Efficacy and effectiveness of the herbal medicinal product BNO 1016 in the management of acute rhinosinusitis in the context of antibiotic stewardship.

OBJECTIVES: To substantiate the clinical efficacy and investigate the real-world effectiveness of the herbal medicinal product BNO 1016 in acute rhinosinusitis (ARS) in the context of antibiotic stewardship. METHODS: We performed a meta-analysis of the clinical trials ARhiSi-1 (EudraCT No. 2008-002794-13) and ARhiSi-2 (EudraCT No. 2009-016682-28) comprising 676 patients, analyzing the reduction of the Major Symptom Score (MSS) and improvement of the Sino-Nasal Outcome Test 20 (SNOT-20) by the herbal medicinal product BNO 1016. In addition, we performed a retrospective cohort study including 203,382 patients, comparing the real-life effectiveness of BNO 1016 in reducing ARS-related adverse outcomes in comparison to antibiotics and several other established therapies. RESULTS: Treatment with BNO 1016 ameliorated symptoms of ARS by reducing MSS by 1.9 points (p < 0.0001) and improved quality of life (QoL) for patients by improving SNOT-20 by 3.5 points (p = 0.001) in comparison to placebo. In patients with moderate/severe symptoms, the positive effects of BNO 1016 were even more pronounced (MSS: -2.3 points (p < 0.0001); SNOT-20: -4.9 points (p = 0.0158)). In addition, treatment with BNO 1016 was as effective or significantly more effective in reducing the risk for adverse ARS-related outcomes such as follow-up antibiotic prescriptions, sick leave ≥7 days or medical appointments due to ARS, especially when compared to antibiotics. CONCLUSION: BNO 1016 is a safe and effective treatment for ARS that can help reduce the overuse of antibiotics.

Prevalence of Antibiotic Prescription in Patients with Acute Rhinosinusitis Treated by General Practitioners and Otolaryngologists in Germany-A Retrospective Cohort Study.

(1) Background: The goal of this retrospective cohort study, based on real-world data and conducted in Germany, was to investigate the prevalence of antibiotic (AB) prescription in patients with acute rhinosinusitis (ARS). (2) Methods: Data from the Disease Analyzer database were used for this cross-sectional study. Patients aged ≥18 years diagnosed with acute sinusitis by general practitioners (GPs) and ear, nose, throat (ENT) specialists between January 2012 and December 2020 were included. The main outcome of the study was the proportion of patients with ARS who received an AB prescription on the day of diagnosis or within three days afterwards. The proportion was estimated separately for patients treated by GPs and ENTs, and also for five age groups, as well as women and men. (3) Results: In total, 308,095 patients were diagnosed with ARS (187,838 by GPs and 120,257 by ENTs). 50.9% of patients treated by GPs and 50.0% treated by ENTs received an AB prescription. AB prevalence increased with age from 46.9% in the age group 18−30 years to 55.5% in the age group > 60 years. (4) Conclusions: We have shown a high prevalence of potentially inappropriate AB prescription for adult patients with ARS in both GP and ENT practices and also among both women and men and in several age groups. There is an urgent need for interventions to reduce inappropriate AB use.

Differential allosteric modulation within dopamine D2R - neurotensin NTS1R and D2R - serotonin 5-HT2AR receptor complexes gives bias to intracellular calcium signalling.

Proceeding investigations of G protein-coupled receptor (GPCR) heterocomplexes have demonstrated that the dopamine D2 receptor (D2R), one of the hub receptors in the physiology of schizophrenia, interacts with both the neurotensin NTS1 (NTS1R) and the serotonin 5-HT2A receptor (5-HT2AR) in cell lines and rodent brain tissue. In situ proximity ligation assay and BRET-based saturation experiments confirmed interacting receptor assemblies in HEK293T and neuronal HT22 cells. The NTS1R agonist NT(8-13) reduces the Gαq-mediated calcium signal in the NTS1R-D2R complex compared to the NTS1R monomer which could be reversed by D2R antagonists. The bivalent ligand CS148 (NTS1R-agonistic, D2R-antagonistic) increased the calcium response addressing the dimer, consistent with the effect of the monovalent ligands suggesting an allosteric D2R-mediated modulation. In contrast, the 5-HT2AR-D2R heteromer did not show a calcium-altering receptor-receptor interaction. Despite their common coupling-preference for Gαq, 5-HT2AR and NTS1R supposedly interact with D2R each in a unique mode. This remarkably diverse ligand-mediated signalling in two different D2R heteroreceptor complexes illustrates the complexity of receptor-receptor interactions and their potential of modifying cell responses to external stimuli. Therefore, GPCR heteromers may provide a very promising novel target for the therapy of neuropsychiatric disorders.