NEJM Audio Summary - June 7, 2012

Excerpted Script

0:47| "Delamanid for Multidrug-Resistant Pulmonary Tuberculosis", by Maria Tarcela Gler, from the Makati Medical Center, Manila in the Philippines. In this study patients with sputum culture–positive multidrug-resistant pulmonary tuberculosis received 2 months of treatment with delamanid, a novel antituberculosis medication, at a higher or lower dose, or placebo in combination with a background drug regimen developed according to World Health Organization guidelines. Among patients who received 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. 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%). The findings were similar with assessment of sputum-culture conversion in solid medium. Delamanid at either dose did not have dose-limiting toxicity; however, patients who received delamanid plus the background drug regimen had more episodes of QT-interval prolongation on scheduled ECG. 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.
2:32| "National Survey of Drug-Resistant Tuberculosis in China", by Yanlin Zhao(赵雁林), from the Chinese Center for Disease Control and Prevention, Beijing. In 2007, the authors carried out a national survey of drug-resistant tuberculosis in China. Among 3037 patients with new cases of tuberculosis and 892 with previously treated cases, 5.7% and 25.6%, respectively, had multidrug-resistant (MDR) tuberculosis. Approximately 8% of the patients with MDR tuberculosis had extensively drug-resistant (XDR) tuberculosis. In 2007, there were 110,000 incident cases of MDR tuberculosis and 8200 incident cases of XDR tuberculosis. Most cases of MDR and XDR tuberculosis resulted from primary transmission. Patients with multiple previous treatments who had received their last treatment in a tuberculosis hospital had the highest risk of MDR tuberculosis (adjusted odds ratio, 13.3). Among 226 previously treated patients with MDR tuberculosis, 43.8% had not completed their last treatment; most had been treated in the hospital system. Among those who had completed treatment, tuberculosis developed again in most of the patients after their treatment in the public health system. China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases.
4:28| Richard Chaisson, from Johns Hopkins University School of Medicine, Baltimore, writes in the editorial that MDR and XDR tuberculosis are now widespread throughout the world, with the increase driven largely by transmission. Efforts to control drug-resistant tuberculosis can no longer focus solely on high-risk patients but must be incorporated into basic tuberculosis-control programs. Creating the capacity to make an accurate diagnosis of MDR tuberculosis and to treat the patients with this disease appropriately is a monumental task but one that cannot be avoided if tuberculosis is to be contained.

呼吸器内科医さんの「ランダム化プラセボ対照試験により多剤耐性結核におけるDelamanidの有効性が証明」を参照。その他、WHOの結核治療ガイドライン、中国CDCの結核のページなど。

NEJM Audio Summary - May 31, 2012

Excerpted Script

0:46| "Drotrecogin Alfa (Activated) in Adults with Septic Shock" by V. Marco Ranieri, from Università di Torino, Turin, Italy. 0:46| The efficacy of drotrecogin alpha (activated) (DrotAA) for sepsis has been controversial. This study tested the hypothesis that DrotAA, as compared with placebo, would reduce mortality in patients with septic shock. At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died. At 90 days, 34.1% in the DrotAA group and 32.7% in the placebo group had died. Among patients with severe protein C deficiency at baseline, 28.7% in the DrotAA group had died at 28 days, as compared with 30.8% in the placebo group. Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group. DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock.
2:17| Richard Wenzel, from the Virginia Commonwealth University, Richmond, writes in the editorial that this large and well-conducted study should end any further pursuit of a niche for DrotAA in the treatment of sepsis. The investigators' findings provide a sad chapter in the noble quest for a truly effective adjunct for the treatment of septic shock. This setback should inspire a redoubling of efforts to seek new approaches to treatment that are based on a more crystalline view of the biology of sepsis.

日本語では、呼吸器内科医「敗血症性ショックにおけるザイグリスdrotrecogin alfa (DrotAA)は死亡率改善もたらさず」とか、ID CONFERENCEの「さようならプロテインC」とかも