INTRODUCTION

Postmenopausal osteoporosis (PMO) is characterized by reduced bone mass leading to an increased risk of fracture. The prevalence of PMO increases with age from approximately 6% at age 50 to over 50% above age 80. The incidence of osteoporotic fractures follows a similar pattern, with wrist fractures peaking at approximately age 70, and vertebral and hip fractures at age 85. Fractures are associated with significant reductions in quality of life caused by disability, pain, and deformity, and they constitute an important cause of death among the elderly.

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Aspirin is the most widely used agent for the prevention of secondary stroke. The An-tiplatelet Trialists studied the effect of an-tiplatelet agents in more than 73,000 elderly patients with stroke and TIAs, unstable angina, and myocardial infarction as well as patients at high risk for other events of atherosclerotic ori-gin.²² Antiplatelet agents, as a whole, reduced the odds of nonfatal stroke in high-risk patients by approximately 30%. Patients with a prior history of stroke and who received antiplatelet therapy experienced a 22% lower incidence of recurrent stroke or TIA. Specifically, aspirin reduced the combined risk of stroke, myocar-dial infarction, or vascular death by 25%.

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Immediately following an acute ischemic stroke, up to 5% of early deaths may be associated with deep venous thrombosis (DVT) or pulmonary embolism (PE). In addition, the NINDS Stroke Data Bank estimated that 30% of neurological worsening of stroke patients during hospitalization occurs in those with atherosclerotic etiologic factors. Therefore, theoretical advantages for anticoagu-lation therapy have been proposed following ischemic strokes, but its general use should be initiated cautiously. Clinical trials evaluating anticoagulation for acute ischemic stroke did not result in significant improvement in primary outcomes, reduced mortality, or prevention of recurrent stroke and revealed a modest but significantly increased risk of hemorrhage.

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Age, sex, race, and family history are nonmodifiable risk factors for cerebrovascular events. Therefore, older patients (i.e., 65 years and above) are at higher risk for stroke-associated mortality and morbidity. Other factors associated with increased risk of stroke include hypertension, blood pressure differences in each arm, heart disease, carotid bruits, diabetes, dyslipidemia, elevated fibrinogen levels, migraine headaches, sickle cell disease, retinal em-boli, and TIAs. The 10-year stroke risk relative to the average risk for a given age and sex can be assessed by means of Framingham data. This estimation of risk is limited to assessment based on sex, age, systolic blood pressure, antihypertensive treatment, cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy. Furthermore, it is unclear how accurately these predictors estimate the risk of cerebrovascular events in patients of advanced age.

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INTRODUCTION

Stroke is a major cause of death and disability among the elderly, typically defined as individuals over the age of 65. More than 750,000 Americans experience strokes annually, and 160,000 of these do not survive. Of the survivors, approximately one-third experience another stroke within five years.

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In a randomized, double-blind, placebo-controlled study (PRISM-2) of interferon | -1a in patients with RRMS, 560 participants were randomly assigned to receive subcutaneous interferon | -1a 22 mcg (n = 189), 44 mcg (n = 184), or placebo (n = 187) three times a week for two years. The mean number of relapses during the two years of the study was lower in both interferon | -1a groups than in the placebo group (P < .005). The percentage reduction for the patients receiving the 22-mcg dose, compared with those receiving placebo, was 27% (95% confidence interval [CI], range, 14%-39%), and the percentage reduction for patients receiving the 44-mcg dose, compared with those patients receiving placebo, was 33% (range, 21%-44%). The mean number of moderate and severe relapses during the two-year follow-up period was also lower in both interferon P-1a groups than in the placebo group (P < .005). The median time to first relapse was delayed by three and five months in the groups receiving 22 mcg and 44 mcg, respectively.

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Interferons are naturally occurring proteins that demonstrate immuno-modulatory, antiviral, and antiprolifera-tive biological activities. They exert their biological effects by binding to specific receptors on the surface of cells. The binding of interferon beta to its receptors initiates a complex cascade of intra-cellular events that leads to the expression of numerous interferon-induced gene products and markers, including 2′,5′-oligoadenylate synthetase, |3₂-micro-globulin, and neopterin, which may mediate some of the biological activities. The specific interferon-induced proteins and the mechanisms by which interferon |3-1a exerts its effects in MS have not been fully defined.

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