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  1. Naing C, Reid SA, Aung K
    BMC Infect Dis, 2017 01 05;17(1):29.
    PMID: 28056834 DOI: 10.1186/s12879-016-2145-3
    BACKGROUND: Network meta-analysis consists of simultaneous analysis of both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common comparator. In this paper, we aimed to characterise the conceptual understanding and the rationale for the use of network meta-analysis in assessing drug efficacy.

    METHODS: We selected randomized controlled trials, assessing efficacy of antibiotics for the treatment of leptospirosis as a case study. A pairwise meta-analysis was conducted using a random effect model, assuming that different studies assessed different but related treatment effects. The analysis was then extended to a network meta-analysis, which consists of direct and indirect evidence in a network of antibiotics trials, using a suite of multivariate meta-analysis routines of STATA (mvmeta command). We also assessed an assumption of 'consistency' that estimates of treatment effects from direct and indirect evidence are in agreement.

    RESULTS: Seven randomised controlled trials were identified for this analysis. These RCTs assessed the efficacy of antibiotics such as penicillin, doxycycline and cephalosporin for the treatment of human leptospirosis. These studies made comparisons between antibiotics (i.e. an antibiotic versus alternative antibiotic) in the primary study and a placebo, except for cephalosporin. These studies were sufficient to allow the creation of a network for the network meta-analysis; a closed loop in which three comparator antibiotics were connected to each other through a polygon. The comparison of penicillin versus the placebo has the largest contribution to the entire network (31.8%). The assessment of rank probabilities indicated that penicillin presented the greatest likelihood of improving efficacy among the evaluated antibiotics for treating leptospirosis.

    CONCLUSIONS: Findings suggest that network meta-analysis, a meta-analysis comparing multiple treatments, is feasible and should be considered as better precision of effect estimates for decisions when several antibiotic options are available for the treatment of leptospirosis.

  2. Naing C, Racloz V, Whittaker MA, Aung K, Reid SA, Mak JW, et al.
    PLoS One, 2013;8(12):e78819.
    PMID: 24312446 DOI: 10.1371/journal.pone.0078819
    BACKGROUND: This study aimed to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHP) in treating uncomplicated Plasmodium vivax malaria in people living in endemic countries.

    METHODOLOGY AND PRINCIPAL FINDINGS: This is a meta-analysis of randomized controlled trials (RCT). We searched relevant studies in electronic databases up to May 2013. RCTs comparing efficacy of (DHP) with other artemisinin-based combination therapy (ACT), non-ACT or placebo were selected. The primary endpoint was efficacy expressed as PCR-corrected parasitological failure. Efficacy was pooled by hazard ratio (HR) and 95% CI, if studies reported time-to-event outcomes by the Kaplan-Meier method or data available for calculation of HR Nine RCTs with 14 datasets were included in the quantitative analysis. Overall, most of the studies were of high quality. Only a few studies compared with the same antimalarial drugs and reported the outcomes of the same follow-up duration, which created some difficulties in pooling of outcome data. We found the superiority of DHP over chloroquine (CQ) (at day > 42-63, HR:2.33, 95% CI:1.86-2.93, I (2): 0%) or artemether-lumefentrine (AL) (at day 42, HR:2.07, 95% CI:1.38-3.09, I (2): 39%). On the basis of GRADE criteria, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

    DISCUSSION/CONCLUSION: Findings document that DHP is more efficacious than CQ and AL in treating uncomplicated P. vivax malaria. The better safety profile of DHP and the once-daily dosage improves adherence, and its fixed co-formulation ensures that both drugs (dihydroartemisinin and piperaquine) are taken together. However, DHP is not active against the hypnozoite stage of P. vivax. DHP has the potential to become an alternative antimalarial drug for the treatment uncomplicated P. vivax malaria. This should be substantiated by future RCTs with other ACTs. Additional work is required to establish how best to combine this treatment with appropriate antirelapse therapy (primaquine or other drugs under development).

  3. Naing C, Reid SA, Aye SN, Htet NH, Ambu S
    PLoS One, 2019;14(5):e0217643.
    PMID: 31141558 DOI: 10.1371/journal.pone.0217643
    Leptospirosis is probably the most widespread zoonotic disease in the world especially in tropical countries. There has been an increase in individual studies, which assessed the frequency of leptospirosis in flood conditions. Some studies showed contact with floods was significantly associated with the occurrence of leptospirosis while other studies reported differently. The objective of this meta-analysis was to synthesize the evidence on the risk factors which are associated with human leptospirosis following flooding. We set up the inclusion criteria and searched for the original studies, addressing leptospirosis in human with related to flood in health-related electronic databases including PubMed, Embase, Ovid Medline, google scholar and Scopus sources. We used the terms 'leptospirosis', 'flood', 'risk factor' and terms from the categories were connected with "OR" within each category and by "AND" between categories. The initial search yielded 557 citations. After the title and abstract screening, 49 full-text papers were reviewed and a final of 18 observational studies met the pre-specified inclusion criteria. Overall, the pooled estimates of 14 studies showed that the contact with flooding was a significant factor for the occurrence of leptospirosis (pooled OR: 2.19, 95%CI: 1.48-3.24, I2:86%). On stratification, the strength of association was greater in the case-control studies (pooled OR: 4.01, 95%CI: 1.26-12.72, I2:82%) than other designs (pooled OR:1.77,95%CI:1.18-2.65, I2:87%). Three factors such as 'being male'(pooled OR:2.06, 95%CI:1.29-2.83), the exposure to livestock animals (pooled OR: 1.95, 95%CI:1.26-2.64), the lacerated wound (pooled OR:4.35, 95%CI:3.07-5.64) were the risk factors significantly associated with the incidence of leptospirosis following flooding in the absence of within-study heterogeneity (I2: 0%). We acknowledge study limitations such as publication bias and type 2 statistical errors. We recommended flood control and other environmental modifications that are expected to reduce the risk of leptospiral infection, and a multi-sectoral effort to this aspect would have long-term benefits.
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