The Effect of Adding Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Undetectable Pretreatment Epstein-Barr Virus DNA

PURPOSE: To assess the effect of adding neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and undetectable pretreatment Epstein-Barr virus (pEBV) DNA. MATERIALS AND METHODS: We enrolled 639 NPC patients with stage II to IVB and undetectable pEBV DNA to receive CCRT with or without NACT. Radiotherapy was 2.0 to 2.27 Gy per fraction with five daily fractions per week for 6 to 7 weeks to the primary tumor and 62 to 70 Gy to the involved neck area. NACT was cisplatin (80-100 mg/m² day 1) and 5-fluorouracil (800-1000 mg/m², 120-hour continuous intravenous infusion) every 3 weeks for two or three cycles. CCRT was cisplatin (80-100 mg/m² day 1) every 3 weeks for three cycles. RESULTS: For all patients, the 5-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 91.9%, 92.2%, 95.0%, and 86.4%, respectively. There was no significant difference in OS (5-year OS 90.8% [NACT + CCRT group] vs 92.7% [CCRT alone]; hazard ratio [HR] 1.24; P = .486), LRFS (HR 1.13, 95% confidence interval [CI] 0.59-2.14, P = .715), DMFS (HR 0.78, 95% CI 0.34-1.78, P = .554), or PFS (HR 1.21, 95% CI 0.75-1.95, P = .472). CONCLUSION: CCRT with or without NACT produced a good treatment outcome in patients with locoregionally advanced NPC and undetectable pEBV DNA, but NACT before CCRT did not significantly improve survival rates.     

Sex-specific differences in the expression levels of estrogen receptor subtypes in colorectal cancer

Background: Altered expression of estrogen receptors alpha and beta (ERα and ERβ) has been hypothesized to play a role in carcinogenesis. However, little is known about the sex-specific differences of ER expression in colorectal cancer (CRC).Objective: This study examined ERα and ERβ protein levels in male and female patients with CRC.Methods: Using Western blot analysis, the intensity of ERα and ERβ protein levels was determined in tumor tissue and in corresponding normal colon mucosa from patients with CRC.Results: All 64 white patients (33 men, mean [SEM] age 64.1 [13.1] years, age range 26-90 years; 31 women, mean age 68.5 [14.5] years, age range 39-91 years [4 were premenopausal at time of surgery]) expressed ERα and ERβ protein in normal colon mucosa, and there were no significant differences between men and women. In tumor tissue, a significantly increased ERα protein level was observed in men (P = 0.02 vs normal tissue), whereas in women, the ERα level did not differ significantly between tumor and normal tissue. The level of ERβ protein in CRC was significantly reduced in both men and women, but more so in men (P = 0.04 vs women). Furthermore, in men, the ERβ level was significantly lower in poorly differentiated tumors than in moderately differentiated tumors (P < 0.03), whereas in women, poor differentiation of the tumor was not associated with a significant decrease of ERβ level.Conclusions: Altered levels of ER subtypes resulting in an increased ERα:ERβ ratio were found in patients with CRC. The observation of significantly greater alterations in men than in women supports the hypothesis of sex-specific differences in the pathogenesis of CRC.     

Osteoporosis Treatment After Osteoporotic Fractures: Data From a Single Medical Center

ObjectiveMost patients do not receive osteoporosis treatment after osteoporotic fracture. This study reviewed osteoporosis treatment after osteoporotic fractures in a center without a Fracture Liaison Service.MethodsWe identified all patients with hip, vertebral, humeral or radial fractures, evaluated in Meir Medical Center, in 2017. The exclusion criteria were not a Clalit Health Services member, high-energy fracture or 30-day postoperative mortality. The primary endpoint was osteoporosis drugs issued within 12 months of fracture. Secondary endpoints included bone densitometry and 1-year mortality.ResultsFive-hundred-eighty-two patients (average age 78.6 ± 11.1 years, 75.8% women) were included. There were 321 (55.5%) hip, 84 (14.1%) humeral, 33 (5.6%) vertebral, and 144 (24.7%) radial fractures. Osteoporosis drugs were issued to 26.5% of the patients; those with humeral fractures received the least (21.4%) and vertebral, the most (30.3%; P = .51). Bone densitometry was performed in 23.2% of patients. One-year mortality after hip fracture was 12.1%, followed by humeral (3.6%; P < .05). Logistic regression showed that previous treatment (odds ratio [OR] = 7.4; 95% confidence interval [CI] 3.6–15.2), bone densitometry (OR = 4.4; 95% CI 2.6–7.4) and endocrinology visit (OR = 2.6; 95% CI, 1.4–4.6) were the most important factors associated with treatment.ConclusionFewer than one third of patients received pharmacotherapy within 1 year after fracture. Because pharmacotherapy reduces future fractures and mortality, we recommend that medical staff who care for patients with fracture adopt practical and effective strategies to increase treatment rates among patients with osteoporotic fractures.     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Overweight as a Prognostic Factor for Triple-Negative Breast Cancers in Chinese Women

Purpose

Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers, but this association is not well established for women with triple-negative breast cancers (TNBC). Here, we investigated the prognostic effects of body mass index (BMI) on clinical outcomes in patients with TNBC.

Methods

We identified 1106 patients with TNBC who met the inclusion criteria and were treated between January 2002 and June 2012. Clinical and biological features were collected to evaluate the relation between BMI and breast cancer-specific survival (BCSS) and overall survival (OS) after controlling for other clinically significant variables.

Results

Of 1106 patients, 656 (59.3%) were normal weight (BMI ≤24) and 450 patients (40.7%) were overweight(BMI>24). Median follow-up time was 44.8 months. Breast cancer specific death was observed in 140 patients. After adjusting for clinicopathologic risk factors, overweight was associated with OS (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.04-2.06, P =0.028) but not BCSS (HR: 1.34, 95% CI: 0.90–2.01, P =0.15)in all the patients with TNBC. When stratified with menopausal status, overweight was associated with BCSS and OS (HR: 2.27, 95% CI: 1.11-4.63, P = 0.024 and HR: 2.16, 95% CI: 1.21-3.87, P = 0.010, respectively) in premenopausal women. BMI was not associated with BCSS or OS in postmenopausal women.

Conclusions

Overweight is an independent prognostic factor of OS in all women with TNBC, and menopause status may be a mitigating factor. Among premenopausal women, overweight women are at a greater risk of poor prognosis than normal weight women. If validated, these findings should be considered in developing preventive programs.     

Women tolerate drug therapy for coronary artery disease as well as men do,but are treated less frequently with aspirin, β-blockers,or statins

Background: Women have worse morbidity, mortality, and health-related quality-of-life outcomes associated with coronary artery disease (CAD) compared with men. This may be related to underutilization of drug therapies, such as aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or statins. No studies have sought to describe the relationship of gender with adverse reactions to drug therapy (ADRs) for CAD in clinical practice.Objective: The aim of this study was to determine the prevalence of ADRs associated with common CAD drug therapies in women and men in clinical practice.Methods: In a cohort of consecutive outpatients with CAD, detailed chart abstraction was performed to determine the use of aspirin, β-blocker, ACE inhibitor, and statin therapy, as well as the ADRs reported for these treatments. Baseline clinical characteristics were also determined to identify the independent association of gender with use of standard drug treatments for CAD.Results: Consecutive patients with CAD (153 men, 151 women) were included in the study. Women and men were observed to have a similar prevalence of cardiac risk factors and comorbidities, except that men had significantly higher prevalence of atrial fibrillation (30 [19.6%] men vs 15 [9.9%] women; P = 0.03) and significantly lower mean (SD) high-density lipoprotein cholesterol concentrations (45 [16] mg/dL for men vs 55 [19] mg/dL for women; P < 0.001). No significant differences were observed between the sexes in the prevalence of ADRs; however, significantly fewer women than men were treated with statins (118 [78.1%] vs 139 [90.8%], respectively; P = 0.003). After adjusting for clinical characteristics, women were also found to be less likely than men to receive aspirin (odds ratio [OR] = 0.164; 95% CI, 0.083–0.322; P = 0.001) and β-blockers (OR = 0.184; 95% CI, 0.096-0.351; P = 0.001).Conclusions: Women and men experienced a similar prevalence of ADRs in the treatment of CAD; however, women were significantly less likely to be treated with aspirin, β-blockers, and statins than were their male counterparts. To optimize care for women with CAD, further study is needed to identify the cause of this gender disparity in therapeutic drug use.     

Hyperthyroidism and Hyperprolactinemia: Is There any Association?

Objective: To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism.Methods: Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age.Results: The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001).Conclusion: The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism.Abbreviations:PRL = prolactinT4 = thyroxineTRH = thyrotropin-releasing hormoneTSH = thyroid-stimulating hormone     

Exposure to Famine in Early Life and the Risk of Osteoporosis in Adulthood: a Prospective Study

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood.Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more.Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (β, -5.07 [-10.226, 0.127]) and BUA (β, -4.321 [-0.88, 0.238]). The early- and mid-childhood–exposed cohorts had significantly lower QUI (β, -7.085 [-11.799, -2.372] versus β, -10.845 [-15.68, -6.01]) and BUA (β, -6.381 [-10.515, -2.246] versus β, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS.Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality.Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound     

Nonalcoholic Fatty Liver Disease and Risk of Diabetes: A Prospective Study in China

Objective: We aimed to investigate whether liver steatosis severity affects the risk of developing diabetes in a large cohort study.Methods: We prospectively examined the association in 41,650 Chinese adults with negative hepatitis-B surface antigen who were free of alcohol consumption, diabetes, and liver cirrhosis at baseline. Cox proportional models were used to estimate the risk of diabetes after a mean of 3.6 years of follow-up. Nonalcoholic fatty liver disease (NAFLD) was assessed with hepatic ultrasonography. Elevated alanine transaminase (ALT) was defined as ALT concentrations >19 and >30 U/L in females and males, respectively. Diabetes was defined as a fasting glucose ³7.0 mmol/L or treatment with hypoglycemic medication.Results: Liver steatosis severity was significantly associated with higher risks of developing diabetes (adjusted hazard ratio [HR] for severe vs. without NAFLD = 2.66, 95% confidence interval [CI]: 2.17–3.25, P-trend<.001) and impaired fasting glucose (fasting glucose between 5.6 and 6.9 mmol/L, adjusted HR = 1.36, 95% CI: 1.16–1.59, P-trend<.001), as well as a faster increase rate of fasting glucose concentrations (P-trend<.001), during 3.6 years of follow-up. Elevated ALT was also associated with incident diabetes (HR = 1.12, 95% CI: 1.02–1.22), adjusting for NAFLD and other covariates.Conclusion: We observed a dose-response relationship between liver steatosis severity and increased diabetes risk, and ALT may predict incident diabetes independently of NAFLD.Abbreviations: ALT = alanine transaminase; BP = blood pressure; CI = confidence interval; HCV = hepatitis C virus; HR = hazard ratio; IFG = impaired fasting glucose; NAFLD = nonalcoholic fatty liver disease; ULN = upper limit of normal     

Predictors for Adverse Outcomes in Diabetic Ketoacidosis in a Multihospital Health System

Objective: To determine predictors of prolonged length of stay (LOS), 30-day readmission, and 30-day mortality in a multihospital health system.Methods: We performed a retrospective review of 531 adults admitted with diabetic ketoacidosis (DKA) to a multihospital health system between November 2015 and December 2016. Demographic and clinical data were collected. Linear regression was used to calculate odds ratios (ORs) for predictors and their association with prolonged LOS (3.2 days), 30-day readmission, and 30-day mortality.Results: Significant predictors for prolonged LOS included: intensive care unit (ICU) admission (OR, 2.12; 95% confidence interval [CI], 1.38 to 3.27), disease duration (nonlinear) (OR, 1.28; 95% CI, 1.10 to 1.49), non-white race (OR, 1.73; 95% CI, 1.15 to 2.60), age at admission (OR, 1.03; 95% CI, 1.01 to 1.04), and Elixhauser index (EI) (OR, 1.21; 95% CI, 1.13 to 1.29). Shorter time to consult after admission (median [Q1, Q3] of 11.3 [3.9, 20.7] vs. 14.8 [7.4, 37.3] hours, P<.001) was associated with a shorter LOS. Significant 30-day readmission predictors included: Medicare insurance (OR, 2.35; 95% CI, 1.13 to 4.86) and EI (OR, 1.31; 95% CI, 1.21 to 1.41). Endocrine consultation was associated with reduced 30-day readmission (OR, 0.51; 95% CI, 0.28 to 0.92). A predictive model for mortality was not generated because of low event rates.Conclusion: EI, non-white race, disease duration, age, Medicare, and ICU admission were associated with adverse outcomes. Endocrinology consultation was associated with lower 30-day readmission, and earlier consultation resulted in a shorter LOS.Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EI = Elixhauser index; HbA1c = hemoglobin A1c; ICD = International Classification of Diseases; ICU = intensive care unit; LOS = length of stay; OR = odds ratio; Q = quartile     

Association between 25-Hydroxyvitamin D and Intact Parathyroid Hormone Levels Across Latitude among Adults with African Ancestry

Objective: To compare levels of 25-hydroxyvitamin D (25[OH]D) associated with a plateauing of intact parathyroid (iPTH) across latitudes among adults with African ancestry.Methods: This study included approximately 500 adults of African ancestry ages 25 to 45 years living in 4 sites: Chicago, Illinois (41°N), Jamaica (17°N), Ghana (6°N), and South Africa (34°S). Multivariate linear regression models, a nonlinear logistic growth curve model, and piecewise linear models with a single knot were fitted to estimate the 25[OH]D level associated with a plateauing of iPTH with adjustment for covariates. Goodness of fit was compared using computer intensive permutation tests.Results: Mean age was 34.7 (SD 6.2) years, and 46.5% were male. Within each site, the percentage of participants with an iPTH level ≥65 pg/mL was higher among females versus males and was most frequent among South African females (17.1%) and lowest among Jamaican males (0.6%). Goodness of fit tests supported linear regression as the preferred model for the association between iPTH and 25[OH]D in the 4 sites with no 25[OH]D level associated with iPTH plateauing in any site. The slope of the association between 25[OH]D and iPTH differed by latitude; it was strongest in the U.S. (β = -0.81; 95% confidence interval [CI] = -1.03, -0.59), and weakest in Jamaica (β = -0.45; 95% CI -0.71, -0.18) with covariate adjustment, but differences in slopes were small.Conclusion: The association between 25[OH]D and iPTH appears linear among adults with African ancestry regardless of latitude within a range of 25[OH]D levels between 10 and 60 ng/mL.Abbreviations:BMI = body mass indexCI = confidence intervaleGFR = estimated glomerular filtration rateiPTH = intact parathryoid hormone25[OH]D = 25-hydroxyvitamin D     

Similar Cardiovascular Outcomes Between Insulin Detemir and Insulin Glargine In Type 2 Diabetic Patients With Extremely Atherosclerotic Cardiovascular Disease Risks

Objective: The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS.Methods: A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke.Results: The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively).Conclusion: Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke.Abbreviations: ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus     

Menopausal Hormone Therapy and Chronic Disease Risk in the Women’S Health Initiative: is Timing Everything?

ObjectiveThis review provides a comprehensive overview of the most recent findings from the Women’s Health Initiative (WHI) hormone therapy (HT) trials and highlights the role of age and other clinical risk factors in risk stratification.MethodsWe review the findings on cardiovascular disease, cancer outcomes, all-cause mortality, and other major endpoints in the two WHI HT trials (conjugated equine estrogens [CEEs, 0.625 mg/day] with or without medroxyprogesterone acetate [MPA, 2.5 mg/day]).ResultsThe hazard ratio (HR) for coronary heart disease (CHD) was 1.18 (95% confidence interval [CI], 0.95 to 1.45) in the CEE + MPA trial and 0.94 (95% CI, 0.78 to 1.14) in the CEE-alone trial. In both HT trials, there was an increased risk of stroke and deep vein thrombosis and a lower risk of hip fractures and diabetes. The HT regimens had divergent effects on breast cancer. CEE + MPA increased breast cancer risk (cumulative HR, 1.28; 95% CI, 1.11 to 1.48), whereas CEE alone had a protective effect (cumulative HR, 0.79; 95% CI, 0.65 to 0.97). The absolute risks of HT were low in younger women (ages 50 to 59 years) and those who were within 10 years of menopause onset. Furthermore, for CHD, the risks were elevated for women with metabolic syndrome or high low-densitylipoprotein cholesterol concentrations but not in women without these risk factors. Factor V Leiden genotype was associated with elevated risk of venous thromboembolism on HT.ConclusionHT has a complex pattern of benefits and risks. Women in early menopause have low absolute risks of chronic disease outcomes on HT. Use of HT for management of menopausal symptoms remains appropriate, and risk stratification will help to identify women in whom benefits would be expected to outweigh risks. (Endocr Pract. 2014;20:1201-1213)     

Metabolic Syndrome and Breast Cancer Risk: A Case-Cohort Study Nested in a Multicentre Italian Cohort

Background

Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies – most confined to postmenopausal women – have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.

Methods

We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.

Results

Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).

Conclusions

These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.     

The influence of gender on adults admitted for asthma

Background: In the United States, the prevalence of asthma is not only higher than in most other countries, it also varies greatly between diverse populations. Only limited data exist that examine the variation of outcomes by gender in patients admitted to a hospital for asthma.Objective: This study assessed outcome differences based on gender in adults who were admitted nationally with the primary diagnosis of asthma.Methods: A retrospective cohort study was conducted of all patients who were admitted to a hospital with the primary diagnosis of asthma in 2002-2005 and were reported in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Patients were excluded if they were aged <18 years or had an additional diagnosis of chronic obstructive pulmonary disease.Results: A total of 590,410 patients (439,991 women, 150,419 men) were included in the study. Patients admitted for asthma were significantly more likely to be female (P < 0.05). Women were significantly older compared with men (mean [SD], 48.5 [17.4] vs 44.6 [17.0] years, respectively), had a longer length of stay (3.44 vs 2.84 days), were more likely to be white (37.9% vs 34.2%), and had a higher total cost of admission ($10,575 vs $9390) (all, P < 0.05). Women were more likely than men to need a tracheostomy (adjusted odds ratio [AOR] = 2.04; 95% CI, 1.77-2.35) and to have a bronchoscopy (AOR =1.12; 95% CI, 1.05-1.21). Men were significantly more likely than women to have arterial blood gases performed (AOR = 1.15; 95% Cl, 1.05-1.27) and to be intubated (AOR = 1.18; 95% Cl, 1.10-1.26) (both, P < 0.05). Men were significantly more likely to be admitted as an emergency admission (AOR = 1.10; 95% Cl, 1.04-1.18) and to die during hospitalization (AOR =1.69; 95% CI, 1.41-2.03).Conclusion: Although they were less likely to be admitted to a hospital, men were more likely to be admitted as an emergency and to experience worse outcomes compared with women, in this study of adults with asthma in the United States.     

Predictors Of Biochemical Remission And Recurrence After Surgical And Radiation Treatments Of Cushing Disease: A Systematic Review And Meta-Analysis

Objective: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease.Methods: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs).Results: First-line TSS was associated with high remission (76% &lsqb;95% CI, 72 to 79%]) and low recurrence rates (10% &lsqb;95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive–adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% &lsqb;95% CI, 61 to 77%]; RT, 66% &lsqb;95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% &lsqb;95% CI, 16 to 60%]; RT, 26% &lsqb;95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence.Conclusion: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.Abbreviations:ACTH = adrenocorticotropic hormoneMRI = magnetic resonance imagingRS = radiosurgeryRT = radiotherapySC = serum cortisolTSS = transsphenoidal surgeryUFC = urinary free cortisol     

Predictors of depressive symptoms post-acute coronary syndrome

Objective: We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS.Methods: Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables.Results: A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003).Conclusions: Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.     

Gender differences in health-related quality of life among healthy aged and old-aged austrians: Cross-sectional analysis

Background: Although they experience lower mortality rates and lower rates of several chronic diseases than do their male counterparts, aging women are more likely to experience functional impairment in mobility and a general diminished health-related quality of life (HRQoL). The determinants of these gender differences have been the subject of controversy.Objective: This study analyzed gender differences in HRQoL in relation to social and biomedical factors such as age, marital status, educational level, and living arrangements.Methods: Participants were recruited via snowball sampling. All were healthy and lived independently in private homes. Data were obtained from personal interviews, based on a 30-item questionnaire, in the private homes of the participants. Additionally, HRQoL was assessed by means of the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) 26-item questionnaire, which contains 1 general health item, 1 general QoL item, and 24 specific items covering 4 broad domains: physical (DOM I), psychological (DOM II), social (DOM III), and environmental (DOM IV).Results: The participants (98 women, 62 men) enrolled in the study ranged in age from 57 to 95 years (mean [SD] age: 71.8 [8.6] years). The younger age group (aged 57-70 years) comprised 54 women and 25 men, and the older age group (aged >70 years) comprised 44 women and 37 men. Women aged ≤70 years rated their health and QoL significantly higher than did men in the same age group (P = 0.02). These women rated physical capacity (DOM I), social relationships (DOM III), and environment (DOM IV) higher, but not statistically significantly different, than did same-aged men. Women and men exhibited nearly identical psychological health (DOM II) values. Physical capacity (DOM I) differed significantly between women and men aged >70 years (P = 0.03). Women aged >70 years rated their QoL lower than their male counterparts did, although not significantly so. These women depended more on medical treatment, felt significantly less safe in everyday life (P = 0.03), and were less satisfied with themselves.The results of the multiple regression analyses suggest that gender may have a significant impact on general QoL for both age groups (P < 0.01 for the younger age group; P > 0.04 for the older age group). In these analyses, gender also had a significant impact on 2 domains, physical capacity and social relationships (P < 0.02 for both domains), among the participants of the younger age group.Conclusion: Depending on the age group (≤70 vs >70 years) in this small sample of Austrian women and men, gender influenced HRQoL.     

Smoking and alcohol consumption in relation to risk of thyroid cancer in postmenopausal women

Background: Few cohort studies have examined smoking and alcohol consumption in relation to risk of thyroid cancer, and their findings are conflicting. Methods: We therefore assessed the association of smoking and alcohol intake with risk of thyroid cancer in a cohort of 159,340 women enrolled in the Women's Health Initiative. Over 12.7 years of follow-up 331 cases of thyroid cancer, of which 276 were papillary thyroid cancer, were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Compared to never smokers, ever smokers did not have altered risk. Current smokers had reduced risk for all thyroid cancer (HR 0.54, 95% CI 0.29–1.00) and for papillary thyroid cancer (HR 0.34, 95% CI 0.15–0.78); however, the number of current smokers among cases was small. No associations or trends were seen for amount smoked, age of starting smoking, or age at quitting. Smokers of ≥40 pack-years had a significantly reduced risk of papillary thyroid cancer (HR 0.44, 95% CI 0.21–0.89). In contrast, women who had smoked for < 20 years had increased risk of thyroid cancer (HR 1.35, 95% CI 1.05–1.74) and papillary cancer (HR 1.43, 95% CI 1.09–1.89). Alcohol intake was not associated with risk. Conclusion: Our findings suggest that current smoking and having higher pack-years of exposure are associated with a modestly reduced risk of thyroid cancer, whereas alcohol consumption does not appear to affect risk.     

Dual-Energy X-Ray Absorptiometry And Calculated Frax Risk Scores May Underestimate Osteoporotic Fracture Risk In Vitamin D-Deficient Veterans With Hiv Infection

Objective: We evaluated the utility of the Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency.Methods: This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures.Results: We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between -1 and -2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant.Conclusion: We found a high prevalence of subclinical vertebral fractures among vitamin D–deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population.Abbreviations:25(OH)D = 25-hydroxyvitamin DBMD = bone mineral densityBMI = body mass indexDEXA = dual-energy X-ray absorptiometryFRAX = Fracture Risk Assessment ToolHIV = human immunodeficiency virusIQR = interquartile rangePTH = parathyroid hormoneVA = Veterans AffairsWHO = World Health Organization