Design features of the Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) clinical trial

Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.)     

Construct and predictive validity of a self-reported measure of preclinical mobility limitation

OBJECTIVES: To validate self-reported preclinical mobility limitation concept and self-report assessment method against muscle power and walking speed, and to study the predictive validity of preclinical mobility limitation with respect to future risk of manifest mobility limitation. DESIGN: Observational prospective cohort study and cross-sectional analysis. SETTING: Research laboratory and community. PARTICIPANTS: A total of 632 community-living (age range, 75-81 y) women and men took part in the baseline assessments and 302 persons in the semi-annual interviews on mobility limitation over 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking speed, muscle power, and self-reported preclinical and manifest mobility limitation. Preclinical mobility limitation was defined as self-reported tiredness or modification of task performance without task difficulty. At baseline, 4 subgroups were created according to self-reported preclinical mobility limitation in any of 3 mobility tasks (walking 2 km, walking 0.5 km, climbing up stairs): no limitation, preclinical limitation, and minor and major manifest limitation. RESULTS: At baseline, participants with preclinical mobility limitation showed intermediate levels of walking speed and muscle power, compared with those with no limitation or manifest mobility limitation. Participants reporting baseline preclinical mobility limitation had 3- to 6-fold higher age- and sex-adjusted risk of progressing to major manifest mobility limitation during the 2-year follow-up compared with participants with no limitation at baseline, whereas the risk among those with minor limitation at baseline was 14- to 18-fold higher compared with those with no limitation. CONCLUSIONS: The self-report assessment tool proved to be a valid measure to capture the early signs of disability and may serve as an inexpensive tool for identifying those nondisabled persons at high risk for future disability.     

Tibial and Fibular Mid-Shaft Bone Traits in Young and Older Sprinters and Non-Athletic Men

High impact loading is known to prevent some of the age-related bone loss but its effects on the density distribution of cortical bone are relatively unknown. This study examined the effects of age and habitual sprinting on tibial and fibular mid-shaft bone traits (structural, cortical radial and polar bone mineral density distributions). Data from 67 habitual male sprinters aged 19–39 and 65–84 years, and 60 non-athletic men (referents) aged 21–39 and 65–80 years are reported. Tibial and fibular mid-shaft bone traits (strength strain index SSI, cortical density CoD, and polar and radial cortical density distributions) were assessed with peripheral quantitative computed tomography. Analysis of covariance (ANCOVA) adjusted for height and body mass indicated that the sprinters had 21 % greater tibial SSI (P < 0.001) compared to the referents, with no group × age-group interaction (P = 0.54). At the fibula no group difference or group × age-group interaction was identified (P = 0.12–0.81). For tibial radial density distribution ANCOVA indicated no group × radial division (P = 0.50) or group × age-group × division interaction (P = 0.63), whereas an age × radial division interaction was observed (P < 0.001). For polar density distribution, no age-group × polar sector (P = 0.21), group × polar sector (P = 0.46), or group × age-group × polar sector interactions were detected (P = 0.15). Habitual sprint training appears to maintain tibial bone strength, but not radial cortical density distribution into older age. Fibular bone strength appeared unaffected by habitual sprinting.     

Too Fit To Fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture

Summary

A consensus process was conducted to develop exercise recommendations for individuals with osteoporosis or vertebral fractures. A multicomponent exercise program that includes balance and resistance training is recommended.

Introduction

The aim was to develop consensus on exercise recommendations for older adults: (1) with osteoporosis and (2) with osteoporotic vertebral fracture(s).

Methods

The Grading of Recommendations Assessment, Development, and Evaluation method was used to evaluate the quality of evidence and develop recommendations. Outcomes important for decision making were nominated by an expert panel and patient advocates. They included falls, fractures, bone mineral density (BMD), and adverse events for individuals with osteoporosis/vertebral fractures, and pain, quality of life, and function for those with vertebral fracture. Meta-analyses evaluating the effects of exercise on the outcomes were reviewed. Observational studies or clinical trials were reviewed when meta-analyses were not available. Quality ratings were generated, and informed the recommendations.

Results

The outcome for which evidence is strongest is falls. Point estimates of the effects of exercise on falls, fractures, and BMD vary according to exercise type. There is not enough evidence to quantify the risks of exercise in those with osteoporosis or vertebral fracture. Few trials of exercise exist in those with vertebral fracture. The exercise recommendations for exercise in individuals with osteoporosis or osteoporotic vertebral fracture are conditional. The panel strongly recommends a multicomponent exercise program including resistance and balance training for individuals with osteoporosis or osteoporotic vertebral fracture. The panel recommends that older adults with osteoporosis or vertebral fracture do not engage in aerobic training to the exclusion of resistance or balance training.

Conclusions

The consensus of our international panel is that exercise is recommended for older adults with osteoporosis or vertebral fracture, but our recommendations are conditional.     

Midlife income,occupation, APOE status,and dementia: a population-based study

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.     

Sleep Duration and Regularity are Associated with Behavioral Problems in 8-year-old Children

Background  

Relatively little is known about the significance of normal variation in objectively assessed sleep duration and its regularity in children's psychological well-being.     

Low-dose aspirin does not improve ovarian responsiveness or pregnancy rate in IVF and ICSI patients: a randomized, placebo-controlled double-blind study

BACKGROUND: Poor ovarian and endometrial responses to gonadotrophin stimulation in assisted reproduction techniques lead to decreased pregnancy rates. The aim of the present study was to test the hypothesis that low-dose aspirin started prior to controlled ovarian stimulation improves ovarian responsiveness, pregnancy rate (PR) and pregnancy outcome. METHODS: A total of 374 women who were to undergo IVF/ICSI were randomized to receive 100 mg of aspirin (n=186) or placebo (n=188) daily. Treatment was started on the first day of controlled ovarian stimulation. It was continued until menstruation or a negative pregnancy test. Pregnant women continued the medication until delivery. The main outcome measures were the number of oocytes, number and quality of embryos, the clinical PR and pregnancy outcome. RESULTS: The mean (+/-SD) number of oocytes (12.0+/-7.0 versus 12.7+/-7.2), the total mean number of embryos (5.82+/-4.35 versus 5.99+/-4.66), the mean number of top quality embryos (0.99+/-1.39 versus 1.18+/-1.51) and the number of embryos transferred (1.64+/-0.64 versus 1.63+/-0.71) did not differ in the aspirin and placebo groups. Between the aspirin and placebo group, there was no statistically significant difference in clinical PR per embryo transfer (25.3%, n=44 out of 174 versus 27.4%, n=48 out of 175) or clinical PR per cycle initiated (23.7% versus 25.5%). Birth rate per embryo transfer did not differ significantly between the aspirin (18.4%) and placebo (21.1%) groups. The incidence of poor responders [12 (6.5%) versus 13 (6.9%)] was similar in both groups. CONCLUSIONS: The present results indicate that low-dose aspirin treatment does not have any beneficial effect on ovarian responsiveness, PR and pregnancy outcome in unselected women undergoing IVF/ICSI.