Use of predicted vital status to improve survival analysis of multidrug-resistant tuberculosis cohorts

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) cohorts often lack long-term survival data, and are summarized instead by initial treatment outcomes. When using Cox proportional hazards models to analyze these cohorts, this leads to censoring subjects at the time of the initial treatment outcome, instead of them providing full survival data. This may violate the non-informative censoring assumption of the model and may produce biased effect estimates. To address this problem, we develop a tool to predict vital status at the end of a cohort period using the initial treatment outcome and assess its ability to reduce bias in treatment effect estimates. Methods We derive and apply a logistic regression model to predict vital status at the end of the cohort period and modify the unobserved survival outcomes to better match the predicted survival experience of study subjects. We compare hazard ratio estimates for effect of an aggressive treatment regimen from Cox proportional hazards models using time to initial treatment outcome, predicted vital status, and true vital status at the end of the cohort period. Results Models fit from initial treatment outcomes underestimate treatment effects by up to 22.1%, while using predicted vital status reduced this bias by 5.4%. Models utilizing the predicted vital status produce effect estimates consistently stronger and closer to the true treatment effect than estimates produced by models using the initial treatment outcome. Conclusions Although studies often use initial treatment outcomes to estimate treatment effects, this may violate the non-informative censoring assumption of the Cox proportional hazards model and result in biased treatment effect estimates. Using predicted vital status at the end of the cohort period may reduce this bias in the analyses of MDR-TB treatment cohorts, yielding more accurate, and likely larger, treatment effect estimates. Further, these larger effect sizes can have downstream impacts on future study design by increasing power and reducing sample size needs

Improvement of strength and performance properties of copper wire during severe plastic deformation and drawing process

The paper studies the evolution of microstructure and mechanical properties of copper wire during a new combined straining process. The main point of the technological process is to strain the wire in a rotating equal-channel step die and subsequent drawing. The die rotates around the wire axis and thereby creates tension due to equal-channel angular pulling and twisting in the die. Transmission electron microscopy and EBSD analysis, as well as tensile testing and microhardness determination investigated the strained copper wire. Ultra-fine grain gradient microstructure with a high component of high-angle grain boundaries was obtained as a result of straining. The tensile strength of the strained copper wire compared to the unstrained one increases more than twice from 302 to 635 MPa, and the yield strength increases from 196 to 406 MPa. The use of such hardened copper wire in construction will reduce the weight of the structure due to the reduction of diameter

Development of Extensively Drug-resistant Tuberculosis during Multidrug-resistant Tuberculosis Treatment

Rationale: Extensively drug-resistant (XDR) tuberculosis (TB) may arise in individuals on treatment for multidrug-resistant (MDR) TB. Preventing this amplification of resistance will likely improve clinical outcomes and delay the secondary spread of XDR-TB

Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method

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

Multidrug-Resistant Tuberculosis Treatment Failure Detection Depends on Monitoring Interval and Microbiological Method Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method behalf of the Col

Citation Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method. ABSTRACT 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. @ERSpublications Monthly culture monitoring is crucial to earlier detection of treatment failure in MDR-TB patient

Sputum culture conversion as a prognostic marker for end- of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies

Summary Background Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis