Metformin can be repurposed as host-directed therapy for tuberculosis.

The aim of this study is to investigate the effects of inhaled furosemide on the sensation of dyspnea produced during exercise in patients with stable chronic obstructive pulmonary disease (COPD). In a double-blind, randomized, crossover study we compared the effect of inhaled furosemide on dyspneic sensation during exercise testing with that of placebo. Spirometry and incremental and constant-load exercise testing were performed after inhalation of placebo or furosemide on 2 separate days in 19 patients with moderate or severe COPD. Subjects were asked to rate their sensation of respiratory discomfort using a 100-mm visual analog scale. There was significant improvement in mean FEV1 and FVC after inhalation of furosemide (p = 0.038 and 0.005, respectively) but not after placebo. At standardized exercise time during constant-load exercise testing but not during incremental exercise, the mean dyspneic visual analog scale score was lower after inhalation of furosemide compared with placebo (33.7 +/- 25.2 vs. 42.4 +/- 24.0 mm, respectively, p = 0.014). We conclude that inhalation of furosemide alleviates the sensation of dyspnea induced by constant-load exercise testing in patients with COPD and that there is significant bronchodilation after inhalation of furosemide compared with placebo in these patients.

Given the high prevalence of LTBI amongst foreign-born residents from regional countries, similar studies should be conducted amongst migrants in Singapore to improve national guidelines on screening and preventive treatment against LTBI.

Background and aimsIsoniazid (INH) is part of the first-line-therapy for tuberculosis (TB) but can cause drug-induced liver injury (DILI). Several candidate single nucleotide polymorphisms (SNPs) have been previously identified but the clinical utility of these SNPs in the prediction of INH-DILI remains uncertain. The aim of this study was to assess the association between selected candidate SNPs and the risk of INH-DILI and to assess the clinical validity of associated variants in a Singaporean population.MethodsThis was a case-control study where 24 INH-DILI cases and 79 controls were recruited from the TB control unit in a tertiary hospital. Logistic regression was used to test for the association between candidate SNPs and INH-DILI. NAT2 acetylator status was inferred from genotypes and tested for association with INH-DILI. Finally, clinical validity measures were estimated for significant variants.ResultsTwo SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30–44.70), 0.10 (0.03–0.33) and 9.98 (3.32–33.80), respectively). Based on an INH-DILI prevalence of 10%, the sensitivity, specificity, positive and negative predictive values of NAT2 SA were 75%, 78%, 28% and 97%, respectively. The population attributable fraction (PAF) and number needed to test (NNT) for NAT2 SA were estimated to be 0.67 and 4.08, respectively. A model with clinical and NAT2 acetylator status provided significantly better prediction for INH-DILI than a clinical model alone (area under receiver operating characteristic curve = 0.863 vs. 0.766, respectively, p = 0.027).ConclusionsWe show the association between NAT2 SA and INH-DILI in a Singaporean population and demonstrated its clinical utility in the prediction of INH-DILI.

Background: Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore. Methods: Retrospective time series analysis was used to study TB notification data collected from 1995 to 2011 from the Singapore Tuberculosis Elimination Program (STEP) registry. A predictive model was developed based on the data collected from 1995 to 2010 and validated using the data collected in 2011.Results: There was a significant difference in demographic characteristics between resident and non-resident TB cases. TB risk was higher in non-residents than in residents throughout the period. We found no significant association between demographic and macro-economic factors and annual incidence of TB with or without adjusting for the population-at-risk. Despite growing non-resident population, there was a significant decrease in the non-resident TB risk (p < 0.0001). However, there was no evidence of trend in the resident TB risk over this time period, though differences between different demographic groups were apparent with ethnic minorities experiencing higher incidence rates. Conclusion: The study found that despite an increasing size of non-resident population, TB risk among non-residents was decreasing at a rate of about 3% per year. There was an apparent seasonality in the TB reporting.