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BMJ Open Respiratory Research May 2024Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated...
Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study.
BACKGROUND
Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score. This real-world study compared the effectiveness of switching patients with COPD in England from MITT to once-daily SITT with FF/UMEC/VI by evaluating rates of COPD exacerbation, healthcare resource use (HCRU) and associated direct medical costs.
METHODS
Retrospective cohort pre-post study using linked primary care electronic health record and secondary care administrative datasets. Patients diagnosed with COPD at age ≥35 years, with smoking history, linkage to secondary care data and continuous GP registration for 12 months pre-switch and 6 months post-switch to FF/UMEC/VI were included. Index date was the first initiation of an FF/UMEC/VI prescription immediately following MITT use from 15 November 2017 to 30 September 2019. Baseline was 12 months prior to index, with outcomes assessed 6/12 months pre-switch and post-switch, and stratified by prior COPD exacerbation status.
RESULTS
We included 2533 patients (mean [SD] age: 71.1 [9.9] years; 52.1% male). In the 6 months post-switch, there were significant decreases in the proportion of patients experiencing ≥1 moderate-to-severe (36.2%-28.9%), moderate only (24.4%-19.8%) and severe only (15.4%-11.8%) COPD exacerbation (each, p<0.0001) compared with the 6 months pre-switch. As demonstrated by rate ratios, there were significant reductions in exacerbation rates of each severity overall (p<0.01) and among patients with prior exacerbations (p<0.0001). In the same period, there were significant decreases in the rate of each COPD-related HCRU and total COPD-related costs (-24.9%; p<0.0001).
CONCLUSION
Patients with COPD switching from MITT to once-daily SITT with FF/UMEC/VI in a primary care setting had significantly fewer moderate and severe exacerbations, and lower COPD-related HCRU and costs, in the 6 months post-switch compared with the 6 months pre-switch.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Retrospective Studies; Female; Aged; Primary Health Care; Middle Aged; Benzyl Alcohols; Chlorobenzenes; England; Drug Combinations; Administration, Inhalation; Nebulizers and Vaporizers; Bronchodilator Agents; Quinuclidines; Treatment Outcome; Muscarinic Antagonists; Androstadienes
PubMed: 38772900
DOI: 10.1136/bmjresp-2023-001890 -
Hospital Pharmacy Jun 2024Revefenacin is a once-daily nebulized long-acting muscarinic antagonist (LAMA). Revefenacin is supplied as single-use nebulized vials, which may be preferable and less...
Revefenacin is a once-daily nebulized long-acting muscarinic antagonist (LAMA). Revefenacin is supplied as single-use nebulized vials, which may be preferable and less costly for hospital and health-system pharmacies to dispense versus multidose tiotropium inhalers. Estimates of LAMA multidose inhaler wasted doses remains unknown. : This was a single-center descriptive cross-sectional study conducted between January 1 2021 and December 31 2021. Adult patients 18 years and older admitted to a 500-bed academic medical center in the southern United States and were ordered multidose tiotropium packages or single-use revefenacin vials during the study period were included. : Among 602 inpatients, there were 705 LAMA orders: 541 tiotropium (76.7%) and 164 revefenacin (23.3%). Four hundred ninety-five tiotropium orders (91.5%) wasted between 20% and 90% of multidose packages. Approximately $24,000 tiotropium doses were wasted versus single-use revefenacin vials. : Multidose inhalers of tiotropium dispensed to hospitalized patients contributed to wasted doses compared to nebulized single-use revefenacin vials. Opportunities exist to minimize wasted doses of multidose long-acting inhalers dispensed to hospitalized patients.
PubMed: 38764992
DOI: 10.1177/00185787231222274 -
Medicine May 2024This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to... (Observational Study)
Observational Study
This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ± 0.33 vs 3.58 ± 0.29 mm, P < .05) and WTW (12.09 ± 0.42 vs 12.30 ± 0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ± 3.00 D to -0.06 ± 3.32 D (P < .05) in overall and a myopic shift from -6.97 ± 4.27 to -8.10 ± 2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.
Topics: Humans; Amblyopia; Strabismus; Retrospective Studies; Male; Female; Child; Biometry; Mydriatics; Child, Preschool; Refraction, Ocular; Cyclopentolate; Refractive Errors; Adolescent; Anterior Chamber; Axial Length, Eye
PubMed: 38758890
DOI: 10.1097/MD.0000000000038143 -
Food & Function Jun 2024protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from...
protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from protein hydrolysates and validate the protective effects of YVYAETY on memory impairment in scopolamine-induced mice. The protein was hydrolyzed by simulated gastrointestinal digestion, followed by purification through ultrafiltration and gel chromatography. The fraction exhibiting the strongest neuroprotective activity was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main identified peptides (SDLKPADF, WNDHYY, YVYAETY, and WFHPLF) effectively mitigated excessive ROS production by increasing SOD and GSH-px activities while inhibiting cell apoptosis and mitochondrial membrane potential (MMP) collapse against oxidative stress in Aβ-induced HT22 cells. By molecular docking, the interaction between peptides and the active site of the Keap1-Kelch domain reveals their capacity to regulate the Keap1/Nrf2/HO-1 pathway. , the peptide YVYAETY had the best effect and can be further validated . The behavioral tests showed that YVYAETY improved scopolamine-induced cognitive impairment in mice. YVYAETY also alleviated neuron damage including neuron vacuolation and pyknotic nuclei in the hippocampus. Furthermore, it significantly inhibited oxidative stress and suppressed the activation of the Nrf2 pathway. Therefore, this study revealed that YVYAETY had the potential to serve as a novel neuroprotective agent.
Topics: Animals; Mice; Scopolamine; Neuroprotective Agents; Cognitive Dysfunction; Protein Hydrolysates; Flammulina; Male; Oxidative Stress; Peptides; Molecular Docking Simulation; Hippocampus; Apoptosis
PubMed: 38757389
DOI: 10.1039/d4fo00871e -
Urologie (Heidelberg, Germany) Jul 2024Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects... (Review)
Review
[Intravesical oxybutynin treatment for neurogenic detrusor overactivity : Efficacy and safety data from clinical practice with the first intravesical oxybutynin treatment authorized in Germany].
Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cm HO ± 26.12 standard deviation (SD) to 21.07 cm HO ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.
Topics: Humans; Mandelic Acids; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Administration, Intravesical; Germany; Treatment Outcome; Muscarinic Antagonists; Urological Agents; Female
PubMed: 38755461
DOI: 10.1007/s00120-024-02351-1 -
Neurosciences (Riyadh, Saudi Arabia) May 2024To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine.
OBJECTIVES
To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine.
METHODS
This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100 mg/kg AST, 2 mg/kg scopolamine (AD group), 100 mg/kg AST+2 mg/kg scopolamine, 3 mg/kg galantamine+2 mg/kg scopolamine, and 100 mg/kg AST+3 mg/kg galantamine+2 mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated.
RESULTS
The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress.
CONCLUSION
The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.
Topics: Animals; Xanthophylls; Alzheimer Disease; Scopolamine; Male; Mice; Neuroprotective Agents; Disease Models, Animal; Oxidative Stress; Hippocampus; Acetylcholinesterase; Galantamine; Memory, Short-Term
PubMed: 38740397
DOI: 10.17712/nsj.2024.2.20230060 -
Biochemical Pharmacology Jul 2024Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report...
Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced intracellular Ca oscillations, mediated through an inhibition of the muscarinic subtype 3 (M) receptor. Patch-clamp recordings and confocal Ca imaging were applied to acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca oscillations. Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca oscillations in a concentration-dependent manner, and this inhibition also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl) channels, and store-operated Ca channels. Together, the results demonstrate that berberine directly inhibits the muscarinic M receptors, further confirmed by evidence of the interaction between berberine and M receptors in pancreatic acinar cells.
Topics: Animals; Berberine; Receptor, Muscarinic M3; Mice; Acinar Cells; Calcium Signaling; Pancreas; Male; Acetylcholine; Calcium; Dose-Response Relationship, Drug
PubMed: 38740221
DOI: 10.1016/j.bcp.2024.116279 -
Harefuah May 2024The importance of myopia management lies in the desire to minimize the potential ocular risks that increase with high myopia.
INTRODUCTION
The importance of myopia management lies in the desire to minimize the potential ocular risks that increase with high myopia.
AIMS
To assess the decrease in myopia progression using topical low dose atropine combined with peripheral blur contact lenses (CL).
METHODS
This retrospective review study included 25 children between the ages of 8.5 years to 14 years. The children all had a minimal increase in myopia of 0.75D during the year prior to treatment. The children were divided into two groups. The control group included 14 children who wore single-vision spectacles )SV) averaging 3.20±0.9D ranging from 1.5-5.3D. The study group included 11 children who wore dual-focus CL, with an average prescription of 3.4±0.7D ranging from 2.5 to 4.3D, for one year. At that point, when an additional myopia increase was observed, the children were additionally treated with topical 0.01% atropine for two years (CL+A0.01).
RESULTS
There was an increase in myopia in the SV group of 1.12±0.52D, 1.08±0.56D and 0.96±0.53D in the first, second, and third years, respectively. The myopia increase in the CL+A0.01 group was 0.57±0.48D, 0.14±0.34D, and 0.17±0.29D in the first, second, and third years, respectively.
CONCLUSIONS
Low-dose atropine combined with peripheral blur contact lenses was effective in decreasing myopia progression in this study. Additional, larger-scale studies are required in the future.
DISCUSSION
This study found a significant decrease in myopia progression in the second and third years of treatment. The CL group showed less effectivity than the CL+A0.01 group.
Topics: Humans; Atropine; Child; Myopia; Retrospective Studies; Adolescent; Contact Lenses; Male; Disease Progression; Female; Treatment Outcome; Mydriatics; Ophthalmic Solutions; Eyeglasses
PubMed: 38734939
DOI: No ID Found -
European Journal of Pharmacology Jul 2024The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique...
The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 18:2) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 18:2 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1β, IL-6, and TNF-α in the hippocampus, serum, and colon were reduced by M 18:2. Furthermore, M 18:2 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified, as well as increased genera Muribaculaceae_unclassified, Muribaculum, Alistipes, and Bacteroides, which may be the possible biomarkers of cognitive aging. In summary, M 18:2 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota.
Topics: Animals; NF-E2-Related Factor 2; Alzheimer Disease; Gastrointestinal Microbiome; Signal Transduction; Neuroprotective Agents; Mice; Male; Disease Models, Animal; Acetylcholinesterase; Scopolamine; Neuronal Plasticity; Molecular Docking Simulation; CA1 Region, Hippocampal; Hippocampus
PubMed: 38734297
DOI: 10.1016/j.ejphar.2024.176638 -
Molecules (Basel, Switzerland) May 2024The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has...
The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than . Thus, the bimolecular rate constant was found to be / = 7.7 × 10 M min. Rough estimates of catalytic parameters provided slow < 40 min and high = 0.3-3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug.
Topics: Butyrylcholinesterase; Atropine; Humans; Kinetics; Hydrolysis; Molecular Docking Simulation; Models, Molecular
PubMed: 38731631
DOI: 10.3390/molecules29092140