Browsing by Subject "Disease Progression"

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    Open Access
    Erratum to: Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials
    (2016) Phillips, Patrick P J; Mendel, Carl M; Burger, Divan A; Crook, Angela M; Nunn, Andrew J; Dawson, Rodney; Diacon, Andreas H; Gillespie, Stephen H
    BackgroundDespite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials.MethodsUsing data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome.ResultsTime to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP.ConclusionsCulture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.
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    Open Access
    The natural history of latent rheumatic heart disease in a 5 year follow-up study: a prospective observational study
    (2016) ZYhlke, Liesl; Engel, Mark E; Lemmer, Carolina E; van de Wall, Marnie; Nkepu, Simpiwe; Meiring, Alet; Bestawros, Michael; Mayosi, Bongani M
    BackgroundLatent rheumatic heart disease (RHD) occurs in asymptomatic individuals with echocardiographic evidence of RHD and no history of acute rheumatic fever. The natural history of latent RHD is unclear but has important clinical and economic implications about whether these children should receive penicillin prophylaxis or not. We performed a 5-year prospective study of this question.MethodsIn August 2013 through September 2014, we conducted a follow-up study of latent RHD among school pupils using the World Heart Federation (WHF) echocardiographic criteria. Contingency tables were used to assess progression, persistence or regression of latent RHD.ResultsForty two borderline and 13 definite cases of RHD (n 55) were identified, 44 (80%; mean age 13.8 ± 4.0years; 29 (65.9%) female) of whom were available for echocardiographic examination at a median follow-up of 60.8months (interquartile range 51.3-63.5). Over the follow-up period, half the participants (n = 23; 52.3%) improved to normal or better WHF category (regressors), a third (n = 14, 31.8%) remained in the same category (persistors), while seven others (15.9%) progressed from borderline to definite RHD (progressors). In total, 21 subjects (47.7%) reverted to a normal status, nine (20.4%) either improved from definite to borderline or remained in the borderline category, and 14 (31.8%) either remained definite or progressed from borderline to a definite status. Two cases (20%) progressed to symptomatic disease.ConclusionsLatent RHD has a variable natural history that ranges from regression to normal in nearly half of cases, to persistence, progression or development of symptoms in the remainder of subjects.