Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Web-Based Peer Navigation for Men with Prostate Cancer and Their Family Caregivers: A Pilot Feasibility Study

This study assessed the feasibility, acceptability and potential effects of True North Peer Navigation (PN)—a web-based peer navigation program for men with prostate cancer (PC) and their family caregivers. A one-arm, pre-post pilot feasibility study was conducted at two cancer centres in Canada. Participants were matched through a web-app with a specially trained peer navigator who assessed needs and barriers to care, provided support and encouraged a proactive approach to health for 3 months. Descriptive statistics were calculated, along with paired t-tests. True North PN was feasible, with 57.9% (84/145) recruitment, 84.5% (71/84) pre-questionnaire, 77.5% (55/71) app registration, 92.7% (51/55) match and 66.7% (34/51) post-questionnaire completion rates. Mean satisfaction with Peer Navigators was 8.4/10 (SD 2.15), mean program satisfaction was 6.8/10 (SD 2.9) and mean app usability was 60/100 (SD 14.8). At 3 months, mean ± SE patient/caregiver activation had improved by 11.5 ± 3.4 points (p = 0.002), patient quality of life by 1.1 ± 0.2 points (p < 0.0001), informational support by 0.4 ± 0.17 points (p = 0.03), practical support by 0.5 ± 0.25 points (p = 0.04) and less need for support related to fear of recurrence among patients by 0.4 ± 19 points (p = 0.03). The True North web-based peer navigation program is highly feasible and acceptable among PC patients and caregivers, and the associated improvements in patient and caregiver activation are promising. A randomized controlled trial is warranted to determine effectiveness.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyResearche

Corrigendum: Graphical comparison of image analysis and laser diffraction particle size analysis data obtained from the measurements of nonspherical particle systems

The purpose of this paper is to describe results from the use of a set of Excel macros written to facilitate the comparison of image analysis (IA) and laser diffraction (LD) particle size analysis (psa) data. Measurements were made on particle systems of differing morphological characteristics including differing average aspect ratios, particle size distribution widths and modalities. The IA and LD psa data were plotted on the same graph treating both the weighting and the size unit of the LD psa data as unknowns. Congruency of the IA and LD plots was considered to indicate successful experimental determination of the weighting and size unit. The weighting of the resulting LD psa data (so-called volume-weighted) is shown to be better correlated with IA area-weighted data. The size unit of LD psa data is shown to be a function of particle shape. In the case of high aspect ratio particles characterized by approximately rectangular faces the LD psa data is shown to be a function of multiple particle dimensions being related to IA size descriptors through a simple variation of the law of mixtures. The results demonstrate that successful correlations between IA and LD psa data can be realized in the case of non-spherical particle systems even in the case of high aspect ratio particles; however, the inappropriateness of the application of the Equivalent Spherical Volume Diameter and the Random Particle Orientation assumptions to the interpretation of the LD psa results must first be acknowledged. Correlation permits cross validation of IA and LD psa results increasing confidence in the accuracy of the data from each orthogonal technique

Commerical reference shape standards use in the study of particle shape effect on laser diffraction particle size analysis

The purpose of this paper is to describe the use of LGC Promochem AEA 1001 to AEA 1003 monosized fiberanalog shape standards in the study of the effect of particle shape on laser diffraction (LD) particle size analysis (psa). The psa of the AEA standards was conducted using LD psa systems from Beckman Coulter, Horiba, and Malvern Instruments. Flow speed settings, sample refractive index values, and sample cell types were varied to examine the extent to which the shape effect on LD psa results is modified by these variables. The volume and number probability plots resulting from these measurements were each characterized by a spread in the particle size distribution that roughly extended from the breadth to the longest dimension of the particles. For most of the selected sample refractive index values, the volume probability plots were characterized by apparent bimodal distributions. The results, therefore, provide experimental verification of the conclusions from theoretical studies of LD psa system response to monosized elliptical particles in which this apparent bimodality was the predicted result in the case of flow-oriented particles. The data support the findings from previous studies conducted over the past 10 years that have called into question the verity of the tenets of, and therefore the value of the application of, the equivalent spherical volume diameter theory and the random particle orientation model to the interpretation of LD psa results from measurements made on nonspherical particles