New indications for already-approved drugs: time trends for the new drug application review phase

For 55 individual drugs, the time required for approval of the original new drug application (NDA) was compared with the time required for approval of supplemental NDAs. The mean time required for the original NDAs was 22.2 +/- 18.1 months; the mean for review of all 46 follow-on indications was similar (19.1 +/- 17.9 months). Since subsequent applications do not ordinarily require new assessment of clinical safety or animal toxicity studies, one would expect the subsequent applications to be processed more expeditiously. Such is not the case. The negative implications of these facts are discussed.     

Non-steroidal anti-inflammatory drugs: indications for use

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used of all therapeutic agents. Although they are effective analgesics they do have significant adverse side-effects. Before treatment is started the prescriber should always weigh efficacy against possible side-effects. NSAIDs vary in their selectivity for inhibiting the two types of cyclo-oxygenase. An NSAID should therefore be chosen on the basis of the incidence of associated side-effects.     

Patient selection: indications and contraindications

Patient selection is critical to the success of PLDD. In general, the herniation must have continuity with the parent disc; rupture of the annulus is not a contraindication. Several other orthopedic conditions constitute absolute or relative contraindications. All patients must be individualized. Our criteria for inclusion is undergoing continuing change. What is unacceptable now may, with modifications, become acceptable in the future. It is important not to adopt a fixed position at this early stage of PLDD.     

Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders

Irbesartan is a long-acting angiotensin II antagonist acting specifically at the level of the Type 1receptor subtype (AT₁receptor). This compound lowers blood pressure dose-dependently in hypertensive patients and has a placebo-like tolerability. The antihypertensive efficacy of irbesartan is greatly enhanced by the coadministration of a diuretic, and fixed-dose combinations of irbesartan and hydrochlorothiazide are now available. Irbesartan-based treatment appears especially effective for high-risk patients, such as those with diabetes, renal disease and cardiac hypertrophy. In patients with Type 2 diabetes, irbesartan delays the development of nephropathy as well as the progression of renal failure. Irbesartan may have antiatherosclerotic properties beyond those expected from blood pressure lowering per se: this AT₁blocker decreases the vascular oxidative stress and prevents the procoagulant as well as the pro-inflammatory effects of angiotensin II. Irbesartan given alone or in combination with a diuretic therefore represents a rational approach to treat hypertensive patients.     

膝关节置换的适应证及假体选择

背景:选择合适的人工膝关节对于膝关节置换患者是非常重要的.目的:结合文献探讨膝关节假体置换的适应证.方法:由第一作者采用电子检索的方式,在万方数据库(http://www.wanfangdata.com.cn/)中检索有关膝关节置换适应证及其相应假体选择的文章,检索时间范围:2000-01/2010-12,关键词为"膝关节置换,适应证,人工假体,生物相容性".经检索共查到相关文献50余篇,排除内容重复、普通综述、Meta分析类文章后,筛选纳入5篇文献进行评价.结果与结论:不同患者应根据病情、关节限制程度、固定方式和半月板功能来选择不同的人工膝关节.不同膝关节假体置换的适应证应由膝关节的骨和软组织条件决定,膝关节韧带的质量和状态、关节畸形以及关节软骨破坏的程度决定假体的选择.     

膝关节置换的适应证及假体选择

背景：选择合适的人工膝关节对于膝关节置换患者是非常重要的。目的：结合文献探讨膝关节假体置换的适应证。方法：由第一作者采用电子检索的方式,在万方数据库（http：//www.wanfangdata.com.cn/）中检索有关膝关节置换适应证及其相应假体选择的文章,检索时间范围：2000-01/2010-12,关键词为＂膝关节置换,适应证,人工假体,生物相容性＂。经检索共查到相关文献50余篇,排除内容重复、普通综述、Meta分析类文章后,筛选纳入5篇文献进行评价。结果与结论：不同患者应根据病情、关节限制程度、固定方式和半月板功能来选择不同的人工膝关节。不同膝关节假体置换的适应证应由膝关节的骨和软组织条件决定,膝关节韧带的质量和状态、关节畸形以及关节软骨破坏的程度决定假体的选择。     

Beta-adrenergic blocking drugs in the treatment of hypertension

In the relatively short time since their introduction, beta-blockers have had an enormous impact on cardiovascular therapeutics and on many areas of clinical and physiological research. This has been quite unmatched by any other group of drugs. The stimulus for much of this work has arisen from continuing attempts to understand the mechanism by which beta-blockers lower blood pressure. Hemodynamic, renin-suppressive, central nervous system and a variety of other effects have been studied in detail but the explanation seems no closer than it was in the first few years of these investigations. On the other hand, this work has made important contributions to the understanding of cardiovascular physiology.The advent of beta-blockers has coincided with a time when views on the nature and treatment of hypertension have undergone considerable change. Hypertension is no longer regarded as a malignant and fulminating disease but rather as a prevalent, chronic and asymptomatic condition whose consequences are largely indistinguishable in type from the normal effects of cardiovascular ageing. This has led to a requirement for therapy in vast numbers of mildly hypertensive asymptomatic individuals, and has consequently shifted the therapeutic emphasis in the direction of patient acceptability. It is this, rather than any advantage in efficacy that has led to the ever-increasing use of beta-blockers now challenging even the place of thiazide diuretics as first choice drugs in essential hypertension. This trend is also apparent in the investigation and use of beta-blockers in certain hypertensive subgroups such as the pregnant and the elderly who in the past had been treated differently, if at all. Thus the advantages and drawbacks of beta-blocker therapy have become more clearly appreciated; at the same time, understanding of drug mechanism is advanced.Over a dozen different beta-blockers are now available. Some of these vary in relatively minor points of detail by the possession of beta₁-adrenoceptor selectivity or partial agonist activity. In general these features have little influence either on therapeutic activity or on the incidence of adverse effects. In some cases, though, the severity of adverse reactions can be reduced, for example by using cardioselective agents in asthmatics and diabetics.In terms of efficacy and adverse effects, there is little to choose between beta-blockers and thiazide diuretics in the short term; equally, there are questions about the long term safety of both drugs still to be answered. However, the choice between these two agents must be influenced by the demonstration that beta-blockers have a modest though undoubted protective effect in patients who have suffered myocardial infarction. This is a major consideration and one which may yet have an important effect on therapeutic practice. It thus seems rational, in view of the predisposition of hypertensives to coronary artery disease, to use beta-blockers as first choice drugs in essential hypertension.