Citations

Abstract Colorectal cancer (CRC) screening rates are often ascertained via self-reports but can be subject to overreporting bias. Asking about intention to get screened before asking about past screening may minimize overreporting of cancer screening. In a statewide survey conducted from July through October of 2005, we embedded an experiment that tested the effect of question ordering (asking about future intention to get screened before or after asking about past screening; “future first” and “future second,” respectively), crossed with survey mode (mail versus telephone), on CRC screening rates. Weighted analysis focused on 752 respondents who were ages 50 years or older. We found (a) that asking about future intentions to get screened before asking about past screening (future first) statistically significantly lowers reports of past CRC screening [70.9% future second versus 58.0% future first; odds ratio (OR), 1.83; 95% confidence interval (95% CI), 1.08-3.13]; (b) that there was no main effect of survey mode; and (c) that the effect of the ordering of the future intentions item varies by survey mode. In the mailed survey, the odds of reporting past CRC screening were almost thrice greater in the future second condition compared with the future first condition (72.4% versus 49.0%, respectively; OR, 2.74; 95% CI, 1.22-6.17). In the telephone condition, the odds of reporting were only 28% higher in the future second (69.5%) condition than in the future first condition (63.9%; OR, 1.28; 95% CI, 0.64-2.57). The results suggest that asking about future intentions to get screened before the actual behavior elicits lower, and arguably more truthful reports of CRC screening but mainly in mailed surveys. (Cancer Epidemiol Biomarkers Prev 2008;17(4):785–90)

AbstractBackground: Limited studies have examined the associations between mammographic density and subsequent breast tumor characteristics.Methods: Eligible women were part of a case-control study of postmenopausal breast cancer, were 40 years or older and had a routine mammogram 4 years or more before their diagnosis. Mammographic density (percent density, dense area, and nondense area) was estimated using a computer-assisted thresholding program. At the time of cancer diagnosis, cases were classified as asymptomatic or symptomatic based on medical record review and breast imaging workup. Pathologic review was done blinded to the density status. Linear regression models and tests for trend examined the association between pathologic characteristics of the breast tumor and the components of density for all participants, and stratified by symptom status at diagnosis.Results: Of the 286 eligible cases, 77% were 60 years or older and mean percent density was 29.5% (SD, 14.6%). Density was not significantly associated with tumor size (P = 0.22), histologic type (P = 0.77), estrogen receptor (P = 0.11) or progesterone receptor (P = 0.37) status, mitotic activity (P = 0.12), or nuclear pleomorphism (P = 0.09; P values for percent density). An inverse association was suggested between tumor grade and percent density (32.0%, 30.3%, 26.7% for grades 1-3; P = 0.06 for trend). The inverse association with tumor grade and its components (nuclear pleomorphism and tubular differentiation) was only evident among the 97 symptomatic women; positive associations of estrogen receptor (P = 0.009) and progesterone receptor (P = 0.04) were also seen with percent density only in this subgroup.Conclusions: The inverse association between tumor grade and percent density in the symptomatic population could inform the biology of the association between mammographic density and breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(4):872–9)

Background— Few studies have compared medium-term outcomes for drug-eluting stents (DES) and bare metal stents, and most are relatively small randomized controlled trials. Furthermore, since the introduction of DES, there has been increased use and duration of use of clopidogrel, statins, and other evidence-based therapies. The purpose of the present study was to compare outcomes for patients who underwent stenting in the eras before and after the introduction of DES. Methods and Results— New York state patients undergoing stenting in all nonfederal hospitals in the state were studied. Patients were excluded if they had a previous revascularization. Risk factors that were significant predictors of adverse outcomes were used to adjust adverse outcome rates. The study included 11 436 patients who received stents between October 1, 2002, and March 31, 2003, and 12 926 patients who underwent stenting between October 1, 2003, and March 31, 2004. Death rates, the combined end point of death and myocardial infarction (MI), nonfatal MI requiring readmission, target vessel revascularization, and target lesion revascularization were compared at 2 years. Patients in the DES era had significantly better risk-adjusted outcomes for death/MI (adjusted hazard ratio, 0.90; 95% confidence interval, 0.83 to 0.97), 9.9% versus 10.8%; nonfatal MI requiring readmission (adjusted hazard ratio, 0.86; 95% confidence interval, 0.76 to 0.97); target vessel revascularization (adjusted hazard ratio, 0.60; 95% confidence interval, 0.56 to 0.64), 11.2% versus 17.9%; and target lesion revascularization (hazard ratio, 0.55; 95% confidence interval, 0.51 to 0.59), 8.4% versus 14.7%. Conclusions— Patients in the DES era experienced lower rates of death/MI, nonfatal MI, target vessel revascularization, and target lesion revascularization, but there were no differences in the rates of death. These improvements are likely a result of increased use of clopidogrel, statins, and dual antiplatelet therapy, in addition to the introduction of DES.

Purpose To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer. Patients and Methods In part A, patients received escalating doses to determine the maximum-tolerated dose (MTD). In both parts, blood samples were collected to assess PK and PD parameters. In part B, patients were stratified by cancer type (melanoma v other) and randomly assigned to receive the MTD or 50% MTD. Biopsies were collected to determine inhibition of ERK phosphorylation, Ki-67 expression, and BRAF, KRAS, and NRAS mutations. Results Fifty-seven patients were enrolled. MTD in part A was 200 mg bid, but this dose was discontinued in part B because of toxicity. The 50% MTD (100 mg bid) was well tolerated. Rash was the most frequent and dose-limiting toxicity. Most other adverse events were grade 1 or 2. The PKs were less than dose proportional, with a median half-life of approximately 8 hours and inhibition of ERK phosphorylation in peripheral-blood mononuclear cells at all dose levels. Paired tumor biopsies demonstrated reduced ERK phosphorylation (geometric mean, 79%). Five of 20 patients demonstrated ≥ 50% inhibition of Ki-67 expression, and RAF or RAS mutations were detected in 10 of 26 assessable tumor samples. Nine patients had stable disease (SD) for ≥ 5 months, including two patients with SD for 19 (thyroid cancer) and 22 (uveal melanoma plus renal cancer) 28-day cycles. Conclusion AZD6244 was well tolerated with target inhibition demonstrated at the recommended phase II dose. PK analyses supported twice-daily dosing. Prolonged SD was seen in a variety of advanced cancers. Phase II studies are ongoing.

Human species C adenovirus serotype 5 (Ad5) is the most common viral vector used in clinical studies worldwide. Ad5 vectors infect liver cells in vivo with high efficiency via a poorly defined mechanism, which involves virus binding to vitamin K-dependent blood coagulation factors. Here, we report that the major Ad5 capsid protein, hexon, binds human coagulation factor X (FX) with an affinity of 229 pM. This affinity is 40-fold stronger than the reported affinity of Ad5 fiber for the cellular receptor coxsackievirus and adenovirus receptor, CAR. Cryoelectron microscopy and single-particle image reconstruction revealed that the FX attachment site is localized to the central depression at the top of the hexon trimer. Hexon-mutated virus bearing a large insertion in hexon showed markedly reduced FX binding in vitro and failed to deliver a transgene to hepatocytes in vivo . This study describes the mechanism of FX binding to Ad5 and demonstrates the critical role of hexon for virus infection of hepatocytes in vivo .

ABSTRACT We tested the activity of anidulafungin against 30 Candida albicans isolates. The planktonic MICs for 50 and 90% of the isolates tested (MIC 50 and MIC 90 ) were ≤0.03 and 0.125 μg/ml, respectively (MIC range, ≤0.03 to 2 μg/ml). The sessile MIC 50 and MIC 90 were ≤0.03 and ≤0.03 μg/ml, respectively (MIC range, ≤0.03 to >16 μg/ml).

OBJECTIVE—Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture. RESEARCH DESIGN AND METHODS—Ten nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU · kg−1 · min−1) plus variable glucose for 160 min. In two studies, clamped hypoglycemia (47 mg/dl plasma glucose for 40 min) was induced and either oral placebo or an amino acid mixture (42 g) was given at 30 min. In the third study, amino acids were given, but euglycemia was maintained. RESULTS—Plasma glucose and insulin were no different in the hypoglycemia studies with both placebo and amino acids (P > 0.2). After the amino acid mixture, plasma amino acid concentrations increased to levels observed after a mixed meal (2.4 ± 0.13 vs. placebo study 1.7 ± 0.1 mmol/l, P = 0.02). During clamped euglycemia, ingestion of amino acids resulted in transient increases in glucagon concentrations, which returned to basal by the end of the study. During clamped hypoglycemia, glucagon response was sustained and increased more in amino acid studies versus placebo in nondiabetic and diabetic subjects (P < 0.05), but other counter-regulatory hormones and total symptom score were not different. β-OH-butyrate was less suppressed after amino acids (200 ± 15 vs. 93 ± 9 μmol/l, P = 0.01). Among the cognitive tests administered, the following indicated less deterioration after amino acids than placebo: Trail-Making part B, PASAT (Paced Auditory Serial Addition Test) (2 s), digit span forward, Stroop colored words, and verbal memory tests for nondiabetic subjects; and Trail-Making part B, digit span backward, and Stroop color tests for diabetic subjects. CONCLUSIONS—Oral amino acids improve cognitive function in response to hypoglycemia and enhance the response of glucagon in nondiabetic and diabetic subjects.