A Bayesian response-adaptive trial in tuberculosis: The endTB trial

2016 ◽  
Vol 14 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Matteo Cellamare ◽  
Steffen Ventz ◽  
Elisabeth Baudin ◽  
Carole D. Mitnick ◽  
Lorenzo Trippa
Keyword(s):  
Statistical Power ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Adaptive Designs ◽  
Primary Study ◽  
Adaptive Randomization ◽  
Resistant Tuberculosis ◽  
Timely Fashion ◽  
Response Adaptive Designs ◽  
New Treatments

Purpose: To evaluate the use of Bayesian adaptive randomization for clinical trials of new treatments for multidrug-resistant tuberculosis. Methods: We built a response-adaptive randomization procedure, adapting on two preliminary outcomes for tuberculosis patients in a trial with five experimental regimens and a control arm. The primary study outcome is treatment success after 73 weeks from randomization; preliminary responses are culture conversion at 8 weeks and treatment success at 39 weeks. We compared the adaptive randomization design with balanced randomization using hypothetical scenarios. Results: When we compare the statistical power under adaptive randomization and non-adaptive designs, under several hypothetical scenarios we observe that adaptive randomization requires fewer patients than non-adaptive designs. Moreover, adaptive randomization consistently allocates more participants to effective arm(s). We also show that these advantages are limited to scenarios consistent with the assumptions used to develop the adaptive randomization algorithm. Conclusion: Given the objective of evaluating several new therapeutic regimens in a timely fashion, Bayesian response-adaptive designs are attractive for tuberculosis trials. This approach tends to increase allocation to the effective regimens.

scholarly journals Multidrug-Resistant Tuberculosis in Portugal: Patients’ Perception of the Challenges Faced during Treatment

2020 ◽  
pp. 1-9
Author(s):  
Marcela Bhering ◽  
Vicente  Sarubbi Junior ◽  
Afrânio Kritski ◽  
Fabiana Barbosa Assumpção Souza ◽  
Raquel Duarte
Keyword(s):  
Health Care ◽  
Public Awareness ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Diagnostic Techniques ◽  
Structured Interviews ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
New Treatments ◽  
Relationship Of

<b><i>Introduction:</i></b> The increase in drug-resistant tuberculosis (TB) threatens global progress in eliminating TB, and constitutes a major challenge for patients, health-care workers and health services. Treatment for multidrug-resistant TB (MDR-TB) can last almost 2 years, and is more expensive, more toxic, and less effective than treating TB caused by drug-sensitive bacilli. This study aims to analyze patients’ narratives about the challenges they face during MDR-TB treatment and identify the support factors that help patients being treated in the most populous district of Portugal. <b><i>Methods:</i></b> Semi-structured interviews were conducted with patients being treated for MDR-TB. The interviews were coded using thematic analysis. They were audio-recorded, transcribed, and transported into NVivo v12 for data management and coding. <b><i>Results:</i></b> Depression, social discrimination, and the side effects of drugs are the main challenges faced by patients with MDR-TB. A good relationship of the patients with the health team, emotional support, and supervised treatment stand out as the factors that generate better adherence and treatment success. <b><i>Conclusion:</i></b> In addition to modern diagnostic techniques and new treatments, MDR-TB can be fought by focusing on the care and needs of patients. We suggest that the Lisbon Tuberculosis Program adopts the following measures: build the health-care team’s capacity to identify symptoms of depression early, increase public awareness of the disease, expand the multidisciplinary team, and expand the options for individualized social support for patients.

scholarly journals Causal inference with multiple concurrent medications: A comparison of methods and an application in multidrug-resistant tuberculosis

2018 ◽  
Vol 28 (12) ◽  
pp. 3534-3549 ◽  
Author(s):  
Arman Alam Siddique ◽  
Mireille E Schnitzer ◽  
Asma Bahamyirou ◽  
Guanbo Wang ◽  
Timothy H Holtz ◽  
...  
Keyword(s):  
Propensity Score ◽  
Simulation Study ◽  
Antimicrobial Agents ◽  
Treatment Success ◽  
Likelihood Estimation ◽  
Multidrug Resistant ◽  
Patient Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Propensity Score Adjustment

This paper investigates different approaches for causal estimation under multiple concurrent medications. Our parameter of interest is the marginal mean counterfactual outcome under different combinations of medications. We explore parametric and non-parametric methods to estimate the generalized propensity score. We then apply three causal estimation approaches (inverse probability of treatment weighting, propensity score adjustment, and targeted maximum likelihood estimation) to estimate the causal parameter of interest. Focusing on the estimation of the expected outcome under the most prevalent regimens, we compare the results obtained using these methods in a simulation study with four potentially concurrent medications. We perform a second simulation study in which some combinations of medications may occur rarely or not occur at all in the dataset. Finally, we apply the methods explored to contrast the probability of patient treatment success for the most prevalent regimens of antimicrobial agents for patients with multidrug-resistant pulmonary tuberculosis.

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

2020 ◽  
Vol 24 (2) ◽  
pp. 233-239
Author(s):  
S. Park ◽  
K-W. Jo ◽  
T. S. Shim
Keyword(s):  
Success Rate ◽  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Treatment Success Rate ◽  
Aminosalicylic Acid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Effective Drugs

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

scholarly journals Epidemiology of drug-resistant tuberculosis in Chongqing, China: a retrospective observational study from 2010 to 2017

2019 ◽  
Author(s):  
Bo Wu ◽  
Ya Yu ◽  
Changting Du ◽  
Ying Liu ◽  
Daiyu Hu
Keyword(s):  
Observational Study ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Policy Support ◽  
Retrospective Observational Study ◽  
Drug Resistant ◽  
Notification Rate ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

AbstractChina is one of the top 30 countries with high multidrug-resistant tuberculosis (MDR-TB) and rifampin-resistant tuberculosis (RR-TB) burden. Chongqing is a southwest city of China with a large rural population. A retrospective observational study has been performed based on routine tuberculosis (TB) surveillance data in Chongqing from 2010 to 2017. The MDR/RR-TB notification rate increased from 0.03 cases per 100,000 population in 2010 to 2.09 cases per 100,000 population in 2017. The extensively drug-resistant TB (XDR-TB) notification rate has increased to 0.09 cases per 100,000 population in 2017. There was a decreasing detection gap between the number of notified MDR/RR-TB cases and the estimate number of MDR/RR-TB cases among all notified TB cases. The treatment success rate of MDR/RR-TB was 50.66% in this period. The rate of MDR/RR-TB in new TB cases was 6.23%, and this rate in previously treated TB cases was 32.7%. Despite the progress achieved, the prevalence of MDR/RR-TB was still high facing challenges including detection gaps, the regional disparity, and the high risk for MDR/RR-TB in elderly people and farmers. Sustained government financing and policy support should be guaranteed in the future.

scholarly journals Effectiveness of Shorter Treatment Regimen in Multidrug-Resistant Tuberculosis Patients in Pakistan: A Multicenter Retrospective Record Review

2021 ◽  
Author(s):  
Abudl Wahid ◽  
Nafees Ahmad ◽  
Abdul Ghafoor ◽  
Abdullah Latif ◽  
Fahad Saleem ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Success Rate ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Retrospective Record Review ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Record Review

In Pakistan, the treatment of multidrug-resistant tuberculosis (MDR-TB) with a shorter treatment regimen (STR), that is, 4–6 months of amikacin, moxifloxacin (Mfx), ethionamide, clofazimine (Cfz), pyrazinamide (Z), ethambutol (E), and high-dose isoniazid, followed by 5 months of Mfx, Cfz, Z, and E, was initiated in 2018. However, there is a lack of information about its effectiveness in Pakistani healthcare settings. Therefore, this retrospective record review of MDR-TB patients treated with STR at eight treatment sites in Pakistan aimed to fill this gap. Data were analyzed using SPSS 23. Multivariate binary logistic regression (MVBLR) analysis was conducted to find factors associated with death and treatment failure, and lost to follow-up (LTFU). A P-value < 0.05 was considered statistically significant. Of 912 MDR-TB patients enrolled at the study sites, only 313 (34.3%) eligible patients were treated with STR and included in the current study. Of them, a total of 250 (79.9%) were cured, 12 (3.8%) completed treated, 31 (9.9%) died, 16 (5.1%) were LTFU, and four (1.3%) were declared as treatment failures. The overall treatment success rate was 83.7%. In MVBLR analysis, patients’ age of 41–60 (odds ratio [OR] = 4.9, P-value = 0.020) and > 60 years (OR = 3.6, P-value = 0.035), being underweight (OR = 2.7, P-value = 0.042), and previous TB treatment (OR = 0.4, P-value = 0.042) had statistically significant association with death and treatment failure, whereas patients’ age of > 60 years (OR = 5.4, P-value = 0.040) and previous TB treatment (OR = 0.2, P-value = 0.008) had statistically significant association with LTFU. The treatment success rate of STR was encouraging. However, to further improve the treatment outcomes, special attention should be paid to the patients with identified risk factors.

scholarly journals Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Biomédica ◽  
2020 ◽  
Vol 40 (4) ◽  
pp. 616-625
Author(s):  
Ángela Tobón ◽  
Johana Rueda ◽  
Diego H. Cáceres ◽  
Gloria I. Mejía ◽  
Elsa M. Zapata ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Chronic Obstructive ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Poor Outcomes ◽  
Lost To Follow Up

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

scholarly journals High Rates of Treatment Success in Pulmonary Multidrug-Resistant Tuberculosis by Individually Tailored Treatment Regimens

2016 ◽  
Vol 13 (8) ◽  
pp. 1271-1278 ◽  
Author(s):  
Ioana D. Olaru ◽  
Christoph Lange ◽  
Alexander Indra ◽  
Liliya Meidlinger ◽  
Steliana Huhulescu ◽  
...  
Keyword(s):  
Treatment Success ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Tailored Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Effectiveness and Safety of Bedaquiline-containing Regimens for Treatment on Patients With Refractory Rifampicin/multidrug-resistant Tuberculosis: A Retrospective Cohort Study in East China

2021 ◽  
Author(s):  
Shao-Jun Zhang ◽  
Yan Yang ◽  
Wen-Wen Sun ◽  
Zhong-Shun Zhang ◽  
He-ping Xiao ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
East China ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Conversion Rates ◽  
Mdr Tb ◽  
Culture Conversion ◽  
Closing Rate

Abstract Objective: To compare the effectiveness and safety of bedaquiline-containing and bedaquiline-free regimens for treatment of patients with refractory rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).Methods: Patients with refractory RR/MDR-TB receiving bedaquiline-containing regimens (bedaquiline group, n=102) and bedaquiline-free regimens (non-bedaquiline group, n=100) were included in this retrospective historical control study across East China. The culture conversion, end-of-treatment outcomes, cavity closing rate, and adverse events (AEs) were compared between the two groups. Univariate and multivariate analyses were performed to identify independent predictors of treatment success and culture reversion.Results: The baseline characteristics of the patients were well balanced between the two groups. The culture conversion rates in the bedaquiline group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs. 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs. 65.0%) were all significantly higher than those in the non-bedaquiline group (all p<0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs. 8.0%, p=0.017) and month 12 (39.2% vs. 15.0%, p<0.001). Patients receiving bedaquiline-containing regimens had more treatment success than those receiving bedaquiline-free regimens (p<0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%). The use of bedaquiline was identified as an independent predictor of both treatment success (OR=7.356, 95% CI: 2.920–18.530, p<0.001) and culture reversion (OR=0.124, 95% CI: 0.035–0.452, p<0.001). AEs were similarly reported in 26.5% of patients in the bedaquiline group and 19.0% in the non-bedaquiline group (p=0.206).Conclusions: Bedaquiline-containing regimens resulted in better treatment outcomes and similar safety relative to bedaquiline-free regimens for patients with refractory pulmonary RR/MDR-TB.

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