Comparison of estimated dietary intake of acrylamide with hemoglobin adducts of acrylamide and glycidamide.

In a study comprising 50 subjects, we investigated the relationship between acrylamide (AA) intake from food using food frequency questionnaires and the concentration of hemoglobin (Hb) adducts of AA and its genotoxic metabolite glycidamide (GA) as a measure of the internal exposure. A method using solid-phase extraction and liquid chromatography with negative electrospray tandem mass spectrometric (MS/MS) detection for the determination of the Hb adducts as phenylthiohydantoin derivatives in human blood was developed. The limit of quantification for AA- and GA-Hb adducts were 2 and 6 pmol/g globin, respectively, and the between-assay precision was below 25%. The estimated dietary intake of AA was (median and range) 13.5 microg/day (4.1-72.6) in nonsmokers and 18.3 microg/day (7.8-32.0) in smokers. In nonsmokers, males had a higher intake than females, 16.6 microg/day (18.6-72.6) and 12.8 microg/day (4.1-30.2), respectively. Nonsmokers had a median AA and GA adduct concentration of 36.8 (range 17.9-65.5) and 18.2 (range 6.7-45.6) pmol/g globin, respectively. In smokers, the values were 165.8 (98.8-211) and 83.2 (29.1-99.0) pmol/g globin, respectively. Using multiple linear regression analysis, a significant positive correlation was found between the AA-Hb adduct concentration and the intake of chips/snacks and crisp bread. GA-Hb adduct did not correlate with consumption of any of the main food groups. Neither AA-Hb nor GA-Hb adduct concentration correlated with total dietary intake of AA as calculated from the reported food intake. Adduct concentrations did not correlate with 24 h urinary excretion of mercapturic acid metabolites of AA and GA in the same subjects reported previously.     

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study

Background  Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality.
Aims  To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population.
Methods  Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios.
Results  Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77–1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73–1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67–3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44–6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03–1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70–1.23).
Conclusions  Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.     

Renal tubular dysfunction and cancer mortality in the Japanese general population living in cadmium-non-contaminated areas

The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause–effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary β2-microglobulin (β2MG) and N-acetyl-β-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02–1.19, pancreas: HR, 1.10, 95%CI, 1.02–1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67–0.96) and for β2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93–1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.     

Hospitalization risks in the treatment of schizophrenia: comparison of antipsychotic medications

This study used administrative claims data to compare the relative risks for hospitalization among commercially insured patients with schizophrenia receiving atypical and typical antipsychotic drugs. Cox proportional hazard regression estimates, adjusted for differences in patient characteristics, suggested that among patients treated with the 4 atypical antipsychotic drugs, only olanzapine had a significantly higher risk for hospitalization than the typical antipsychotic drugs (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.20-2.75). In addition, risk for hospitalization with olanzapine was significantly higher than that for risperidone (HR, 1.34; 95% CI, 1.03-1.74) and numerically higher than that for quetiapine (HR, 1.40; 95% CI, 0.94-2.07). Overall, olanzapine was associated with a higher risk for hospitalization than the typical antipsychotic drugs and among the atypical antipsychotic drugs, risperidone and, potentially, quetiapine.     

No difference in mortality in undetected coeliac disease compared with the general population: a UK cohort study

Aliment Pharmacol Ther 2011; 34: 1012–1019

Summary

Background Studies of mortality in undetected coeliac disease compared with the general population give contradictory findings, suggesting it is either increased fourfold compared with the general population or not at all. Aim To establish all‐cause and cause‐specific mortality in undiagnosed coeliac disease, identified by anti‐endomysial antibody (EMA) positivity, in the Cambridge GP Health Survey cohort. Method This cohort was recruited in 1990 from the general population aged 45–76 years. All deaths were ascertained from the Office for National Statistics. Mortality rates were calculated per 1000 person years and adjusted for age, gender, smoking and socioeconomic group using multivariate Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results There were 117 914 patient years of follow‐up (median 16.8 years) from 7527 participants. Eighty‐seven had undetected coeliac disease, their all‐cause mortality rate was 9.4 per 1000 person years (95% CI 5.4–16.1) compared with 12.7 (95% CI 12.1–13.4) in EMA‐negative participants. The adjusted all‐cause mortality HR was 0.98 (95% CI 0.57–1.69). Death due to cancer and circulatory diseases was not increased, adjusted HR were 1.27 (95% CI 0.57–2.85) and 1.39 (95% CI 0.66–2.92) respectively. Conclusions We observed no excess overall mortality in people aged over 45 years with undetected coeliac disease compared with the general population, nor any increase in deaths related to circulatory disease or cancer. Our findings do not support screening the general population aged over 45 years, for coeliac disease for the purpose of improving life expectancy.     

All‐cause mortality increased by environmental cadmium exposure in the Japanese general population in cadmium non‐polluted areas

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all‐cause mortality in the Japanese general population. A 19‐year cohort study was conducted in 1067 men and 1590 women aged 50 years or older who lived in three cadmium non‐polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U‐Cd (µg g^?1 cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U‐Cd or the quartiles of U‐Cd were estimated for all‐cause mortality using a proportional hazards regression.The all‐cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U‐Cd (+1 µg g^?1 cre) was significantly related to the all‐cause mortality in men (HR 1.05, 95% CI: 1.02–1.09) and women (HR 1.04, 95% CI: 1.01–1.07). Furthermore in men, the third (1.96–3.22 µg g^?1 cre) and fourth quartile (≥3.23 µg g^?1 cre) of U‐Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03–1.77, fourth: HR 1.64, 95% CI: 1.26–2.14) for all‐cause mortality compared with the first quartile (<1.14 µg g^?1 cre). In women, the fourth quartile of U‐Cd (≥4.66 µg g^?1 cre) also showed a significant HR (1.49, 95% CI 1.11–2.00) for all‐cause mortality compared with the first quartile (<1.46 µg g^?1 cre).In the present study, U‐Cd was significantly associated with increased mortality in the Japanese general population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non‐polluted areas in Japan. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of cardiovascular drug classes on all-cause mortality among atrial fibrillation patients treated in primary care in Sweden: a cohort study

Background

Risk factors for stroke are well known in atrial fibrillation (AF) patients, while less is known on the effect of these factors on total mortality.

Objective

Our aim was to study the impact of cardiovascular drug classes on mortality in AF patients treated in primary care.

Methods

The study population was chosen based on patient data from 75 primary care centres in Sweden compiled in a database. Individuals diagnosed with AF who were older than 45 years were enrolled (n?=?12,302, of whom?6,660 were men). Cox regression analysis with mortality (years to death) as outcome was conducted in the men and women separately, as well in the age categories <80 and ≥80 years, with cardiovascular drugs as independent factors, and age, cardiovascular diagnoses and educational level as covariates.

Results

Lower mortality was shown for anticoagulant treatment among men, both younger (<80 years) [adjusted hazard ratio (HR) 0.43, 95 % confidence interval (CI) 0.31–0.61] and older (≥80 years) (adjusted HR 0.47, 95 % CI 0.32–0.69), and among younger women (adjusted HR 0.46, 95 % CI 0.29–0.74), and for antiplatelet treatment in older men (adjusted HR 0.51, 95 % CI 0.35–0.74). Treatment with thiazides was associated with lower mortality among younger men (adjusted HR 0.68, 95 % CI 0.48–0.96), older men (adjusted HR 0.67, 95 % CI 0.46–0.98) and older women (adjusted HR 0.70, 95 % CI 0.52–0.94). Statins were associated with lower mortality among younger patients, in both men (adjusted HR 0.47, 95 % CI 0.32–0.68) and women (adjusted HR 0.54, 95 % CI 0.35–0.82).

Conclusions

The differences in age and gender patterns need further exploration.     

胰岛素治疗的系统风险

目的：胰岛素是常用降血糖注射剂。本文旨在分析胰岛素治疗的风险,为临床治疗提供参考。方法临床研究包括2型糖尿病（T2Dm）患者和危症患者。前瞻性研究观察华人 T2Dm 2906例（其中胰岛素治疗971例）,连续随访7年。横断面资料研究中美国 T2Dm 25964例,英国 T2Dm 84622例。死亡、癌症、慢性并发症、低血糖与危症是主要临床终点。结果胰岛素治疗显著增加 T2Dm 临床终点事件风险：死亡（ HR ＝2.2;95% CI ＝2.0-2.4）,癌症（HR ＝1.4;95% CI ＝1.2-1.7）,肾病（HR ＝3.5;95% CI ＝2.7-4.5）,心肌梗死（HR ＝2.0;95% CI ＝1.5-2.6）,主要不良心脏事件（HR ＝1.7;95% CI ＝1.4-2.1）,中风（HR ＝1.4;95% CI ＝1.2-1.8）。胰岛素治疗的危症患者6026例,出现低血糖,其死亡风险呈线性升高：中度低血糖组 HR ＝1.4,95% CI ＝1.2-1.6;严重性低血糖组 HR ＝2.1,95% CI ＝1.6-2.8。结论糖尿病患者及危症患者应慎用胰岛素治疗,胰岛素治疗的系统风险不容低估。     

Exogenous estrogen does not attenuate the association between rofecoxib and myocardial infarction in perimenopausal women

Rofecoxib has been proposed to increase the risk of myocardial infarction (MI) through suppression of cyclooxygenase 2–mediated prostacyclin. Estrogen may have protective effects through augmenting cyclooxygenase 2 expression and subsequently increasing prostacyclin. Estrogen may attenuate the association between rofecoxib and MI. We used 1999–2002 Medicaid claims data to measure the MI hazard ratio (HR) attributed to rofecoxib exposure in estrogen-exposed and unexposed 45- to 65-year-old women.We identified 184,169 female rofecoxib users who contributed 309,504 person-years and experienced 1217 first MIs. Estrogen exposure seemed protective [MI-HR 0.72; 95% confidence interval (CI), 0.62–0.84] in this cohort. Rofecoxib was associated with an elevated MI-HR in both estrogen-exposed (2.01; 95% CI, 1.60–2.54) and estrogen-unexposed women (1.69; 95% CI, 1.43–1.99). The rofecoxib–estrogen interaction ratio was not significantly different from 1 (1.19; 95% CI, 0.91–1.57). Although estrogen use was associated with a lower risk of MI, it did not seem to attenuate the association between rofecoxib and MI.     

Sulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women

BACKGROUND: Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, catalyzes the sulfation of a variety of phenolic and estrogenic compounds. A functional polymorphism of the SULT1A1 gene has been implicated in a decreased activity and thermostability when the wild-type arginine (Arg) at codon 213 is substituted by a histidine (His). METHODS: We investigated the association between the His allele and the risk breast cancer in 213 cases and 430 matched controls in Chinese women, and the interaction between His allele and endogenous estrogen and dietary mutagens exposure factors were also determined by use of logistic regression analysis. RESULTS: There was no significant difference in genotypes between the cancer patients and control populations. However, the frequency of the His allele in cases (13.6%) were significant higher than that in controls (9.5%), P = 0.03. Compared with women carrying the Arg/Arg genotype, the adjusted odds ratio (OR) of Arg/His was 1.48 (95% CI = 0.59-3.31) and His/His was 2.28 (95% CI = 0.69-9.58), P trend was 0.04. The adjusted OR of Arg/His + His/His was 2.60 (95% CI = 1.12-6.05). His allele strengthen the effect of endogenous estrogen exposure with interaction index r > 1, and weaken the effect of heterocyclic amines and polycyclic aromatic hydrocarbons derived from dietary with interaction index r > 1, both were multiplicative interaction model. CONCLUSIONS: Our findings suggest that the SULT1A1 His allele was positively associated with the risk of breast cancer in Chinese women. And there was interaction between SULT1A1 polymorphism and related exposure factors.     

Palbociclib and beyond for the treatment of HR + HER2- metastatic breast cancer: an Asian-Pacific perspective and practical management guide on the use of CDK4/6 inhibitors

Abstract

Breast cancer is the most frequent cancer amongst women worldwide including in Asia where the incidence rate is rapidly increasing. Even with treatment, around 30% of patients with early breast cancer progress to metastatic disease, with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer the most common phenotype. First-line endocrine therapy targeting the estrogen receptor signaling pathway provides a median progression-free survival or time to progression of 6–15?months in HR?+?HER2- metastatic breast cancer. Recently, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, combined with endocrine therapy, have achieved more than two years median progression-free survival in HR?+?HER2- metastatic breast cancer. However, the characteristics of the Asian breast cancer population differ from those of Western populations and need to be considered when selecting a suitable treatment. Breast cancer is diagnosed at a younger age in Asian populations and late stage at presentation is generally more common in low-/middle-income countries than high-income countries. Consequently, the proportion of premenopausal women with metastatic breast cancer is higher in Asian compared with Western populations. While CDK4/6 inhibitors have been approved in the USA (FDA) since 2015, experience with them in Asia is more limited. We review the experience with the CDK4/6 inhibitor palbociclib in Asian patients with HR?+?HER2- metastatic breast cancer and provide guidance on the use of palbociclib in these patients.     

Serum levels of polychlorinated biphenyls in Mexican women and breast cancer risk

The most prevalent female cancer across the world is breast cancer. Current established breast cancer risk factors explain only a fraction of the breast cancer cases diagnosed, and for this reason, other environmental factors have been studied. Exposure to organochlorine compounds has been linked to an increased incidence of breast cancer, although not all data have been consistent. This study was designed to evaluate the relation between polychlorinated biphenyls (PCB) exposure and breast cancer risk in Mexican women. We recruited 140 women from the General Hospital. The cases were 70 newly diagnosed women. We collected environmental and reproductive information by questionnaire. Blood samples were taken for measurement of serum levels of 20 PCB congeners. Risk of breast cancer was found to be positively associated with heavy congeners, age, postmenopausal status, family history of breast cancer and living close to an industrial facility. When PCB were grouped by structure–activity relationships, the risk of breast cancer was positively associated with groups 2b (odds ratio, OR = 1.90, 95% confidence interval, CI, 1.25–2.88), 3 (OR = 1.81, 95% CI 1.08–3.04) and group 4 (OR = 1.57, 95% CI 1.20–2.07). Among postmenopausal women, PCB levels from groups 1a, 2b, and 4 and total PCB were higher in cases, and an association between risk of breast cancer with groups 1a (OR = 7.59, 95% CI 1.1–51.4), 2b (OR = 3.7, 95% CI 1.2–11.2) and 4 (OR = 1.8, 95% CI 1.1–3.1) was found in this group of women. This study showed an association between heavy and potentially estrogenic PCB congeners and breast cancer risk. Copyright © 2011 John Wiley & Sons, Ltd.     

Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk.

BACKGROUND AND OBJECTIVE: The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. However, following their introduction into the market, concerns have developed regarding their safety, particularly their cardiovascular safety. The purpose of this study was to assess the cardiovascular risk (events included were myocardial infarction, stroke and myocardial infarction-related deaths) associated with long-term (>180 days of exposure) and short-term (or=35 years of age who received celecoxib, rofecoxib, ibuprofen, etodolac and naproxen from 1 January 1999 through 31 December 2001, were included. Multivariate Cox proportional hazard models were used to analyse the relationship between cardiovascular risk and NSAID use, including selective COX-2 inhibitor use, while adjusting for various risk factors. RESULTS: We identified 12 188 exposure periods (11 930 persons) and 146 cardiovascular events over the entire study period. Compared with long-term ibuprofen use, long-term use of celecoxib (adjusted hazard ratio [HR] 3.64; 95% CI 1.36, 9.70) and rofecoxib (adjusted HR 6.64; 95% CI 2.17, 20.28) was associated with a significant increase in cardiovascular risk. When restricted to patients >or=65 years of age, the cardiovascular risks associated with long-term celecoxib (adjusted HR 7.36; 95% CI 1.62, 33.48) and rofecoxib (adjusted HR 13.24; 95% CI 2.59, 67.68) use increased. Short-term use of celecoxib (adjusted HR 0.75; 95% CI 0.42, 1.35) and rofecoxib (adjusted HR 0.85; 95% CI 0.39, 1.86) was not associated with any significant change in cardiovascular risk when compared with short-term ibuprofen use. Neither long- nor short-term exposure to naproxen and etodolac was associated with cardionegative or cardioprotective effects when compared with ibuprofen use. CONCLUSIONS: The findings of this observational study, along with recent clinical trial results, suggest that prolonged exposure to selective COX-2 inhibitors may be associated with an increased risk of adverse cardiovascular outcomes.     

Comparative safety of long-acting inhaled bronchodilators: a cohort study using the UK THIN primary care database.

BACKGROUND: Use of a long-acting inhaled bronchodilator, either an anticholinergic or a beta-adrenergic receptor agonist (beta-agonist), is recommended for maintenance treatment of chronic obstructive pulmonary disease (COPD). In COPD, the organ system most frequently requiring medical care, other than the respiratory system, is the cardiac system. OBJECTIVES: To compare the risk of total mortality and certain respiratory and cardiac adverse events among users of the two types of recommended long-acting bronchodilators, we conducted a cohort study. Specifically, the study compared the safety of the only approved long-acting anticholinergic, tiotropium bromide, with the single-ingredient long-acting beta-agonists (LABAs) salmeterol or formoterol in a broad population of users. METHODS: We used automated general practitioner data from the UK THIN (The Health Information Network) database as the data source for this study. We used Cox proportional hazards models to compute hazard ratio (HR) estimates and 95% CI controlling for propensity scores comprising various baseline demographic variables, medical therapies and illnesses. RESULTS: The 1061 tiotropium users and 1801 LABA users were similar with regard to risk of total mortality (HR 0.93; 95% CI 0.59, 1.44) and most cardiac events, including angina (HR 0.77; 95% CI 0.37, 1.59), atrial fibrillation or flutter (HR 0.60; 95% CI 0.25, 1.42), myocardial infarction (HR 1.29; 95% CI 0.45, 3.66) and tachycardia (HR 0.66; 95% CI 0.29, 1.51). Though imprecise, there was evidence of a decreased risk of heart failure (HR 0.65; 95% CI 0.37, 1.12) in tiotropium users. As regards respiratory endpoints, the risk of COPD exacerbation (HR 1.15; 95% CI 0.79, 1.67) and pneumonia (HR 1.11; 95% CI 0.38, 3.26) were similar among users of each type of drug, although there was a decreased risk of asthma exacerbation (HR 0.41; 95% CI 0.26, 0.64) in tiotropium users compared with LABA users. CONCLUSIONS: Users of tiotropium and single-ingredient LABA had similar risk of total mortality and cardiovascular endpoints. The decreased risk of asthma exacerbations with tiotropium may be due to residual confounding by indication. Confidence limits for most events include reduced risks for tiotropium and also small increases in risk. Nevertheless, the point estimates suggest that tiotropium was associated with a lower risk of each cardiac event except myocardial infarction. However, the small number of cases means that further studies are needed to confirm these results.     

Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment

This is a register-based cohort study of 20,581 individuals in treatment for illicit substance use disorders in Denmark between 1996 and 2006. All in all, 1441 deaths were recorded during 111,445 person-years of follow-up. Standardized mortality ratios (SMRs) associated with different primary substance types were calculated and Cox-regression analyses were performed in order to establish hazard ratios (HR) associated with injection drug use and psychiatric comorbidity. SMRs for primary users of specific substances were: cannabis: 4.9 (95% confidence interval (CI): 4.2-5.8), cocaine: 6.4 (CI: 3.9-10.0), amphetamine: 6.0 (CI: 4.2-8.3), heroin: 9.1 (CI: 8.5-9.8), and other opioids 7.7 (CI: 6.6-8.9). For MDMA ('ecstasy') the crude mortality rate was 1.7/1000 person-years (CI: 0.4-7.0) and the SMR was not significantly elevated. Injection drug use was associated with significantly increased hazard ratios in users of opioids and cocaine/amphetamine. Overall, psychiatric comorbidity was not associated with increased mortality (HR: 1.1 [CI: 0.9-1.2], p=.28), but an association was found specifically among cocaine/amphetamine users (HR: 3.6 [CI: 2.1-6.4], p<.001).     

Fulvestrant: a new type of estrogen receptor antagonist for the treatment of advanced breast cancer

Postmenopausal women with hormone receptor- positive tumors are candidates for endocrine treatment. Current treatment options include the selective estrogen receptor modulators (e.g., tamoxifen and toremifene), which inhibit estrogen receptor signaling, and the aromatase inhibitors (e.g., anastrozole and letrozole), which prevent the conversion of androgens into estrogen in postmenopausal women. As most patients eventually become resistant to endocrine agents, there is a need for new treatments that are effective, well tolerated and lack cross-resistance with currently available therapies. This review describes the development of fulvestrant (Faslodex), a new type of endocrine agent, which is an estrogen receptor antagonist with no agonist effects. Phase III clinical trials have found that fulvestrant is as effective and well tolerated as anastrozole for treating postmenopausal patients with advanced breast cancer who have progressed on one prior endocrine therapy. In addition, fulvestrant has first-line efficacy similar to that of tamoxifen in patients with estrogen receptor-positive and/or progesterone receptor-positive breast cancer. Moreover, in a compassionate-use program, it has become clear that fulvestrant is not cross-resistant with other therapies. Therefore, fulvestrant is a versatile new treatment option for postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy.     

Cause-specific mortality and cancer incidence rates in relation to urinary beta2-microglobulin: 23-year follow-up study in a cadmium-polluted area

A longitudinal study was performed to investigate the associations of exposure to environmental cadmium (Cd) with cause-specific mortality and cancer incidence rates. The study population comprised 275 adults living in a Cd-polluted area, Nagasaki Prefecture, Japan. The follow-up period extended from 1982 to 2005 for the analysis of cancer mortality, and from 1985 to 2002 for the analysis of cancer incidence. In the study area, the daily Cd intake from foods had decreased after 1980-1983 because of the restoration of Cd-polluted rice fields. The mortality rate among those with urinary beta2-microglobulin (U-beta2M)>/=1000 microg/g creatinine was significantly higher than that of the Japanese population for death from causes other than cancer, but not for cancers (177 at the 95% confidence interval [CI] 94-303). From analysis within the Cd-polluted area, the age-adjusted rate ratio of cancer deaths associated with increased U-beta2M was 2.58 (95% CI 1.25-5.36). The incidence rate of cancer among those with U-beta2M>/=1000 microg/g creatinine was 1.38 (95% CI 0.69-2.47) times that of the regional reference rate. Within the Cd-polluted area, the age-adjusted rate ratio of developing cancer associated with high U-beta2M was 1.79 (95% CI 0.84-3.82). In summary, there was a significant association between U-beta2M excretion and cancer mortality. However, there was neither a significantly increased standardized incidence ratio of cancer, nor significant relationship between U-beta2M and cancer incidence rate, though the point estimates were higher than unity. Continued follow-up and investigation of a larger cohort may be required before drawing a conclusion for the association between exposure to environmental Cd and cancer risk.     

Predictors of mortality in atypical antipsychotic-treated community-dwelling elderly patients with behavioural and psychological symptoms of dementia: a prospective population-based cohort study from Italy

Purpose

To evaluate the effect of a broad range of covariates on the survival of a real-life long-term follow-up cohort of community-dwelling patients with behavioural and psychological symptoms of dementia who were new users of atypical antipsychotic medications (APMs).

Methods

This was a prospective cohort study of 1,618 subjects aged ≥65 years with dementia and BPSD (“behavioural and psychological symptoms of dementia”) who were new users of atypical APMs and registered in a Dementia Evaluation Unit of Campania Region (Italy) from September 2006 to March 2010. The potential of baseline features to predict mortality was assessed with the Cox proportional hazards model.

Results

The average follow-up was 309 days. Of the 1,618 new users of atypical antipsychotics, 9.3 % experienced at least one adverse event, including death (5.1 %), drug therapeutic failure (3.0 %), extrapyramidal symptoms (0.5 %) and stroke (0.2 %). The crude all-cause mortality rate was 6.0 per 100 person-years [95 % confidence interval (CI) 4.8–7.4]; the rate was higher in patients aged >85 years (9.0 per 100 person-years, 95 % CI 6.4–12.7) and among male patients (7.5 per 100 person-years, 95% CI 5.3–10.6). In the multivariate analysis, only age was associated to all-cause mortality [hazard ratio (HR) 1.1; 95 % CI 1.0–1.1 and HR 1.4; 95 % CI: 0.9–2.2, respectively). In contrast, hallucination (HR 0.4; 95 % CI 0.2–0.6) and dosage change (HR 0.4; 95 % CI 0.2–0.78) were significantly associated with a lower risk of all-cause mortality.

Conclusions

Among our patient cohort, the mortality rate of patients with BPSD receiving long-term treatment with atypical APMs was lower than that reported in other studies, and only age was found to be significant predictor factor of mortality.