BACKGROUNDCohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODSWe conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTSOf 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group -a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], −7.5 to 9.5) (P = 0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, −10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONSIn persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety.

Background: Although death rates are often used to monitor the quality of health care, in industrialized countries maternal deaths have become rare. Severe maternal morbidity has therefore been proposed as a supplementary indicator for surveillance of the quality of maternity care. Our purpose in this study was to describe severe maternal morbidity in Canada over a 10-year period, among women with or without major pre-existing conditions. Methods: We carried out a retrospective cohort study of severe maternal morbidity involving 2 548 824 women who gave birth in Canadian hospitals between 1991 and 2000. Thirteen conditions that may threaten the life of the mother (e.g., eclampsia) and 11 major pre-existing chronic conditions (e.g., diabetes) that could be identified from diagnostic codes were noted. Results: The overall rate of severe maternal morbidity was 4.38 per 1000 deliveries. The fatality rate among these women was 158 times that of the entire sample. Rates of venous thromboembolism, uterine rupture, adult respiratory distress syndrome, pulmonary edema, myocardial infarction, severe postpartum hemorrhage requiring hysterectomy, and assisted ventilation increased substantially from 1991 to 2000. The presence of major pre-existing conditions increased the risk of severe maternal morbidity to 6-fold. Interpretation: Severe maternal morbidity occurs in about 1 of 250 deliveries in Canada, with marked recent increases in certain morbid conditions such as pulmonary edema, myocardial infarction, hemorrhage requiring hysterectomy, and the use of assisted ventilation.Cite this article as CMAJ 2005;173(7).