Min Xiang

A pooled analysis of case–control studies of thyroid cancer: cigarette smoking and consumption of alcohol, coffee, and tea

Objective: To analyze the role of smoking, alcohol, coffee and tea in relation to thyroid cancer, we conducted a pooled analysis of 14 case–control studies conducted in the United States, Europe, and Asia. Methods: The sample consisted of 2725 thyroid cancer cases (2247 females, 478 males) and 4776 controls (3699 females, 1077 males). Conditional logistic regression with stratification on study, age at diagnosis, and gender was used to compute odds ratios and 95% confidence intervals. Results: Thyroid cancer risk was reduced in persons who had ever smoked. The relationship was more pronounced in current smokers (OR = 0.6, 95% CI = 0.6–0.7) than former smokers (OR = 0.9, 95% CI = 0.8–1.1). There were significant trends of reduced risk with greater duration and frequency of smoking. For consumption of wine and beer, there was a significant trend of decreasing thyroid cancer risk (p = 0.02) that was not maintained after adjustment for current smoking (p = 0.12). Thyroid cancer risk was not associated with consumption of coffee or tea. These findings were consistent in both gender-specific and histology-specific (papillary and follicular) analyses. Conclusions: Pooled analyses of these geographically diverse case–control data indicate a reduced thyroid cancer risk associated with current smoking. A reduced risk associated with alcohol was eliminated after adjustment for smoking, and caffeinated beverages did not alter thyroid cancer risk.

Postmenopausal oral estrogen therapy and blood pressure in normotensive and hypertensive subjects: The Estrogen in the Prevention of Atherosclerosis Trial

Objective:To determine if 17β-estradiol increases blood pressure in postmenopausal women. Design:A total of 222 healthy postmenopausal women were randomly assigned to either 1 mg micronized 17β-estradiol daily or placebo for 2 years. Blood pressure measurements were obtained every other month and common carotid artery intima-media thickness measured every 6 months. Statistical analyses comparing longitudinal changes in systolic and diastolic blood pressure between treatment groups used a mixed general linear model including interaction terms to evaluate variations by age or estradiol level. Results:Both placebo and estradiol groups showed small declines in systolic and diastolic blood pressure during the trial among the normotensive subjects and subjects on antihypertensive medications. However, the decline did not differ significantly between the groups. Treatment effects on systolic blood pressure differed significantly by the age of the subject (interaction P value = 0.04) with younger women on estradiol showing on average a rise in systolic blood pressure, and older women a decline. The association between serum estradiol level and systolic blood pressure showed a similar modification with age (P = 0.03). Changes in systolic blood pressure in women on estradiol were positively correlated with intima-media thickness progression (P = 0.03). Conclusions:Overall, 17β-estradiol did not influence changes in blood pressure in normotensive or hypertensive women. The effect of 17β-estradiol treatment on systolic blood pressure may be influenced by a womans age. Estradiol may increase systolic blood pressure in younger postmenopausal women, while having the opposite effect in older postmenopausal women.

Inflammatory Markers and Progression of Subclinical Atherosclerosis in Healthy Postmenopausal Women (from the Estrogen in the Prevention of Atherosclerosis Trial)

The objective of this study was to determine whether high-sensitivity C-reactive protein (hs-CRP) and serum soluble intercellular adhesion molecule-1 (sICAM-1) correlate with progression of subclinical atherosclerosis. Secondarily, the long-term effect of oral estradiol on hs-CRP and sICAM-1 were determined. Data were analyzed from 180 healthy postmenopausal women aged 45 to 80 years randomly assigned to either unopposed micronized 17beta-estradiol 1 mg/day or placebo in the Estrogen in the Prevention of Atherosclerosis Trial (EPAT). Carotid artery intima-media thickness (CIMT), hs-CRP, and sICAM-1 were measured at baseline and every 6 months thereafter for 2 years. Unopposed 17beta-estradiol significantly increased hs-CRP (p = 0.01) and decreased sICAM-1 compared with placebo (p = 0.04). Changes in hs-CRP and sICAM-1 did not correlate with changes in carotid artery intima-media thickness. In conclusion, although unopposed 17beta-estradiol significantly altered hs-CRP and sICAM-1, neither marker was associated with progression of subclinical atherosclerosis.

Unopposed estradiol therapy in postmenopausal women: results from two randomized trials.

OBJECTIVE: To estimate the rates of endometrial hyperplasia, bleeding episodes, and interventions among menopausal women receiving unopposed oral estradiol or placebo therapy with ultrasound monitoring over 3 years. METHODS: Two-hundred eighteen healthy women with intact uteri enrolled in the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) or the Women’s Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial (WELL-HART) were randomly assigned to either 1 mg of micronized 17&bgr;-estradiol (n=96) or placebo (n=122) daily for up to 3 years in a double-blind fashion. Patients were followed with annual measurement of endometrial thickness using transvaginal ultrasonography. Logistic regression was used to identify predictors of uterine bleeding and endometrial biopsy. RESULTS: Over the study periods, nine women (9.4% of patients, 95% confidence interval [CI] 3.6–15.2%) in the estradiol group developed hyperplasia. Eight of the nine cases (88.9%) of hyperplasia were simple without atypia. Women receiving estradiol were more likely than those receiving placebo to have at least one episode of uterine bleeding (67% versus 11% at 3 years, respectively, P<.001). Women in the estradiol group were also more likely to have an endometrial biopsy (48% versus 4% at 3 years, P<.001). Among women on estradiol, obesity (body mass index [BMI] greater than 30 kg/m2) significantly increased the odds of uterine bleeding compared with normal-weight patients (BMI 25 or less) (OR 3.7, 95% CI 1.2–11.8). CONCLUSION: Short-term, unopposed estradiol therapy with gynecologic monitoring may be an option for the treatment of menopausal symptoms. Menopausal women choosing estradiol therapy, especially if obese, should anticipate uterine bleeding and the possibility of an endometrial biopsy. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT 00000559 and NCT 00115024 LEVEL OF EVIDENCE: I

Fluorophotometry in patients with human immunodeficiency virus with and without cytomegalovirus retinitis

OBJECTIVE To study the aqueous humor dynamics in subjects with human immunodeficiency virus (HIV) with and without cytomegalovirus (CMV) retinitis. DESIGN Prospective cross-sectional study. PARTICIPANTS Fourteen HIV-positive subjects (27 eyes, 19 with CMV retinitis and 8 without CMV retinitis), and a control group of 9 HIV-negative subjects (17 eyes). TESTING Fluorophotometry. MAIN OUTCOME MEASURES Aqueous flow rates as measured by fluorophotometry and intraocular pressure (IOP). RESULTS Analysis of variance of the mean corrected aqueous flow rate revealed that both HIV-positive groups had significantly lower aqueous flow rates than did the control group (P < 0.03). No difference in mean aqueous flow rates was found between the HIV-positive eyes with or without CMV retinitis. Comparison of mean IOP revealed that HIV-positive eyes with CMV retinitis had significantly lower IOP than did the HIV-positive eyes without CMV retinitis (P = 0.03) and HIV-negative subjects (P = 0.002). There was no correlation between aqueous flow rate and IOP in HIV-positive subjects (P > 0.5). CONCLUSION The lack of correlation between the aqueous flow rate and IOP suggests that there may be some disassociation between these parameters in HIV-positive patients. Further studies are needed to better understand the mechanism of aqueous formation and in the management of disorders affecting IOP in this population.

Efficacy of Two Lipid-Lowering Treatments on Quantitative Coronary Angiographic Endpoints

This study contrasts the sensitivity of four quantitative coronary angiography (QCA) measures (percent diameter stenosis [%S], minimum lumen diameter, average segment diameter, and percent involvement) in detecting 2-year treatment effects of two lipid-lowering therapies and reports on the longitudinal pattern after 4 years of treatment on the primary QCA trial endpoint (%S) for all, mild/moderate (<50%S), and severe lesions (≥50%S). Patient cohorts were followed up from two randomized, placebo-controlled clinical trials of lipid-lowering therapies—colestipol/niacin in the Cholesterol Lowering Atherosclerosis Study (CLAS) and lovastatin in the Monitored Atherosclerosis Regression Study (MARS). Identical QCA methodology was used. In CLAS, the largest 2-year treatment effect size (=0.60) was noted for %S. In MARS, equivalent 2-year effect sizes (=0.15) were noted for three QCA measures. The largest 2-year effect size in %S was found in CLAS for mild/moderate lesions (=0.55) and in MARS for severe lesions (=0.31). Treatment in CLAS led to regression of disease in the first 2 years; treatment in MARS slowed progression of disease in the first 2 years and led to regression of disease after 4 years. Colestipol/niacin reduced progression of mild/moderate and severe lesions over the first 2 years of therapy; lovastatin reduced the progression of severe lesions over the last 2 years of therapy. We conclude that reducing the progression of atherosclerosis is not a simple proposition; maximal therapy for reducing and stabilizing atherosclerosis most likely will result from the selection of agents targeted at specific lesions.