[Show abstract][Hide abstract] ABSTRACT: In randomized clinical trials designed to compare the magnitude of vaccine-induced immune responses between vaccination regimens, the statistical method used for the analysis typically does not account for baseline participant characteristics. This article shows that incorporating baseline variables predictive of the immunogenicity study endpoint can provide large gains in precision and power for estimation and testing of the group mean difference (requiring fewer subjects for the same scientific output) compared to conventional methods, and recommends the "semiparametric efficient" method described in Tsiatis et al. [Tsiatis AA, Davidian M, Zhang M, Lu X. Covariate adjustment for two-sample treatment comparisons in randomized clinical trials: a principled yet flexible approach. Stat Med 2007. doi:10.1002/sim.3113] for practical use. As such, vaccine clinical trial programs can be improved (1) by investigating baseline predictors (e.g., readouts from laboratory assays) of vaccine-induced immune responses, and (2) by implementing the proposed semiparametric efficient method in trials where baseline predictors are available.
[Show abstract][Hide abstract] ABSTRACT: Women with depressive symptoms may use preventive services less frequently and experience poorer health outcomes. We investigated the association of depressive symptoms with breast and colorectal cancer screening rates and stage of cancer among a cohort of postmenopausal women.
In The Women's Health Initiative Observational Study, 93,676 women were followed on average for 7.6 years. Depressive symptoms were measured at baseline and at 3 years using the 6-item scale from the Center for Epidemiological Studies Depression scale (CES-D). We calculated a cancer screening rate expressed as a proportion of the years that women were current with recommended cancer screening over the number of follow-up visits in the study. Breast and colorectal cancers were staged based on Surveillance, Epidemiology and End Results (SEER) classification.
At baseline, 15.8% (12,621) women were positive for depressive symptoms, and 6.9% (4,777) were positive at both baseline screening and at 3 years. The overall average screening rate was 71% for breast cancer and 53% for colorectal cancer. The breast cancer screening rate was 1.5% (CI 0.9%-2.0%) lower among women who reported depressive symptoms at baseline than among those who did not. Depressive symptoms were not a predictor for colorectal cancer screening. Stage of breast and colorectal cancer was not found to be associated with depressive symptoms after adjusting for covariates.
Among a healthy and self-motivated cohort of women, self-reported depressive symptoms were associated with lower rates of screening mammography but not with colorectal cancer screening.
Journal of Women's Health 10/2008; 17(8):1353-61. DOI:10.1089/jwh.2007.0544 · 2.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The evidence linking cigarette smoking to the risk of colorectal cancer is inconsistent. We investigated the associations between active and passive smoking and colorectal cancer among 146,877 Women's Health Initiative participants. Women reported detailed smoking histories at enrollment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between smoking and overall and site-specific risk of colorectal cancer. Invasive colorectal cancer was diagnosed in 1242 women over an average of 7.8 years (range = 0.003-11.2 years) of follow-up. In adjusted analyses, statistically significant positive associations were observed between most measures of cigarette smoking and risk of invasive colorectal cancer. Site-specific analyses indicated that current smokers had a statistically significantly increased risk of rectal cancer (HR = 1.95, 95% CI = 1.10 to 3.47) but not colon cancer (HR = 1.03, 95% CI = 0.77 to 1.38), compared with never smokers. Passive smoke exposure was not associated with colorectal cancer in adjusted analyses. Thus, active exposure to cigarette smoking appears to be a risk factor for rectal cancer.
Journal of the National Cancer Institute 12/2007; 99(22):1729-35. DOI:10.1093/jnci/djm176 · 12.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Women are more likely than men to have nonspecific chest pain (NSCP) symptoms. The long-term outcomes in women discharged with a diagnosis of NSCP are unknown.
The Women's Health Initiative Observational Study enrolled postmenopausal women aged 50-79 years. After excluding those with prior cardiovascular disease (CVD), 83,622 women were studied. NSCP cases were defined as having an initial primary hospital discharge diagnosis of NSCP (ICD-9 codes 786.50, 786.51, 786.59) without a prior diagnosis of coronary heart disease (CHD). Risks of subsequent CHD events were estimated from Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for baseline age, cardiovascular risk factors, and hormone use.
Over an average of 8 years of follow-up, 11% (230 of 2,092) of women with NSCP experienced a cardiovascular event compared with 9.5% (7,724 of 81,530) who did not. Compared with women without a hospitalization for NSCP during follow-up, those with NSCP had a greater than 2-fold higher risk of a subsequent hospitalization for clinically diagnosed angina (HR 2.18, 95% CI 1.66-2.86) and at least a 1.5-fold higher risk of nonfatal myocardial infarction (MI) (HR 1.59, 1.10-2.31), revascularization (HR 1.67, 1.28-2.20), and congestive heart failure (HR 1.75, 1.27-2.41). Women with NSCP who subsequently experienced a CHD event were more likely to be over age 65 or to have cardiovascular risk factors.
Older women discharged with a diagnosis of NSCP may be at increased risk of CHD morbidity. Further research is needed to replicate these findings in other populations.
Journal of Women's Health 01/2007; 15(10):1151-60. DOI:10.1089/jwh.2006.15.1151 · 2.05 Impact Factor