The effects of bedaquiline, delamanid, and pretomanid on QT interval prolongation among patients with tuberculosis: A systematic review and meta-analysis
Bibliographic record
Abstract
INTRODUCTION Certain anti-tuberculosis drugs, i.e. bedaquiline (BDQ), pretomanid (Pa), and delamanid (DLM) have been shown to prolong corrected QT interval (QTc), which can be fatal.We aimed to estimate the incidence and risk of QTc prolongation among tuberculosis patients receiving either BDQ, DLM, or Pa alone or in combination.METHODS This meta-analysis systematically explored seven electronic databases (Clinicaltrials.gov,Cochrane CENTRAL, Embase, PROQUEST, PubMed, ScienceDirect, and SinoMed).Studies considered eligible if they were randomized clinical trials (RCTs) or non-randomized clinical trials (NRCTs) assessing QTc interval prolongation in patients receiving BDQ, DLM, and/or Pa, non-clinical trial study designs and studies of non-tuberculous mycobacterial infection were excluded.Risk of bias was assessed using the Delphi list for the RCTs and the Newcastle-Ottawa Scale for the NRCTs.Main outcomes were the incidence and risks compared to standard of care (SOC) of grades 3 and 4 QTc prolongation and the mean change of QTc interval (milliseconds).Limitations include inadequate subgroup analysis for potentially important and relevant confounders, variability in the period of drug administration, follow-up duration, as well as the incorporation of NRCTs.RESULTS Eighteen trials were eligible out of 1184 retrieved records.Combination therapy was associated with higher incidence of grade ≥3 QTc prolongation (BDQ+DLM 25.0%; BDQ+Pa 7.3%) compared with single-drug use (DLM 3.1%; BDQ 2.6%; Pa 5.1%; SOC 3.4%).Compared to SOC, DLM receiving arms significantly increased the risk of QTc prolongation (RR=2.27;95% CI: 1.21-4.24).In contrast, no significant difference in the risk of prolonged QTc interval was found with either BDQ alone (RR=1.03;95% CI: 0.82-1.29)or BDQ+Pa (RR=0.31;95% CI: 0.05-1.85).CONCLUSIONS In comparison to standard treatment, the incidence of QTc was significantly higher when BDQ, DLM, or Pa were administered in combination, but not when used alone.These findings highlight the need for periodic ECG follow-up when these drugs are prescribed in combination.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.037 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".