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BACKGROUNDCryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis. METHODSIn this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole. RESULTSThe trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P = 0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P = 0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P = 0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P = 0.003), renal events (22 vs. 7, P = 0.004), and cardiac events (8 vs. 0, P = 0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites. CONCLUSIONSDexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo.

BackgroundThe irrational overuse of antibiotics should be minimized as it drives the development of antibiotic resistance, but changing these practices is challenging. A better understanding is needed of practices and economic incentives for antibiotic dispensing in order to design effective interventions to reduce inappropriate antibiotic use. Here we report on both quantitative and qualitative aspects of antibiotic sales in private pharmacies in northern Vietnam.MethodA cross-sectional study was conducted in which all drug sales were observed and recorded for three consecutive days at thirty private pharmacies, 15 urban and 15 rural, in the Hanoi region in 2010. The proportion of antibiotics to total drug sales was assessed and the revenue was calculated for rural and urban settings. Pharmacists and drug sellers were interviewed by a semi-structured questionnaire and in-depth interviews to understand the incentive structure of antibiotic dispensing.ResultsIn total 2953 drug sale transactions (2083 urban and 870 rural) were observed. Antibiotics contributed 24% and 18% to the total revenue of pharmacies in urban and rural, respectively. Most antibiotics were sold without a prescription: 88% in urban and 91% in rural pharmacies. The most frequent reported reason for buying antibiotics was cough in the urban setting (32%) and fever in the rural area (22%). Consumers commonly requested antibiotics without having a prescription: 50% in urban and 28% in rural area. The qualitative data revealed that drug sellers and customer’s knowledge of antibiotics and antibiotic resistance were low, particularly in rural area.ConclusionOver the counter sales of antibiotic without a prescription remains a major problem in Vietnam. Suggested areas of improvement are enforcement of regulations and pricing policies and educational programs to increase the knowledge of drug sellers as well as to increase community awareness to reduce demand-side pressure for drug sellers to dispense antibiotics inappropriately.

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BackgroundCommunity-acquired pneumonia (CAP) is a major cause of adult mortality in Asia. Appropriate empirical treatment depends on knowledge of the pathogens commonly responsible. However, assessing the aetiological significance of identified organisms is often difficult, particularly with sputum isolates that might represent contamination with oropharyngeal flora.MethodsA systematic review of all adult CAP aetiology studies from Asia, excluding the Middle East, published in English between 1 January 1990 and 1 March 2012 was conducted. Forty-eight studies reporting on 10 423 patients were included, representing data from China, India, Indonesia, Japan, Malaysia, The Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam. Data from large parts of Asia were unavailable and there was substantial heterogeneity in methodology.ResultsAs in western studies, Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella spp. and Haemophilus influenzae were all significant pathogens. However, compared with western studies, S. pneumoniae was of less relative importance. Gram-negative bacilli and Mycobacterium tuberculosis were more important, and in northeast Thailand Burkholderia pseudomallei was a major pathogen.ConclusionThese data have major implications for diagnostic strategies and empirical treatment. Narrow-spectrum antibiotics targeting S. pneumoniae may be inappropriate in many Asian settings, and agents active against TB may lead to partial response and delayed TB diagnosis.