Reflections upon the article “Evaluation of the impact that the changes in tuberculosis treatment implemented in Brazil in 2009 have had on disease control in the country”

Maciel, Ethel Leonor Nóia; Braga, José Ueleres; Bertolde, Adelmo Inácio; Zandonade, Eliana; Rabahi, Marcelo Fouad; Júnior, José Laerte Rodrigues da Silva; Conde, Marcus Barreto

doi:10.1590/s1806-37562018000000096

Cited by 3 publications

(1 citation statement)

References 7 publications

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“…8 Interrupted time series analyzes can help to evaluate interventions when confounders do not change or change slowly over time. 9 However, the determinants of the tuberculosis burden have a wide variability in the country and several epidemiological and socioeconomic phenomena may have affected the disease prognosis in recent decades. 10,11 For this reason, to estimate the effects of the new treatment regimen on tuberculosis outcomes, controlling for potential confounding associated with the characteristics of the patients is justified.…”

Section: Introductionmentioning

confidence: 99%

Effect of introducing ethambutol and integrating drugs into fixed-dose tablets on mortality in patients with tuberculosis

Díaz-Quijano

Bartholomay

Andrade

et al. 2023

Preprint

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At the end of 2009, due to the increase in primary resistance to isoniazid, the Brazilian Ministry of Health established changes in the treatment regimen for tuberculosis. The changes included the addition of ethambutol as the fourth drug in the intensive treatment phase and the integration of the four drugs into fixed-dose combination tablets. The introduction of fixed combination doses also led to changes in the dosage of isoniazid and pyrazinamide in the intensive and maintenance phases. Objective: To estimate the effect of changing the tuberculosis treatment regimen on all-cause mortality and, secondly, outcomes such as mortality due to tuberculosis, cure, and loss to follow-up. Methods: We compared the cohorts of people diagnosed with tuberculosis from 2008 to 2013, aged ten years or older, who started treatment for tuberculosis in Brazil before and after the change in the regimen adopted in 2009 (n: 145528 vs. 161264). Data were extracted from the Notifiable Diseases (Sinan) and Mortality (SIM) information systems. The missing data were imputed, and the effects were estimated using multilevel logistic models, with the state as the aggregation cluster. A directed acyclic graph guided the selection of covariates. Results: The current (modified) regimen was not associated with significant changes in all-cause mortality (Relative Risk [RR]: 1.01; 95% confidence interval [95%CI]: 0.98 - 1.04), or tuberculosis mortality (RR: 0.98; 95%CI: 0.95 - 1.02). For cure, when transfers and missing outcome data (MOD) were considered an absence of outcome, there were no differences between treatments. When they were assumed as cured or imputed, the cure was less frequent in the current treatment. When transfers and MOD were imputed or considered an absence of loss to follow-up, the latter was more frequent in the current treatment. There were no differences in loss to follow-up between treatments when transfers and MOD were interpreted as that outcome. Conclusion: The implementation of the modified treatment regimen was not associated with increased mortality in tuberculosis patients. Although there was a lower record of cures and a higher frequency of loss to follow-up during the second period, the sensitivity analysis indicated that a reduction in transfers and unknown outcomes could explain these associations.

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Section: Introductionmentioning

confidence: 99%

Effect of introducing ethambutol and integrating drugs into fixed-dose tablets on mortality in patients with tuberculosis

Díaz-Quijano

Bartholomay

Andrade

et al. 2023

Preprint

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Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

Godman

McCabe

Leong

2020

Expert Review of Pharmacoeconomics & Outcomes Research

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Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower-and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country's essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed.

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The Snowmelt Niche Differentiates Three Microbial Life Strategies That Influence Soil Nitrogen Availability During and After Winter

et al. 2020

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Soil microbial biomass can reach its annual maximum pool size beneath the winter snowpack and is known to decline abruptly following snowmelt in seasonally snow-covered ecosystems. Observed differences in winter versus summer microbial taxonomic composition also suggests that phylogenetically conserved traits may permit winter-versus summer-adapted microorganisms to occupy distinct niches. In this study, we sought to identify archaea, bacteria, and fungi that are associated with the soil microbial bloom overwinter and the subsequent biomass collapse following snowmelt at a high-altitude watershed in central Colorado, United States. Archaea, bacteria, and fungi were categorized into three life strategies (Winter-Adapted, Snowmelt-Specialist, Spring-Adapted) based upon changes in abundance during winter, the snowmelt period, and after snowmelt in spring. We calculated indices of phylogenetic relatedness (archaea and bacteria) or assigned functional attributes (fungi) to organisms within life strategies to infer whether phylogenetically conserved traits differentiate Winter-Adapted, Snowmelt-Specialist, and Spring-Adapted groups. We observed that the soil microbial bloom was correlated in time with a pulse of snowmelt infiltration, which commenced 65 days prior to soils becoming snow-free. A pulse of nitrogen (N, as nitrate) occurred after snowmelt, along with a collapse in the microbial biomass pool size, and an increased abundance of nitrifying archaea and bacteria (e.g., Thaumarchaeota, Nitrospirae). Winter-and Spring-Adapted archaea and bacteria were phylogenetically clustered, suggesting that phylogenetically conserved traits allow Winter-and Spring-Adapted archaea and bacteria to occupy distinct niches. In contrast, Snowmelt-Specialist archaea and bacteria were phylogenetically overdispersed, suggesting that the key mechanism(s) of the microbial biomass crash are likely to be density-dependent (e.g., trophic interactions, competitive exclusion) and affect organisms across a broad phylogenetic spectrum. Saprotrophic fungi were the dominant functional group across fungal life strategies, however, ectomycorrhizal

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Reflections upon the article “Evaluation of the impact that the changes in tuberculosis treatment implemented in Brazil in 2009 have had on disease control in the country”

Cited by 3 publications

References 7 publications

Effect of introducing ethambutol and integrating drugs into fixed-dose tablets on mortality in patients with tuberculosis

Effect of introducing ethambutol and integrating drugs into fixed-dose tablets on mortality in patients with tuberculosis

Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

The Snowmelt Niche Differentiates Three Microbial Life Strategies That Influence Soil Nitrogen Availability During and After Winter

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