Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile.

OBJECTIVE: To evaluate the effects of a tissue-selective estrogen complex (TSEC) composed of bazedoxifene/conjugated estrogens (BZA/CE) on menopausal symptoms, metabolic parameters, and overall safety. DESIGN: Multicenter, double-blind, placebo- and active-controlled phase 3 trial (Selective estrogens, Menopause, And Response to Therapy [SMART]-1). SETTING: Outpatient clinical. PATIENT(S): Healthy, postmenopausal women (n = 3,397) age 40 to 75 with an intact uterus. INTERVENTION(S): Single tablets of BZA (10, 20, or 40 mg), each with CE (0.625 or 0.45 mg); raloxifene 60 mg; or placebo taken daily for 2 years. MAIN OUTCOME MEASURE(S): Hot flushes, breast pain, vaginal atrophy, metabolic parameters, and adverse events. RESULT(S): BZA (20 mg)/CE (0.625 or 0.45 mg) significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy compared with placebo. At week 12, the daily number of hot flushes decreased by 51.7% to 85.7% with all BZA/CE doses vs. 17.1% for placebo. BZA/CE improved lipid parameters and homocysteine levels, did not significantly change carbohydrate metabolism, and had only minor effects on some coagulation parameters. The incidences of breast pain and adverse events were similar between BZA/CE and placebo. CONCLUSION: The TSEC composed of BZA (20 mg)/CE (0.625 or 0.45 mg) is an effective and safe treatment for menopausal symptoms.

In vivo light scattering for the detection of cancerous and precancerous lesions of the cervix.

A noninvasive optical diagnostic system for detection of cancerous and precancerous lesions of the cervix was evaluated in vivo. The optical system included a fiber-optic probe designed to measure polarized and unpolarized light transport properties of a small volume of tissue. An algorithm for diagnosing tissue based on the optical measurements was developed that used four optical properties, three of which were related to light scattering properties and the fourth of which was related to hemoglobin concentration. A sensitivity of ~77% and specificities in the mid 60% range were obtained for separating high grade squamous intraepithelial lesions and cancer from other pathologies and normal tissue. The use of different cross-validation methods in algorithm development is analyzed, and the relative difficulties of diagnosing certain pathologies are assessed. Furthermore, the robustness of the optical system for use by different doctors and to changes in fiber-optic probe are also assessed, and potential improvements in the optical system are discussed.

Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering.

OBJECTIVE: To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. MATERIALS AND METHODS: A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. RESULTS: Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. CONCLUSIONS: The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating "see and treat" protocols is a longer term goal. Improvements in accuracy are essential.

In vivo light scattering measurements for detection of precancerous conditions of the cervix.

OBJECTIVE: To examine the utility of in vivo elastic light scattering measurements to diagnose high grade squamous interepithelial lesions (HSIL) of the cervix. METHODS: A newly developed fiber optic probe was used to measure light transport in the cervical epithelium of 36 patients undergoing standard colposcopy. Both unpolarized and polarized light transport were measured in the visible and near-infrared. Spectroscopic results of 29 patients were compared with histopathology of the measured sites using ROC curves, MANOVA and logistic regression. RESULTS: Three spectroscopic parameters are statistically different for HSIL compared with low-grade lesions and normal tissue. When these three spectroscopic parameters are combined, retrospective sensitivities and specificities for HSIL versus non-HSIL are 100% and 80%, respectively. CONCLUSIONS: Reflectance measurements of elastically scattered light show promise as a non-invasive, real-time method to discriminate HSIL from other abnormalities and normal tissue. These results compare favorably with those obtained by fluorescence alone and by fluorescence combined with light scattering.

Obstetrics and gynecology residents as teachers of medical students: predictors of excellence.

OBJECTIVE: The purpose of this study was to assess variables that might predict which intern candidates will become excellent teachers of medical students. STUDY DESIGN: This retrospective cohort study compared demographic characteristics, previous work experience, United States Medical Licensing Examinations scores, honors on core clerkships, membership in Alpha Omega Alpha, and match list ranking of 43 residents to identify predictors of excellent teaching evaluations during residency. RESULTS: Fifteen residents (35%) were identified as excellent teachers. They were more likely to have had previous work experience, to be older, or to be male. They were not more likely to have higher United States Medical Licensing Examinations test scores, more honors grades, Alpha Omega Alpha membership, or a higher rank list position. CONCLUSION: Work experience, age, and male gender are associated with increased likelihood of being identified as an excellent teacher by medical students. Programs in which residents have a significant role as teachers of students may consider these factors in the residency selection process.

Is there a difference in survival for IA1 and IA2 adenocarcinoma of the uterine cervix?

OBJECTIVE: The goal of this study was to determine if International Federation of Obstetrics and Gynecology (FIGO) subdivision into IA1 versus IA2 is predictive of survival differences for early invasive adenocarcinoma. METHODS: The Surveillance, Epidemiology, and End-Results (SEER) Public-Use Database was used to identify all cases of IA1 and IA2 adenocarcinoma diagnosed between 1983 and 1997. A systematic literature search (MEDLINE 1966-2000) was used to identify all previously published cases. Stage, depth of invasion, node status, therapy, and survival were analyzed using Fisher's exact and log-rank tests. RESULTS: In SEER, 560 cases were identified: 200 IA1, 286 IA2, and 74 localized. Simple hysterectomy was performed in 272 (48.6%) and radical hysterectomy in 210 (37.5%). Positive lymph nodes were found in 3 of 197 (1.5%) who underwent lymphadenectomy, 2 of whom died. The censored survival by stage (mean follow-up 51.6 months) was not significantly different (P = 0.77) for IA1 versus IA2 (98.5% vs 98.6%). Combining these data with all other published series of early cervical adenocarcinoma, 1170 cases were identified, including 585 IA1, 358 IA2, and 227 "others," with less defined early disease. Of 531 (45.4%) who underwent lymphadenectomy, 15 (1.28%) had one or more positive nodes; of these, 11 (73.3%) recurred or died. For IA1 versus IA2 disease, there were no significant differences in the frequency of positive lymph nodes, recurrence, or death. However, "others," those with less well-defined lesions, or larger than IA2, were at increased risk. CONCLUSION: Early invasive adenocarcinoma (IA1 and IA2) has an excellent prognosis and conservative surgery may be appropriate. Since current FIGO staging definitions do not distinguish high- from low-risk disease, individualization of therapy based on pathology review, risk assessment, and patient preference is recommended.