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Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trial

Title: Identifying heterogeneity of treatment effect for antibiotic duration in bloodstream infection: an exploratory post-hoc analysis of the BALANCE randomised clinical trial
Authors: Ong, SWX; Pinto, R; Rishu, A; Tong, SYC; Commons, RJ; Conly, JM; Evans, GA; Fralick, M; Kandel, C; Lagacé-Wiens, PRS; Lee, TC; Lother, SA; MacFadden, DR; Marshall, JC; Martel-Laferrière, V; Mayette, M; McDonald, EG; Neary, JD; Prazak, J; Raby, E; Regli, A; Rogers, BA; Smith, S; Taggart, LR; Wang, HT; Wuerz, T; Yahav, D; Young, PJ; Fowler, RA; Daneman, N
Publisher Information: Elsevier
Publication Year: 2025
Collection: The University of Melbourne: Digital Repository
Description: Background: The BALANCE trial demonstrated non-inferiority of 7 (vs 14) day antibiotic durations in patients with uncomplicated non-S. aureus/lugdunensis bacterial bloodstream infections (BSI). However, there may be patient subgroups who benefit from longer durations. We aimed to evaluate if bedside clinical decision rules could identify these subgroups. Methods: In this post-hoc analysis of the multicentre, randomised BALANCE trial (October 17, 2014–May 5, 2023), we applied three clinical decision rules to investigate heterogeneity of treatment effect in 7-day vs 14-day antibiotic durations on 90-day all-cause mortality. We used the rules to categorize patients in BALANCE into different risk groups and calculated the unadjusted absolute risk difference (RD) for 90-day mortality in patients receiving 7- vs 14-day antibiotics within each risk group. Statistical significance was tested using an interaction test. The BALANCE trial is registered with ClinicalTrials.gov (NCT03005145). Findings: 3581 patients were included. All three rules predicted mortality risk, but none identified statistically significant effect modification: (a) static rule (low-risk: RD −0.58, 95% CI −8.91 to 7.73; moderate-risk: RD −.01, 95% CI −3.86 to 1.83; high-risk: RD −2.65, 95% CI −7.12 to 1.81; p = 0.74); (b) dynamic rule (met rule on day 7: RD −2.18, 95% CI −4.81 to 0.45; did not meet rule: RD 1.75, 95% CI −3.89 to 7.40; p = 0.16); and (c) early clinical failure criteria (score
Document Type: article in journal/newspaper
Language: English
ISSN: 2589-5370
Relation: https://hdl.handle.net/11343/360459
Availability: https://hdl.handle.net/11343/360459
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND
Accession Number: edsbas.29DEC571
Database: BASE