METHODS

In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative

for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months.

RESULTS

Among patients who received XL184 a background drug regimen

plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly VE-822 research buy distributed across groups. Although no clinical events due to QT prolongation on electrocardiography Dipeptidase were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid.

CONCLUSIONS

Delamanid was associated with

an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.)”
“Memory is prone to distortions that can have serious consequences in everyday life. Here we integrate emerging evidence that several types of memory distortions imagination inflation, gist-based and associative memory errors, and post-event misinformation – reflect adaptive cognitive processes that contribute to the efficient functioning of memory, but produce distortions as a consequence of doing so. We consider recent cognitive and neuroimaging studies that link these distortions with adaptive processes, including simulation of future events, semantic and contextual encoding, creativity, and memory updating. We also discuss new evidence concerning factors that can influence the occurrence of memory distortions, such as sleep and retrieval conditions, as well as conceptual issues related to the development of an adaptive perspective.