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[This corrects the article DOI: 10.3389/fmicb.2022.814448.].
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The priority pathogen list of the World Health Organization classified Pseudomonas aeruginosa as the second top critical pathogen. Hence, the development of novel antibacterial strategies to tackle this bacterium is highly necessary. Herein we explore the potential antibacterial effect of a standardized extract of cultured mycelium of Lentinula edodes (AHCC®) on P. aeruginosa. AHCC® was found to inhibit the growth rate and biofilm formation of strain PAO1. No change in swarming was observed, but AHCC® hampered swimming and twitching motility. In accordance, a decreased expression of metabolism, growth, and biofilm formation genes was shown. AHCC® also diminished the levels of exotoxin A and bacteria inside IEC18 cells and the secretion of IL-6, IL-10 and TNF by infected macrophages. This effect was related to a reduced phosphorylation of MAPKs and to bacteria internalization. Taken together, our data suggest that AHCC® has a potential role to prevent P. aeruginosa infections and may lead to the development of new therapies.
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CONTEXT AND OBJECTIVE: Risk-sharing agreements(RSA) allow decision-makers to manage the uncertainty associated with effectiveness and costs of treatments. Our objective was to estimate the economic impact of RSA implementation on treatment of patients diagnosed with rheumatoid arthritis(RA) with certolizumab pegol(CZP) and assess the potential impact of alternative RSA. METHODS: Under original RSA, treatment with CZP was reimbursed when the response was optimal (DAS28 score <3.2) or satisfactory (DAS28 score ≥3.2 and reduction from baseline ≥1.2) at 12 weeks. Alternative RSA would additionally include a 50 % reimbursement for moderate responders(DAS28 score >3.2 and ≤5.1, and reduction from baseline between 0.6 and 1.2). We estimated average savings per patient for hospital's pharmacy service(HPS) at 12 weeks, taking into account the pharmacological cost of CZP. Uncertainty associated with effectiveness of CZP was assessed through 1000 Monte Carlo simulations. RESULTS: After 12 weeks of treatment, 57.8 % (n = 52) and 22.2 %(n = 20) of patients had optimal and satisfactory responses, respectively, and average disease activity improved by 1.77 points. Average savings for HPS amounted to 876.9 and 706.4 per patient under original and alternative RSA, respectively. Savings in simulated cohort reached 846.2 and 681.8 per patient, respectively, leading to estimated net savings for HPS of 846,209 and 681,790, respectively. CONCLUSIONS: RSA implementation on patients with RA treated with CZP has generated savings and improved efficiency within HPS.
