An All-Oral 6-Month Regimen for Multidrug-Resistant Tuberculosis: A Multicenter, Randomized Controlled Clinical Trial (the NExT Study).

Rationale: Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Objectives: To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e., without resistance to fluoroquinolones or aminoglycosides). Methods: Participants were randomly assigned (1:1 ratio) to a ∼6-month all-oral regimen that included levofloxacin, bedaquiline, and linezolid, or the standard-of-care (SOC) ⩾9-month World Health Organization (WHO)-approved injectable-based regimen. The primary endpoint was a favorable WHO-defined treatment outcome (which mandates that prespecified drug substitution is counted as an unfavorable outcome) 24 months after treatment initiation. The trial was stopped prematurely when bedaquiline-based therapy became the standard of care in South Africa. Measurements and Main Results: In total, 93 of 111 randomized participants (44 in the comparator arm and 49 in the interventional arm) were included in the modified intention-to-treat analysis; 51 (55%) were HIV coinfected (median CD4 count, 158 cells/ml). Participants in the intervention arm were 2.2 times more likely to experience a favorable 24-month outcome than participants in the SOC arm (51% [25 of 49] vs. 22.7% [10 of 44]; risk ratio, 2.2 [1.2-4.1]; P = 0.006). Toxicity-related drug substitution occurred more frequently in the SOC arm (65.9% [29 of 44] vs. 34.7% [17 of 49]; P = 0.001)], 82.8% (24 of 29) owing to kanamycin (mainly hearing loss; replaced by bedaquiline) in the SOC arm, and 64.7% (11 of 17) owing to linezolid (mainly anemia) in the interventional arm. Adverse event-related treatment discontinuation in the safety population was more common in the SOC arm (56.4% [31 of 55] vs. 32.1% [17 of 56]; P = 0.007). However, grade 3 adverse events were more common in the interventional arm (55.4% [31 of 56] vs. 32.7 [18 of 55]; P = 0.022). Culture conversion was significantly better in the intervention arm (hazard ratio, 2.6 [1.4-4.9]; P = 0.003) after censoring those with bedaquiline replacement in the SOC arm (and this pattern remained consistent after censoring for drug replacement in both arms; P = 0.01). Conclusions: Compared with traditional injectable-containing regimens, an all-oral 6-month levofloxacin, bedaquiline, and linezolid-containing MDR/RR-TB regimen was associated with a significantly improved 24-month WHO-defined treatment outcome (predominantly owing to toxicity-related drug substitution). However, drug toxicity occurred frequently in both arms. These findings inform strategies to develop future regimens for MDR/RR-TB.Clinical trial registered with www.clinicaltrials.gov (NCT02454205).

Basal cortisol levels and correlates of hypoadrenalism in patients with human immunodeficiency virus infection.

OBJECTIVE: To determine the frequency of occurrence of hypoadrenalism in patients with human immunodeficiency virus (HIV) infection and document the clinical correlates of hypoadrenalism for this group of patients. SUBJECTS AND METHODS: A descriptive study was carried out on 66 hospitalized HIV patients in a semi-urban setting of South Africa. Hypoadrenalism was diagnosed based on a basal cortisol level of less than 400 nmol/l with or without overt signs and symptoms. Clinical and biochemical parameters of hypoadrenalism were compared between subjects with suboptimal and normal cortisol levels. Statistical analysis included Student's t test, χ(2) and Pearson's correlation coefficient tests. RESULTS: The prevalence of hypoadrenalism was 27% with a high occurrence of contributory factors (cytomegalovirus infection in 100% and tuberculosis in 68.2% of the study subjects). Typical features of hypoadrenalism included: hyponatremia, 19.6%; hyperkalemia, 6.1%; mucosal hyperpigmentation, 12%, and loss of axillary hair, 15%. Comparison of clinical and biochemical parameters of hypoadrenalism did not show a correlation between CD4 count and cortisol levels (r = 0.1 and p = 0.3). CONCLUSION: The prevalence of hypoadrenalism in our patients with HIV infection was high and the clinical features were comparable in subjects with normal and subnormal cortisol levels.

An audit of spirometry at the University of Ilorin Teaching Hospital, Ilorin, Nigeria (2002-2009).

BACKGROUND: Spirometry is a noninvasive and cost-effective physiologic test that greatly complements other investigative procedures in evaluation of respiratory conditions. This study was aimed at auditing the spirometry performed at the University of Ilorin Teaching Hospital (UITH) Ilorin, Nigeria, and highlighting some of the challenges associated with the procedure. METHODS: We reviewed and analyzed the record of spirometry performed at the cardiopulmonary unit of the hospital from June 2002 to December 2009. RESULTS: A total of 119 patients had spirometry tests from 2002 to 2009 and their age ranged from 15 to 85 years with a mean of 47.6 +/- 14.8 years. There were 69 (58%) males and the male:female ratio was 1.4:1. More than half (65%) of the tests were in patients <50 years old. The rate of spirometry performed annually increased from 12 (10.1%) in 2002 to 31 (26.1%) in year 2009. Evaluation of bronchial asthma was the most common indication for spirometry (43 patients; 36.1%). Majority of the requests (84 patients; 70.6%) were from adult respiratory physicians. The identified challenges were lack of awareness of the range of diseases that could be investigated by spirometry, lack of skills in interpreting the results, lack of time and delays in replacing exhausted consumables and faulty components of spirometer. CONCLUSION: Gradually, the trend of spirometry request is increasing in UITH; however, a wider acceptability could be achieved for this test by raising the level of awareness and improving the skills of all doctors on the usefulness and interpretation of spirometry.