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BackgroundThe recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit.ObjectiveTo see if a higher dose of amoxicillin will lead to more rapid improvement.Design, setting, and participantsDouble-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines.InterventionsStandard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR).Main measureThe primary outcome was the percentage in each group reporting a major improvement—defined as a global assessment of sinusitis symptoms as “a lot better” or “no symptoms”—after 3 days of treatment.Key resultsMajor improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048).ConclusionsAdults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings.Trial registrationClinicalTrials.gov Identifier: NCT02340000.

Purpose: To characterize and minimize the magnetization transfer (MT) effect in MR fingerprinting (MRF) relaxation measurements with a 2-pool (2P) MT model of multiple tissue types. Theory and Methods: Semisolid MT effect in MRF was modeled using 2P Bloch-McConnell equations. The combinations of MT parameters of multiple tissues (white [WM] and gray matter [GM]) were used to build the MRF dictionary. Both 1-pool (1P) and 2P models were simulated to characterize the dependence on MT. Relaxations measured using MRF with spin-echo saturation-recovery (SR) or inversion-recovery preparations were compared with conventional SR-prepared T 1 and multiple spinecho T 2 measurements. The simulations results were validated with phantoms and brain tissue samples. Results: The MRF signal was different from the 1P and 2P models. 1P MRF produced significantly (P < .05) underestimated T 1 in WM (20-30%) and GM (7-10%), while 2P MRF measured consistent T 1 and T 2 in both WM and GM with conventional measurements (pairwise test P > .1; correlated P < .05). Simulations showed that SRprepared MRF measuring T 1 had much less errors against the variation of the macromolecular fraction. Compared with inversion-recovery preparation, SR-prepared MRF produced higher relaxation correlations (R > 0.9) with conventional measurements in both WM and GM across samples, suggesting that SR-prepared MRF was less sensitive to the compositive effect of multiple MT parameters variations. Conclusions: 2P MRF using a combination of MT parameters for multiple tissue types can measure consistent relaxations with conventional methods. With the 2P models, SR-prepared MRF would provide an option for robust relaxation measurement under heterogeneous MT. K E Y W O R D S MRF, MT, saturation-recovery 728 | MENG Et al.