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Objective This study aimed to explore the longitudinal, 6-month symptom course of older adults newly started on an antidepressant or anxiolytic by non-psychiatrist physicians and enrolled in a care management program. Method This is a naturalistic cohort study of older adults (age ≥65 years) receiving pharmacotherapy and telephone-based care management. Participants are non-institutionalized adults participating in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly who completed telephone-based clinical assessments including demographic data, self-report on history of psychiatric treatment and adherence, and standardized symptom scales. Results A total of 162 participants with an average age of 77.2 years (SD 6.8) were followed and, for analysis, split into two groups by PHQ-9 score: 75 (46.3%) scoring 0–4 (minimally symptomatic group, MSG) and 87 (53.7%) scoring ≥5 (symptomatic group, SG). Over 6 months, the SG improved with PHQ-9 scores beginning on average at 10.0 (SD 4.6) and falling to 5.4 (SD 4.2) (F(1, 86) = 29.53, p

BACKGROUND Obesity and androgen metabolism have been implicated in the progression of prostate cancer. Obesity has been associated with increased risk for advanced disease and biochemical failure after treatment. This association may be the result of changes in androgen metabolism that occur with obesity and are mediated by the androgen receptor (AR). METHODS To evaluate the effects of obesity and AR polymorphisms on biochemical failure, we conducted a study of 536 Caucasian prostate cancer cases. We determined the relationship between time to biochemical failure and obesity stratified by short and long AR-CAG and AR-GGN repeat sequence. The AR repeat groups were dichotomized at the median number of repeats for each polymorphism. RESULTS An association was found for obesity in the short CAG group (HR = 3.45, 95% CI = 1.00–11.96). Among obese patients diagnosed with localized disease (T1/T2), the risk of biochemical failure was significantly higher (HR = 7.05, 95% CI = 1.55–32.06). No difference was observed for high stage (T3/T4) obese patients. Additionally, no differences in biochemical failure were observed in obese and non-obese men grouped by number of AR-GGN repeats. CONCLUSIONS Obesity is significantly associated with increased risk of biochemical failure in men with the high-risk short CAG sequence on the AR gene. This effect is not observed in men with long CAG repeats. Therefore, it appears that the relationship between biochemical failure and obesity may be modified by the AR-CAG repeat pattern. The short AR-CAG genotype may be more responsive to an altered hormonal milieu created by obesity. Prostate 72:984–990, 2012. © 2011 Wiley Periodicals, Inc.

Background: As cancer treatments evolve, it is important to reevaluate their effect on lymphedema risk in breast cancer survivors. Methods: A population-based random sample of 631 women from metropolitan Philadelphia, Pennsylvania, diagnosed with incident breast cancer in 1999 to 2001, was followed for 5 years. Risk factor information was obtained by questionnaire and medical record review. Lymphedema was assessed with a validated questionnaire. Using Cox proportional hazards models, we estimated the relative incidence rates [hazard ratios (HR)] of lymphedema with standard adjusted multivariable analyses ignoring interactions, followed by models including clinically plausible treatment interactions. Results: Compared with no lymph node surgery, adjusted HRs for lymphedema were increased following axillary lymph node dissection [ALND; HR, 2.61; 95% confidence interval (95% CI), 1.77-3.84] but not sentinel lymph node biopsy (SLNB; HR, 1.04; 95% CI, 0.58-1.88). Risk was not increased following irradiation [breast/chest wall only: HR, 1.18 (95% CI, 0.80-1.73); breast/chest wall plus supraclavicular field (+/− full axilla): HR, 0.86 (95% CI, 0.48-1.54)]. Eighty-one percent of chemotherapy was anthracycline based. The HR for anthracycline chemotherapy versus no chemotherapy was 1.46 (95% CI, 1.04-2.04), persisting after stratifying on stage at diagnosis or number of positive nodes. Treatment combinations involving ALND or chemotherapy resulted in approximately 4- to 5-fold increases in HRs for lymphedema [e.g., HR of 4.16 (95% CI, 1.32-12.45) for SLNB/chemotherapy/no radiation] compared with no treatment. Conclusion: With standard multivariable analyses, ALND and chemotherapy increased lymphedema risk whereas radiation therapy and SLNB did not. However, risk varied by combinations of exposures. Impact: Treatment patterns should be considered when counseling and monitoring patients for lymphedema. Cancer Epidemiol Biomarkers Prev; 19(11); 2734–46. ©2010 AACR.

Background: Disparities in cancer defined by race, age, or gender are well established. However, demographic metrics are surrogates for the complex contributions of genotypes, exposures, health care, socioeconomic and sociocultural environment, and many other factors. Macroenvironmental factors represent novel surrogates for exposures, lifestyle, and other factors that are difficult to measure but might influence cancer outcomes. Methods: We applied a “multilevel molecular epidemiology” approach using a prospective cohort of 444 White prostate cancer cases who underwent prostatectomy and were followed until biochemical failure (BF) or censoring without BF. We applied Cox regression models to test for joint effects of 86 genome-wide association study–identified genotypes and macroenvironment contextual effects after geocoding all cases to their residential census tracts. All analyses were adjusted for age at diagnosis and tumor aggressiveness. Results: Residents living in census tracts with a high proportion of older single heads of household, high rates of vacant housing, or high unemployment had shorter time until BF postsurgery after adjustment for patient age and tumor aggressiveness. After correction for multiple testing, genotypes alone did not predict time to BF, but interactions predicting time to BF were observed for MSMB (rs10993994) and percentage of older single heads of households (P = 0.0004), and for HNF1B/TCF2 (rs4430796) and census tract per capita income (P = 0.0002). Conclusions: The context-specific macroenvironmental effects of genotype might improve the ability to identify groups that might experience poor prostate cancer outcomes. Impact: Risk estimation and clinical translation of genotype information might require an understanding of both individual- and macroenvironment-level context. Cancer Epidemiol Biomarkers Prev; 19(9); 2115–23. ©2010 AACR.

Purpose The purpose was to identify risk factors associated with in-hospital mortality among emergency department (ED) patients with severe sepsis and septic shock managed with early protocolized resuscitation. Methods This was a retrospective, observational cohort study in an academic, tertiary care ED. We enrolled 411 adult patients with severe sepsis and lactate ≥ 4.0 mmol/L (n = 203) or septic shock (n = 208) who received protocolized resuscitation from 2005 to 2009. Emergency department variables, microbial cultures, and in-hospital outcomes were obtained from the medical record. Multivariable regression was used to identify factors independently associated with in-hospital mortality. Results Mean age was 59.5 ± 16.3 years; 57% were male. Mean lactate was 4.8 mmol/L (3.5-6.7), 54% had positive cultures, and 27% received vasopressors in the ED. One hundred and five (26%) patients died in-hospital. Age, active cancer, do-not-resuscitate status on ED arrival, lack of fever, hypoglycemia, and intubation were independently associated with increased in-hospital mortality. Lactate clearance and diabetes were associated with a decreased risk of in-hospital death. Conclusions We identified a number of factors that were associated with in-hospital mortality among ED patients with severe sepsis or septic shock despite treatment with early protocolized resuscitation. These findings provide insights into aspects of early sepsis care that can be targets for future intervention.

This study evaluated recent inconsistent findings that adding progestins to postmenopausal estrogen replacement therapy protects against endometrial cancer. Using a population-based case-control study, the authors compared 511 endometrial cancer cases aged 50-79 years in the Philadelphia, Pennsylvania, region during 1999-2002 with 1,412 random-digit-dialing controls regarding postmenopausal hormone replacement therapy (HRT) use. Telephone interviews were performed with memory aids mailed in advance. An increased risk of endometrial cancer was observed among postmenopausal women using only unopposed estrogen for 3 or more years, compared with women who never used HRT (adjusted odds ratio = 3.4, 95% confidence interval (CI): 1.4, 8.3). Using combination HRT (of any duration) was associated with a substantial reduction in risk (odds ratio = 0.8, 95% CI: 0.6, 1.1). Comparing women using only combined estrogen and progestin for 3 or more years with women using only unopposed estrogen for 3 or more years, the authors found that the adjusted odds ratio was 0.2 (95% CI: 0.1, 0.6). Long-term use of unopposed estrogen is associated with increased risk for endometrial cancer, whereas combined estrogen plus progestin hormone therapy is not. Thus, if HRT is to be used in women with an intact uterus, this study confirms the benefit of adding progestins to the regimen.

We studied the benefit of modern mammography screening in community settings, evaluating age-related differences in rates of late-stage breast cancer detection.Our multicenter population-based case-control study included 931 black and white women with incident breast cancer (American Joint Commission on Cancer Stage IIB or higher) diagnosed 1994-1998 and 4,016 randomly sampled controls never diagnosed with breast cancer. Adjusted odds ratios (ORs) estimated the relative rate of late-stage diagnosis in screened and non-screened women.Women aged 50-64 at diagnosis with at least one screening mammogram in the previous 2 years were significantly less likely to have late-stage diagnosis (OR = 0.41, 95% CI 0.33-0.52). Results for women aged 40-49 were consistent with a screening benefit, although the confidence interval marginally overlapped the null (OR = 0.81, 95% CI 0.64-1.02). Mammography screening was associated with lower rates of late-stage breast cancer among both premenopausal (OR = 0.64, 95% CI 0.50-0.81) and postmenopausal (OR = 0.44, 95% CI 0.35-0.56) women.With modern mammography in the community, rates of late-stage breast cancer diagnoses are lower in screened compared to non-screened women ages 40 and older, but age-related differences persist.

Objectives: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship. Methods: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately. Results: Recent consumption (at reference age minus two) of ≥7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor–positive/progesterone receptor–negative tumors (OR 1.6; 95% CI, 1.2-2.3). Conclusions: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.

Animal data indicate that both estrogens and progestins could be carcinogenic and that progestins could serve as tumor promoters. Human studies have not confirmed an increased risk of breast cancer from long-term use of oral contraceptives, but have shown an increased risk from hormone replacement therapy including progestins. The present study analyzed the relationship between breast cancer and use of injectable and implantable progestin-only contraceptives. Analyses were performed on data collected in a population-based, multicenter, case-control study, the Women's Contraceptive and Reproductive Experiences Study of the National Institute of Child Health and Human Development. The study involved 4575 randomly sampled cases with invasive breast cancer diagnosed between 1994 and 1998, and 4682 controls, identified using random digit dialing. We assessed the association between exposure to injectable contraceptives and risk of breast cancer. The use of injectable contraceptives was not associated with an increased risk of breast cancer [odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7, 1.2]. Risk was not increased among current users, defined as women who used injectable contraceptives within 1 year of the reference date (OR = 0.7, 95% CI: 0.4, 1.3) or those who initiated use in the 5 years immediately preceding the reference date (OR = 0.9, 95% CI: 0.5, 1.4), or with use beginning before age 35 (OR = 0.9, 95% CI: 0.6, 1.3). Among users, risk increased with increasing duration of use (p = 0.03). However, short-term users (

Objective: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. Methods: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case–control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. Results: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01–1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97–1.03). Conclusions: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.

Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long-term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Women's Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use.A multicenter, population-based, case-control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35-64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two-sided P values for trend were computed from the likelihood ratio statistic. Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P =.01). There were no positive associations between breast cancer risk and other HRT regimens. Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

This study examined whether there were differences in the rate of depressive and anxiety disorders between HIV-infected women (N=93) and a comparison group of uninfected women (N=62). Secondary objectives were to examine correlates of depression in HIV-infected women-including HIV disease stage and protease inhibitor use-and the associations between symptoms of depression or anxiety and other potential predictor variables.Subjects underwent extensive semiannual clinical, psychiatric, neuropsychological, and immunological evaluations. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. Symptoms of depression and anxiety were evaluated with the Hamilton Depression Rating Scale (the 17-item version and a modified 11-item version) and the Hamilton Anxiety Rating Scale, respectively.The rate of current major depressive disorder was four times higher in HIV-seropositive women (19.4%) than in HIV-seronegative women (4.8%). Mean depressive symptom scores on the 17-item Hamilton depression scale also were significantly higher, overall, in the HIV-infected women (mean=8.7, SD=8.0) relative to comparison subjects (mean=3.3, SD=5.8). There was no significant between-group difference in the rate of anxiety disorders. However, HIV-seropositive women had significantly higher anxiety symptom scores (mean=8.8, SD=8.9) than did HIV-seronegative women (mean=3.6, SD=5.5). Both groups had similar substance abuse/dependence histories, but adjusting for this factor had little impact on the relationship of HIV status to current major depressive disorder.HIV-seropositive women without current substance abuse exhibited a significantly higher rate of major depressive disorder and more symptoms of depression and anxiety than did a group of HIV-seronegative women with similar demographic characteristics. These controlled, clinical findings extend recent epidemiologic findings and underscore the importance of adequate assessment and treatment of depression and anxiety in HIV-infected women.

In view of the paucity of national data on the associations between predictor variables and teacher retention, school transfer, and attrition in special education, we sought to provide such data from a national probability sample of 4,798 public school teachers from the 1989 Teacher Followup Survey (Faupel, Bobbitt, & Friedrichs, 1992). The analysis focused on teacher retention and turnover (i.e., school transfer and attrition) of special education teachers (SETs) in comparison with general education teachers (GETs). Results showed that teacher turnover decreased as the following variables increased: teacher age (until retirement age), the number of dependent children, the level of certification, the number of years since the last degree was earned, teaching experience and salary level. The importance of these and other relationships for designing strategies to maximize teacher retention is discussed.

Gender- and ethnicity-specific groups face different risks for obesity, but little is understood about the factors that predict group-specific risks. We evaluated individual and neighborhood factors in relation to obesity.Cross-sectional surveys of adults (ages 18-100 years) from southeastern Pennsylvania were analyzed. Individual- and neighborhood-level factors were included in fully-adjusted regression models to estimate relationships with obesity for specific gender-ethnic groups. The study included 679 Asian women, 655 Asian men, 4190 African-American women, 1568 African-American men, 1248 Hispanic women, 586 Hispanic men, 11791 European American women, and 6547 European American men.There were significant differences in the predictors of obesity by gender-ethnic groups. Obesity was differentially associated with age (p0.001, positively associated with middle age in African-American men and in all women except Asian; positively associated with older age in European American women but inversely in African-American men and European American men), employment (p0.01, positively associated in African-American men and European American men) and poverty (p0.001, positively associated in Asian men, African-American women, and European American women). Reporting good/excellent health was differentially associated with less obesity (p0.01, no association for African-American men and Asians). Interestingly, neighborhood-level effects, however, did not differ significantly by gender-ethnic group. Inverse neighborhood effects on obesity prevalence were observed in most groups for higher neighborhood education and family income. Direct associations with obesity were observed for neighborhood poverty and neighborhood smoking.We observed that individual- and neighborhood-level variables are associated with obesity. Several individual-level effects differ by gender-ethnic group.

Background Perceived stress (PS) is a risk factor for a variety of diseases. However, relatively little is known about age- or ethnicity-specific differences in the effect of potential predictors of PS in men. Methods We used a population-based survey of 6,773 White, 1,681 Black, and 617 Hispanic men in Southeastern Pennsylvania to evaluate the relationship of self-reported PS and financial security, health status, social factors, and health behaviors. Interactions across levels of age and ethnicity were tested using logistic regression models adjusted for overall health status, education, and household poverty. Results High PS decreased significantly with age (p < 0.0001) and varied by ethnicity (p = 0.0001). Exposure to health-related and economic factors were more consistently associated with elevated PS in all ethnicities and ages, while social factors and health behaviors were less strongly or not at all associated with PS in most groups. Significant differences in the relationship of high PS by age and ethnicity were observed among men who are medically uninsured (p = 0.0002), reported missing a meal due to cost (p < 0.0001), or had spent a night in the hospital (p = 0.020). In contrast, not filling a prescription due to cost and diagnosed with a mental health condition were associated with high PS but did not differ by age and ethnicity subgroup. Conclusions These data suggest that some, but not all, factors associated with high PS differ by age and/or ethnicity. Research, clinical, or public health initiatives that involve social stressors should consider differences by age and ethnicity.

This study aimed to explore the longitudinal, 6-month symptom course of older adults newly started on an antidepressant or anxiolytic by non-psychiatrist physicians and enrolled in a care management program.This is a naturalistic cohort study of older adults (age ≥65 years) receiving pharmacotherapy and telephone-based care management. Participants are non-institutionalized adults participating in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly who completed telephone-based clinical assessments including demographic data, self-report on history of psychiatric treatment and adherence, and standardized symptom scales.A total of 162 participants with an average age of 77.2 years (SD 6.8) were followed and, for analysis, split into two groups by PHQ-9 score: 75 (46.3%) scoring 0-4 (minimally symptomatic group, MSG) and 87 (53.7%) scoring ≥5 (symptomatic group, SG). Over 6 months, the SG improved with PHQ-9 scores beginning on average at 10.0 (SD 4.6) and falling to 5.4 (SD 4.2) (F(1, 86) = 29.53, p 0.0001). The MSG had no significant change in depressive symptoms. Emotional health as measured by SF-12 Mental Composite Score mirrored the PHQ-9 change and lack thereof in the SG and MSG, respectively. No clinical or demographic features were associated with symptom improvement in the SG although they were more likely to report medication adherence (66.7% vs. 44.0%, χ(2) (1) = 8.4, p = 0.0037) compared with the MSG.Participation of symptomatic older adults initiated on psychotropic medication in a telephone-based care management program was associated with improvement in depressive symptoms and overall emotional well-being, notable findings given participants' advanced age, state-wide distribution, and history of limited utilization of mental health care.

Purpose Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen-plus-progestin therapy (CHT) increases risk of developing fatal breast cancer i.e., developing and dying of breast cancer. Using a population-based case-control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non-users by type, duration, and recency of HT use. Methods HT use prior to breast cancer diagnosis in 278 women who died of breast cancer within 6 years of diagnosis (cases) was compared with use in 2224 controls never diagnosed with breast cancer using conditional logistic regression. Measures taken to address potential bias and confounding inherent in case-control studies included collecting and adjusting for detailed data on demographic and other factors potentially associated both with HT use and breast cancer. Results Fifty-six per cent of cases and 68% of controls reported HT use. Among current 3+ year HT users, odds ratios and 95% confidence intervals for death were 0.83 (0.50, 1.38) and 0.69 (0.44, 1.09), respectively, for exclusive use of CHT or of ET, and were 0.94 (0.59, 1.48) and 0.70 (0.45, 1.07) for any use of CHT or of ET regardless of other hormone use. Conclusion Point estimates suggest no increased risk of fatal breast cancer with HT use, although 50% increases in risk in longer-term current CHT users cannot be ruled out. Copyright © 2010 John Wiley & Sons, Ltd.

Purpose To examine the incidence, degree, time course, treatment, and symptoms of lymphedema in breast cancer survivors. Methods We conducted a 5-year, population-based prospective study of 631 randomly selected Philadelphia and Delaware County, Pennsylvania female residents with incident breast cancer who were diagnosed from 1999 to 2001. Using a questionnaire previously validated against physical therapists’ measurement-based clinical criteria, we assigned a score indicating the degree of lymphedema (none, mild, or moderate/severe) to each month of follow-up based on the respondent's perceived differences in hand/arm size. Standard survival analysis methods permitted maximum use of follow-up. Results Five-year cumulative incidence of lymphedema was 42 (42%) per 100 women. Among the 238 affected women, lymphedema first occurred within 2 years of diagnosis in 80% and within 3 years in 89%. Among 433 women observed for 3 years, 23% reported no more than mild lymphedema, 12% reported moderate/severe lymphedema, and 2% reported chronically moderate/severe lymphedema. Women with mild lymphedema were more than three times more likely to develop moderate/severe lymphedema than women with no lymphedema. Thirty-seven percent of women with mild lymphedema and 68% with moderate/severe lymphedema received treatment. Increasing proportions of women with increasing degree of lymphedema reported symptoms (eg, jewelry too tight, tired/thick/heavy arm). Symptoms present before the first occurrence of lymphedema were associated with a higher probability of later lymphedema (eg, hazard ratio for jewelry too tight = 7.37; 95% CI, 4.26 to 12.76). Conclusion Lymphedema after breast cancer is common but mostly mild. Subtle differences in self-reported hand/arm size and symptoms can be early signs of progressing lymphedema.

This study assessed the efficacy of community-based screening mammography in protecting against breast cancer death, asking whether age differences in efficacy persisted in the 1990s.In a case-control study with follow-up, odds ratios (OR) were used to estimate the relative mortality rates from invasive breast cancer among women with at least one screening mammogram in the two years prior to a baseline reference date compared to non-screened women, adjusting for potential confounding. The multicenter population-based study included 553 black and white women diagnosed during 1994-1998 who died in the following five years, and 4016 controls without breast cancer.Efficacy for reducing the rate of breast cancer death within five years after diagnosis was greater at ages 50-64 years (OR = 0.47, 95% confidence interval (CI) 0.35-0.63) than at ages 40-49 (OR = 0.89, 95% CI 0.65-1.23), and greater among postmenopausal (OR = 0.45, 95% CI 0.33-0.62) than premenopausal women (OR = 0.74, 95% CI 0.53-1.04). Estimates of efficacy were conservative, as shown by sensitivity analyses addressing whether cancer was discovered by a screening mammogram, age at which screening was received, the length of the screening observation window, and years of follow-up after diagnosis.Despite the persistence of age differences in efficacy of mammography screening, with greater observed benefit for women aged 50-64 years, these findings support current screening recommendations for women 40-64 years old.

ContextRetrospective drug utilization review is required of all state Medicaid programs and is performed by most private-sector prescription programs. However, it has not been shown to improve clinical outcomes or reduce the rate of potential prescribing errors, known as "exceptions."ObjectiveTo look for an effect of retrospective drug utilization review on the rate of exceptions and of clinical outcomes in patients with an exception.Design, Setting, and ParticipantsLongitudinal ecologic study of the rate of exceptions, controlling for preintervention trends and calendar time; and a cohort study of all-cause and cause-specific hospitalizations in patients with an exception, controlling for potential individual-level confounders in 6 Medicaid programs using the same software in the mid-1990s.Main Outcome MeasuresThe rate of exceptions was examined as a function of retrospective drug utilization review implementation. In addition, before-after comparisons were made of the incidence of all-cause and cause-specific hospitalization in patients with exceptions.ResultsWe found no reduction in the rate of exceptions coincident with retrospective drug utilization review implementation (rate increase, 0.064 exceptions per 1000 prescriptions per month; 95% confidence interval [CI], −0.006 to 0.133). We also found no effect of retrospective drug utilization review on the incidence of all-cause hospitalization (odds ratio, 0.99; 95% CI, 0.98-1.00) or cause-specific hospitalization. These results persisted in multiple subgroup analyses. Study states intervened using physician alerts in between 1% and 25% of exceptions.ConclusionsWe were unable to identify an effect of retrospective drug utilization review on the rate of exceptions or on clinical outcomes. Given the lack of evidence for effectiveness, and suggestions from previous research of possible harm, policymakers should consider withdrawing the legislative mandate for retrospective drug utilization review.

Purpose To examine the integrity of six Medicaid databases for use in pharmacoepidemiology research. Methods We performed descriptive analyses to examine four categories of potential data errors: incomplete claims for certain time periods; absence of an accurate indicator of inpatient hospitalizations; missing hospitalizations for those aged 65 years and over; and diagnostic codes in demographic groups in which those conditions should be rare. Results Prescription claims appeared to be missing intermittently in some states. No valid marker of inpatient hospitalizations could be found for three of six states. Hospitalizations appeared to be missing to varying degrees for those aged 65 years and over. Gross errors in diagnostic codes and demographic data did not appear to be widespread. Conclusions Whenever possible, investigators using administrative data should perform macro-level descriptive analyses on the parent data set. In particular, researchers should examine the number of medical and pharmacy claims over time, looking for gaps. Validity of markers of hospitalization should be assessed. The accuracy of diagnosis and demographic data should be examined. Such a descriptive macro-level approach should be used to supplement, and perhaps precede validation of study outcomes using clinical records. Copyright © 2002 John Wiley & Sons, Ltd.

To compare differences in AIDS patients' 30-day mortality and satisfaction with care in dedicated AIDS units, scattered-bed units in hospitals with and without dedicated AIDS units, and in magnet hospitals known to provide good nursing care.Data were obtained on 1,205 consecutively admitted patients in 40 units in 20 hospitals and on 820 of their nurses.Mortality was lower and satisfaction was higher for AIDS patients in dedicated AIDS units and in nursing magnet hospitals. Primary nursing, end-of-life care counseling, and discharge planning were also more common. Higher nurse to patient ratios and AIDS physician specialty services were strongly associated with lower mortality. Patient satisfaction was strongly associated with organizational control of care by bedside nurses. Homosexuals were more likely to be admitted to dedicated AIDS units, which largely explains the under-representation of minorities and women.Dedicated AIDS units and magnet hospitals offer important benefits to AIDS patients, including lower odds on dying within 30 days of admission, higher patient satisfaction, and care meeting professional standards. Better nurse staffing, AIDS physician specialty services, and more organizational control by bedside nurses improve patient outcomes.

Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long-term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Women's Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use.A multicenter, population-based, case-control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35-64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two-sided P values for trend were computed from the likelihood ratio statistic. Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P =.01). There were no positive associations between breast cancer risk and other HRT regimens. Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

target to prevent adverse outcomes? Michal A. Elovitz, Jamie Bastek, Anita Weber, Megan McShea, Markley Foreman, Sindhu Srinivas University of Pennsylvania Perelman School of Medicine, Maternal and Child Research Program; Department of OBGYN, Philadelphia, PA, University of Pennsylvania Perelman School of Medicine, CCEB, Philadelphia, PA, University of Pennsylvania Perelman School of Medicine, Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Philadelphia, PA OBJECTIVE: Prenatal inflammation, as noted by histological (HCA) or clinical chorioamnionitis (CCA), has been considered a risk factor for prematurity and adverse neonatal outcomes. However, prior studies have been limited by their retrospective nature with more recent studies suggesting that only gestational age at delivery, not the intrauterine environment, is the main predictor of neonatal outcome. We sought to assess if prenatal inflammation, as measured by HCA, CCA or maternal temperature 38 (T38), was associated with adverse neonatal outcomes. STUDY DESIGN: A prospective cohort of women with singleton pregnancies and preterm labor was performed. HCA was determined by a pathologist and CCA by provider. The highest maternal temperature within 24 hours prior to delivery was recorded. Gestational age at delivery (GA-DEL) and neonatal outcomes within the first 30 days of life were recorded. Associations between categorical variables were determined usgin chi-square analyses. MVLR was performed to determine the association between prenatal inflammation (CCA, HCA, T38) on adverse neonatal outcomes (a composite and individualFigure). RESULTS: 595 women and their infants were studied. The PTB rate was 40%. Rates of exposures and outcomes are on Table I. 30% of women with T38 did not have a diagnosis of CCA. GA-DEL was associated with COMP; for each increase in gestational age by 1 week, COMP was decreased by 33% (0.61-.72, P 0.001). HCA was not associated with COMP. In contrast, CCA and T38 were strongly associated with outcomes (FIG 1). Excluding women with CCA, T38 remained associated with adverse outcome (OR 3.5). CONCLUSION: Prenatal inflammation as measured by both CCA and maternal temperature 38 is strongly associated with adverse neonatal outcomes. Whether HCA is a poor marker of intrauterine inflammation or represents a lower risk inflammatory environment than CCA or T38 requires further investigation. These data support the role of prenatal inflammation in adverse neonatal outcomes. Clinical trials that investigate therapies for these mothers/neonates at increased risk should begin. MOD#21FY08-539 513 Antenatal glucocorticoids and postnatal surfactant treatment partially rescues neonatal lethality and pulmonary immaturity in an ERK3-/knockout (ko) murine model of intrauterine growth restriction (IUGR) Milenka Cuevas-Guaman, Elena Sbrana, Cynthia Shope, R. Alan Harris, Stephen Welty, Sylvain Meloche, Kjersti Aagaard Baylor College of Medicine, Department of Pediatrics, Division of Neonatology, Houston, TX, The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX, Baylor College of Medicine, ObstetricsG PNAS 106:16710) but did not rescue neonatal lethality. Using high throughput discovery platforms (whole transcriptome RNA shotgun sequencing), we then identified the critical molecular mediators in fetal pulmonary maturation (i.e., corticotropin releasing hormone (CRH) and surfactant B (SPB)). Here we sought to functionally validate these molecular discoveries in a relevant translational model, hypothesizing that neonatal surfactant (Survanta) with antenatal glucocorticoids could enhance neonatal survival. STUDY DESIGN: In a double crossover design, we administered 0.4mg/kg prenatal dexamethasone (dex) or saline at E16.5 and E17.5, alongside phospholipids-enriched surfactant (Survanta) or saline at 50mg/kg via inhalation intubation at birth. Confirmation of pulmoPoster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org

5001 Background: Raloxifene, a selective estrogen receptor modulator, has been shown to reduce breast cancer risk in women with osteoporosis, and is currently being compared to tamoxifen for breast cancer chemoprevention in the “STAR” trial. In contrast to tamoxifen, raloxifene does not stimulate endometrial estrogen receptors, and may therefore be associated with a lower risk of endometrial cancer compared with tamoxifen. However, there are few data available on the absolute risk of endometrial cancer in users of raloxifene, or the relative risks of endometrial cancer among raloxifene and tamoxifen users in the general population. Methods: We performed a population-based, case-control study of breast and endometrial cancer. Cases had pathologically-confirmed endometrial cancer, and resided in a 9-county area surrounding Philadelphia. Controls with no history of endometrial cancer were obtained through random-digit dialing and matched to cases by age and race. Only African-American and Caucasian women wer...

Persistent estrus and free-running activity cycles of female albino rats have been shown in previous studies to develop in long photoperiods and non-24 h light cycles. In the present study, estrous cyclicity and running activity were monitored simultaneously in varying photoperiods (LD 12:12, 20:4, 22:2 and 23:1) and cycle lengths (22, 23, 24, 25 and 26.5 h). Contrary to expectations, there was no correlation between the induction of persistent estrus and a freerunning activity cycle. The data support the notion that although estrous cyclicity and running activity are related, the controlling elements for these rhythms are separable.

Blakemore and Campbell (1969) found that a square-wave adapting grating, unlike a sinewave grating of the same period, elevates threshold contrast for test gratings whose frequency is in the vicinity of the third harmonic in the square-wave. Because of its important bearing on the frequency-specificity of adaptation to gratings, we attempted to replicate this finding. Our attempt was successful with one of two observers when the method of adjustment was used to determine thresholds. With the temporal two alternative, forced-choice method, individual differences in this regard disappeared. For all three observers a 3 c/deg adapting square-wave and a 3 c/deg sinewave were equally ineffective in raising the contrast threshold for a 9 c/deg test grating, whereas a 9 c/deg adapting grating, matched to the 3rd harmonic in the square-wave, raised the test grating's threshold by 0.2 log units. Our failure to find consistent evidence that the third harmonic in a square-wave does any adapting whatever casts doubt on the frequency-specificity of adaptation to gratings.

The normal ovarian cycle of female rats is typically replaced by persistent estrus when these animals are housed under constant light. Evidence presented here shows that the maintenance of periodicity in the environment can at least delay (if not prevent) the photic induction of persistent vaginal estrus. Female rats in constant light were exposed to vaginal smearing at random times or at the same time every day. In another experiment, female rats were exposed to either constant bright light, constant dim light, or a 24-hour photic cycle of bright and dim light. The onset of persistent vaginal estrus was delayed in rats exposed to 24-hour time cues even though the light intensities were the same as or greater than those for the aperiodic control groups. The results suggest that the absence of 24-hour time cues in constant light contributes to the induction of persistent estrus.

Two light cycles were presented simultaneously to house mice. One cycle had a period of 23.7 hr, the free-run period of the activity cycle in constant darkness, and the other a period of 24.0 hr. The activity cycles of all 31 subjects synchronized temporarily with the 24.0 hr light cycle. In contrast, only 10 mice also showed temporary synchronization with the 23.7 hr light cycle and only 2 of these spent more time synchronized with the 23.7 than the 24.0 hr light cycle. The results suggest that a relaxation oscillator is not an adequate model of the mouse circadian activity cycle. The results may have practical significance for the design of human temporal environments.