Imidacloprid-induced mortality, histopathology and biochemical impairments in the larvae of oriental latrine fly (Chrysomya megacephala).

The concentration-mortality response of third instar larvae of Chrysomya megacephala (Diptera: Calliphoridae) to a synthetic insecticide, imidacloprid, and its impact on histopathological, histochemical, and biochemical parameters were determined in laboratory assays. Larvae displayed a concentration and time-dependent mortality response for the insecticide. Histopathological studies exhibited quite noticeable modifications in the epithelial cells, peritrophic membrane, basement membrane and muscular layer of the larval midgut. The ultrastructural analysis demonstrated alterations in nuclei, lipid spheres, microvilli, mitochondria, rough endoplasmic reticulum and lysosomes. In addition, histochemical tests on the midgut were performed, which revealed a strong reaction for proteins and carbohydrates in the control group and a weak reaction in the group exposed to imidacloprid in a dose and time-dependent manner. Imidacloprid also caused a significant reduction in the total midgut content of carbohydrates, proteins, lipids and cholesterol. Larvae treated with imidacloprid also showed a reduction in the activities of acid and alkaline phosphatases at all concentrations compared to untreated larvae.

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.

Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.

Safety evaluation and therapeutic efficacy of Habb-e-Asgand, a commonly used antirheumatic polyherbal Unani formulation.

CONTEXT: Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Habb-e-Asgand (HEA) is a polyherbal, Unani formulation widely used in the treatment of RA. Traditional systems of medicine or plant-based drugs are an attractive alternative treatment because of their professed efficacy in curing the disease. Medicinal herbs and herbal formulations are generally considered to be safer than the conventional drugs for RA. Unani drugs are known not to produce toxic effects and are presumed to be nontoxic. However, no objective, verifiable data exists to support the claims of nontoxicity and efficacy. OBJECTIVES: The present study was designed to evaluate the safety and therapeutic efficacy of HEA in Wistar rats. SETTING: The study took place at the University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi, India. DESIGN: Oral toxicity studies--one acute (14 d) and one long-term (90 d)--were carried out using three doses of HEA--57.5, 115, and 230 mg/kg body weight (BWT)--in both male and female rats. The research team also carried out a study on antirheumatic activity. The team induced arthritis in three groups of male rats using collagen type II (CII), and for 20 d, one group was treated once weekly with saline; a second group was treated once weekly with methotrexate (MTX) at 0.25 mg/kg BWT IP; and a third group was treated daily with HEA at 115 mg/kg BWT orally. A control group received saline but was not induced with RA. OUTCOME MEASURES: Rheumatoid factor (RF); anticyclic citrullinated peptide (a-CCP) antibody; antinuclear antibody (ANA); and C-reactive protein (CRP) were measured. RESULTS: The acute and long-term, oral toxicity studies showed that HEA administration did not produce any overt toxicity or mortality and that it was safe at all dose levels tested. No major alterations were observed in hematology, serum biochemistry, necropsy, and histopathology at the therapeutic equivalent dose (ie, 115 mg/kg BWT). HEA administration for 20 d in arthritis-induced rats significantly reduced the levels of autoantibodies and CRP, and the results were comparable with those of MTX, the standard, disease-modifying antirheumatic drug (DMARD). CONCLUSION: The study's results provided evidence that HEA is not toxic at the therapeutic dose. The antiarthritic activity of HEA may be due to its disease-modifying activities, thus supporting the traditional use of this formulation for treatment of RA.

Breast cancer after use of estrogen plus progestin in postmenopausal women.

BACKGROUND: Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial. METHODS: We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use. RESULTS: In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged. CONCLUSIONS: The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.

Evaluating breast cancer risk projections for Hispanic women.

For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model") combines 1990-1996 breast cancer incidence for Hispanic women with relative risks for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk projections have never been comprehensively evaluated for Hispanic women. We compared the relative risks and calibration of BCRAT risk projections for 6,353 Hispanic to 128,976 NHW postmenopausal participants aged 50 and older in the Women's Health Initiative (WHI). Calibration was assessed by the ratio of the number of breast cancers observed with that expected by the BCRAT (O/E). We re-evaluated calibration for an updated BCRAT that combined BCRAT relative risks with 1993-2007 breast cancer incidence that is contemporaneous with the WHI. Cox regression was used to estimate relative risks. Discriminatory accuracy was assessed using the concordance statistic (AUC). In the WHI Main Study, the BCRAT underestimated the number of breast cancers by 18% in both Hispanics (O/E = 1.18, P = 0.06) and NHWs (O/E = 1.18, P < 0.001). Updating the BCRAT improved calibration for Hispanic women (O/E = 1.08, P = 0.4) and NHW women (O/E = 0.98, P = 0.2). For Hispanic women, relative risks for number of breast biopsies (1.71 vs. 1.27, P = 0.03) and age at first birth (0.97 vs. 1.24, P = 0.02) differed between the WHI and BCRAT. The AUC was higher for Hispanic women than NHW women (0.63 vs. 0.58, P = 0.03). Updating the BCRAT with contemporaneous breast cancer incidence rates improved calibration in the WHI. The modest discriminatory accuracy of the BCRAT for Hispanic women might improve by using risk factor relative risks specific to Hispanic women.

Screening mammography beliefs and recommendations: a web-based survey of primary care physicians.

BACKGROUND: The appropriateness and cost-effectiveness of screening mammography (SM) for women younger than 50 and older than 74 years is debated in the clinical research community, among health care providers, and by the American public. This study explored primary care physicians' (PCPs) perceptions of the influence of clinical practice guidelines for SM; the recommendations for SM in response to hypothetical case scenarios; and the factors associated with perceived SM effectiveness and recommendations in the US from June to December 2009 before the United States Preventive Services Task Force (USPSTF) recently revised guidelines. METHODS: A nationally representative sample of 11,922 PCPs was surveyed using a web-based questionnaire. The response rate was 5.7% (684); (41%) 271 family physicians (FP), (36%) 232 general internal medicine physicians (IM), (23%) 150 obstetrician-gynaecologists (OBG), and (0.2%) 31 others. Cross-sectional analysis examined PCPs perceived effectiveness of SM, and recommendation for SM in response to hypothetical case scenarios. PCPs responses were measured using 4-5 point adjectival scales. Differences in perceived effectiveness and recommendations for SM were examined after adjusting for PCPs specialty, race/ethnicity, and the US region. RESULTS: Compared to IM and FP, OBG considered SM more effective in reducing breast cancer mortality among women aged 40-49 years (p = 0.003). Physicians consistently recommended mammography to women aged 50-69 years with no differences by specialty (p = 0.11). However, 94% of OBG "always recommended" SM to younger and 86% of older women compared to 81% and 67% for IM and 84% and 59% for FP respectively (p = < .001). In ordinal regression analysis, OBG specialty was a significant predictor for perceived higher SM effectiveness and recommendations for younger and older women. In evaluating hypothetical scenarios, overall PCPs would recommend SM for the 80 year woman with CHF with a significant variation by specialty (38% of OBG, 18% of FP, 17% of IM; p = < .001). CONCLUSIONS: A majority of physicians, especially OBG, favour aggressive breast cancer screening for women from 40 through 79 years of age, including women with short life expectancy. Policy interventions should focus on educating providers to provide tailored recommendations for mammography based on individualized cancer risk, health status, and preferences.

Comorbidities and mammography use interact to explain racial/ethnic disparities in breast cancer stage at diagnosis.

BACKGROUND: Interactions with comorbidity burden and comorbidity-related care have not been examined as potential explanations for racial/ethnic disparities in advanced-stage breast cancer at diagnosis. METHODS: The authors used linked Surveillance, Epidemiology, and End Results-Medicare data to determine whether comorbidity burden and comorbidity-related care are associated with stage at diagnosis, whether these associations are mediated by mammography use, and whether they explain racial/ethnic disparities. Stage at diagnosis and mammography use were analyzed in multivariate regression models, adjusting for comorbidity burden and comorbidity-race interactions among 118,742 women diagnosed with breast cancer during 1993 to 2005. RESULTS: Mammography utilization was higher among women with ≥ 3 stable comorbidities than among those without comorbidities. Advanced stage at diagnosis was associated with black race (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6-1.8), Hispanic ethnicity (OR, 1.3; 95% CI, 1.2-1.5), unstable comorbidity, and age ≥ 80 years. Mammography was protective in all racial/ethnic groups, but neither mammography use (OR, 0.3; 95% CI, 0.3-0.3 and OR, 0.2; 95% CI, 0.2-0.2 for women with 1 and ≥ 2 prior mammograms, respectively) nor overall physician service use (OR, 0.7; 95% CI, 0.7-0.8 for women with ≥ 16 visits) explained the association between race/ethnicity and stage at diagnosis. The black/white OR fell to 1.2 (95% CI, 0.9-1.5) among women with multiple stable comorbidities who received ≥ 2 screening mammograms, and 1.0 (95% CI, 0.8-1.3) among mammography users with unstable comorbidities. CONCLUSIONS: Comorbidity burden was associated with regular mammography and earlier stage at diagnosis. Racial/ethnic disparities in late stage disease were reduced among women who received both regular mammograms and comorbidity-related care.

Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women.

PURPOSE: Little is known about the risk factors for triple-negative breast cancer (TNBC), which has a worse prognosis compared to hormone receptor-positive breast cancer. We examined the association of smoking and alcohol intake with TNBC and estrogen receptor-positive (ER+) breast cancer. METHODS: Among 148,030 women enrolled in the Women's Health Initiative, 300 TNBC cases and 2,479 ER+ cases were identified over a median of 8.0 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Cigarette smoking was not associated with TNBC, whereas drinkers had reduced risk compared to never drinkers. In contrast, both exposures showed slight positive associations with ER+ breast cancer: for women with ≥ 40 pack-years of smoking, the HR was 1.24, 95% CI 1.06-1.44; for women consuming ≥ 7 servings of alcohol per week, the HR was 1.26, 95% CI 1.06-1.50. Intakes of wine and hard liquor were also significantly positively associated with ER+ breast cancer. CONCLUSIONS: These findings from a large cohort of postmenopausal women suggest that smoking and alcohol consumption are not associated with increased risk of TNBC, but may be modestly associated with increased risk of ER+ breast cancer.

Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.

CONTEXT: In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. OBJECTIVE: To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. DESIGN, SETTING, AND PARTICIPANTS: A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants. MAIN OUTCOME MEASURES: Invasive breast cancer incidence and breast cancer mortality. RESULTS: In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. CONCLUSIONS: Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

Multiple autoimmune syndrome: Hashimoto's thyroiditis, coeliac disease and systemic lupus erythematosus (SLE).

Various autoimmune diseases have association with each other but it is very rare to see multiple autoimmune diseases in one patient. Presence of more than two autoimmune diseases in one patient is known as multiple autoimmune syndrome (MAS). We report the case of an 11 years old girl who presented with history of swelling in front of the neck along with constipation, anorexia, weight gain and increasing pallor over a period of six months. Additionally she had an episodic history of joint pains and abdominal pain with no specific relation to diet, time, other gastrointestinal or genitourinary symptom. Hypothyroid goiter (Autoimmune thyroiditis, Hashimoto's thyroidits) was diagnosed by raised thyroid stimulating hormone (TSH), low T4 and presence of thyroid specific antibodies in blood. Patient was discharged on tablet Levothyroxine to which she responded well with reduction in size of the swelling and relief of the symptoms except for the joint pains and abdominal pain. To evaluate the persistent symptoms she was investigated further for other autoimmune diseases and was diagnosed to be having systemic lupus erythematosus (SLE) and Coeliac disease also. The final diagnosis was multiple autoimmune syndrome (Hashimoto's thyroiditis, Coeliac disease and SLE).

Interaction of Selected Terpenoids From Dalbergia sissoo With Catalytic Domain of Matrix Metalloproteinase-1: An In Silico Assessment of Their Anti-wrinkling Potential.

Matrix metalloproteinase-1 (MMP-1) is a predominant collagenase enzyme that cleaves collagen fibers, contributing to skin wrinkling. Matrix metalloproteinase-1 inhibitors of herbal origin may provide an earnest probability to offer a novel curative approach against MMP-1-mediated collagenolysis, prompted by ultraviolet (UV)-induced overexpression of MMP-1. In this in silico study, we have explored the MMP-1 inhibitory potential of selected terpenoids from Dalbergia sissoo extracts. Two triterpenoids (lupeol and betulin), 1 diterpenoid (phytol), and 1 ester derivative of lupeol (lupeol acetate) were studied along with a reference inhibitor (doxycycline) using molecular docking approach. Non covalent interaction between the target ligands was found. Lupeol was found interacting with amino acid (AA) residues in the catalytic domain of MMP-1 with 3 hydrogen bonds (H-bond) formation, phytol with 1 and doxycycline with 2 H-bonds, whereas betulin and lupeol acetate were not able to form any H-bond with the AA residues in the catalytic site of the target protein. However, hydrophobic interaction between these ligands and protein was evident with select residues. The binding affinity of lupeol was highest (binding free energy, ΔG = -8.24 kcal/mol), which was greater than reference drug, doxycycline (ΔG = -8.05 kcal/mol). Lupeol acetate and phytol displayed a ΔG value of -7.12 and -7.06 kcal/mol, respectively, whereas betulin holds less binding affinity for the target receptor (ΔG = -4.66 kcal/mol). In silico pharmacokinetic studies demonstrated drug-like properties of the ligand compounds. This study shows that hydroxyl groups present in the ligands play a substantial role in establishing protein ligand interaction via hydrogen bonding.

Incidence of cervical cytological abnormalities with aging in the women's health initiative: a randomized controlled trial.

OBJECTIVE: To estimate the incidence of cytological abnormalities and cervical cancer and to determine the effect of oral estrogen and progestin on cervical cytology among postmenopausal women participating in a multi-institution clinical trial. METHODS: The study was a longitudinal analysis of a prospective cohort of 16,608 postmenopausal women (aged 50-79 years) participating in the Women's Health Initiative (WHI) clinical trial of estrogen plus progestin. Eligible participants had a cervical smear within 1 year before randomization and at 3- and 6-year follow-ups. Outcomes measured were low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical cancer at follow-up years 3 and 6. RESULTS: Of 15,733 eligible participants with a uterus, 7,663 were assigned to placebo and 8,070 to estrogen plus progestin. At baseline, 318 women (2%) had low-grade abnormalities on cervical cytology. The annual incidence rate of any new cytological abnormality in the estrogen plus progestin group was significantly higher than that in the placebo group (hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.6). Independent risk factors for HSIL and cervical cancer over a 6-year follow-up (after stratifying for baseline cytologic abnormalities) included sexual activity in the past year while not being married or living as married (hazard ratio 3.5, 95% CI 1.5-8.3). Risk factors did not include age or use of estrogen plus progestin. CONCLUSION: Use of estrogen plus progestin was associated with increased incidence of any cytologic abnormality, although it had no impact on the incidence of HSIL or cervical cancer. Sexually active older women who are not married or living as married may benefit from continued cervical cancer screening. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00000611.

Accuracy of obstetric diagnoses and procedures in hospital discharge data.

OBJECTIVE: The objective of the study was to estimate the validity of obstetric procedures and diagnoses in California patient discharge data. STUDY DESIGN: We randomly sampled 1611 deliveries from 52 of 267 California hospitals that performed more than 678 eligible deliveries in 1992 to 1993. We compared hospital-reported procedures and diagnoses against our recoding of the same records. RESULTS: Cesarean, forceps, and vacuum delivery were accurately reported, with sensitivities and positive predictive values exceeding 90%. Episiotomy was underreported (70% sensitivity). Cesarean indications were reported with at least 60% sensitivity, except uterine inertia, herpes, and long labor. Among comorbidities, sensitivity exceeded 60% for chorioamnionitis, diabetes, premature labor, preeclampsia, and intrauterine death. Sensitivity was poor (less than 60%) for anemia, asthma, thyroid disorders, mental disorders, drug abuse, genitourinary infections, obesity, fibroids, excessive fetal growth, hypertension, premature rupture, polyhydramnios, and postdates. CONCLUSION: The validity of hospital-reported obstetric procedures and diagnoses varies, with moderate to high accuracy for some codes but poor accuracy for others.

Frequency and predictive value of a mammographic recommendation for short-interval follow-up.

BACKGROUND: A recommendation for short-interval follow-up of "probably benign finding" is associated with up to 11% of screening mammograms, but its predictive value for breast cancer is unclear. We examined the predictive values (i.e., the percentage of women with a diagnosis of breast cancer 2 years after a short-interval follow-up recommendation) and likelihood ratios (derived from the pretest and post-test odds of breast cancer in the Women's Health Initiative sample) for breast cancer that are associated with a recommendation for short-interval follow-up among postmenopausal women. METHODS: We performed a longitudinal analysis of a prospective cohort of 68 126 postmenopausal women (aged 50-79 years) who were participating in clinical trials as part of the Women's Health Initiative at 40 centers across the United States. Eligible participants had screening mammograms at baseline and at least 2 years of follow-up that included a repeat mammography. Outcomes measured were breast cancer events at 1 and 2 years after baseline and the results of subsequent mammograms. All P values were two-sided. RESULTS: A total of 2927 (5%) of the 58 408 eligible women had baseline mammograms that included recommendations for short-interval follow-up. The incidence of breast cancer for women with a short-interval follow-up recommendation was 1.0% at 2 years after the baseline mammogram compared with breast cancer incidences of 0.6% and 0.5% for women whose baseline mammograms were described as "benign" and "negative," respectively. Across the 40 participating centers, the prevalence of short-interval follow-up recommendations among baseline mammograms varied from 1.2% to 9.8% (P<.001), even when the analysis was adjusted for key variables in regression models. Centers reporting higher frequencies of such recommendations did not have lower positive predictive values for breast cancer than centers reporting lower frequencies. The likelihood ratio for breast cancer after a recommendation for short-interval follow-up on a subsequent mammogram was 2.20 (95% confidence interval = 1.65 to 2.86). CONCLUSION: Having a mammographic recommendation for short-interval follow-up was associated with a low positive predictive value for breast cancer among postmenopausal women during a 2-year follow-up. This result suggests that the current criteria for this recommendation-repeat mammography within 6 months-should be reconsidered.

Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy.

CONTEXT: The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis. OBJECTIVE: To determine the effects of CEE on breast cancers and mammographic findings. DESIGN, SETTING, AND PARTICIPANTS: Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included. INTERVENTION: A dose of 0.625 mg/d of CEE or an identical-appearing placebo. MAIN OUTCOME MEASURES: Breast cancer incidence, tumor characteristics, and mammogram findings. RESULTS: After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up. CONCLUSIONS: Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

Coding of perineal lacerations and other complications of obstetric care in hospital discharge data.

OBJECTIVE: To assess the validity of obstetric complications, including the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Core Measure on perineal lacerations, in the California Patient Discharge Data Set. METHODS: We randomly sampled 1,611 deliveries from 52 of the 267 hospitals that performed more than 678 eligible deliveries in California in 1992-1993. We compared hospital-reported complications against our recoding of the same records. RESULTS: Third- and fourth-degree perineal lacerations were reported accurately, with estimated sensitivities exceeding 90% and positive predictive values exceeding 65% (weighted to account for the stratified sampling design) or 85% (unweighted). Based on in-depth review of discrepant cases, we estimate the actual positive predictive value at over 90%. Most coding discrepancies were between no injury and first degree, or between first and second degree. Most postpartum complications, including urinary tract and wound infections, endometritis, anesthesia complications, and postpartum hemorrhage were reported with less than 70% sensitivity, but at least 80% positive predictive value. Composite measures from HealthGrades and Solucient, which include these complication codes, also suffer from high false-negative rates. CONCLUSION: Third- and fourth-degree perineal lacerations are accurately reported on hospital discharge abstracts, confirming the validity of related quality indicators sponsored by the Agency for Healthcare Research and Quality and JCAHO. Administrative data seem less useful for monitoring other in-hospital postpartum complications.

Is grandmultiparity an independent risk factor for adverse perinatal outcomes?

OBJECTIVE: To compare maternal and neonatal outcomes among grandmultiparous women to those of multiparous women 30 years or older. METHODS: A database of the vast majority of maternal and newborn hospital discharge records linked to birth/death certificates was queried to obtain information on all multiparous women with a singleton delivery in the state of California from January 1, 1997 through December 31, 1998. Maternal and neonatal pregnancy outcomes of grandmultiparous women were compared to multiparous women who were 30 years or older at the time of their last birth. RESULTS: The study population included 25,512 grandmultiparous and 265,060 multiparous women 30 years or older as controls. Grandmultiparous women were predominantly Hispanic (56%). After controlling for potential confounding factors, grandmultiparous women were at significantly higher risk for abruptio placentae (odds ratio OR: 1.3; 95% confidence intervals CI: 1.2-1.5), preterm delivery (OR: 1.3; 95% CI: 1.2-1.4), fetal macrosomia (OR: 1.5; 95% CI: 1.4-1.6), neonatal death (OR: 1.5; 95% CI: 1.3-1.8), postpartum hemorrhage (OR: 1.2; 95% CI: 1.1-1.3) and blood transfusion (OR: 1.5; 95% CI: 1.3-1.8). CONCLUSION: Grandmultiparous women had increased maternal and neonatal morbidity, and neonatal mortality even after controlling for confounders, suggesting a need for closer observation than regular multiparous patients during labor and delivery.

Medical costs of fourteen occupational illnesses in the United States in 1999.

OBJECTIVES: This study estimated the annual medical costs associated with 14 occupational illnesses in the United States in 1999. METHODS: National data sets collected by the National Center for Health Statistics, the Health Care Financing Administration, and the Agency for Healthcare Research and Quality were aggregated and analyzed. The cost assessment began with estimates of national health expenditures. These included categories for hospital care, professional services, nursing homes, and medical products, including drugs, administration, public health activities, research and construction. The total disease burden was assessed from estimates of hospital days and number of outpatient visits. The occupational disease burden was assessed by multiplying the total disease burden by a given percentage of the proportionate attributable risk for the disease in question. The occupational burden was then combined with costs for each disease. Adjustments were made for unique inpatient and outpatient costs. RESULTS: In the preferred model, the 14 diseases generated USD 14.5 billion in medical costs in 1999. Roughly USD 10.7 billion was attributed to men and USD 3.8 billion to women. The diseases generating the most costs were as follows: circulatory diseases in the age group 24-64 years (USD 4.7 billion), cancer (USD 4.3 billion), chronic obstructive pulmonary disease (USD 2.2 billion), and asthma (USD 1.5 billion). A sensitivity analysis generated alternative estimates. An upper age limit of 74 years increased the circulatory disease estimate by USD 3.7 billion. The range of the sensitivity analysis was USD 9.6-19.7 billion. CONCLUSION: This study significantly improves over the methodology of previous literature. Our methods were transparent. Occupational illnesses were a major contributor to the total cost of medical care.

Benign mediastinal teratoma with intrapulmonary and bronchial rupture presenting with recurrent hemoptysis.

Mediastinal teratomas are usually asymptomatic tumors, located most commonly in the anterior mediastinum. Very rarely, such tumors may rupture into the tracheobronchial tree, lung, pleura or pericardium. Computed Tomography (CT) is helpful in the diagnosis and differentiation of ruptured and unruptured tumors. We report a case of ruptured anterior mediastinal teratoma in a 20-year-old female presenting with recurrent hemoptysis and cough; thus, mimicking a lung malignancy or tuberculosis. CT demonstrated a heterogeneous fat containing lesion in the anterior mediastinum with extension into the lingular lobe. Subsequent fine needle aspiration cytology (FNAC) yielded plenty of anucleate squames and debris, and a clear cut diagnosis could not be made. Total excision of the tumor was performed and histopathology of the surgically excised mass confirmed the CT diagnosis.