Biomedical subjects

T A Louis

Publications and source records attributed to T A Louis.

At least 19 recordsLinked to original sources

PubMed1998

A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics and private practice offices specializing in the care of people with HIV. Interventions were oral GCV (1000 mg three times/day) or placebo. Protocol amendment allowed switch to open-label oral GCV. Main outcome measures were confirmed CMV retinal or gastrointestinal mucosal disease, and death. The study enrolled 994 people co-infected with CMV and HIV, with at least one CD4 count recorded < 100 x 10(6) cells/l. RESULTS: At study completion (15 months median follow-up), CMV event rates in the oral GCV and control groups were 13.1 and 14.6 per 100 person years, respectively, a hazard ratio (HR) of 0.92 [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event rates were 12.7 and 15.0, respectively (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45). At study completion, event rates for death were 26.6 and 32.0 (HR, 0.84; P = 0.09), and at protocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78), respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment effect was associated with baseline use of didanosine (ddI). For patients taking ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was 0.62 (P = 0.04). These HR were statistically different (P = 0.0006). CONCLUSIONS: In our study, 3 g/day oral GCV did not significantly reduce CMV disease incidence, but there was a suggestion of a death-rate reduction. Furthermore, results suggest that oral GVC decreased risk of CMV disease in patients not prescribed ddI, and increased risk in those prescribed ddI. For the CMV endpoint, our study differs markedly from the only similar study, although for the death endpoint, a combined analysis of studies indicated significant reduction in death rate.

AIDS-Related Opportunistic Infections↗

PubMed1997

Colorectal epithelial cell proliferative kinetics and risk factors for colon cancer in sporadic adenoma patients.

Colorectal epithelial cell proliferative kinetics are altered in patients at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that includes the entire crypt (higher phi(h)). To assess factors associated with LI and phi(h), we performed a cross-sectional analysis using baseline rectal mucosal biopsies from sporadic adenoma patients participating in a chemoprevention trial. Biopsies (taken without preparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. High-quality, scorable biopsies were obtained for 115 patients, and using analysis of covariance and multiple linear regression, the LI and phi(h) were evaluated in relation to diet and other lifestyle factors, demographics, anthropometrics, family history of colon cancer, and polyp history. Statistically significant findings included the following: (a) The LI for those in the upper versus the lowest tertile of vegetable and fruit consumption was, proportionately, 35% lower (3.4% versus 5.3%; P < 0.001); for vitamin supplement users versus nonusers, it was 36% lower (3.3 versus 5.2%; P < 0.001); for recurrent versus incident polyp patients, it was 36% higher (6.2 versus 4.0%; P < 0.001); and for those with rectal polyps only versus those with colon polyps only, it was 28% higher (6.0 versus 4.3%; P = 0.05); and (b) the phi(h) for those in the upper versus the lowest tertile of sucrose consumption was, proportionately, 48% higher (7.1% versus 3.7%; P = 0.01). These results indicate that (a) colorectal epithelial cell proliferation rates are higher in recurrent adenoma patients than in incident adenoma patients and in patients with rectal adenomas only versus those with colon adenomas only, but they are lower in patients with higher intakes of vegetables and fruit and in those who take vitamin/mineral supplements, and (b) the distribution of proliferating cells is shifted toward more inclusion of the upper 40% of the crypt in patients with higher intakes of sucrose. The pattern of positive, negative, and null associations of potential risk factors with cell proliferation is similar to that commonly found with colonic neoplasms.

Adenoma↗

PubMed1996

What makes quality assurance effective? Results from a randomized, controlled trial in 16 primary care group practices.

OBJECTIVES: The authors estimate separately contributions of each component intervention to overall effectiveness of quality assurance cycles used to improve practice performance. METHODS: In a randomized, controlled trial, experimental cycles of quality assurance were conducted for eight patient-care guidelines, with two experimental cycles assigned to each of 16 group practices. For three separate interventions per cycle, practitioners: (1) were notified of the name of the experimental guideline, (2) discussed criteria of conformance to the guideline, and (3) received feedback on performance. Actions taken in response to interventions were documented. Using medical records data for a baseline year and for 3 months after each intervention and an additional 9 months, the authors scored each practice for conformance to two experimental guidelines and to control guidelines. RESULTS: For all patient-care guidelines combined, and for four of five guidelines showing improvement, knowledge of guidelines and review criteria alone produced no change. After feedback, performance improved and improvement persisted for at least 9 months. The number of corrective actions implemented contributed significantly to effectiveness of quality assurance. CONCLUSIONS: Feedback to providers of data on their performance is a more powerful stimulus for quality improvement than is knowledge of guidelines or discussion of review criteria.

Ambulatory Care↗

PubMed1996

Leadership for quality improvement in group practices.

OBJECTIVES: The authors studied influence of physician leaders on their colleagues' performance using data from a randomized, controlled trial of quality assurance interventions in 16 primary care practices. METHODS: The authors examined whether leaders performed better than their colleagues and looked for evidence of leaders' influence on their colleagues before intervention. As behavioral indicators of each leader's influence for improvement in response to quality assurance interventions, the authors (1) change in the leader's performance score and (2) an index of leader commitment derived from the leader's participation in quality assurance interventions; these indicators were used as covariates in a comparison in experimental practice sites of leaders' and colleagues' mean case performance scores before and after intervention. RESULTS: Leaders did not outscore their colleagues or influence their colleagues' performance scores before intervention. In response to quality assurance interventions, a leader's change in performance score significantly improved colleagues' score if the leader improved. A positive leader commitment index predicted colleagues' improvement independently of the leader change score. CONCLUSIONS: As hypothesized, physician leaders, by the example of their behavior, influenced colleagues' performance. However, leaders exerted their influence only after receiving external stimulation for quality improvement.

Adult↗

PubMed1996

Consistency in performance among primary care practitioners.

OBJECTIVES: The authors studied the consistency of performance of individual physicians to evaluate the identification of outlier practitioners as a strategy for improving patient care. METHODS: The authors used a data base containing information on 430 practitioners caring for 6,090 patients in 16 group practices. The authors analyzed inter- and intraphysician differences in performance on the basis of review criteria for 8 patient care guidelines. These criteria allowed for a variety of acceptable clinical strategies, incorporated decision tree logic, and included input from participating practitioners. The authors took steps to maximize validity and controlled for potentially confounding characteristics of patients and practitioners. The authors identified outliers, evaluated the significance of differences between outliers and nonoutliers, and studied variations in performance across cases and guidelines in conformance with guidelines. RESULTS: The authors identified a few statistically significant outliers. Correlations for performance across cases seen by a given physician were low. The highest positive correlation for performance between any pair of guidelines was 0.32. CONCLUSIONS: The performance of a given practitioner is highly variable from patient to patient and from guideline to guideline. Thus, strategies focusing solely on substandard outliers will miss opportunities to improve performance.

Adult↗

PubMed1996

Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case-Control Study.

Evidence of a role for steroid hormones and reproduction in colon neoplasia remains tantalizing but unclear. Hormone replacement therapy (HRT) has been reported in a number of recent studies to be associated with a reduced risk of colon cancer. A case-control study was undertaken to establish whether HRT is associated with lower risk of adenomatous polyps. This case-control study was undertaken as a project of the Minnesota Cancer Prevention Research Unit. Cases (n = 219) were women, ages 30-74 years with colonoscopy-proven, pathology-confirmed, adenomatous polyps of colon and rectum recruited at Digestive Healthcare PA (Minneapolis, MN). Two control groups were selected: women without polyps at colonoscopy (n = 438) at Digestive Healthcare and age- and zip code-matched women selected from the general community (n = 247). Response rates were 68% among those colonoscoped and 65% among community controls. Parity, age at first live birth, and oral contraceptive use did not distinguish cases from either control group. Multivariate adjusted odds ratios and 95% confidence limits for use of HRT for less than 5 years (compared with never use) among postmenopausal women were 0.52 (0.32-0.85) versus colonoscopy-negative controls and 0.74 (0.44-1.26) versus community controls. For 5 years of use or greater, the corresponding figures were 0.39 (0.23-0.67) and 0.61 (0.34-1.07). These results were not materially different when stratified on body mass index, oophorectomy, hysterectomy, aspirin use, or family history. There is no marked increase in risk even 5 years after cessation of HRT use. HRT appears to lower risk of colorectal adenomatous polyps, suggesting that it acts quite early in the neoplastic process. Mechanisms remain unclear. Reduction of risk of colorectal neoplasia is an additional benefit of postmenopausal HRT.

Adenocarcinoma↗

PubMed1996

Tests of independence for bivariate survival data.

We propose two test statistics based on the covariance process of the martingale residuals for testing independence of bivariate survival data. The first test statistic takes the supremum over time of the absolute value of the covariance process, and the second test statistic is a time-weighted summary of the process. We derive asymptotic properties of the two test statistics under the null hypothesis of independence. In addition, we derive the asymptotic distribution of the weighted test and construct optimal weights for contiguous alternatives to independence. Through simulations, we compare the performance of the proposed tests and the inner product of the Savage scores statistics of Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-108). These demonstrate that the supremum test is generally more powerful with comparatively little power loss relative to their test when Clayton's family alternative holds, and the weighted test is more powerful when the weight is appropriately chosen.

Analysis of Variance↗

PubMed1995

Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: The kinetics of colorectal epithelial cell proliferation is altered in patients at increased risk for colon cancer. Calcium administration ameliorates such proliferative changes in rodents. Findings in preliminary clinical trials have suggested similar effects in humans. PURPOSE: A randomized, double-blind, placebo-controlled, clinical trial was designed to determine whether calcium supplementation will reduce the colorectal epithelial cell proliferation rate and normalize the distribution of proliferating cells within colorectal crypts (i.e., shift the zone of proliferation from the entire crypt to the lower 60% of the crypt, which is thought to be the normal proliferative zone of the crypt) in patients with sporadic adenomas. METHODS: Sporadic adenoma patients (n = 193) were treated with placebo (n = 66), 1.0 g calcium (n = 64), or 2.0 g calcium (n = 63) daily for 6 months. Rectal mucosa biopsy specimens were obtained at base line and at 1-, 2-, and 6-month follow-up. Cell proliferation was measured by detection of S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. The cell proliferation rate, called labeling index (LI), was calculated as the proportion of labeled cells in the crypts. The deviation of the proliferative zone from the normal location in the lower 60% of the crypt was calculated as the proportion of labeled cells in the upper 40% of the crypt, called distributional index (phi h). The effects of calcium treatment on the LI and phi h were expressed as relative effects--(calcium follow-up/calcium base line)/(placebo follow-up/placebo base line). Calculations and inference testing of the relative effects were accomplished using a repeated-measures mixed model on log-transformed LI and phi h values. All statistical tests were two-sided. RESULTS: Scorable biopsy specimens were obtained on 170 patients at base line, 164 at 1 month, 161 at 2 months, and 163 at 6 months. The difference in the change in the LI between the combined calcium groups and the placebo group was insignificant, with a relative effect of calcium versus placebo of 0.97 (P = .87). However, for the phi h, the relative effect of calcium versus placebo was 0.50 (P = .05) in the combined calcium groups, 0.56 (P = .16) in the 1.0-g calcium group, and 0.44 (P = .05) in the 2.0-g calcium group. CONCLUSIONS: Calcium supplementation normalizes the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients. IMPLICATIONS: These results support further study of whether alterations in colon cell proliferative kinetics represent true intermediate steps in colon carcinogenesis that can be used to investigate the etiology and prevention of, and whether a higher calcium consumption can reduce the risk of, colon cancer.

Adult↗

PubMed1995

Long-term effects of antihypertensive agents on proteinuria and renal function.

BACKGROUND: Although many studies have examined the effects of antihypertensive agents on proteinuria and glomerular filtration rate in patients with kidney disease, many questions remain unresolved. These questions include whether the effects of agents differ, whether their effects are similar in diabetic and nondiabetic patients with renal disease, and whether the effects of any agents are independent of blood pressure reductions. METHODS: We conducted a meta-analysis of studies obtained with MEDLINE and bibliographies from comprehensive reviews but included only investigations with follow-up times of at least 6 months. We combined data (1) in an analysis of randomized controlled trials, (2) in a separate univariate analysis of controlled and uncontrolled trials, and (3) using weighted multiple linear regression. RESULTS: In 14 randomized controlled trials, angiotensin-converting enzyme inhibitors caused a greater decrease in proteinuria (pooled mean [95% confidence intervals], -0.51[-0.68 to -0.35], ln [treatment/control]), improvement in glomerular filtration rate (0.13 mL/min per month [0.10 to 0.16 mL/min per month]), and decline in mean arterial pressure (-4.0 mm Hg [-4.9 to -3.0 mm Hg]) compared with controls. In a multivariate analysis of controlled and uncontrolled trials, each 10-mm Hg reduction in blood pressure decreased proteinuria (regression coefficient [95% confidence interval] -0.14 [-0.22 to -0.06] ln [after/before]), but angiotensin-converting enzyme inhibitors (-0.45 [-0.58 to -0.32]) and nondihydropyridine calcium antagonists (-0.38 [-0.70 to -0.06]) were associated with additional declines in proteinuria that were independent of blood pressure changes and diabetes. Each 10-mm Hg reduction in blood pressure caused a relative improvement in glomerular filtration rate (0.18 mL/min per month [0.04 to 0.31 mL/min per month]), but among diabetic patients there was a tendency for dihydropyridine calcium antagonists to cause a relative reduction in glomerular filtration rate (-0.68 mL/min per month [-1.31 to -0.04 mL/min per month]). CONCLUSIONS: Long-term beneficial effects of antihypertensive agents on proteinuria and glomerular filtration rate are proportional to blood pressure reductions and are similar in diabetic and nondiabetic patients with renal disease. In addition, angiotensin-converting enzyme inhibitors, and possibly nondihydropyridine calcium antagonists, have additional beneficial effects on proteinuria that are independent of blood pressure reductions.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Effects of antihypertensive therapy on serum lipids.

PURPOSE: To compare and contrast the effects of antihypertensive agents on serum lipids and blood pressure in different patient populations. DATA SOURCES: A MEDLINE search and bibliographies from recent comprehensive reviews were used to identify trials that provided sufficient data to calculate the change in one or more serum lipid values measured before and after antihypertensive therapy. STUDY SELECTION: 474 controlled and uncontrolled clinical trials investigated the effects of 85 antihypertensive agents on lipids and blood pressure in more than 65,000 patients. DATA EXTRACTION: Data on triglyceride and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; blood pressure; patient characteristics; and study design. DATA SYNTHESIS: Differences in the effects of agents, adjusted for differences in patient populations and study design, were examined using multiple linear regression analysis that was weighted by study quality and inverse variance. Diuretics caused relative increases in cholesterol levels (regression coefficient = 0.13 mmol/L; 95% CI, 0.09 to 0.18 mmol/L) that were greater with higher doses (additional effect of high dose, 0.12 mmol/L; CI, 0.04 to 0.20 mmol/L) and were worse in blacks than in nonblacks (additional effect in blacks, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Beta-blockers caused increases in triglyceride levels (0.35 mmol/L; CI, 0.31 to 0.39 mmol/L) that were substantially smaller for agents with intrinsic sympathomimetic activity (amelioration of beta-blocker increase, -0.21 mmol/L; CI, -0.27 to -0.16 mmol/L). When combined with cardioselectivity, beta-blockers with intrinsic sympathomimetic activity favorably affected lipids and reduced both total (-0.14 mmol/L; CI, -0.24 to -0.04 mmol/L) and LDL cholesterol levels (-0.17 mmol/L; CI, -0.28 to -0.07 mmol/L). alpha-Blockers beneficially affected total cholesterol (-0.23 mmol/L; CI, -0.28 to -0.18 mmol/L), LDL cholesterol (-0.20 mmol/L; CI, -0.25 to 0.15 mmol/L), triglycerides (-0.07 mmol/L; CI, -0.11 to -0.03 mmol/L), and, in younger persons, HDL cholesterol (0.02 mmol/L; 0.01 to 0.04 mmol/L). Converting enzyme inhibitors reduced triglycerides (-0.07 mmol/L; CI, -0.12 to -0.02 mmol/L), and, in patients with diabetes, total cholesterol (-0.22 mmol/L; CI, -0.34 to -0.10 mmol/L). Vasodilators reduced total (-0.22 mmol/l; CI, -0.30 to -0.10 mmol/L) and LDL cholesterol (-0.22 mmol/L; CI, -0.29 to -0.11 mmol/L) and increased HDL cholesterol (0.06 mmol/L; CI, 0.02 to 0.09 mmol/L). CONCLUSION: With the exception of calcium antagonists, nearly all antihypertensive agents affect serum lipids. These effects differ among patient populations.

Adult↗

PubMed1995

Assessing gamma frailty models for clustered failure time data.

Proportional hazards frailty models use a random effect, so called frailty, to construct association for clustered failure time data. It is customary to assume that the random frailty follows a gamma distribution. In this paper, we propose a graphical method for assessing adequacy of the proportional hazards frailty models. In particular, we focus on the assessment of the gamma distribution assumption for the frailties. We calculate the average of the posterior expected frailties at several followup time points and compare it at these time points to 1, the known mean frailty. Large discrepancies indicate lack of fit. To aid in assessing the goodness of fit, we derive and estimate the standard error of the mean of the posterior expected frailties at each time point examined. We give an example to illustrate the proposed methodology and perform sensitivity analysis by simulations.

Adult↗

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↗