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The Annals of Otology, Rhinology, and... Jun 2024This retrospective review documents the experience of ipratropium bromide use among pediatric patients with sialorrhea at our multidisciplinary sialorrhea clinic at...
OBJECTIVE
This retrospective review documents the experience of ipratropium bromide use among pediatric patients with sialorrhea at our multidisciplinary sialorrhea clinic at Children's Hospital at London Health Sciences Centre (LHSC).
METHODS
A retrospective chart review of patients diagnosed with sialorrhea at our multidisciplinary clinic between January 2015 and June 2021 was completed. Data on patient demographics, comorbidities, clinical presentation, previous interventions, quality of life, and medication adverse side effects was collected. Drooling Frequency and Severity Scale (DFSS) scores were reviewed to compare sialorrhea management pre- and post-treatment with topical 0.03% ipratropium bromide nasal solution. A descriptive analysis and Wilcoxon signed rank tests were conducted to compare pre- versus post-treatment DFSS scores.
RESULTS
A total of 12 patients presented for follow-up and were included in the final analysis. At the pre-treatment visit, the median DFSS score was 4 for frequency and 5 for severity. Post-treatment, median DFSS score was 3 for frequency and 4.5 for severity, ( = .020 and .129, respectively). Minimal adverse effects were encountered.
CONCLUSIONS
Ipratropium bromide provided a statistically significant benefit for drooling frequency in the patients studied and may present an additional topical medical option for pediatric sialorrhea with limited adverse effects.
Topics: Humans; Sialorrhea; Retrospective Studies; Female; Male; Child; Ipratropium; Child, Preschool; Adolescent; Treatment Outcome; Severity of Illness Index; Quality of Life; Administration, Intranasal
PubMed: 38433339
DOI: 10.1177/00034894241235523 -
Advances in Therapy Apr 2024This study aimed to assess overactive bladder (OAB) treatment patterns and factors associated with effectiveness and persistence. (Observational Study)
Observational Study
INTRODUCTION
This study aimed to assess overactive bladder (OAB) treatment patterns and factors associated with effectiveness and persistence.
METHODS
A prospective, longitudinal, observational registry study of adults starting OAB therapy with mirabegron or antimuscarinics was undertaken. Primary endpoints were time from treatment initiation to discontinuation/switching; proportion who discontinued/switched; and reasons for discontinuation/switching. Secondary endpoints included OAB Symptom Score (OABSS), OAB Questionnaire: Short Form, and OAB Bladder Assessment Tool scores; factors associated with effectiveness and persistence; and safety.
RESULTS
In total, 556 patients initiating mirabegron and 250 initiating antimuscarinics were enrolled. There was no treatment switch, change, or discontinuation in 68.5% of the mirabegron initiator group and median time to treatment change was not reached. Mean initial treatment duration was 130.8 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, and patients with mild and moderate OAB had significantly better persistence with mirabegron than those with severe OAB. Urinary tract infection was the most common adverse event with mirabegron. There was no treatment switch, change, or discontinuation in 60.4% of the antimuscarinics initiator group and median time to treatment change was not reached. Solifenacin was the most frequent initial treatment (66.0%). Mean treatment duration was 122.2 days. In multivariable models, baseline OABSS was the only variable significantly associated with change from baseline in OABSS, while patients with OAB medication in the 12 months before enrollment had significantly better persistence with antimuscarinics than those with no previous OAB medication. Dry mouth was the most common adverse event with antimuscarinics.
CONCLUSIONS
Mirabegron and solifenacin were commonly prescribed as first-line OAB medications. There was no treatment switch, change, or discontinuation in more than 60% of the mirabegron initiator and antimuscarinics initiator groups. Mean initial treatment duration was 130.8 days and 122.2 days for mirabegron and antimuscarinics, respectively. Graphical Abstract available for this article.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03572231.
Topics: Adult; Humans; Acetanilides; Muscarinic Antagonists; Prospective Studies; Registries; Republic of Korea; Solifenacin Succinate; Taiwan; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents
PubMed: 38430402
DOI: 10.1007/s12325-024-02784-2 -
BMJ Open Ophthalmology Mar 2024This study investigated the agreement between objective wavefront-based refraction and subjective refraction in myopic children. It also assessed the impact of...
OBJECTIVE
This study investigated the agreement between objective wavefront-based refraction and subjective refraction in myopic children. It also assessed the impact of cyclopentolate and refraction levels on the agreement.
METHODS
A total of 84 eyes of myopic children aged 6-13 years were included in the analysis. Non-cycloplegic and cycloplegic objective wavefront-based refraction were determined and cycloplegic subjective refraction was performed for each participant. The data were converted into spherical equivalent, J and J, and Bland-Altman plots were used to analyse the agreement between methods.
RESULTS
Linear functions were used to determine the dependency between the central myopic refractive error and the difference between the method of refraction (=bias). The influence of central myopia was not clinically relevant when analysing the agreement between wavefront results with and without cyclopentolate (comparison 1). The bias for wavefront-based minus subjective spherical equivalent refraction (comparison 2) was ≤-0.50 D (95% limits of agreement -0.010 D to -1.00 D) for myopia of -4.55 D and higher when cycloplegia was used (p<0.05). When no cyclopentolate was used for the wavefront-based refraction (comparison 3), the bias of -0.50 D (95% limits of agreement -0.020 D to -0.97 D) was already reached at a myopic error of -2.97 D. Both astigmatic components showed no clinically relevant bias.
CONCLUSION
The spherical equivalent, measured without cycloplegic agents, led to more myopic measurements when wavefront-based refraction was used. The observed bias increased with the amount of myopic refractive error for comparisons 2 and 3, which needs to be considered when interpreting wavefront-refraction data.
TRIAL REGISTRATION NUMBER
NCT05288335.
Topics: Child; Humans; Mydriatics; Cyclopentolate; Refractive Errors; Myopia; Pupil
PubMed: 38429067
DOI: 10.1136/bmjophth-2023-001322 -
Toxicology Letters Apr 2024The Göttingen minipig is fast becoming the standard for assessing dermal chemical hazards because, like most swine, its skin is predictive of human skin response and...
The Göttingen minipig is fast becoming the standard for assessing dermal chemical hazards because, like most swine, its skin is predictive of human skin response and because this strain's smaller size makes laboratory manipulations and husbandry easier. Unfortunately, standard behavioral tests and apparatus have not been developed for behavioral assessments of this swine strain. Indeed, computer-controlled automated behavioral testing procedures are much needed. The present research advanced this goal by producing a home-cage behavioral testing system that could accommodate minipigs of various sizes (ages). An aluminum frame housed three levers for recording operant responses, and LEDs above and below each lever served as discriminative stimuli. A commercially available food pellet dispenser was attached to a specialized pellet receptacle capable of measuring pellet retrieval. Two behavioral tests were selected and adapted from our commonly used non-human primate behavioral assessments: delayed match-to-sample (a memory test) and temporal response differentiation (a time-estimation test). Minipigs were capable of learning both tests and attaining stable performance. Next, scopolamine was used to validate the sensitivity of the behavioral tests for gauging behavioral perturbations in this swine strain. Scopolamine dose-effect functions were comparable to those observed in other species, including non-human primates, wherein 37.5 µg/kg of scopolamine (administered intramuscularly) reduced responding approximately 50%. Thus, we were successful in developing the apparatus and automated operant behavioral tests necessary to characterize drug safety in this swine strain. This capability will be valuable for characterizing chemical agent toxicity as well as the safety and efficacy of medical countermeasures.
Topics: Swine; Animals; Swine, Miniature; Behavior Rating Scale; Skin; Learning; Scopolamine
PubMed: 38428545
DOI: 10.1016/j.toxlet.2024.02.009 -
BMC Pulmonary Medicine Mar 2024Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and... (Observational Study)
Observational Study
BACKGROUND
Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting.
METHODS
Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes.
RESULTS
In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed.
CONCLUSION
Without statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds.
Topics: Humans; Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Cost of Illness; Drug Therapy, Combination; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quality of Life; Retrospective Studies
PubMed: 38424530
DOI: 10.1186/s12890-024-02902-4 -
Respiratory Research Feb 2024Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which...
BACKGROUND
Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.
METHODS
We investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses.
RESULTS
IL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction.
CONCLUSION
This study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.
Topics: Humans; Muscarinic Antagonists; NF-kappa B; Interleukin-5; Asthma; Adrenal Cortex Hormones; Administration, Inhalation; Epithelial Cells; Adrenergic beta-2 Receptor Agonists; Pulmonary Disease, Chronic Obstructive
PubMed: 38419021
DOI: 10.1186/s12931-024-02710-8 -
European Journal of Anaesthesiology May 2024Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines...
Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.
Topics: Humans; Neuromuscular Blockade; Rocuronium; Vecuronium Bromide; Delayed Emergence from Anesthesia; Monitoring, Intraoperative
PubMed: 38410855
DOI: 10.1097/EJA.0000000000001967 -
Schizophrenia Research Apr 2024Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better...
Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.
Topics: Adult; Humans; Schizophrenia; Cholinergic Antagonists; Benzodiazepines; Serotonin and Noradrenaline Reuptake Inhibitors; Cognitive Dysfunction; Cognition; Neuropsychological Tests; Antidepressive Agents
PubMed: 38401410
DOI: 10.1016/j.schres.2024.02.025 -
Toxins Feb 2024Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer, with a poor prognosis. GBM cells, which develop in the environment of neural tissue, often...
Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer, with a poor prognosis. GBM cells, which develop in the environment of neural tissue, often exploit neurotransmitters and their receptors to promote their own growth and invasion. Nicotinic acetylcholine receptors (nAChRs), which play a crucial role in central nervous system signal transmission, are widely represented in the brain, and GBM cells express several subtypes of nAChRs that are suggested to transmit signals from neurons, promoting tumor invasion and growth. Analysis of published GBM transcriptomes revealed spatial heterogeneity in nAChR subtype expression, and functional nAChRs of α1*, α7, and α9 subtypes are demonstrated in our work on several patient-derived GBM microsphere cultures and on the U87MG GBM cell line using subtype-selective neurotoxins and fluorescent calcium mobilization assay. The U87MG cell line shows reactions to nicotinic agonists similar to those of GBM patient-derived culture. Selective α1*, α7, and α9 nAChR neurotoxins stimulated cell growth in the presence of nicotinic agonists. Several cultivating conditions with varying growth factor content have been proposed and tested. The use of selective neurotoxins confirmed that cell cultures obtained from patients are representative GBM models, but the use of media containing fetal bovine serum can lead to alterations in nAChR expression and functioning.
Topics: Humans; Receptors, Nicotinic; Glioblastoma; alpha7 Nicotinic Acetylcholine Receptor; Nicotinic Agonists; Proteins; Peptides; Cell Line; Cell Proliferation; Nicotinic Antagonists
PubMed: 38393158
DOI: 10.3390/toxins16020080 -
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