Publications

BACKGROUND

In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup.

METHODS

Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided.

RESULTS

As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)-positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer.

CONCLUSION

Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis.

OBJECTIVE

Colonoscopy, the "gold standard" screening test for colorectal cancer (CRC), has known diagnostic limitations. Advances in endoscope technology have focused on improving mucosal visualisation. In addition to increased angle of view and resolution features, recent colonoscopes have non-white-light optics, such as narrow band imaging (NBI), to enhance image contrast. We aimed to study the neoplasia diagnostic characteristics of NBI, by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light (WL).

DESIGN

Randomised controlled trial.

SETTING

US Veterans hospital.

PATIENTS

Elective colonoscopy adults.

INTERVENTION

We randomly assigned patients to undergo a colonoscopic examination using NBI or WL. All patients underwent a second examination using WL, as the reference standard.

MAIN OUTCOME MEASURES

The primary end point was the difference in the neoplasm miss rate, and secondary outcome was the neoplasm detection rate.

RESULTS

In 276 tandem colonoscopy patients, there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques. Of the 135 patients in the NBI group, 17 patients (12.6%; 95% confidence interval (CI) 7.5 to 19.4%) had a missed neoplasm, as compared with 17 of the 141 patients (12.1%; 95% CI 7.2 to 18.6%) in the WL group, with a miss rate risk difference of 0.5% (95% CI -7.2 to 8.3). 130 patients (47%) had at least one neoplasm. Missed lesions with NBI showed similar characteristics to those missed with WL. All missed neoplasms were tubular adenomas, the majority (78%) was < or = 5 mm and none were larger than 1 cm (one-sided 95% CI up to 1%). Nonpolypoid lesions represented 35% (13/37) of missed neoplasms.

INTERPRETATION

NBI did not improve the colorectal neoplasm miss rate compared to WL; the miss rate for advanced adenomas was less than 1% and for all adenomas was 12%. The neoplasm detection rates were similar high using NBI or WL; almost a half the study patients had at least one adenoma. Clinicaltrials.gov identifier: NCT00628147.

OBJECTIVE

Glucocorticoid (GC) excess induces alterations in bone metabolism that weaken bone structure and increase fracture risk. The aim of this study was to identify genes associated with bone metabolism in GC-treated mice, by performing a microarray analysis.

METHODS

Long bones from mice exposed to GC excess were collected after 0, 7, 28, and 56 days of treatment, to measure bone microarchitecture and extract RNA for microarray analyses.

RESULTS

Bone loss in this animal model was confirmed by changes in bone turnover markers as well as bone architecture, as measured by microfocal computed tomography. GC excess induced an early up-regulation of genes involved in osteoclast activation, function, and adipogenesis, which peaked on day 7. The expression of genes associated with osteoclast cytoskeletal reorganization and genes associated with matrix degradation peaked on day 28. On day 28 and day 56, the expression of genes associated with osteoblast activation and maturation was decreased from baseline, while the expression of Wnt antagonists was increased. In addition, the expression of genes expressed in osteocytes associated with bone mineralization was significantly higher at the later time points, day 28 and day 56. Reverse transcription-polymerase chain reaction confirmed the results of microarray analysis in selected genes.

CONCLUSION

GC excess is associated with early activation of genes associated with osteoclastogenesis and adipogenesis and a later suppression of genes associated with osteogenesis and mineralization. Novel interventions with agents that modulate either Wnt signaling or mineralization may be effective in GC-induced osteoporosis.

OBJECTIVES

To provide chlamydia and gonorrhea screening and treatment to adolescents presumed to be at high risk, school screening was conducted among the 11th and 12th graders in San Francisco.

STUDY DESIGN

Two schools in neighborhoods with high chlamydia and gonorrhea rates and student populations > or = 15% black were chosen. Students viewed a 10-minute presentation and received test kits. Students decided in a private bathroom stall whether to test. All students were encouraged to return a test kit (whether they returned a urine specimen).

RESULTS

Of 967 eligible students, 853 (88%) were in attendance. Of these, 21 (2%) declined to participate and 537 (63%) returned a specimen for testing. Students who tested were predominately heterosexual (93%) and nonwhite (99%). No students tested positive for gonorrhea; 7 (1.3%) tested positive for chlamydia. Positivity was 2.2% (5 of 227) for female students and 0.6% (2 of 310) for male students. Positivity by race/ethnicity was 5.4% (4 of 74) for blacks, 2.0% (2 of 98) for Hispanics, 0.3% (1 of 342) for Asian/Pacific Islanders, and 0% (0 of 4) for whites. The highest positivity was among black female students: 9.3% (4 of 43). Not including planning and follow-up, each case identified used 63 staff hours.

CONCLUSIONS

Despite high participation among students attending school in high morbidity neighborhoods, few infections were identified. This is likely because students have low rates of sexual activity and do not necessarily attend neighborhood schools. Screening used substantial resources. Sexually transmitted disease control programs considering school screening should consider local epidemiology and whether schools have substantial proportions of students likely at high risk for sexually transmitted diseases.