Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

BACKGROUND: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS: We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS: Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

Dying in honour: experiences of end-of-life palliative care during the 2013-2016 Ebola outbreak in Guinea.

With no cure and a high mortality rate, Ebola virus disease (EVD) outbreaks require preparedness for the provision of end-of-life palliative care. This qualitative study is part of a larger project on palliative care in humanitarian contexts. Its goal was to document and deepen understanding of experiences and expectations related to end-of-life palliative care for patients infected with Ebola virus disease (EVD) in West African Ebola treatment centres (ETCs) during the 2013-2016 epidemic. It consisted of 15 in-depth semi-structured interviews with individuals impacted by EVD in a Guinean ETC: either as patients in an ETC, healthcare providers, healthcare providers who were also EVD patients at one point, family relations who visited patients who died in an ETC, or providers of spiritual support to patients and family. Analysis was team based and applied an interpretive descriptive approach. Healthcare delivery in humanitarian emergencies must remain respectful of patient preferences but also local and contextual values and norms. Of key importance in the Guinean context is the culturally valued experience of "dying in honour". This involves accompaniment to facilitate a peaceful death, the possibility of passing on final messages to family members, prayer, and particular practices to enact respect for the bodies of the deceased. Participants emphasized several challenges to such death in Ebola treatment centres (ETCs), as well as practices they deemed helpful to alleviating dying patients' suffering. An overarching message in participants' accounts was that ideally more would have been done for the dying in ETCs. Building on participants' accounts, we outline a number of considerations for optimizing end-of-life palliative care during current and future public health emergencies, including for COVID-19.