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Open AccessJournal ArticleDOI

Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis.

TLDR
It is suggested that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.
Abstract
Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease. Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments. Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB. This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.

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Journal ArticleDOI

Advances in the development of new tuberculosis drugs and treatment regimens

TL;DR: Current concepts and recent advances in TB drug discovery and development are covered, including an update of ongoing TB treatment trials, newer clinical trial designs, TB biomarkers and adjunct host-directed therapies.
Journal ArticleDOI

Towards tuberculosis elimination: an action framework for low-incidence countries

Knut Lönnroth, +72 more
TL;DR: An action framework for countries with low tuberculosis (TB) incidence sets out priority interventions required for these countries to progress first towards “pre-elimination” and eventually the elimination of TB as a public health problem.
Journal ArticleDOI

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

TL;DR: Several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis.
References
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Book ChapterDOI

World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects

TL;DR: Comparing the socialist nature of many European counties, there is a requirement that provision be made for patients to be made whole regardless of the outcomes of the trial or if they happened to have been randomized to a control group that did not enjoy the benefits of a successful experimental intervention.
Journal Article

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

WMADo Helsinki
- 19 Dec 2000 - 
TL;DR: The Helsinki Declaration on Ethical Principles for Medical Research Involving Human Subjects, adopted by the World Medical Assembly, is presented.
Journal ArticleDOI

Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa

TL;DR: MDR tuberculosis is more prevalent than previously realised in a rural area in KwaZulu Natal, South Africa and has been transmitted to HIV co-infected patients and is associated with high mortality.
Journal ArticleDOI

OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice

TL;DR: OPC-67683 has the potential to be used as a TB drug to help combat the unmet needs in TB treatment and is a mycolic acid biosynthesis inhibitor found to be free of mutagenicity and to possess highly potent activity against TB, including MDR-TB.
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