Biomedical subjects

Stephen R Cole

Publications and source records attributed to Stephen R Cole.

4 recordsLinked to original sources

PubMed2003

Impact of HIV infection and HAART on serum lipids in men.

CONTEXT: Alterations in serum lipid values have been widely reported among persons infected with human immunodeficiency virus (HIV) type 1 treated with highly active antiretroviral therapy (HAART), but no data have yet been reported on changes from preseroconversion lipid values. OBJECTIVE: To describe changes in serum cholesterol levels associated with HIV infection and antiretroviral medication exposure, and 1-time assessment of triglyceride levels post-HAART initiation. DESIGN, SETTING, AND PARTICIPANTS: The Multicenter AIDS Cohort Study, a prospective study in which homosexual and bisexual men were enrolled and from which 50 of 517 HIV seroconverters were drawn for the analysis herein, who later initiated HAART, involving measurements of stored serum samples obtained between 1984 and 2002. MAIN OUTCOME MEASURES: Changes in levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at 6 time points during an average of 12 years; 1-time assessment of triglyceride levels from the third post-HAART clinic visit. RESULTS: Among the 50 men, notable declines in mean serum TC (-30 mg/dL [-0.78 mmol/L]), HDL-C (-12 mg/dL [-0.31 mmol/L]), and LDL-C values (-22 mg/dL [-0.57 mmol/L]) were observed after HIV infection. Following HAART initiation, there were large increases in mean TC and LDL-C values (50 and 21 mg/dL [1.30 and 0.54 mmol/L], respectively); however, the mean changes from the preseroconversion values were 20 mg/dL (0.52 mmol/L) (95% confidence interval [CI], -1 to 41) and -1 mg/dL (-0.03 mmol/L) (95% CI, -25 to 22), respectively. Mean HDL-C remained below baseline levels throughout follow-up. The median value (interquartile range) of triglycerides was 225 mg/dL (2.54 mmol/L) (147-331 mg/dL). CONCLUSIONS: Before treatment, HIV infection results in substantial decreases in serum TC, HDL-C, and LDL-C levels. Subsequent HAART initiation is associated with increases in TC and LDL-C but little change in HDL-C. Increases in TC and LDL-C observed after about 3 years of HAART possibly represent a return to preinfection serum lipid levels after accounting for expected age-related changes.

Adult↗

PubMed2002

Use of a marginal structural model to determine the effect of aspirin on cardiovascular mortality in the Physicians' Health Study.

The 1982-1988 aspirin component of the Physicians' Health Study, a randomized trial of aspirin and beta-carotene in primary prevention of cardiovascular disease and cancer among 22,071 US male physicians, was terminated early primarily because of a statistically extreme 44% reduction in first myocardial infarction, with inadequate precision and no apparent effect on the primary endpoint, cardiovascular death. Because of the demonstrated efficacy of aspirin in secondary prevention of cardiovascular death, nonfatal cardiovascular events may simultaneously be time-dependent confounders and intermediate variables. Aspirin use is strongly influenced by these as well as other diseases, side effects, and cardiovascular risk factors. The authors used a marginal structural model with time-dependent inverse probability weights to estimate the underlying causal effect of aspirin on cardiovascular mortality. Although intention-to-treat analyses found no effect (rate ratio = 1.00, 95% confidence interval (CI): 0.72, 1.38), the estimated causal rate ratio was altered to 0.75 but remained nonsignificant (95% CI: 0.48, 1.16). As-treated analyses suggested a more modest effect of aspirin use (rate ratio = 0.90, 95% CI: 0.65, 1.25). Although the numbers of cardiovascular deaths were insufficient to evaluate this endpoint definitively, use of such methods holds much potential for controlling time-varying confounders affected by previous exposure.

Adult↗

PubMed2002

Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses.

The objective of this work was to assess the effect of interferon beta-1a (Avonex) on the rate of development of clinically definite multiple sclerosis and brain magnetic resonance imaging changes in subgroups based on type of presenting event, baseline brain magnetic resonance imaging parameters, and demographic factors in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) trial. After the onset of a first demyelinating event, 383 patients with brain magnetic resonance imaging evidence of subclinical demyelination were treated with corticosteroids and randomly assigned to receive weekly intramuscular injections of 30 microg interferon beta-1a or placebo. The treatment effect within subgroups was assessed in proportional hazards models both for the development of clinically definite multiple sclerosis and for a combined outcome of development of clinically definite multiple sclerosis or >1 new or enlarging T2 lesions on brain magnetic resonance imaging. A beneficial effect of treatment was noted in all subgroups evaluated. Adjusted rate ratios for the development of clinically definite multiple sclerosis in the optic neuritis, brainstem-cerebellar, and spinal cord syndrome subgroups were 0.58 (p = 0.05), 0.40 (p = 0.03), and 0.30 (p = 0.01) and for the development of the combined clinically definite multiple sclerosis/magnetic resonance imaging outcome were 0.50 (p < 0.001), 0.41 (p = 0.001), and 0.40 (p = 0.004), respectively. A treatment benefit on both outcome measures also was seen in subgroups based on baseline brain magnetic resonance imaging parameters, gender, and age. Interferon beta-1a is beneficial when initiated at the first clinical demyelinating event in patients with brain magnetic resonance imaging evidence of subclinical demyelination. The beneficial effect is present for optic neuritis, brainstem-cerebellar syndromes, and spinal cord syndromes.

Adjuvants, Immunologic↗

PubMed2002

Fallibility in estimating direct effects.

We use causal graphs and a partly hypothetical example from the Physicians' Health Study to explain why a common standard method for quantifying direct effects (i.e. stratifying on the intermediate variable) may be flawed. Estimating direct effects without bias requires that two assumptions hold, namely the absence of unmeasured confounding for (1) exposure and outcome, and (2) the intermediate variable and outcome. Recommendations include collecting and incorporating potential confounders for the causal effect of the mediator on the outcome, as well as the causal effect of the exposure on the outcome, and clearly stating the additional assumption that there is no unmeasured confounding for the causal effect of the mediator on the outcome.

Aspirin↗