Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Neutral endopeptidase inhibition increases the potency of ANP in isolated rat pulmonary resistance vessels and isolated blood perfused lungs

We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature.     

Downward comparison, prejudice, and evaluations of others: Effects of self-esteem and threat.

In two studies, we explored the effects of trait self-esteem and threats to the self-concept on evaluations of others. In Study 1, subjects high, moderate, and low in self-esteem received either success, failure, or no feedback on a test and later evaluated three pairs of targets: ingroups and outgroups based on a minimal intergroup manipulation, those who scored above average and those who scored below average on the test, and themselves and the average college student. Study 2 explored the effects of self-esteem and threat on ingroup favoritism in a real-world setting, campus sororities. Together, the results of these studies indicate that individuals high in self-esteem, but not those low in self-esteem, respond to threats to the self-concept by derogating outgroups relative to the ingroup when the group boundaries have evaluative implications. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The design of robots and intelligent manipulators using modern composite materials

The operating speed and endpoint positional accuracy of existing industrial manipulators are limited by the inertial and stiffness characteristics of the articulating members of the robot's mechanical linkage. This limitation may be overcome by developing members having high structural stiffness and strength with low mass, and this has been recognized for some time. These characteristics can be obtained by fabricating the moving members of manipulators in fiber reinforced composite materials. In order to establish a basis for the dynamic analysis of robots fabricated in viscoelastic composites, a variational theorem is developed herein. A preliminary comparative study is then undertaken for manipulators manufactured in a graphite-epoxy composite material and also steel in order to demonstrate some of the advantages to be accrued from this proposed new design philosophy.     

Consent to treatment by minors attending accident and emergency departments: guidelines

The absolute right to refuse medical treatment, even if the reasons are irrational, is confined to competent adults. Children under 16 years can give legal consent to treatment in the absence of consent from those with parental responsibility. Children under 18 years do not, however, have an absolute right to consent, or refuse to consent, to treatment. The views of children assume increasing importance with age and maturity. Accident and emergency medical and nursing staff may face difficult decisions when children, or those with parental responsibility, refuse to consent to medical treatment. This paper presents guidelines designed to guide the decision making process in immediately or potentially life threatening conditions and in non-life-threatening conditions.     

The INTELSAT VII/VIIA generation of global communications satellites

Developed primarily to provide continuation of services from the INTELSAT V satellites in the Pacific Ocean Region, this latest generation of satellites also has utility for operation in other roles. Several new technologies are combined to give cost-effective international satellite communications on a global, regional and domestic basis. This new higher power satellite will form a fundamental part of the INTELSAT global network, having been designed to match the projected traffic demands and future service requirements.     

Influence of heat transfer on anodic oxidation of aluminium

The influence of convective heat transfer on constant current density anodizing of aluminium in sulfuric acid has been examined in a wall-jet electrode reactor. The uniformity of the anodic film thickness is related to the local electrode temperature distribution, which is dependent on the convection. The higher the local temperature, the greater the local oxide thickness. An increased local temperature enhances local field assisted oxide dissolution at the pore bases, and consequently acts to increase the local current density. At relatively high current densities, local features develop on the electrode surface, accompanied by high initial, local temperature rises. The relevance of such local features, limiting useful oxide growth, is considered further.     

Psychological adjustment of children with sickle cell disease: Stability and change over a 10-month period.

Rates of poor psychological adjustment of children with sickle cell disease remained relatively constant over initial and follow-up assessment points. 50 children (aged 7–12 yrs) and their mothers completed the initial protocol. 30 children completed the follow-up plus 5 additional children and their mothers. These Ss were aged 7–24 yrs at follow-up. With initial levels of adjustment controlled, children's strategies for coping with pain accounted for a significant increment in child-reported symptoms and mother-reported internalizing behavior problems at follow-up beyond the contribution of illness and demographic parameters and follow-up interval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Is the Promissory Note of Personality as Vulnerability to Depression in Default? Reply to Zuroff, Mongrain, and Santor (2004).

In contrast to D. C. Zuroff, M. Mongrain, and D. A. Santor (2004), the current authors find the promissory note of dependency-sociotropy (DEP-SOC) and self-criticism-autonomy (SC-AUT) as a model of risk for depression to be in default. The authors propose reorganizing what has been cast as unitary effort into 3 distinct endeavors: a psychoanalytic clinical theory, development of a refined empirical model of risk for clinical depression, and research examining the effects of DEP-SOC and SC-AUT on interpersonal relationships in nonclinical samples. The authors identify some issues that need to be accommodated regardless of whether the assessment of Zuroff et al. (2004) or their own is accepted. DEP-SOC and SC-AUT are best construed as correlated, continuous dimensions. Future work also needs to accommodate depression as chronic recurrent condition, advances in developmental psychopathology, and more stringent criteria for positing a risk factor for clinical disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)