The Safety and Tolerability of Linezolid in Novel Short-Course Regimens Containing Bedaquiline, Pretomanid, and Linezolid to Treat Rifampicin-Resistant Tuberculosis: An Individual Patient Data Meta-analysis.

BACKGROUND: Effectiveness, safety, tolerability, and adherence are critical considerations in shifting to shorter tuberculosis (TB) regimens. Novel 6-month oral regimens that include bedaquiline (B), pretomanid (Pa), and linezolid (L), with or without a fourth drug, have been shown to be as or more effective than the established longer regimens for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). We aimed to evaluate the safety and tolerability of linezolid in BPaL-containing regimens for the treatment of MDR/RR-TB among recently completed clinical trials. METHODS: A review and meta-analysis was undertaken including published and unpublished data from clinical trials, conducted between 2010 and 2021, that evaluated regimens containing BPaL for the treatment of MDR/RR-TB. Individual patient data were obtained. For each BPaL-containing regimen, we evaluated the frequency and severity of treatment-related adverse events. The risk difference of adverse events for each regimen was calculated, in comparison to patients assigned to receiving the lowest cumulative exposure of linezolid. RESULTS: Data from 3 clinical trials investigating 8 unique BPaL-containing regimens were included, comprising a total of 591 participants. Adverse events were more frequent in groups randomized to a higher cumulative linezolid dose. Among patients who were randomized to a daily dose of 1200 mg linezolid, 68 of 195 (35%) experienced a grade 3-4 adverse event versus 89 of 396 (22%) patients receiving BPaL-containing regimens containing 600 mg linezolid. CONCLUSIONS: Regimens containing BPaL were relatively well tolerated when they included a daily linezolid dose of 600 mg. These novel regimens promise to improve the tolerability of treatment for MDR/RR-TB.

Fear of cancer recurrence in patients undergoing germline genome sequencing.

PURPOSE: Fear of cancer recurrence/occurrence (FCR/O) is prevalent and associated with poorer psychological outcomes but can also motivate individuals to pursue genomic information about cancer risk. Guided by Protection Motivation Theory, this study investigated FCR/O prevalence and associated factors among probands previously diagnosed with a cancer of likely heritable origin, and their relatives, who had agreed to have germline genome sequencing. METHODS: Three hundred and forty-eight probands and 167 relatives completed the Concerns about Recurrence Questionnaire (adapted for occurrence for some relatives) within 1 month of agreeing to undertake genome sequencing. Linear regressions investigated demographic, disease, attitude and behavioral associations with FCR/O. RESULTS: Probands demonstrated greater FCR compared to relatives. In probands, greater FCR was associated with being female, non-English speaking at home, less time since diagnosis, greater intention to change behavior if gene variant found, lower perceived ability to cope with results, higher perceived susceptibility to having a recurrence, and more negative attitudes towards uncertainty. For relatives with cancer, greater FCR was associated with being male, greater intention to change behavior if a gene variant found, and higher perceived susceptibility to recurrence. In relatives without cancer, greater FCO was associated with not having had genetic testing prior to this study, lower perceived ability to cope with results, and higher perceived susceptibility to developing cancer. CONCLUSION: Current findings on FCR/O prevalence and associated demographic and attitudinal variables in those who pursue genomic risk information might be used to target interventions that can prevent adverse psychological outcomes in vulnerable patients.