Women��s interest in taking tamoxifen and raloxifene for breast cancer prevention: response to a tailored decision aid

Although tamoxifen can prevent primary breast cancer, few women use it as a preventive measure. A second option, raloxifene, has recently been approved. The objective of the study was to determine women's interest in tamoxifen and raloxifene after reading a decision aid (DA) describing the risks and benefits of each medication. Women with 5-year risk of breast cancer ≥ 1.66 from two large health maintenance organizations were randomized to receive a DA versus usual care. After reading an on-line DA that discussed the risks and benefits of tamoxifen and raloxifene, women completed measures of risk perception, decisional conflict, behavioral intentions, and actual behavior related to tamoxifen and raloxifene. 3 months following the intervention, 8.1% of participants had looked for additional information about breast cancer prevention drugs, and 1.8% had talked to their doctor about tamoxifen and/or raloxifene. The majority, 54.7%, had decided to not take either drug, 0.5% had started raloxifene, and none had started tamoxifen. Participants were not particularly worried about taking tamoxifen or raloxifene and did not perceive significant benefits from taking these drugs. Over 50% did not perceive a change in their risk of getting breast cancer if they took tamoxifen or raloxifene. After reading a DA about tamoxifen and raloxifene, few women were interested in taking either breast cancer prevention drug.     

Antibody-mediated inhibition of fibroblast growth factor 19 results in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys

Fibroblast growth factor 19 (FGF19) represses cholesterol 7α-hydroxylase (Cyp7α1) and inhibits bile acid synthesis in vitro and in vivo. Previous studies have shown that anti-FGF19 antibody treatment reduces growth of colon tumor xenografts and prevents hepatocellular carcinomas in FGF19 transgenic mice and thus may be a useful cancer target. In a repeat dose safety study in cynomolgus monkeys, anti-FGF19 treatment (3-100 mg/kg) demonstrated dose-related liver toxicity accompanied by severe diarrhea and low food consumption. The mechanism of anti-FGF19 toxicity was investigated using in vitro and in vivo approaches. Our results show that anti-FGF19 antibody had no direct cytotoxic effect on monkey hepatocytes. Anti-FGF19 increased Cyp7α1, as expected, but also increased bile acid efflux transporter gene (bile salt export pump, multidrug resistant protein 2 [MRP2], and MRP3) expression and reduced sodium taurocholate cotransporting polypeptide and organic anion transporter 2 expression in liver tissues from treated monkeys and in primary hepatocytes. In addition, anti-FGF19 treatment increased solute transporter gene (ileal bile acid-binding protein, organic solute transporter α [OST-α], and OST-β) expression in ileal tissues from treated monkeys but not in Caco-2 cells. However, deoxycholic acid (a secondary bile acid) increased expression of FGF19 and these solute transporter genes in Caco-2 cells. Gas chromatography-mass spectrometry analysis of monkey feces showed an increase in total bile acids and cholic acid derivatives. These findings suggest that high doses of anti-FGF19 increase Cyp7α1 expression and bile acid synthesis and alter the expression of bile transporters in the liver resulting in enhanced bile acid efflux and reduced uptake. Increased bile acids alter expression of solute transporters in the ileum causing diarrhea and the enhanced enterohepatic recirculation of bile acids leading to liver toxicity.     

All rodents are not the same: a modern synthesis of cortical organization

Rodents are a major order of mammals that is highly diverse in distribution and lifestyle. Five suborders, 34 families, and 2,277 species within this order occupy a number of different niches and vary along several lifestyle dimensions such as diel pattern (diurnal vs. nocturnal), terrain niche, and diet. For example, the terrain niche of rodents includes arboreal, aerial, terrestrial, semi-aquatic, burrowing, and rock dwelling. Not surprisingly, the behaviors associated with particular lifestyles are also highly variable and thus the neocortex, which generates these behaviors, has undergone corresponding alterations across species. Studies of cortical organization in species that vary along several dimensions such as terrain niche, diel pattern, and rearing conditions demonstrate that the size and number of cortical fields can be highly variable within this order. The internal organization of a cortical field also reflects lifestyle differences between species and exaggerates behaviorally relevant effectors such as vibrissae, teeth, or lips. Finally, at a cellular level, neuronal number and density varies for the same cortical field in different species and is even different for the same species reared in different conditions (laboratory vs. wild-caught). These very large differences across and within rodent species indicate that there is no generic rodent model. Rather, there are rodent models suited for specific questions regarding the development, function, and evolution of the neocortex.     

Elongated eustachian valve dividing the right atrium

A 64-year-old man underwent transthoracic echocardiography after a syncopal event. Two-dimensional imaging demonstrated a linear density that appeared to divide the right atrium. Color doppler imaging demonstrated that inflow from the inferior vena cava, but not from the superior vena cava, was obstructed by this density. Injection of agitated saline through an upper extremity vein demonstrated that the linear density did create a functional separation of the right atrium. The contrast material also crossed the interatrial septum within two cardiac cycles. This constellation of findings is consistent with an elongated eustachian valve and a patent foramen ovale.     

Atrial septal defect closure in the elderly is associated with excellent quality of life, functional improvement, and ventricular remodelling

Background

While atrial septal defect (ASD) closure is known to improve morbidity and mortality in children and adults, data are only beginning to emerge about its role in elderly cohorts. The goals of this study were to compare outcomes after device or surgical closure of ASDs in the elderly, and to quantitatively assess quality of life.

Methods

Patients > 60 years old who underwent ASD repair were studied. Functional status, arrhythmia burden, biventricular size and function were compared before and after ASD closure. Quality of life after ASD closure was assessed with the RAND SF-36 instrument.

Results

Sixty-seven patients, mean age of 68 years (range 60-86 years), were followed for 3.3 years. Nineteen percent underwent surgical closure and 81% underwent device closure. Major complication rates were 23% and 7% respectively with no procedure- related deaths. After surgical and device closure, quality of life was comparable to age-matched healthy controls, right ventricular end-diastolic dimension decreased by 10 mm (P < 0.001), left ventricular end-diastolic dimension increased by 4 mm (P = 0.001), biventricular function improved (right ventricular, P < 0.001; left ventricular, P = 0.007) and New York Heart Association class improved (P < 0.001). Prevalence of atrial arrhythmias however, was unchanged. Beneficial effects were similar for patients treated surgically or with device closure.

Conclusions

Given the favorable structural, functional, and quality of life outcomes after ASD closure in the elderly, advanced age alone should not be a contraindication to recommending surgical or device closure of an ASD.     

Open access to an outpatient intravenous diuresis program in a systolic heart failure disease management program

In order to provide efficient utilization of resources in an outpatient setting for acute exacerbation of heart failure (HF), the authors piloted an open-access outpatient intravenous (IV) diuretic program (IVDP) to evaluate utilization in an HF disease management program (HFDMP), patient characteristics for users of the program, and safety. An outpatient HFDMP at Jackson Memorial Hospital in Miami, Florida, enrolling 577 patients 18 years and older with an ejection fraction ≤40% was implemented. For symptoms or weight gain ≥5 pounds, patients were eligible to use an open-access IVDP during clinic hours. A total of 130 HFDM patients (22.5%) used the IVDP. IVDP users were more likely to be diabetic, with lower body mass indices than non-IVDP users. New York Heart Association class IV patients and previously hospitalized patients were more likely to use the IVDP. There were no documented adverse reactions for patients receiving treatment and no difference in mortality between groups. This open-access outpatient IVDP model for patients with HF was readily utilized by the HFDMP participants and appears safe for use in this population. This unique model may provide alternative access for acute HF treatment. Congest Heart Fail.     

Cerebral metabolism, cognition, and functional abilities in Alzheimer disease

Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD.     

The Distinct Role of Comparative Risk Perceptions in a Breast Cancer Prevention Program

Background

Comparative risk perceptions may rival other types of information in terms of effects on health behavior decisions.

Purpose

We examined associations between comparative risk perceptions, affect, and behavior while controlling for absolute risk perceptions and actual risk.

Methods

Women at an increased risk of breast cancer participated in a program to learn about tamoxifen which can reduce the risk of breast cancer. They reported comparative risk perceptions of breast cancer and completed measures of anxiety, knowledge, and tamoxifen-related behavior intentions. Three months later, the women reported their behavior.

Results

Comparative risk perceptions were positively correlated with anxiety, knowledge, intentions, and behavior 3 months later. After controlling for participants’ actual risk of breast cancer and absolute risk perceptions, comparative risk perceptions predicted anxiety and knowledge, but not intentions or behavior.

Conclusions

Comparative risk perceptions can affect patient outcomes like anxiety and knowledge independently of absolute risk perceptions and actual risk information.