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BMJ Open Feb 2024Management of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting β-agonist (ICS/LABA) improves lung function and health status and...
Treatment pathways, economic burden and clinical outcomes in new users of inhaled corticosteroid/long-acting B-agonist dual therapy with chronic obstructive pulmonary disease in a primary care setting in England: a retrospective cohort study.
OBJECTIVE
Management of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroid/long-acting β-agonist (ICS/LABA) improves lung function and health status and reduces COPD exacerbation risk versus monotherapy. This study described treatment use, healthcare resource utilisation (HCRU), healthcare costs and outcomes following initiation of single-device ICS/LABA as initial maintenance therapy (IMT).
DESIGN
Retrospective cohort study.
SETTING
Primary care, England.
DATA SOURCES
Linked data from the Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets.
PARTICIPANTS
Patients with COPD and ≥1 single-device ICS/LABA prescription between July 2015 and December 2018 were included.
PRIMARY AND SECONDARY OUTCOME MEASURES
Treatment pathways, COPD-related HCRU and healthcare costs, COPD exacerbations, time to triple therapy, medication adherence (proportion of days covered ≥80%) and indexed treatment time to discontinuation. Data for patients without prior maintenance therapy history (IMT users) and non-triple users were assessed over a 12-month follow-up period.
RESULTS
Of 13 451 new ICS/LABA users, 5162 were IMT users (budesonide/formoterol, n=1056; beclomethasone dipropionate/formoterol, n=2427; other ICS/LABA, n=1679), for whom at 3 and 12 months post-index, 45.6% and 39.4% were still receiving any ICS/LABA. At >6 to ≤12 months, the proportion of IMT users with ≥1 outpatient visit (10.1%) and proportion with ≥1 inpatient stay (12.6%) had increased from those at 3 months (9.0% and 7.4%, respectively). Inpatient stays contributed most to total COPD-related healthcare costs. For non-triple IMT users, at 3 and 12 months post-index, 4.5% and 13.7% had ≥1 moderate-to-severe COPD exacerbation. Time to triple therapy initiation and time to discontinuation of index medication ranged from 45.9 to 50.2 months and 2.3 to 2.8 months between treatments. Adherence was low across all time points (21.5-27.6%). Results were similar across indexed therapies.
CONCLUSIONS
In the year following treatment initiation, ICS/LABA adherence was poor and many patients discontinued or switched therapies, suggesting that more consideration and optimisation of treatment is required in England for patients initiating single-device ICS/LABA therapy.
Topics: Humans; Bronchodilator Agents; Retrospective Studies; Financial Stress; Drug Therapy, Combination; Adrenergic beta-2 Receptor Agonists; Muscarinic Antagonists; Administration, Inhalation; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Formoterol Fumarate; Primary Health Care
PubMed: 38326272
DOI: 10.1136/bmjopen-2023-072361 -
Lung Apr 2024This study aimed to examine reports of cardiovascular adverse events (CV AEs) observed in the real-world during treatment with aclidinium, tiotropium, glycopyrronium,...
PURPOSE
This study aimed to examine reports of cardiovascular adverse events (CV AEs) observed in the real-world during treatment with aclidinium, tiotropium, glycopyrronium, and umeclidinium alone or in combination with a LABA and, in the context of triple therapy, with the addition of an ICS, and submitted to the food and drug administration adverse event reporting system (FAERS).
METHODS
A retrospective disproportionality analysis was conducted utilizing CV AE reports submitted to the FAERS from January 2020 to 30 September 2023. Disproportionality was measured by calculating the reporting odds ratio.
RESULTS
Compared with ipratropium, tiotropium was associated with fewer reports of CV AEs. Compared with tiotropium, other LAMAs were more likely to be associated with reports of CV AEs. Combinations of glycopyrronium with indacaterol or formoterol and umeclidinium with vilanterol significantly reduced reports of CV AEs compared with the respective LAMA. The addition of an ICS to these combinations further reduced the risk of CV AE reports.
CONCLUSION
Our study suggests that inhaled LAMAs are not free from cardiac AE risks. This risk may be more evident when the newer LAMAs are used, but it is generally significantly reduced when COPD patients are treated with dual bronchodilators or triple therapy. However, these results do not prove that LAMAs cause CV AEs, as FAERS data alone are not indicative of a drug's safety profile. Given the frequency with which COPD and cardiovascular disease co-exist, a large study in the general population could shed light on this very important issue.
Topics: United States; Humans; Tiotropium Bromide; Glycopyrrolate; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; United States Food and Drug Administration; Adrenergic beta-2 Receptor Agonists; Drug Combinations; Muscarinic Antagonists; Bronchodilator Agents; Cardiovascular Diseases; Receptors, Muscarinic; Administration, Inhalation
PubMed: 38321329
DOI: 10.1007/s00408-024-00677-3 -
Investigative Ophthalmology & Visual... Feb 2024To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye...
PURPOSE
To sequence, identify, and perform phylogenetic and recombination analysis on three clinical adenovirus samples taken from the vitreous humor at the Bascom Palmer Eye Institute.
METHODS
The PacBio Sequel II was used to sequence the genomes of the three clinical adenovirus isolates. To identify the isolates, a full genome-based multiple sequence alignment (MSA) of 722 mastadenoviruses was generated using multiple alignment using fast Fourier transform (MAFFT). MAFFT was also used to generate genome-based human adenovirus B (HAdV-B) MSAs, as well as HAdV-B fiber, hexon, and penton protein-based MSAs. To examine recombination within HAdV-B, RF-Net 2 and Bootscan software programs were used.
RESULTS
In the course of classifying three new atypical ocular adenovirus samples, taken from the vitreous humor, we found that all three isolates were HAdV-B species. The three Bascom Palmer HAdV-B genomes were then combined with over 300 HAdV-B genome sequences, including nine ocular HAdV-B genome sequences. Attempts to categorize the penton, hexon, and fiber serotypes using phylogeny of the three Bascom Palmer samples were inconclusive due to incongruence between serotype and phylogeny in the dataset. Recombination analysis using a subset of HAdV-B strains to generate a hybridization network detected recombination between nonhuman primate and human-derived strains, recombination between one HAdV-B strain and the HAdV-E outgroup, and limited recombination between the B1 and B2 clades.
CONCLUSIONS
The discordance between serotype and phylogeny detected in this study suggests that the current classification system does not accurately describe the natural history and phylogenetic relationships among adenoviruses.
Topics: Humans; Animals; Adenoviridae; Vitreous Body; Phylogeny; Serogroup; Adenoviruses, Human; Hexamethonium; Recombination, Genetic
PubMed: 38319669
DOI: 10.1167/iovs.65.2.12 -
Drugs & Aging Feb 2024Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is...
BACKGROUND
Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing.
METHODS
Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.g., by recommending alternative drugs with lower risk, were developed. An accompanying test battery was assembled by focusing on instruments that sensitively reflect anticholinergic load and may be sensitive to depict changes (Neuropsychological Assessment Battery to measure memory and attention, validated assessments for constipation, urinary symptoms, and xerostomia, as well as blood biomarkers). The approach was pilot-tested in a geriatric rehabilitation unit, with clinician feedback as the primary outcome and characterization of anticholinergic symptoms as the secondary outcome. The intervention was delivered by a pharmacist and a clinical pharmacologist who used the algorithms to generate personalized recommendation letters.
RESULTS
We included a total of 20 patients, 13 with anticholinergic drugs and 7 without. Recommendations were made for 22 drugs in nine patients from the intervention group, of which seven letters (78%) were considered helpful and 8/22 (36%) anticholinergic drugs were discontinued, reducing anticholinergic load in seven patients. In contrast to patients without drug change, memory assessment in patients with reduced anticholinergic load improved significantly after 2 weeks (6 ± 3 vs. -1 ± 6 points).
CONCLUSIONS
The approach was well received by the participating physicians and might support standardized anticholinergic deprescribing.
Topics: Humans; Aged; Cholinergic Antagonists; Deprescriptions; Patients; Physicians; Constipation
PubMed: 38319492
DOI: 10.1007/s40266-023-01089-3 -
The Journal of Allergy and Clinical... May 2024Findings from CAPTAIN (NCT02924688) suggest that treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Findings from CAPTAIN (NCT02924688) suggest that treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 inflammation markers in patients with moderate to severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management.
OBJECTIVE
To investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting β-agonist combination FF/VI, or doubling the FF dose.
METHODS
Prespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough FEV], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire]) following addition of UMEC to FF/VI or doubling the FF dose in FF/VI or FF/UMEC/VI.
RESULTS
Adding UMEC to FF/VI led to greater improvements in trough FEV versus doubling the FF dose across all baseline characteristics assessed. Doubling the FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling the FF dose generally led to improvements in Asthma Control Questionnaire scores irrespective of baseline characteristics.
CONCLUSIONS
Unlike previous findings with type 2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.
Topics: Humans; Asthma; Male; Female; Adult; Middle Aged; Benzyl Alcohols; Quinuclidines; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Muscarinic Antagonists; Chlorobenzenes; Administration, Inhalation; Treatment Outcome; Drug Combinations; Androstadienes; Aged; Anti-Asthmatic Agents; Bronchodilator Agents; Young Adult
PubMed: 38309696
DOI: 10.1016/j.jaip.2024.01.039 -
Food Chemistry Jun 2024In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their...
In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their anti-cholinergic, anti-inflammatory, and antioxidant activities were evaluated. Luteolin-7-O-glucoside, isoharmnentin, and apigenin were involved in the acetylcholinesterase (AChE) inhibitory activity, while oleuropein and hydroxytyrosol showed noteworthy potential. Secoiridoids contributed to the cyclooxygenase-2 inhibitory activity and antioxidant capacity. Compounds such as oleuropein, ligstroside and luteolin-7-O-glucoside, may exert an important role in the ferric reducing antioxidant capacity. It should be also highlighted the role of hydroxytyrosol, hydroxycoumarins, and verbascoside concerning the antioxidant activity. This research provides valuable insights and confirms that specific compounds within OL extracts contribute to distinct anti-cholinergic, anti-inflammatory, and anti-oxidative effects.
Topics: Antioxidants; Acetylcholinesterase; Olea; Cyclooxygenase 2; Plant Extracts; Iridoids; Phytochemicals; Plant Leaves; Anti-Inflammatory Agents; Cholinergic Antagonists; Phenylethyl Alcohol; Iridoid Glucosides
PubMed: 38306771
DOI: 10.1016/j.foodchem.2024.138516 -
British Journal of Hospital Medicine... Jan 2024Polypharmacotherapy is an ever-increasing issue with an ageing patient population. Anticholinergic medications make up a large proportion of patient medication but cause... (Review)
Review
Polypharmacotherapy is an ever-increasing issue with an ageing patient population. Anticholinergic medications make up a large proportion of patient medication but cause significant side effects, contributing to well-documented issues within the older population and in hospital medicine. This review explores the documented impact of anticholinergic burden in older surgical patients on postoperative delirium, infection, length of stay and readmission, urinary retention, ileus and mortality. It also highlights the need for further high-quality research into anticholinergic burden management among older surgical patients to further impact practice and policy in the area.
Topics: Humans; Aged; Aging; Cholinergic Antagonists; Hospital Medicine; Intestinal Obstruction; Urinary Retention
PubMed: 38300682
DOI: 10.12968/hmed.2023.0034 -
Urology Apr 2024Anticholinergic medications have long been a mainstay of overactive bladder (OAB) treatment. Oxybutynin, a first-generation anticholinergic, still accounts for more than... (Review)
Review
Anticholinergic medications have long been a mainstay of overactive bladder (OAB) treatment. Oxybutynin, a first-generation anticholinergic, still accounts for more than half of all OAB medication prescriptions, despite associations with impaired memory and cognition, as well as mounting evidence that it may increase the risk of incident dementia. This review details the current literature regarding oxybutynin and cognition, including evidence from preclinical, clinical, and real-world studies that show that oxybutynin binds nonspecifically to muscarinic receptors in the brain and is associated with adverse cognitive outcomes. We also discuss society recommendations to reduce use of oxybutynin and other anticholinergics to treat OAB.
Topics: Humans; Urinary Bladder, Overactive; Cholinergic Antagonists; Mandelic Acids; Cognitive Dysfunction; Muscarinic Antagonists
PubMed: 38296001
DOI: 10.1016/j.urology.2023.11.033 -
ELife Jan 2024Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the...
Quinidine has been used as an anticonvulsant to treat patients with KCNT1-related epilepsy by targeting gain-of-function KCNT1 pathogenic mutant variants. However, the detailed mechanism underlying quinidine's blockade against KCNT1 (Slack) remains elusive. Here, we report a functional and physical coupling of the voltage-gated sodium channel Na1.6 and Slack. Na1.6 binds to and highly sensitizes Slack to quinidine blockade. Homozygous knockout of Na1.6 reduces the sensitivity of native sodium-activated potassium currents to quinidine blockade. Na1.6-mediated sensitization requires the involvement of Na1.6's N- and C-termini binding to Slack's C-terminus and is enhanced by transient sodium influx through Na1.6. Moreover, disrupting the Slack-Na1.6 interaction by viral expression of Slack's C-terminus can protect against Slack-induced seizures in mice. These insights about a Slack-Na1.6 complex challenge the traditional view of 'Slack as an isolated target' for anti-epileptic drug discovery efforts and can guide the development of innovative therapeutic strategies for KCNT1-related epilepsy.
Topics: Animals; Humans; Mice; Anticonvulsants; Epilepsy; Homozygote; NAV1.6 Voltage-Gated Sodium Channel; Nerve Tissue Proteins; Quinidine; Sodium
PubMed: 38289338
DOI: 10.7554/eLife.87559 -
Journal of Integrative Neuroscience Jan 2024Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central...
BACKGROUND
Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated.
METHODS
The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed.
RESULTS
Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM.
CONCLUSIONS
We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus.
Topics: Rats; Animals; Cycloheximide; Memory Consolidation; Antioxidants; Memory Disorders; Oxidative Stress; Neurotransmitter Agents; Isoflavones
PubMed: 38287862
DOI: 10.31083/j.jin2301017