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Scientific Reports Feb 2024Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The...
Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The association between systemic anticholinergics and lung function has not been reported. The aim of this study was to investigate if exposure to systemic anticholinergics influences lung function in older adults. Participants of the southernmost centres of the Swedish National study on Aging and Care (SNAC) were followed from 2001 to 2021. In total, 2936 subjects (2253 from Good Aging in Skåne and 683 from SNAC-B) were included. An extensive medical examination including spirometry assessments was performed during the study visits. The systemic anticholinergic burden was described using the anticholinergic cognitive burden scale. The effect of new use of systemic anticholinergics on the annual change in forced expiratory volume (FEV1s) was estimated using mixed models. During follow-up, 802 (27.3%) participants were exposed to at least one systemic anticholinergic medicine. On average, the FEV1s of participants without systemic anticholinergic exposure decreased 37.2 ml/year (95% CI [33.8; 40.6]) while participants with low and high exposure lose 47.2 ml/year (95% CI [42.4; 52.0]) and 43.7 ml/year (95% CI [25.4; 62.0]). A novel association between new use of medicines with systemic anticholinergic properties and accelerated decrease in lung function in older adults was found. The accelerated decrease is comparable to that observed in smokers. Studies are needed to further explore this potential side effect of systemic anticholinergics.
Topics: Humans; Aged; Cholinergic Antagonists; Aging; Lung
PubMed: 38388652
DOI: 10.1038/s41598-024-54879-z -
Archivos de Bronconeumologia Apr 2024Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, increasing the prevalence of both entities and impacting on symptoms...
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, increasing the prevalence of both entities and impacting on symptoms and prognosis. CVD should be suspected in patients with COPD who have high/very high risk scores on validated scales, frequent exacerbations, precordial pain, disproportionate dyspnea, or palpitations. They should be referred to cardiology if they have palpitations of unknown cause or angina pain. COPD should be suspected in patients with CVD if they have recurrent bronchitis, cough and expectoration, or disproportionate dyspnea. They should be referred to a pulmonologist if they have rhonchi or wheezing, air trapping, emphysema, or signs of chronic bronchitis. Treatment of COPD in cardiovascular patients should include long-acting muscarinic receptor antagonists (LAMA) or long-acting beta-agonists (LABA) in low-risk or high-risk non-exacerbators, and LAMA/LABA/inhaled corticosteroids in exacerbators who are not controlled with bronchodilators. Cardioselective beta-blockers should be favored in patients with CVD, the long-term need for amiodarone should be assessed, and antiplatelet drugs should be maintained if indicated.
Topics: Humans; Cardiovascular Diseases; Administration, Inhalation; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Drug Therapy, Combination; Adrenal Cortex Hormones; Dyspnea; Pain; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents
PubMed: 38383272
DOI: 10.1016/j.arbres.2024.01.013 -
The American Journal of Managed Care Feb 2024For patients with asthma who remain symptomatic on a medium-dose inhaled corticosteroid/long-acting β2 agonist, addition of a long-acting muscarinic antagonist as a...
OBJECTIVES
For patients with asthma who remain symptomatic on a medium-dose inhaled corticosteroid/long-acting β2 agonist, addition of a long-acting muscarinic antagonist as a supplementary controller is a recommended option. However, real-world data on the characteristics and treatment patterns of these patients are limited. This study described the demographics and clinical characteristics of new users of single- or multiple-inhaler triple therapy and treatment patterns preceding triple-therapy initiation.
STUDY DESIGN
This retrospective cohort study used medical and pharmacy claims data from the IQVIA PharMetrics Plus database.
METHODS
The study population comprised adults with asthma with or without chronic obstructive pulmonary disease (COPD) initiating triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25 μg) or multiple-inhaler triple therapy (MITT) between September 18, 2017, and September 30, 2019. Demographics, clinical characteristics, and treatment patterns in the 12 months preceding triple-therapy initiation were described (baseline period).
RESULTS
A total of 12,395 patients were included. Among FF/UMEC/VI initiators with asthma (n = 1301), the mean age was 49.0 years and 59.3% were women. During the baseline period, 81.5% of patients used controller therapy, 94.7% used rescue medications, and 42.0% reported at least 1 asthma-related exacerbation; the annual mean exacerbation rate was 0.96. Similar trends were observed among patients with asthma initiating MITT and patients with comorbid asthma-COPD initiating FF/UMEC/VI or MITT.
CONCLUSION
In real-world practice, triple therapy is often utilized following other asthma controller medication use. High disease burden, as evidenced by substantial use of rescue medications and continued asthma-related exacerbations, suggests that patients may not have achieved adequate asthma control prior to triple-therapy initiation.
Topics: Adult; Humans; Female; Middle Aged; Male; Bronchodilator Agents; Retrospective Studies; Administration, Inhalation; Asthma; Pulmonary Disease, Chronic Obstructive; Fluticasone; Muscarinic Antagonists; Drug Combinations
PubMed: 38381542
DOI: 10.37765/ajmc.2024.89494 -
European Review For Medical and... Feb 2024Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate...
OBJECTIVE
Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment.
MATERIALS AND METHODS
Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins.
RESULTS
When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin.
CONCLUSIONS
This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.
Topics: Animals; Rats; Acetylcholinesterase; Benzopyrans; Brain-Derived Neurotrophic Factor; Caspase 3; Hippocampus; Maze Learning; Memory Disorders; Oxidative Stress; Scopolamine
PubMed: 38375702
DOI: 10.26355/eurrev_202402_35334 -
International Journal of Chronic... 2024Patients with chronic obstructive pulmonary disease (COPD) who are hospitalized are more likely to die from their illness and have increased likelihood of re-admission...
PURPOSE
Patients with chronic obstructive pulmonary disease (COPD) who are hospitalized are more likely to die from their illness and have increased likelihood of re-admission than those who are not. Subsequent re-admissions further increase the burden on healthcare systems. This study compared inpatient admission rates and time-to-first COPD-related inpatient admission among Medicare beneficiaries with COPD indexed on umeclidinium/vilanterol (UMEC/VI) versus tiotropium (TIO).
PATIENTS AND METHODS
This retrospective study used the All-Payer Claims Database to investigate hospital admission and re-admission outcomes in Medicare beneficiaries with COPD with an initial pharmacy claim for UMEC/VI or TIO from 1 January 2015 to 28 February 2020. Inpatient admissions, baseline, and follow-up variables were assessed in patients indexed on UMEC/VI and TIO after propensity score matching (PSM), with time-to-first on-treatment COPD-related inpatient admission as the primary endpoint. Re-admissions were assessed among patients with a COPD-related inpatient admission in the 30- and 90-days post-discharge.
RESULTS
Post-PSM, 7152 patients indexed on UMEC/VI and 7069 on TIO were eligible for admissions analysis. The mean (standard deviation [SD]) time-to-first COPD-related inpatient admission was 46.71 (87.99) days for patients indexed on UMEC/VI and 44.96 (85.90) days for those on TIO (p=0.06). The mean (SD) number of inpatient admissions per patient was 1.24 (2.92) for patients indexed on UMEC/VI and 1.26 (3.05) for those on TIO (p=0.49). Proportion of patients undergoing re-admissions was similar between treatments over both 30 and 90 days, excluding a significantly lower proportion of patients indexed on UMEC/VI than those indexed on TIO for COPD-related re-admissions for hospital stays of 4-7 days and 7-14 days, and all-cause re-admissions for stays of 4-7 days.
CONCLUSION
Patients with COPD using Medicare in the US and receiving UMEC/VI or TIO reported similar time-to-first inpatient admission and similar proportion of re-admissions.
Topics: Humans; Aged; United States; Tiotropium Bromide; Pulmonary Disease, Chronic Obstructive; Bronchodilator Agents; Inpatients; Retrospective Studies; Aftercare; Treatment Outcome; Forced Expiratory Volume; Administration, Inhalation; Patient Discharge; Medicare; Benzyl Alcohols; Chlorobenzenes; Drug Combinations; Quinuclidines
PubMed: 38374817
DOI: 10.2147/COPD.S436654 -
BMC Geriatrics Feb 2024Urinary incontinence (UI) is a common geriatric syndrome with high health and socio-economic impacts in nursing home (NH) residents.
BACKGROUND
Urinary incontinence (UI) is a common geriatric syndrome with high health and socio-economic impacts in nursing home (NH) residents.
OBJECTIVES
To estimate the prevalence and types of UI and its associated factors in older people living in NHs in Central Catalonia (Spain). We also determined the proportion of residents who were receiving behavioural strategies to prevent/manage UI.
DESIGN AND SETTING
Cross-sectional study in 5 NHs conducted from January to March 2020.
METHODS
We included consenting residents aged 65 + permanently living in the NHs. Residents who were hospitalized, in a coma or palliative care were excluded. UI was assessed using Section H of the Minimum Data Set. Sociodemographic and health-related variables were examined. Descriptive, bivariate, and multivariate (logistic regression) analyses were performed.
RESULTS
We included 132 subjects (82.6% women), mean age of 85.2 (SD = 7.4) years. The prevalence of UI was 76.5% (95% CI: 68.60-82.93). The most common type was functional UI (45.5%), followed by urgency UI (11.4%). Only 46.2% of residents received at least one behavioural strategy to manage UI. Most sedentary behaviour (SB) variables presented a p-value lower than 0.001 in the bivariate analyses, but none remained in the final model. Moderate-severe cognitive impairment (OR = 4.44, p =.003), anticholinergic activity (OR = 3.50, p =.004) and risk of sarcopenia using SARC-F (OR = 2.75, p =.041) were associated with UI.
CONCLUSIONS
The prevalence of UI was high in this sample of NH residents compared to the literature, yet less than half received prompted voiding as a strategy to prevent/reduce UI.UI was associated with cognitive impairment, anticholinergic activity, and risk of sarcopenia.
Topics: Humans; Female; Aged; Aged, 80 and over; Male; Cross-Sectional Studies; Prevalence; Sarcopenia; Nursing Homes; Urinary Incontinence; Cholinergic Antagonists
PubMed: 38368318
DOI: 10.1186/s12877-024-04748-1 -
Environmental Science and Pollution... Mar 2024The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study....
The uptake, translocation, and metabolization of four widely used drugs, amitriptyline, orphenadrine, lidocaine, and tramadol, were investigated in a laboratory study. Cress (Lepidium sativum L.) and pea (Pisum sativum L.) were employed as model plants. These plants were grown in tap water containing the selected pharmaceuticals at concentrations ranging from 0.010 to 10 mg L, whereby the latter concentration was employed for the (tentative) identification of drug-related metabolites formed within the plant. Thereby, mainly phase I metabolites were detected. Time-resolved uptake studies, with sampling after 1, 2, 4, 8, and 16 days, revealed that all four pharmaceuticals were taken up by the roots and further relocated to plant stem and leaves. Also in these studies, the corresponding phase I metabolites could be detected, and their translocation from root to stem (pea only) and finally leaves could be investigated.
Topics: Amitriptyline; Pisum sativum; Brassicaceae; Orphenadrine; Tramadol; Lidocaine; Plants; Vegetables; Pharmaceutical Preparations; Plant Roots
PubMed: 38363510
DOI: 10.1007/s11356-024-32379-x -
International Journal of Molecular... Feb 2024Griseb. and L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant,...
Griseb. and L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of are well documented, the cognitive benefits of remain unexplored. This study assessed the potential effect of on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of . Over a 21-day period, rats orally received extracts of cultivated (200 mg/kg) and (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. excelled in preserving spatial working memory, while exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.
Topics: Rats; Male; Animals; Scopolamine; Sideritis; Rats, Wistar; Acetylcholinesterase; Plant Extracts; Antioxidants; Memory Disorders; Cognitive Dysfunction; Dementia; Maze Learning
PubMed: 38339117
DOI: 10.3390/ijms25031840 -
Molecules (Basel, Switzerland) Jan 2024The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain...
The Impact of LY487379 or CDPPB on eNOS Expression in the Mouse Brain and the Effect of Joint Administration of Compounds with NO Releasers on MK-801- or Scopolamine-Driven Cognitive Dysfunction in Mice.
The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer's disease (AD). Positive allosteric modulators (PAMs) of metabotropic glutamate (mGlu) receptors were shown to be effective procognitive compounds, but little is known about their impact on eNOS expression and stability. Here, we investigated the influence of the acute and chronic administration of LY487379 or CDPPB (mGlu2 and mGlu5 PAMs), on eNOS expression in the mouse brain and the effect of the joint administration of the ligands with nitric oxide (NO) releasers, spermineNONOate or DETANONOate, in different combinations of doses, on MK-801- or scopolamine-induced amnesia in the novel object recognition (NOR) test. Our results indicate that both compounds provoked eNOS monomer formation, and CDPPB at a dose of 5 mg/kg exaggerated the effect of MK-801 or scopolamine. The coadministration of spermineNONOate or DETANONOate enhanced the antiamnesic effect of CDPPB or LY487379. The best activity was observed for ineffective or moderate dose combinations. The results indicate that treatment with mGluR2 and mGluR5 PAMs may be burdened with the risk of promoting eNOS uncoupling through the induction of dimer dissociation. Administration of the lowest possible doses of the compounds with NO donors, which themselves have procognitive efficacy, may be proposed for the treatment of schizophrenia or AD.
Topics: Mice; Animals; Dizocilpine Maleate; Nitric Oxide; Scopolamine; Nitric Oxide Synthase Type III; Cognitive Dysfunction; Brain; Allosteric Regulation; Nitroso Compounds; Pyrazoles; Benzamides; Sulfonamides; Pyridines
PubMed: 38338372
DOI: 10.3390/molecules29030627 -
Journal of Psychopharmacology (Oxford,... Mar 2024Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new...
BACKGROUND
Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new treatments to reduce tobacco and nicotine use. Glucocorticoid receptor blockade shows promise as a novel treatment for drug abuse and stress-related disorders.
AIM
These studies aim to investigate whether glucocorticoid receptor blockade with mifepristone diminishes the reinforcing properties of nicotine in rats with intermittent or daily long access to nicotine.
METHODS
The rats self-administered 0.06 mg/kg/inf of nicotine for 6 h per day, with either intermittent or daily access for 4 weeks before treatment with mifepristone. Daily nicotine self-administration models regular smoking, while intermittent nicotine self-administration models occasional smoking. To determine whether the rats were dependent, they were treated with the nicotinic acetylcholine receptor antagonist mecamylamine, and somatic signs were recorded.
RESULTS
The rats with intermittent access to nicotine had a higher level of nicotine intake per session than those with daily access but only the rats with daily access to nicotine showed signs of physical dependence. Furthermore, mecamylamine increased nicotine intake during the first hour of access in rats with daily access but not in those with intermittent access. Mifepristone decreased total nicotine intake in rats with intermittent and daily access to nicotine. Moreover, mifepristone decreased the distance traveled and rearing in the open field test and operant responding for food pellets.
CONCLUSION
These findings indicate that mifepristone decreases nicotine intake but this effect may be partially attributed to the sedative effects of mifepristone.
Topics: Humans; Rats; Animals; Nicotine; Mecamylamine; Mifepristone; Smoking; Receptors, Glucocorticoid; Tobacco Use Disorder; Substance Withdrawal Syndrome; Rats, Wistar; Self Administration; Dose-Response Relationship, Drug
PubMed: 38332661
DOI: 10.1177/02698811241230255