Journal Article > Meta-AnalysisFull Text
PLOS Med. 2012 August 28; Volume 9 (Issue 8); DOI:10.1371/journal.pmed.1001300
Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bayona J, et al.
PLOS Med. 2012 August 28; Volume 9 (Issue 8); DOI:10.1371/journal.pmed.1001300
Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.
Journal Article > ResearchFull Text
Eur Respir J. 2016 September 1; Volume 48 (Issue 4); DOI:10.1183/13993003.00462-2016
Mitnick CD, White RA, Lu C, Rodriguez CA, Bayona J, et al.
Eur Respir J. 2016 September 1; Volume 48 (Issue 4); DOI:10.1183/13993003.00462-2016
Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
Journal Article > Meta-AnalysisFull Text
PLOS Med. 2018 July 11; Volume 15 (Issue 7); e1002591.; DOI:10.1371/journal.pmed.1002591
Harausz EP, Garcia-Prats AJ, Law S, Schaaf HS, Kredo T, et al.
PLOS Med. 2018 July 11; Volume 15 (Issue 7); e1002591.; DOI:10.1371/journal.pmed.1002591
Journal Article > ReviewFull Text
Lancet Infect Dis. 2015 June 1; Volume 15 (Issue 6); 711-720.; DOI:10.1016/S1473-3099(15)00007-9
Nachman S, Ahmed AO, Amanullah F, Becerra M, Botgros R, et al.
Lancet Infect Dis. 2015 June 1; Volume 15 (Issue 6); 711-720.; DOI:10.1016/S1473-3099(15)00007-9
Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.