The use of placebo control groups (e.g., subjects using calcium and vitamin D) in osteoporosis trials with subjects at high risk for fracture has been systematically questioned by institutional ...review boards (IRBs). Regulatory agencies, on the other hand, continue to not only recommend but also require that placebo-controlled trials be presented for the registration of new drugs for osteoporosis treatment. The Declaration of Helsinki and its updates have upheld the principle that protection of research subjects' rights is of primary concern. Nevertheless, even the Declaration keeps clearly opening the possibility of using placebo-control designs if it is justified for "compelling and scientifically sound methodological reasons." The use of intermediary endpoints or surrogates to establish the efficacy or safety of new medications in the management of osteoporosis is currently considered scientifically insufficient. This concept has led regulatory agencies, such as the Food and Drug Administration in the United States and the European Medicines Agency in the European Union, to require "fragility fracture reduction" as the primary endpoint in clinical trials for the registration of new drugs. Superiority or noninferiority trials are alternatives to placebo-controlled designs. However, factors such as sample size, cost, and statistical limitations render these models impractical for the registration of new medications for osteoporosis. We recommend collaboration among regulatory agencies, IRBs, scientists, and ethicists on the design of clinical trials for the registration of new medications for reduction of fracture risk. Delay in developing mutually acceptable models may impair scientific development in the field and possibly deprive patients of potentially beneficial treatments.
Planners can apply a relatively simple and user-friendly tool to control the expansion of urban areas in developing countries. This tool, presented here, is based on a traditional accessibility ...index, which may be taken as a measure of urban development. The entire process of construction and analysis of the networks based on the accessibility index was carried out using a geographic information system for transportation (GIS-T). The tool has been tested in São Carlos, a medium-sized Brazilian city, in which the effects of some proposed real estate developments on the accessibility patterns have been studied. The results of this application show that the tool is suitable for selecting the best site for a new development among many alternatives, promoting more efficient use of the urban area.
Early Results of Aortic Valve Homograft Replacement Zerbini, E.J.; de Oliveira, Sérgio Almeida; Fileggi, Fulvio ...
Diseases of the chest,
January 1969, 1969-Jan, 1969-01-00, 19690101, Volume:
55, Issue:
1
Journal Article
Peer reviewed
The authors present the early results hi 50 cases of aortic valve homograft replacement. The homografts were sterilized and preserved in 4.0 percent formaldehyde solution buffered to a 5.6 pH, as ...proposed by Paneth. Aortic valve replacement only was performed in 34 cases, open mitral commisurotomy in 11 cases, and mitral valve replacement with a Starr-Edwards prosthesis in five cases. The immediate mortality was 4 percent and the late mortality was 6 percent The most important postoperative complications were myocardial infarction, transient atrioventricular block, acute bacterial endocarditis and the appearance of an aortic diastolic murmur of aortic insufficiency. The five deaths were caused by (1) cardiac arrest (2) myocardial infarction, (3) and (4) low cardiac output due to aortic incompetence, and (5) acute bacterial endocarditis.
