Bayesian separate and joint modeling for controlled clinical trial data using BUGS. In: Applied Bayesian Statistical Analysis

Many clinical trials and other medical studies generate both longitudinal (repeated measurements) and survival (time to event) data. The existing methods are inappropriate when the longitudinal variable is correlated. Earlier articles proposed a joint model for longitudinal and survival data, obtaining maximum likelihood estimates via the EM algorithm based on Bayesian approach implementing via Markov Chain Monte Carlo (MCMC) methods. The longitudinal and survival responses are assumed independent given a linking latent bivariate Gaussian process and available covariates. We use the approach to jointly model the longitudinal and survival data from a clinical trial comparing treatments and also its interactions. The joint Bayesian approach appears to offer significantly improved and enhanced estimation of survival times and other parameters of interest like gender, age and weight. In spite of the complexity the model, we find it to be relatively straight forward to implement and understand using the WinBUGS software

Long term follow up of HIV-infected patients with tuberculosis treated with 6-month intermittent short course chemotherapy

Background . Tuberculosis occurs in 60%–70% of HIVpositive persons in India. The outcome of HIV-positive patients treated with 6-month intermittent short course antituberculosis regimens in India is not well described. Methods . This was a prospective observational feasibility study of 71 patients with HIV and tuberculosis who were treated with category I regimen of the Revised National Tuberculosis Control Programme (ethambutol, isoniazid, rifampicin and pyrazinamide thrice weekly for the initial 2 months followed by rifampicin and isoniazid thrice weekly for the next 4 months). Sputum was examined by smear and culture for Mycobacterium tuberculosis every month up to 24 months. Chest X-ray, CD4 cell count and viral load were done prior to and at the end of treatment. None of the patients received antiretroviral therapy. Results . We present here the treatment response of patients with sputum culture-positive pulmonary tuberculosis to category I regimen. By efficacy analysis, among 43 patients treated with category I regimen, sputum smear conversion was observed in 79% and culture conversion in 82% at the second month. A favourable response was seen in 72% of patients. The mean (SD) CD4% fell from 12.6 (5.9) to 8.9 (4.9) (p<0.001) with no significant change in mean (SD) CD4 cell count (169 [126] to 174 [158]; ns) at the end of treatment. Viral load change from 1.8x105 at baseline to 1.3x105 at the end of treatment was not statistically significant. Thirty-one patients, who completed the full course of treatment, were declared cured and were followed up for 24 months. Twelve had recurrent tuberculosis (39%); 16 of 43 (37%) patients had died by the end of 24 months, twothirds due to causes other than tuberculosis. Conclusion . Though the early bacteriological response to intermittent short course antituberculosis regimen was satisfactory, the overall outcome was adversely affected by the high mortality (during and after completion of treatment) and recurrence rate among HIV-infected patients with tuberculosis. Immune status deteriorated in spite of antituberculosis treatment, highlighting the need for antiretroviral treatment in addition to antituberculosis treatment to improve the long term outcome. The results of this pilot study need to be confirmed by larger studies

Evaluation of Directly Observed Treatment providers in the revised national tuberculosis control programme

Background: Non-governmental personnel such as Anganwadi workers and community volunteers have been used as directly observed treatment (DOT) providers in the Revised National Tuberculosis Control Programme (RNTCP), but their effectiveness has not been documented. Aim: To assess the treatment outcome and problems encountered by patients managed by different DOT providers in the RNTCP. Material and Methods: Patients diagnosed with tuberculosis at 17 Primary Health Institutions (PHIs) in Tiruvallur District during a 3-year period received DOT from one of the four types of trained DOT providers (PHI staff, governmental outreach workers, Anganwadi workers, community volunteers), and their treatment outcomes were compared. Of the 1131 new smear-positive patients treated between May 1999 through June 2002, 199 (18%) received DOT from PHI staff, 238(21%) from outreach workers, 496 (44%) from Anganwadi workers, and 170 (15%) from community volunteers. Twenty-eight patients (2%) collected drugs for self-administration. Results: Treatment success rates among patients treated by different DOT providers, Anganwadi workers (80%), governmental outreach workers (81%), community volunteers (76%) and PHI staff (76%), were statistically similar. Patients who received drugs for self-administration were significantly more likely to fail to treatment or die than patients who were treated by a DOT provider (5/28 versus 84/1103; odds ratio=4.1; 95% confidence interval=1.2-12.6; p=0.02). Conclusion: In addition to governmental staff, Anganwadi workers and community volunteers can be effectively utilized as DOT providers