The adherence to and utility of the Global Initiative for Chronic Obstructive Lung Disease guidelines for treating COPD among pulmonary specialists: a retrospective analysis

Abstract Background Despite the evidence-based guidelines promoted by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the overuse of prescription drugs to manage COPD, particularly inhaled corticosteroids (ICS), remains a persistent challenge. In this real-world study, we evaluated how patients with COPD were divided into ABCD groups based on the 2017 GOLD guidelines, determined the rate of adherence to the GOLD treatment recommendations, described the rate of ICS usage, and determined the rate of triple therapy (TT) prescription. Methods The charts of 2291 patients diagnosed with COPD were retrospectively analyzed, of which 1438 matched the eligibility criteria. Results The average patient age was 69.6 ± 10.9 years; 52% of patients were female. The average COPD assessment test (CAT) score was 18.3 ± 9.1. The ABCD breakdown was as follows: group A 19.5%, group B 64.1%, group C 1.8%, and group D 14.6%. All groups, except group D, showed discordance in COPD treatment relative to the proposed GOLD guidelines. Only 18.9% of group A and 26% of group B were treated in concordance with the guidelines. TT was primarily used in group D (63.3%) and overused in groups A (30.6%) and B (47.8%). ICS was overused in all groups, particularly in groups A (56.2%) and B (67.3%). Conclusion Studies from the last decade have consistently revealed a lack of conformity between what physicians prescribe and what GOLD guidelines recommend. The excessive usage of ICS, which continues despite all the associated adverse effects and the attributable costs, is concerning. The awareness of GOLD guidelines among primary care physicians (PCPs) and respiratory specialists needs to be improved

Identification of neurotherapeutic constituents in Ocimum gratissimum with cholinesterase and mono amine oxidase inhibitory activities, using GC-MS analysis, in vitro, and in silico approaches

Neuroprotective activities of various extracts of Ocimum gratissimum (OG), have been reported, but there is paucity of information on its neurotherapeutic constituents. This study is aimed at identifying the neurotherapeutic constituents in OG leaves using in vitro assays, GC-MS chemical investigation and in silico studies including molecular docking, ensemble-based docking, molecular dynamics (MD) simulation, clustering and ADMET filtering analysis. Methanol extract of O gratissimum (MEOG) and solvent-partition (n-hexane, ethylacetate, and methanol residue fraction) of MEOG were investigated for in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) inhibition at concentration of 0.65, 12.5, 2.5, 5, and 10 mg/mL, using donepezil, phenazine methosulfate and selegiline as reference inhibitors for AChE, BChE and MAO B respectively. n-hexane solvent partition fraction was further investigated using GC-MS analysis. Identified compounds were screened against human AChE, BChE and MAO-B activities using molecular docking and molecular dynamics. The lead phytochemicals were further analysed for ADMET in silico analysis. MEOG and the 3 fractions (n-hexane, ethylacetate, and methanol residue fraction) inhibited the activities of AChE, BChE and MAO-B in a concentration-dependent manner with AChE (IC50 = 2.380, 2.022, 2.066 and 1.079 mg/mL respectively), BChE (IC50 = 2.261, 2.126, 2.630 and 1.465 mg/mL respectively) and MAO-B (IC50 = 2.345, 1.584, 2.933 and 2.935 mg/mL respectively). From the 38 GC-MS identified compounds, 7 hit compounds were further subjected to ensemble-docking, the lead phytochemicals (LP): cholestane and 3-methoxy-morphanin presented highest multiple binding tendencies to the three enzymes. Cholestane had the highest binding energies of −9.9, −9.0 and −11 kcal/mol, while 3-methoxy-morphanin presented the second-best binding energies of −9.3, −8.2 and −10.1 kcal/mol respectively. When compared with the binding pattern of reference inhibitors of the enzyme, lead phytochemicals were orientated in the catalytic sites of the enzyme and interacted with important catalytic residues. The LP-enzyme complexes were stable during the MD simulation analysis. Cholestane and 3-methoxy-morphanin presented favorable ADMET properties over several molecular descriptors and filters, with druggable properties and ability to cross the blood-brain barrier. Hence, cholestane and 3-methoxy-morphanin, in part, or in synergy with other hit phytochemicals, may be responsible for the neurotherapeutic activities of MEOG leaves