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WHO recommends a 2-month optimal duration for new drug regimens for rifampicin-susceptible tuberculosis. We aimed to investigate the efficacy and safety of the 8-week regimens that were assessed as part of the TRUNCATE management strategy of the TRUNCATE-TB trial. TRUNCATE-TB was a multi-arm, multi-stage, open-label, randomised controlled trial in which participants aged 18–65 years with rifampicin-susceptible pulmonary tuberculosis were randomly assigned via a web-based system, using permuted blocks, to 24-week standard treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) or the TRUNCATE management strategy comprising initial 8-week treatment, then post-treatment monitoring and re-treatment where needed. The four 8-week regimens comprised five drugs, modified from standard treatment: high-dose rifampicin and linezolid, or high-dose rifampicin and clofazimine, or bedaquiline and linezolid, all given with isoniazid, pyrazinamide, and ethambutol; and rifapentine, linezolid, and levofloxacin, given with isoniazid and pyrazinamide. Here, we report the efficacy (proportion with unfavourable outcome; and difference from standard treatment, assessed via Bayesian methods) and safety of the 8-week regimens, assessed in the intention-to-treat population. This prespecified exploratory analysis is distinct from the previously reported 96-week outcome of the strategy in which the regimens were deployed. This trial is registered with ClinicalTrials.gov (NCT03474198). Between March 21, 2018, and March 26, 2020, 675 participants (674 in the intention-to-treat population) were enrolled and randomly assigned to the standard treatment group or one of the four 8-week regimen groups. Two 8-week regimens progressed to full enrolment. An unfavourable outcome (mainly relapse) occurred in seven (4%) of 181 participants on standard treatment; 46 (25%) of 184 on the high-dose rifampicin and linezolid-containing regimen (adjusted difference 21·0%, 95% Bayesian credible interval [BCI] 14·3–28·1); and 26 (14%) of 189 on the bedaquiline and linezolid-containing regimen (adjusted difference 9·3% [4·3–14·9]). Grade 3–4 adverse events occurred in 24 (14%) of 181 participants on standard treatment, 20 (11%) of 184 on the rifampicin-linezolid regimen, and 22 (12%) of 189 on the bedaquiline-linezolid regimen. Efficacy was worse with 8-week regimens, although the difference from standard treatment varied between regimens. Even the best 8-week regimen (bedaquiline-linezolid) should only be used as part of a management strategy involving post-treatment monitoring and re-treatment if necessary. Singapore National Medical Research Council; UK Department of Health and Social Care; UK Foreign, Commonwealth, and Development Office; UK Medical Research Council; Wellcome Trust; and UK Research and Innovation Medical Research Council.

Objective To describe clinical features, treatment strategies and visual acuity changes of eyes with uveitic macular oedema (UMO) in ocular tuberculosis (OTB) patients from a non-TB-endemic country. Methods This retrospective study was conducted using a 10-year period registry of OTB patients diagnosed in Erasmus MC, Rotterdam. Longitudinal analysis of visual acuity trajectory in eyes with and without UMO was performed using linear mixed effect model. Results Out of 93 included patients, 23 (24.7%; 26 eye episodes) presented with baseline UMO. Older age ( p  = 0.024) and diabetes coexistence ( p  = 0.048) were associated with UMO. Eyes with baseline UMO showed lower presenting best-corrected visual acuity (BCVA) ( p  = 0.024). Posterior uveitis ( p  = 0.005), the presence of active vitreous cells ( p  = 0.016) and retinal vasculitis ( p  = 0.008) were ocular signs associated with UMO. A step-wise treatment approach primarily initiated with local steroids, followed by a combination with oral acetazolamide and, if necessary, additional systemic immunosuppressants. Overall, this approach resulted in complete UMO resolution in 77% (20/26) of cases. UMO resolution was shorter among eyes co-managed with ATT, although statistically not significant ( p  = 0.144). Eyes experiencing at least one UMO episode exhibited lower visual acuity at the last-follow-up than those without ( p  = 0.020). Conclusions Active vitreous cells, retinal vasculitis and posterior uveitis are associated with UMO among OTB patients. The time-to-resolution of UMO for eyes co-managed with ATT was shorter compared to those without, suggesting that patients with UMO in OTB should be treated with ATT.