Browsing by Author "Cooke, Graham"

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    Impact of a novel molecular TB diagnostic system in patients at high risk of TB mortality in rural South Africa (Uchwepheshe): study protocol for a cluster randomised trial
    (BioMed Central Ltd, 2013) Lessells, Richard; Cooke, Graham; McGrath, Nuala; Nicol, Mark; Newell, Marie-Louise; Godfrey-Faussett, Peter
    BACKGROUND: Tuberculosis control in sub-Saharan Africa has long been hampered by poor diagnostics and weak health systems. New molecular diagnostics, such as the Xpert(R) MTB/RIF assay, have the potential to improve patient outcomes. We present a cluster randomised trial designed to evaluate whether the positioning of this diagnostic system within the health system has an impact on important patient-level outcomes.METHODS/DESIGN:This pragmatic cluster randomised clinical trial compared two positioning strategies for the Xpert MTB/RIF system: centralised laboratory versus primary health care clinic. The cluster (unit of randomisation) is a 2-week time block at the trial clinic. Adult pulmonary tuberculosis suspects with confirmed human immunodeficiency virus infection and/or at high risk of multidrug-resistant tuberculosis are enrolled from the primary health care clinic. The primary outcome measure is the proportion of culture-confirmed pulmonary tuberculosis cases initiated on appropriate treatment within 30 days of initial clinic visit. Univariate logistic regression will be performed as the primary analysis using generalised estimating equations with a binomial distribution function and a logit link. CONCLUSION: Diagnostic research tends to focus only on performance of diagnostic tests rather than on patient-important outcomes. This trial has been designed to improve the quality of evidence around diagnostic strategies and to inform the scale-up of new tuberculosis diagnostics within public health systems in high-burden settings.TRIAL REGISTRATION:Current Controlled Trials ISRCTN18642314; South African National Clinical Trials Registry DOH-27-0711-3568.
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    Treatment outcomes of treatment-naïve Hepatitis C patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts
    (Public Library of Science, 2013) Davies, Anna; Singh, Kasha P; Shubber, Zara; duCros, Philipp; Mills, Edward J; Cooke, Graham; Ford, Nathan
    Introduction Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor. METHODS: We conducted a systematic review and meta-analysis to assess HCV treatment outcomes in observational cohorts. Two databases (Medline and EMBASE) were searched using a compound search strategy for cohort studies reporting HCV treatment outcomes (as determined by a sustained virological response, SVR) in HIV-positive patients initiating HCV treatment for the first time. RESULTS: 40 studies were included for review, providing outcomes on 5339 patients from 17 countries. The pooled proportion of patients achieving SVR was 38%. Significantly poorer outcomes were observed for patients infected with HCV genotypes 1 or 4 (pooled SVR 24.5%), compared to genotypes 2 or 3 (pooled SVR 59.8%). The pooled proportion of patients who discontinued treatment due to drug toxicities (reported by 33 studies) was low, at 4.3% (3.3-5.3%). Defaulting from treatment, reported by 33 studies, was also low (5.1%, 3.5-6.6%), as was on-treatment mortality (35 studies, 0.1% (0-0.2%)). CONCLUSIONS: These results, reported under programmatic conditions, are comparable to those reported in randomised clinical trials, and show that although HCV treatment outcomes are generally poor in HIV co-infected patients, those infected with HCV genotypes 2 or 3 have outcomes comparable to HIV-negative patients.