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BACKGROUND Atazanavir (ATV), the first once-daily protease inhibitor approved for the treatment of HIV-1 infection, is recommended for use in antiretroviral (ARV) treatment-naive and -experienced patients. Study AI424-089 was a prospective, randomized, open-label, 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients. METHODS Adults with HIV RNA levels > or =2000 copies/mL were randomized (1:1) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg (ATV300/RTV) or ATV at a dose of 400 mg (ATV400); both regimens included lamivudine and an investigational extended-release formulation of stavudine. The primary endpoint for this noninferiority study was the proportion of patients (response rate) with an HIV RNA load

Objective To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA). Methods The study was a randomized, double-blind, placebo-controlled, proof-of-concept trial. Intraarticular sprifermin was evaluated at doses of 10 μg, 30 μg, and 100 μg. The primary efficacy end point was change in central medial femorotibial compartment cartilage thickness at 6 months and 12 months as determined using quantitative magnetic resonance imaging (qMRI). The primary safety end points were nature, incidence, and severity of local and systemic treatment-emergent adverse events (AEs) and acute inflammatory reactions, as well as results of laboratory assessments. Secondary end points included changes in total and compartment femorotibial cartilage thickness and volume as assessed by qMRI, changes in joint space width (JSW) seen on radiographs, and pain scores on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results One hundred ninety-two patients were randomized and evaluated for safety, 180 completed the trial, and 168 were evaluated for the primary efficacy end point. We found no statistically significant dose response in change in central medial femorotibial compartment cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume and in JSW narrowing in the lateral femorotibial compartment. All groups had improved WOMAC pain scores, with statistically significantly less improvement at 12 months in patients receiving the 100-μg dose of sprifermin as compared with those receiving placebo. There was no significant difference in serious AEs, treatment-emergent AEs, or acute inflammatory reactions between sprifermin and placebo groups. Conclusion No statistically significant relationship between treatment group and reduction in central medial femorotibial compartment cartilage thickness was observed; however, prespecified structural secondary end points showed statistically significant dose-dependent reductions after sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns.

Recent studies have demonstrated subadditivity of human probability judgment: The judged probabilities for an event partition sum to more than 1. We report conditions under which people's probability judgments are superadditive instead: The component judgments for a partition sum to less than 1. Both directions of deviation from additivity are interpreted in a common framework, in which probability judgments are often mediated by judgments of evidence. The 2 kinds of nonadditivity result from differences in recruitment of supporting evidence together with reduced processing of nonfocal propositions. Suppose that an event, E, has been partitioned into two or more mutually exclusive subevents and that probability assessments are made for E and for each of these subevents. The assessments are said to be additive if the probability assigned to E is approximately equal to the sum of the probabilities of the subevents. They are subadditive if the probability assigned to E falls short of the subevent sum, and they are superadditive if the assignment to E exceeds the subevent sum. Superadditivity is a feature of Shafer's theory of evidence (Shafer, 1976) and has been found previously for evidence judgments (Briggs & Krantz, 1992) but not for probability judgments. Subadditive probability judgment has been widely reported in the literature and helped to motivate Support Theory (Rottenstreich & Tversky, 1997; Tversky & Koehler, 1994). The purpose of the present article is to document the existence of superadditive probability judgment in special conditions. Our findings suggest modifications of Support Theory. Tversky and colleagues (Rottenstreich & Tversky, 1997; Tversky & Koehler, 1994) pointed out that subadditivity is common in both nonexpert and expert probability judgments. In a dramatic example (Redelmeier, Koehler, Liberman, & Tversky, 1995), physicians were asked to provide probabilities for the following events, with respect to a particular hospitalized patient whose case had been summarized to them