS: These results provide an illustration of bias due to the healthy worker effect and an example of the failure to detect a true work-related health effect in a study based only on a 'survivor' population.

Adult↗
PubMed1995

Inferences on the association parameter in copula models for bivariate survival data.

We investigate two-stage parametric and two-stage semi-parametric estimation procedures for the association parameter in copula models for bivariate survival data where censoring in either or both components is allowed. We derive asymptotic properties of the estimators and compare their performance by simulations. Both parametric and semi-parametric estimators of the association parameter are efficient at independence, and the parameter estimates in the margins have high efficiency and are robust to misspecification of dependency structures. In addition, we propose a consistent variance estimator for the semi-parametric estimator of the association parameter. We apply the proposed methods to an AIDS data set for illustration.

AIDS-Related Opportunistic Infections↗
PubMed1994

Survival and disease progression according to gender of patients with HIV infection. The Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To compare disease progression and mortality between women and men infected with human immunodeficiency virus (HIV). DESIGN: Multicenter cohort. SETTING: Seventeen community-based centers participating in the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). PATIENTS: A total of 768 women and 3779 men enrolled in one or more of 11 protocols between September 7, 1990, and September 30, 1993. MAIN OUTCOME MEASURES: Survival and opportunistic events. RESULTS: The median CD4+ cell count at enrollment into the cohort was 0.240 x 10(9)/L (240/microL) for women and 0.137 x 10(9)/L for men (P < .001). Compared with men, women were younger (36 vs 38 years), more likely to be African American or Hispanic (78% vs 44%), and more likely to have reported a history of injection drug use (49% vs 27%). Women had been followed up for a median of 14.5 months and men for 15.5 months. The adjusted relative risk (RR) for death among women compared with men was 1.33 (95% confidence interval [CI], 1.06 to 1.67; P = .01) and for disease progression (including death) was 0.97 (95% CI, 0.82 to 1.15; P = .72). Women were at increased risk for bacterial pneumonia (RR, 1.38; 95% CI, 1.05 to 1.92) and at reduced risk for the development of Kaposi's sarcoma (RR, 0.16; 95% CI, 0.04 to 0.65) and oral hairy leukoplakia (RR, 0.54; 95% CI, 0.31 to 0.94). The increased risk of death and bacterial pneumonia for women compared with men was primarily evident among those with a history of injection drug use (RR, 1.68 for death, 95% CI, 1.20 to 2.35, P = .003; RR, 1.53 for bacterial pneumonia, 95% CI, 1.03 to 2.29, P = .04). Among patients without a history of disease progression at entry, death was the first event reported for more women than men (27.5% vs 12.2%). CONCLUSIONS: Compared with men, HIV-infected women in the CPCRA were at increased risk of death but not disease progression. Risks of most incident opportunistic diseases were similar for women and men; however, women were at an increased risk of bacterial pneumonia. These findings may reflect differential access to health care and standard treatments or different socioeconomic status and social support for women compared with men.

AIDS-Related Opportunistic Infections↗
PubMed1994

Statistical analysis of proliferative index data in clinical trials.

Measurements of proliferative activity in colonic epithelial cells are being used as surrogate endpoints in clinical trials for colon cancer prevention. Proliferative index data exemplify an important type of clinical trial endpoint. The outcome variable is a proportion in which the denominator is an ancillary statistic and in which measurement error and technician judgement are important sources of variability. The paper proposes a statistical model for a repeated measures clinical trial with this type of endpoint, in the context of proliferative activity data. The model is a two-stage random effects linear model in the log scale. In addition to fixed effects covariates, it explicitly incorporates two major sources of variability: the number of epithelial cells counted and the reader effect. Although the resulting likelihood is complicated, one can fit an approximate likelihood with minimal loss of efficiency using standard packages. We apply the model to a pilot randomized clinical trial.

Cell Division↗
PubMed1994

A constrained empirical Bayes estimator for incidence rates in areas with small populations.

Maps that show the geographic distribution of incidence rates can be useful tools for analysing spatial variation in mortality and morbidity. To attain the necessary geographic resolution, however, production of such maps often requires estimation of incidence in areas with small populations where the observed rates may be highly unstable. Manton et al. have presented an empirical Bayes stabilization procedure in which the observed rate is combined with an area-specific estimate of the underlying incidence. The approach allows for the mapping of outcomes with varied and possibly unknown etiologies without necessitating covariate dependent modelling of the expected rate. The empirical distribution of a collection of these estimates, however, may not provide an adequate description of the dispersion among the true rates. As a result, decisions based on the histogram of the empirical Bayes estimates may be suspect. We propose a modified version of the approach in which the mean and sample variance of the ensemble of estimates are constrained to equal the appropriate moments of the posterior distribution. The resulting collection of constrained empirical Bayes estimators has nearly the stability of the unconstrained approach and provides an improved estimator of the true rate distribution. We illustrate use of the estimator by producing stabilized county-level maps of U.S. fire- and burn-related mortality rates and validate the analytic results using a simulation analysis.

Adolescent↗
PubMed1994

Chronic conditions that lead to functional limitation in the elderly.

BACKGROUND: The role of chronic medical conditions in elderly persons' loss of functional abilities is intuitively important but not well defined. This analysis was designed to identify chronic medical conditions that lead to the development of severe functional limitation. METHODS: Functionally intact members of a multistage probability sample (n = 6,862) of all noninstitutionalized U.S. civilians age 70 years or older were interviewed in 1984. Based on data from the National Death Index and from follow-up telephone interviews in 1988 with survivors, subjects were classified as functionally intact, functionally limited (unable to perform one or more of seven essential activities), or decreased. RESULTS: After adjusting for the effects of exercise habits and demographic, socioeconomic, and psychosocial factors, we found that the best predictors of the development of functional limitation were cerebrovascular disease (OR = 2.14; 95% CL = 1.16, 3.98) and arthritis (OR = 1.51; 95% CL = 1.08, 2.11). The contribution of coronary artery disease also approached statistical significance (OR = 1.49; 95% CL = 0.99, 2.27). CONCLUSION: In the future, the primary prevention or effective treatment of cerebrovascular disease, arthritis, and possibly coronary artery disease may produce a modest reduction in the incidence of severe functional limitation.

Activities of Daily Living↗
PubMed1994

Empirical Bayes methods for stabilizing incidence rates before mapping.

The epidemiologic utility of mapping and ranking incidence rates is often questioned owing to instability of the observed incidence values in areas with small populations. Spurious fluctuations in the observed rates caused by this instability can mask true spatial and temporal trends in risk. To produce maps with the required level of geographic resolution, yet based on reliable estimates, it is desirable to reduce the random variation in the observed rates before mapping. In this paper, we describe the empirical Bayes approach for obtaining stabilized incidence estimates. We begin by deriving Bayes rate estimators and then illustrate how using the observed rates to estimate unknown distributional information leads to the empirical Bayes formulation. A drawback of the approach is that the histogram of the empirical Bayes rate estimates may be narrower than the true distribution of risk. We outline a constrained empirical Bayes approach that produces improved estimators for the true distribution of the unknown rates. We include discussions of relevant previous applications of empirical Bayes methods to rate mapping problems and an evaluation of the strengths and weaknesses of the approach.

Bayes Theorem↗
PubMed1994

Association between survival time and ordinal covariates.

An application of the method of rank correlation is proposed for testing independence between a censored survival time and an ordinal covariate. The test statistic counts the number of concordances minus the number of discordances at each time with event(s) and adds across times; it is expressible as a score statistic within the proportional hazards framework. The proposed test includes, as a special case, a generalization of Jonckheere's test against ordered alternatives and as applied to the analysis of categorical data, it can be seen as a generalization of the Mantel-Haenszel procedure.

Analysis of Variance↗
PubMed1993

Calcium and colorectal epithelial cell proliferation: a preliminary randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Colonic epithelial cell proliferation is increased in patients at high risk for colon cancer. Calcium administration has ameliorated the proliferative changes in rodents, and findings in small, uncontrolled clinical trials have suggested similar effects in humans. PURPOSE: This preliminary, double-blind, randomized clinical trial was designed 1) to investigate whether supplemental calcium will reduce colonic epithelial cell proliferation in patients with sporadic adenomas who consume a high-fat, Western-style diet; 2) to determine the sample size (number of scorable crypts per person) needed to achieve adequate statistical power; and 3) to evaluate the feasibility of full-scale clinical trials. METHODS: Twenty-one sporadic adenoma patients were treated daily with placebo or 1200 mg of supplemental calcium. To determine colonic epithelial cell proliferation, we used tritiated thymidine labeling of colon crypt epithelial cells in rectal biopsy specimens and calculated the percentage of labeled cells (labeling index [LI]). Two pathology technician "readers" independently scored each specimen, and inter-reader reliability was determined. Subjects remained on their usual diet during the study, and intake of calories, calcium, total fat, and vitamin D did not differ substantially among them. We calculated curves for statistical power to determine the number of scorable crypts needed per person for detection of a statistically significant difference (P < .05) of 1.0% in mean LI. RESULTS: The pooled baseline LI was 4.7%. In the calcium-treated group, the LI increased 0.6% (proportional increase, 12.8%); in the placebo-treated group, it decreased 0.5% (proportional decrease, 10.6%). The difference between change in the mean LI from baseline to 8 weeks' follow-up in the placebo group versus the calcium group was not statistically significant. The intraclass correlation coefficient for inter-reader reliability for the baseline LI was .66. Analyses indicated scoring eight crypts sufficient for estimates of the LI adequate for between-group comparisons, a level achieved in 81% of biopsy specimens. CONCLUSIONS: Calcium carbonate supplements delivering 1200 mg elemental calcium daily may not decrease colonic epithelial cell proliferation over an 8-week period in sporadic adenoma patients. In future trials measuring the LI, consideration should be given to ensuring adequate numbers of scorable crypts and to the impact of inadequate biopsy procedures, labeling failure, reader reliability, and participant withdrawal. Our findings support the feasibility of a full-scale clinical trial to further study the relationships among dietary calcium, colonic epithelial cell proliferation, and colorectal cancer.

Adenoma↗
PubMed1991

Variance components and their implications for statistical information in medical data.

We discuss general issues concerning the design and analysis of medical experiments involving repeated measures or hierarchical groupings of subjects within larger study units. Depending on the types of questions being investigated, the correlations induced by clustering can have dramatic impact on the effective sample size. The unique aspects of such experiments must be accounted for during analysis and during interpretation of the results. We illustrate these issues by using a variance components model to investigate the role of leadership in medical practice.

Ambulatory Care↗
PubMed1991

Using empirical Bayes methods in biopharmaceutical research.

A compound sampling model, where a unit-specific parameter is sampled from a prior distribution and then observed are generated by a sampling distribution depending on the parameter, underlies a wide variety of biopharmaceutical data. For example, in a multi-centre clinical trial the true treatment effect varies from centre to centre. Observed treatment effects deviate from these true effects through sampling variation. Knowledge of the prior distribution allows use of Bayesian analysis to compute the posterior distribution of clinic-specific treatment effects (frequently summarized by the posterior mean and variance). More commonly, with the prior not completely specified, observed data can be used to estimate the prior and use it to produce the posterior distribution: an empirical Bayes (or variance component) analysis. In the empirical Bayes model the estimated prior mean gives the typical treatment effect and the estimated prior standard deviation indicates the heterogeneity of treatment effects. In both the Bayes and empirical Bayes approaches, estimated clinic effects are shrunken towards a common value from estimates based on single clinics. This shrinkage produces more efficient estimates. In addition, the compound model helps structure approaches to ranking and selection, provides adjustments for multiplicity, allows estimation of the histogram of clinic-specific effects, and structures incorporation of external information. This paper outlines the empirical Bayes approach. Coverage will include development and comparison of approaches based on parametric priors (for example, a Gaussian prior with unknown mean and variance) and non-parametric priors, discussion of the importance of accounting for uncertainty in the estimated prior, comparison of the output and interpretation of fixed and random effects approaches to estimating population values, estimating histograms, and identification of key considerations in the use and interpretation of empirical Bayes methods.

Bayes Theorem↗
PubMed1991

Forecasting the number of future disabled elderly using Markovian and mathematical models.

The accuracy of forecasting the number of future disabled elderly people depends on the accuracy of projecting mortality rates and the rates of transition to and from functional disability. We describe a new two-step method for constructing mathematical models that project these future rates dynamically. (1) A Markovian model of elders' transitions between functional states is specified. (2) A mathematical model of the probability of each transition is created. We conducted pilot studies of the fundamental mathematical processes of this method using data from the Longitudinal Study of Aging. First we constructed prototypic mathematical models of the probabilities of remaining functionally able and of making transitions to disability and to death within 2 years. Then we used these models to project hypothetical rates of transition for white women of selected ages, morbidity ratings and health statuses.

Activities of Daily Living↗
PubMed1991

Assessing, accommodating, and interpreting the influences of heterogeneity.

Heterogeneity, ranging from measurement error to variation among individuals or regions, influences all levels of data collected for risk assessment. In its role as a nemesis, heterogeneity can reduce the precision of estimates, change the shape of a population model, or reduce the generalizability of study results. In many contexts, however, heterogeneity is the primary object of inference. Indeed, some degree of heterogeneity in excess of a baseline amount associated with a statistical model is necessary in order to identify important determinants of response. This report outlines the causes and influences of heterogeneity, develops statistical methods used to estimate and account for it, discusses interpretations of heterogeneity, and shows how it should influence study design. Examples from dose-response modeling, identification of sensitive individuals, assessment of small area variations and meta analysis provide applied contexts.

Animals↗
PubMed1990

Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma.

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).

Adult↗
PubMed1990

Longitudinal and cross-sectional estimates of pulmonary function decline in never-smoking adults.

This paper describes methods for simultaneous cross-sectional and longitudinal analysis of repeated measurements obtained in cohort studies with regular examination schedules, then uses these methods to describe age-related changes in pulmonary function level among nonsmoking participants in the Six Cities Study, a longitudinal study of air pollution and respiratory health conducted between 1974 and 1983 in Watertown, Massachusetts; Kingston and Harriman, Tennessee; St. Louis, Missouri; Steubenville, Ohio; Portage, Wisconsin; and Topeka, Kansas. The subjects, initially aged 25-74, were examined on three occasions at 3-year intervals. Individual rates of loss increased more rapidly with age than predicted from the cross-sectional model. For example, for a male of height 1.75 m, the cross-sectional model predicted an increase in the annual rate of loss of FEV1 from 23.7 ml/yr at age 25 to 39.0 ml/yr at age 75, while the longitudinal model gave rates of loss increasing from 12.9 ml/yr at age 25 to 58.2 ml/yr at age 75. These results contrast with those of other studies comparing longitudinal and cross-sectional estimates of pulmonary function loss.

Adult↗