The most important aspect of management of hemophilia is to provide adequate replacement of safe clotting factor concentrates to prevent or treat bleeding episodes. There has been considerable progress in many countries in the developing world with regard to this aspect of care. However, very little data are available in the literature on the types of products being used for factor replacement and the doses being administered for control or treatment of bleeding in different countries. These data are important to document because only then can data from different centers be compared. This article provides data from seven countries: Korea, Malaysia, Thailand, Venezuela, Argentina, Iran, and India. It shows that there is wide variability not only in the types of products used (plasma to recombinant factor concentrates) but also in the doses administered (minimal to very high) for similar indications. Prospective documentation of data on musculoskeletal outcome at these centers and correlation with dose of factor replacement could help identify different models of care. Comparing such data and collating the experience in different countries could be useful for optimizing care and establishing cost-effective models. The combined experience in the developing world in providing hemophilia services should be used to define standards of care that are practical and to set achievable goals.
Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.