Time-dependent endpoints as predictors of overall survival in multiple myeloma.

BACKGROUND: Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients. METHODS: Studies (excluding allogeneic transplantation) published from 1970 to 2011 were systematically searched (PubMed). The nonparametric Spearman's rank correlation coefficient measured the association between median TDE and OS. The quantitative relationship between TDEs and OS was estimated with a two-step approach to a simultaneous Tobit model. RESULTS: We identified 153 studies: 230 treatment arms, 22,696 patients and mean study duration of 3.8 years. Mean of median TDEs was 22.5 months and median OS was 39.1 months. Correlation coefficients of median TTP, PFS, and EFS with median OS were 0.51 (P = 0.003), 0.75 (P < 0.0001), and 0.84 (P < 0.0001), respectively. We estimate a 2.5 month (95% confidence interval, 1.7-3.2) increase in median OS for each additional month reported for median TDEs. There was no evidence that this relationship differed by type of surrogate. CONCLUSION: TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.

Assessment of yeast diversity in a marine environment in the south of Portugal by microsatellite-primed PCR.

The occurrence and diversity of yeasts in seawater was investigated in a study site located 20 Km off Faro, Portugal, above the Alvares Cabral Trench. A total of 43 water samples from different layers (above the permanent thermocline, under the thermocline and near the bottom) and directly from the surface, originated 234 isolates. All the isolates were identified using a molecular approach that included, in a first stage, MSP-PCR fingerprinting. A total of 31 MSP-PCR classes were formed, 8 for the pigmented yeasts and 23 for the non-pigmented yeasts. The pink coloured isolates were identified by direct comparison of the new fingerprints with those obtained for representative strains of the various species. For identification of the non-pigmented yeasts, a representative isolate of each MSP-PCR class was selected for sequence analysis and compared with reference sequences. The five most abundant yeast species were Sakaguchia dacryoidea, Pseudozyma aphidis, Rhodosporidium babjevae, R. diobovatum and Debaryomyces hansenii. The distribution of isolates and species in the major taxonomic groups indicated that the number of basidiomycetous yeasts and their diversity are prevalent in relation to their ascomycetous counterpart. Diversity indices were determined and superficial water and water near the bottom had the highest diversity. The sampling effort effectiveness was estimated, and found to correspond to approximately 60% of the species present. MSP-PCR identification proved suitable for pigmented basidiomycetous yeasts and, when used in conjunction with sequence analysis, was effective for the characterization of non-pigmented populations. Our results indicate that the MSP-PCR fingerprinting method is appropriate for the characterization of large groups of isolates due to its simplicity and good reproducibility.