A systematic overview, or meta-analysis, of the randomised evidence on maximum androgen blockade (MAB) in advanced prostate cancer identified 25 trials that compared conventional castration (surgical or medical) versus MAB (castration plus prolonged use of an antiandrogen such as flutamide, cyproterone acetate, or nilutamide). Individual patient data were obtained from 22 of the trials. Median follow-up was 40 months, during which 57% of patients died (3283/5710). Crude mortality rates were 58% for castration alone and 56% for MAB. Life-table estimates of the corresponding 5-year survival rates were 22.8% and 26.2%, representing a non-significant improvement of 3.5% (95% CI 0-7%). Logrank time-to-death analyses found no significant heterogeneity between trials (or between the effects of different types of MAB) and no significant evidence of additional benefit in an overview of all these MAB trial results (2p > 0.1). The currently available evidence from randomised trials does not show that MAB results in longer survival than conventional castration.

The hypothesis that oxidative modification of low density lipoprotein contributes to the progression of atherosclerosis is supported by an impressive body of in-vitro findings and by persuasive results in animal models of atherosclerosis. The hypothesis was originally proposed specifically to account for foam cell formation but oxidation of LDL has now been shown to confer on it a long list of new biological properties any one of which could in principle enhance its atherogenicity. The relative importance of these altered biological properties in vivo remains uncertain. Whatever the precise mechanisms, we know that antioxidants can slow the atherogenic process in several experimental models, including LDL-receptor-deficient rabbits, cholesterol-fed rabbits, and cholesterol-fed non-human primates. Of 18 published studies, 13 have given strongly positive results, the rate of progression of lesions being reduced by 50-80%; 2 have yielded marginally positive results; and 3 have been negative (see ref 3 for references). Furthermore, the fact that four different antioxidant compounds have been used--probucol, butylated hydroxytoluene, N,N'-diphenyl-phenylenediamine, and vitamin E--supports the conclusion that they are working via the property they all share, namely, their antioxidant potential.

Drug therapy for individuals of any age is difficult but prescribing for older patients offers special challenges. Older people take about three times as many prescription medications as younger individuals do, mainly because of their increased prevalence of chronic medical conditions. However, taking several drugs together substantially increases the risk of drug interactions, unwanted effects, and adverse reactions. Many medications need to be used with special caution because of age-related changes in pharmacokinetics and pharmacodynamics. For some drugs, an increase in the volume of distribution (eg, diazepam) or a reduction in drug clearance (eg, digoxin) may lead to higher plasma concentrations in older than in younger patients. Pharmacodynamic changes with ageing may result in an increased sensitivity to the effects of certain drugs (eg, opioids) for any given plasma concentration. While a physician can usually do little to alter the characteristics of individual older patients to affect the kinetics or dynamics of drugs, the decision whether to prescribe anything at all, the choice of drug, and the manner in which it is to be used (eg, dose and duration of therapy) are all factors that are under control of the prescriber. Patient adherence to the regimen prescribed is important, and there should be a partnership between physician and patient in therapeutic decision making. We will discuss here ways of improving prescribing for older patients. Specifically, we will examine the scarcity of information to guide prescribing decisions, the general principles of prudent prescribing, and the opportunities to clarify and expand knowledge about drug therapy in the elderly.