ABSTRACT
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.
Subject(s)
Emergency Service, Hospital , Fever/epidemiology , Hypoglycemia/epidemiology , Neoplasms/epidemiology , Shock, Septic/mortality , Academic Medical Centers , Adult , Age Factors , Aged , Aged, 80 and over , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/epidemiology , Blood Glucose , Blood Urea Nitrogen , Clinical Protocols , Cohort Studies , Comorbidity , Early Medical Intervention , Female , Hospital Mortality , Humans , International Normalized Ratio , Lactic Acid/blood , Logistic Models , Male , Middle Aged , Multivariate Analysis , Resuscitation , Resuscitation Orders , Retrospective Studies , Risk Factors , Sepsis/blood , Sepsis/mortality , Sepsis/therapy , Shock, Septic/blood , Shock, Septic/therapy , Tertiary Care Centers , Vasoconstrictor Agents/therapeutic useABSTRACT
OBJECTIVE: The purpose of this study was to determine whether prenatal inflammation (as assessed by clinical chorioamnionitis, maternal temperature >38°C, or histologic chorioamnionitis) is associated with a composite adverse neonatal outcome. STUDY DESIGN: We performed a prospective cohort study of women at 22 weeks to 33 weeks 6 days' gestation with symptoms of labor (April 2009 to March 2012). Relevant maternal and neonatal exposures and outcomes were recorded. Multivariable logistic regression was performed to determine the association between prenatal inflammation and neonatal outcomes that were controlled for potential confounders. RESULTS: We analyzed 871 mother-infant pairs. The preterm birth rate was 42.0%. When we controlled for infant sex and modified the data by gestational age at delivery, prenatal inflammation remains a significant risk factor for adverse neonatal outcomes, despite advancing gestational age: clinical chorioamnionitis at 32 weeks' gestation (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.02-9.52], at 36 weeks' gestation (OR, 8.88; 95% CI, 4.32-18.25), and at 40 weeks' gestation (OR, 25.30; 95% CI, 9.25-69.19); maternal temperature >38°C at 32 weeks' gestation (OR, 3.18; 95% CI, 0.66-15.42), at 36 weeks gestation (OR, 8.40; 95% CI, 3.60-19.61), and at 40 weeks gestation (OR, 22.19; 95% CI, 8.15-60.44); histologic chorioamnionitis at 32 weeks gestation (OR, 1.25; 95% CI, 0.64-2.46), at 36 weeks gestation (OR, 2.56; 95% CI, 1.54-4.23), and at 40 weeks gestation (OR, 5.23; 95% CI, 1.95-13.99). CONCLUSION: The protective association with advancing gestational age is diminished when prenatal inflammation is present.
Subject(s)
Chorioamnionitis/epidemiology , Inflammation/epidemiology , Pregnancy Outcome/epidemiology , Adult , Area Under Curve , Female , Gestational Age , Humans , Logistic Models , Pregnancy , Prospective Studies , Risk Factors , Young AdultABSTRACT
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.
Subject(s)
Black or African American/psychology , Health Status Disparities , Hispanic or Latino/psychology , Stress, Psychological/ethnology , White People/psychology , Adolescent , Adult , Black or African American/statistics & numerical data , Age Factors , Aged , Cross-Sectional Studies , Hispanic or Latino/statistics & numerical data , Humans , Male , Middle Aged , Pennsylvania , Risk Factors , Socioeconomic Factors , White People/statistics & numerical data , Young AdultABSTRACT
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 < 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. CONCLUSIONS: 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.
Subject(s)
Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Patient Care Management/methods , Telephone , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , MaleABSTRACT
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.
Subject(s)
Antineoplastic Agents/adverse effects , Breast Neoplasms/therapy , Lymph Node Excision/adverse effects , Lymphedema/epidemiology , Lymphedema/etiology , Radiotherapy/adverse effects , Aged , Antineoplastic Agents/therapeutic use , Combined Modality Therapy/adverse effects , Female , Humans , Middle Aged , Proportional Hazards Models , Risk Factors , Sentinel Lymph Node Biopsy/adverse effects , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Aged , Cohort Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Humans , Male , Molecular Epidemiology , Prospective Studies , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Risk Factors , Treatment Failure , United States/epidemiologyABSTRACT
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.
Subject(s)
Breast Neoplasms/chemically induced , Breast Neoplasms/mortality , Estrogen Replacement Therapy/adverse effects , Adult , Case-Control Studies , Estrogens/adverse effects , Female , Humans , Incidence , Logistic Models , Menopause , Middle Aged , Pharmacoepidemiology , Progesterone Congeners/adverse effects , Risk , SEER Program , United States/epidemiologyABSTRACT
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.
Subject(s)
Breast Neoplasms/complications , Lymphedema/epidemiology , Aged , Aged, 80 and over , Female , Humans , Lymphedema/pathology , Lymphedema/physiopathology , Middle Aged , Prospective Studies , Surveys and QuestionnairesABSTRACT
PURPOSE: Raloxifene reduces breast cancer risk in women with osteoporosis, and both tamoxifen and raloxifene prevent breast cancer in high-risk women. However, in vitro, raloxifene does not share the pro-estrogenic effects of tamoxifen on the endometrium. Randomized trials of these agents have provided limited information about endometrial cancer risk in the general population. We sought to compare endometrial cancer risks associated with raloxifene, tamoxifen, and nonusers of a selective estrogen receptor modulator (SERM) in the general population and characterize the endometrial tumors occurring in these groups. METHODS: We performed a case-control study of white and African American women age 50 to 79 years in the Philadelphia area. Patients were diagnosed with endometrial cancer between July 1999 and June 2002. Controls were identified through random-digit dialing. RESULTS: We analyzed 547 cases and 1,410 controls. Among cases, 3.3% had taken raloxifene; 6.2% had taken tamoxifen. Among controls, 6.6% had taken raloxifene; 2.4% had taken tamoxifen. After adjustment for other risk factors, the odds of endometrial cancer among raloxifene users was 50% that of nonusers (odds ratio [OR] = 0.50; 95% CI, 0.29 to 0.85), whereas tamoxifen users had three times the odds of developing endometrial cancer compared with raloxifene users (OR = 3.0; 95% CI, 1.3 to 6.9). Endometrial tumors in raloxifene users had a more favorable histologic profile and were predominantly International Federation of Gynecology and Obstetrics stage I and low grade. CONCLUSION: Raloxifene users had significantly lower odds of endometrial cancer compared with both tamoxifen users and SERM nonusers, suggesting a role for raloxifene in endometrial cancer prevention and individualization of SERM therapy.
Subject(s)
Endometrial Neoplasms/chemically induced , Raloxifene Hydrochloride/adverse effects , Selective Estrogen Receptor Modulators/adverse effects , Tamoxifen/adverse effects , Aged , Anticarcinogenic Agents/therapeutic use , Case-Control Studies , Endometrial Neoplasms/prevention & control , Endometrium/drug effects , Female , Humans , Middle Aged , Odds Ratio , Risk , Risk Factors , Surveys and QuestionnairesABSTRACT
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Mammography/statistics & numerical data , Mass Screening/methods , Adult , Black People/statistics & numerical data , Breast Neoplasms/epidemiology , Case-Control Studies , Cohort Studies , Confidence Intervals , Female , Follow-Up Studies , Humans , Interviews as Topic , Middle Aged , Multicenter Studies as Topic , Neoplasm Staging , Odds Ratio , Postmenopause , Premenopause , Risk Factors , Time Factors , White People/statistics & numerical dataABSTRACT
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.
Subject(s)
Endometrial Neoplasms/epidemiology , Estrogen Replacement Therapy , Progestins/administration & dosage , Aged , Case-Control Studies , Confounding Factors, Epidemiologic , Endometrial Neoplasms/chemically induced , Estrogen Replacement Therapy/adverse effects , Female , Humans , Incidence , Interviews as Topic , Logistic Models , Middle Aged , Philadelphia/epidemiology , Postmenopause , Risk FactorsABSTRACT
OBJECTIVE: We studied the benefit of modern mammography screening in community settings, evaluating age-related differences in rates of late-stage breast cancer detection. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Breast Neoplasms/diagnosis , Mammography/statistics & numerical data , Mass Screening/methods , Adult , Age Distribution , Breast Neoplasms/epidemiology , Case-Control Studies , Early Diagnosis , Female , Humans , Middle Aged , Neoplasm Staging , Odds Ratio , Postmenopause , Premenopause , Risk Factors , SEER Program , United States/epidemiology , White PeopleABSTRACT
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.
Subject(s)
Alcohol Drinking/adverse effects , Breast Neoplasms/etiology , Adult , Age Factors , Breast Neoplasms/pathology , Case-Control Studies , Female , Humans , Middle Aged , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Regression AnalysisABSTRACT
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 (<6 months duration) were at decreased risk relative to never users (OR = 0.6, 95% CI: 0.4, 1.0). When the short-term users were then excluded from the duration-response analysis, the slope of the duration-response became slightly (and nonsignificantly) negative. Risk was not increased among women with 24 or more months of use relative to never users (OR = 1.4, 95% CI: 0.8, 2.5). No increased risk was seen from implantable contraceptives either, although the sample sizes were small. This study does not support an increased risk of breast cancer associated with the use of injectable or implantable progestin-only contraceptives in women aged 35 to 64.
Subject(s)
Breast Neoplasms/epidemiology , Progestins/adverse effects , Absorbable Implants , Adult , Breast Neoplasms/chemically induced , Case-Control Studies , Female , Humans , Injections, Intramuscular , Middle Aged , Progestins/administration & dosage , United States/epidemiologyABSTRACT
CONTEXT: Retrospective 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." OBJECTIVE: To 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 PARTICIPANTS: Longitudinal 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 MEASURES: The 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. RESULTS: We 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. CONCLUSIONS: We 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.
Subject(s)
Drug Utilization Review , Medication Errors/statistics & numerical data , Outcome Assessment, Health Care , Health Services Research , Hospitalization/statistics & numerical data , Humans , Longitudinal Studies , Medicaid/standards , United StatesABSTRACT
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.
Subject(s)
Breast Neoplasms/chemically induced , Contraceptives, Oral/adverse effects , Estrogen Replacement Therapy/adverse effects , Postmenopause , Adult , Breast Neoplasms/epidemiology , California/epidemiology , Case-Control Studies , Drug Therapy, Combination , Female , Georgia/epidemiology , Humans , Incidence , Michigan/epidemiology , Middle Aged , Pennsylvania/epidemiology , Risk Factors , Washington/epidemiology , Women's HealthABSTRACT
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.
Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Hormone Replacement Therapy/adverse effects , Hormone Replacement Therapy/methods , Adult , Age Distribution , Age of Onset , Breast Neoplasms/pathology , Case-Control Studies , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Logistic Models , Middle Aged , Odds Ratio , Postmenopause , Prevalence , Probability , Prognosis , Reference Values , Risk Factors , Time Factors , United States/epidemiologyABSTRACT
OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.