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Scientific Reports Oct 2022To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in... (Meta-Analysis)
Meta-Analysis
Efficacy, according to urodynamics, of OnabotulinumtoxinA compared with antimuscarinic drugs, for neurogenic detrusor overactivity: a systematic review and network meta-analysis.
To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdet endpoints. OnabotulinumtoxinA 200U was more effective on the urodynamic endpoint of BC than other drugs or doses of OnabotulinumtoxinA. According to the MCC urodynamic results, oxybutynin, solifenacin 10 mg, and tolterodine 4 mg also had positive effects. OnabotulinumtoxinA 300U, 200U and 100U were better in improving the urodynamic results of NDO, and the current evidence also shows that selective injection of onabotulinumtoxinA can effectively improve the urodynamic results.
Topics: Humans; Botulinum Toxins, Type A; Urodynamics; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Solifenacin Succinate; Network Meta-Analysis; Tolterodine Tartrate; Bayes Theorem; Treatment Outcome; Urinary Bladder, Overactive
PubMed: 36289427
DOI: 10.1038/s41598-022-22765-1 -
Scientific Reports Sep 2022A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids... (Meta-Analysis)
Meta-Analysis
A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids (ICS) in stable chronic obstructive pulmonary disease (COPD). We selected 26 parallel randomized controlled trials (41,366 patients) comparing triple therapy with ICS/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), and LAMA in patients with stable COPD for ≥ 12 weeks from PubMed, EMBASE, the Cochrane Library, and clinical trial registries (search from inception to June 30, 2022). Triple therapy with high dose (HD)-ICS exhibited a lower risk of total exacerbation in pre-specified subgroups treated for ≥ 48 weeks than that with low dose (LD)-ICS (odds ratio [OR] = 0.66, 95% credible interval [CrI] = 0.52-0.94, low certainty of evidence) or medium dose (MD)-ICS (OR = 0.66, 95% CrI = 0.51-0.94, low certainty of evidence). Triple therapy with HD-ICS exhibited a lower risk of moderate-to-severe exacerbation in pre-specified subgroups with forced expiratory volume in 1 s < 65% (OR = 0.6, 95% CrI = 0.37-0.98, low certainty of evidence) or previous exacerbation history (OR = 0.6, 95% CrI = 0.36-0.999, very low certainty of evidence) than triple therapy with MD-ICS. Triple therapy with HD-ICS may reduce acute exacerbation in patients with COPD treated with other drug classes including triple therapy with LD- or MD-ICS or dual therapies.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive
PubMed: 36127353
DOI: 10.1038/s41598-022-18353-y -
Contrast Media & Molecular Imaging 2022Chronic obstructive pulmonary disease (COPD) is a major and difficult disease of the chronic respiratory system that is common and frequent, with a huge disease burden....
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a major and difficult disease of the chronic respiratory system that is common and frequent, with a huge disease burden. The aim of this study was to investigate the efficacy and safety of budesonide/glyburide/formoterol fumarate (BGF) in the treatment of COPD.
METHODS
A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The basic features of the seven pieces of literature were identified using the search strategy. The sample size range was 130∼1264.
RESULTS
The effects of BGF increased FEV1 in patients with COPD (mean difference = 2.86, 95%CI: 2.71-3.01, < 0.00001). The effects of BGF improved in patients with ≥1 TEAE in patients with COPD, and was not statistically significant after treatment (Odds rate = 1.00, 95%CI: 0.85-1.17, =0.97). The effects of BGF increased in patients with TEAEs related a to study treatment in patients with COPD (odds rate = 1.27, 95% CI: 1.03-1.57, =0.02). The effects of BGF in decreased patients with serious TEAEs in patients with COPD (odds rate = -0.02, 95% CI: -0.03--0.00, =0.04). The effects of BGF decreased the death rate in patients with COPD, and were not statistically significant after treatment (odds rate = 0.77, 95% CI: 0.31-1.97, =0.59). The effects of BGF decreased the hypertension rate in patients with COPD (odds rate = 0.92, 95% CI: 0.44-1.89, =0.81), and was not statistically significant after treatment. The effects of BGF increased pneumonia in patients with COPD (odds rate = 1.55, 95% CI: 0.81-2.97, =0.19), and were not statistically significant after treatment. The effects of BGF increased FEV1, increased patients with TEAEs related a to study treatment, and decreased patients with serious TEAEs in patients with COPD.
CONCLUSION
This study elucidates the efficacy and safety of BGF in the treatment of COPD with a view to providing a clinical reference.
Topics: Aged; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Glycopyrrolate; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 36072633
DOI: 10.1155/2022/8382295 -
Respiratory Research Aug 2022Although asthma is more prevalent in women and the prevalence of COPD is increasing in women, the current international recommendations for the management and prevention...
BACKGROUND
Although asthma is more prevalent in women and the prevalence of COPD is increasing in women, the current international recommendations for the management and prevention of asthma and COPD provide no sex-related indication for the treatment of these diseases. Therefore, we systematically reviewed the evidence across literature on the sex-related effectiveness of asthma and COPD therapy.
METHODS
This systematic review has been registered in PROSPERO and performed according to PRISMA-P. The PICO framework was applied for the literature search strategy: "patient problem" included adult patients suffering from asthma or COPD, "Intervention" regarded the pharmacological treatments for asthma or COPD, "Comparison" was vs. baseline, active controls, or placebo, "Outcome" was any difference sex-related in the effectiveness of interventions.
RESULTS
In asthma 44% of the evidence reported that men responded better than women to the therapy, whereas this percentage was 28% in COPD. ICS was generally less effective in women than in men to treat asthma, and consistent evidence suggests that in asthmatic patients ICS/LABA/LAMA combination may be equally effective in both men and women. Due to the inconsistent available evidence, it is not possible to identify specific treatments whose effectiveness is related to sex difference in COPD patients.
CONCLUSIONS
There is a strong need of investigating the sex-related impact of asthma and COPD treatments. Pre-specified analyses in men and women should be planned in future trial protocols, a necessary condition that should be requested also by the regulatory agencies to overcome the anachronistic "one-size-fits-all" approach to therapeutics associated with suboptimal outcomes for patients.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Sex Characteristics
PubMed: 36038873
DOI: 10.1186/s12931-022-02140-4 -
European Journal of Clinical... Oct 2022Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring... (Review)
Review
PURPOSE
Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled β-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs.
METHODS
We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning.
RESULTS
We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects.
CONCLUSION
Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.
Topics: Adrenal Cortex Hormones; Adult; Aminophylline; Anti-Asthmatic Agents; Asthma; Child; Cholinergic Antagonists; Fentanyl; Humans; Ketamine; Multicenter Studies as Topic; Prospective Studies
PubMed: 36008492
DOI: 10.1007/s00228-022-03374-3 -
The Cochrane Database of Systematic... Aug 2022Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor.
OBJECTIVES
Our primary objective was to assess whether anticholinergic burden, as defined at the level of each individual scale, was a prognostic factor for further cognitive decline or neuropsychiatric disturbances in older adults with pre-existing diagnoses of dementia or cognitive impairment. Our secondary objective was to investigate whether anticholinergic burden was a prognostic factor for other adverse clinical outcomes, including mortality, impaired physical function, and institutionalisation.
SEARCH METHODS
We searched these databases from inception to 29 November 2021: MEDLINE OvidSP, Embase OvidSP, PsycINFO OvidSP, CINAHL EBSCOhost, and ISI Web of Science Core Collection on ISI Web of Science.
SELECTION CRITERIA
We included prospective and retrospective longitudinal cohort and case-control observational studies, with a minimum of one-month follow-up, which examined the association between an anticholinergic burden measurement scale and the above stated adverse clinical outcomes, in older adults with pre-existing diagnoses of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and undertook data extraction, risk of bias assessment, and GRADE assessment. We summarised risk associations between anticholinergic burden and all clinical outcomes in a narrative fashion. We also evaluated the risk association between anticholinergic burden and mortality using a random-effects meta-analysis. We established adjusted pooled rates for the anticholinergic cognitive burden (ACB) scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. MAIN RESULTS: We identified 18 studies that met our inclusion criteria (102,684 older adults). Anticholinergic burden was measured using five distinct measurement scales: 12 studies used the ACB scale; 3 studies used the Anticholinergic Risk Scale (ARS); 1 study used the Anticholinergic Drug Scale (ADS); 1 study used the Anticholinergic Effect on Cognition (AEC) Scale; and 2 studies used a list developed by Tune and Egeli. Risk associations between anticholinergic burden and adverse clinical outcomes were highly heterogenous. Four out of 10 (40%) studies reported a significantly increased risk of greater long-term cognitive decline for participants with an anticholinergic burden compared to participants with no or minimal anticholinergic burden. No studies investigated neuropsychiatric disturbance outcomes. One out of four studies (25%) reported a significant association with reduced physical function for participants with an anticholinergic burden versus participants with no or minimal anticholinergic burden. No study (out of one investigating study) reported a significant association between anticholinergic burden and risk of institutionalisation. Six out of 10 studies (60%) found a significantly increased risk of mortality for those with an anticholinergic burden compared to those with no or minimal anticholinergic burden. Pooled analysis of adjusted mortality hazard ratios (HR) measured anticholinergic burden with the ACB scale, and suggested a significantly increased risk of death for those with a high ACB score relative to those with no or minimal ACB scores (HR 1.153, 95% confidence interval (CI) 1.030 to 1.292; 4 studies, 48,663 participants). An exploratory pooled analysis of adjusted mortality HRs across anticholinergic burden scales also suggested a significantly increased risk of death for those with a high anticholinergic burden (HR 1.102, 95% CI 1.044 to 1.163; 6 studies, 68,381 participants). Overall GRADE evaluation of results found low- or very low-certainty evidence for all outcomes. AUTHORS' CONCLUSIONS: There is low-certainty evidence that older adults with dementia or cognitive impairment who have a significant anticholinergic burden may be at increased risk of death. No firm conclusions can be drawn for risk of accelerated cognitive decline, neuropsychiatric disturbances, decline in physical function, or institutionalisation.
Topics: Aged; Cholinergic Antagonists; Cognitive Dysfunction; Dementia; Humans; Prospective Studies; Retrospective Studies
PubMed: 35994403
DOI: 10.1002/14651858.CD015196.pub2 -
Academic Emergency Medicine : Official... Jan 2023Adjunct therapy with anticholinergic agents has been proposed to reduce the incidence of extrapyramidal side effects such as akathisia following treatment with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Adjunct therapy with anticholinergic agents has been proposed to reduce the incidence of extrapyramidal side effects such as akathisia following treatment with neuroleptics or metoclopramide. This systematic review assessed the effectiveness of anticholinergic agents to prevent neuroleptic or metoclopramide-induced akathisia in patients presenting to the emergency department (ED) with benign headache.
METHODS
Eight electronic databases and the gray literature were searched to identify randomized controlled trials involving adult patients presenting to the ED with primary headache treated with neuroleptic or metoclopramide. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Individual or pooled meta-analysis of dichotomous outcomes were calculated as relative risks (RRs) with 95% confidence intervals (CIs) using a random-effects model. Heterogeneity was assessed using the I statistic.
RESULTS
A total of 1032 studies were screened, of which two studies were included in the review. Both studies provided patients with diphenhydramine following treatment with neuroleptics or metoclopramide. Treatment with diphenhydramine did not reduce the incidence of akathisia compared to treatment with placebo (RR 0.83, 95% CI 0.43-1.61, I = 0%). The impact of diphenhydramine on pain relief, need for rescue medications, and relief of other extrapyramidal side effects was reported in one of the two studies, with no significant differences noted in any outcomes compared to patients treated with placebo.
CONCLUSION
This review found insufficient evidence to recommend the use of diphenhydramine as an adjunct therapy to prevent akathisia in ED patients treated with neuroleptics or metoclopramide for primary headache. This finding relies on the results of two small randomized controlled trials with incomplete outcome reporting. Additional high-quality studies are needed to better understand the clinical efficacy of agents with anticholinergic properties in the ED management of patients with primary headaches.
Topics: Adult; Humans; Antipsychotic Agents; Cholinergic Antagonists; Diphenhydramine; Emergency Service, Hospital; Headache; Metoclopramide; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 35962748
DOI: 10.1111/acem.14581 -
British Journal of Clinical Pharmacology Dec 2022Despite numerous studies on quinidine therapies for epilepsies associated with KCNT1 gene mutations, there is no consensus on its clinical utility. Thus, we reviewed... (Review)
Review
AIMS
Despite numerous studies on quinidine therapies for epilepsies associated with KCNT1 gene mutations, there is no consensus on its clinical utility. Thus, we reviewed studies evaluating the efficacy and safety of quinidine in KCNT1-related epileptic disorders.
METHODS
Electronic databases were queried for in vivo and in vitro studies on quinidine therapy in KCNT1-related epilepsies published on or before 1 May 2022. The evaluation of evidence was done as per the American Academy of Neurology's classification scheme. Identification of significant factors that possibly influenced therapeutic effects of quinidine were performed using χ tests.
RESULTS
Twenty-seven studies containing 82 patient records were reviewed. Records of 80 patients with 33 KCNT1 mutations were analysed, of which 20 patients had gained ≥50% seizure reduction due to quinidine therapy. However, quinidine therapy often had different effects on patients with the same KCNT1 mutation. Age, genotypes of KCNT1 mutations, seizure types and brain MRI did not significantly influence the therapeutic effect of quinidine. Prolonged QTc was the most common among all adverse events with quinidine. Notably, results of in vitro quinidine tests did not correspond with in vivo tests.
CONCLUSIONS
Therapeutic effects of quinidine on KCNT1-related epilepsies remained indefinite as contradictory results were detected in similar patients. Age, seizure types, genotypes of KCNT1 mutations and brain MRI did not influence the therapeutic effects of quinidine. Insensitivity to quinidine by a certain Kcnt1 genotype in molecular tests is predictive of its inefficacy in human populations of the respective mutation.
Topics: Humans; Quinidine; Potassium Channels, Sodium-Activated; Anticonvulsants; Nerve Tissue Proteins; Epilepsy; Seizures; Mutation
PubMed: 35940594
DOI: 10.1111/bcp.15479 -
American Journal of Obstetrics and... Jan 2023The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies... (Review)
Review
OBJECTIVE
The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes.
DATA SOURCES
We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021.
STUDY ELIGIBILITY CRITERIA
Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone.
METHODS
A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder.
RESULTS
A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes.
CONCLUSION
Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.
Topics: Humans; Urinary Bladder, Overactive; TRPV Cation Channels; Genetic Markers; Cholinergic Antagonists; Receptors, Cholinergic; Receptors, Purinergic; Receptor, Muscarinic M3
PubMed: 35932882
DOI: 10.1016/j.ajog.2022.07.044 -
Journal of the American Medical... Sep 2022To summarize current evidence regarding facility and prescriber characteristics associated with potentially harmful medication (PHM) use by residents in nursing homes... (Review)
Review
OBJECTIVES
To summarize current evidence regarding facility and prescriber characteristics associated with potentially harmful medication (PHM) use by residents in nursing homes (NHs), which could inform the development of interventions to reduce this potentially harmful practice.
DESIGN
Scoping review.
SETTING AND PARTICIPANTS
Studies conducted in the United States that described facility and prescriber factors associated with PHM use in NHs.
METHODS
Electronic searches of PubMed/MEDLINE were conducted for articles published in English between April 2011 and November 2021. PHMs were defined based on the Beers List criteria. Studies testing focused interventions targeting PHM prescribing or deprescribing were excluded. Studies were characterized by the strengths and weaknesses of the analytic approach and generalizability.
RESULTS
Systematic search yielded 1253 articles. Of these, 29 were assessed in full text and 20 met inclusion criteria. Sixteen examined antipsychotic medication (APM) use, 2 anticholinergic medications, 1 sedative-hypnotics, and 2 overall PHM use. APM use was most commonly associated with facilities with a higher proportion of male patients, younger patients, and patients with severe cognitive impairment, anxiety, depression, and aggressive behavior. The use of APM and anticholinergic medications was associated with low registered nurse staffing ratios and for-profit facility status. No studies evaluated prescriber characteristics.
CONCLUSIONS AND IMPLICATIONS
Included studies primarily examined APM use. The most commonly reported facility characteristics were consistent with previously reported indicators of poor NH quality and NHs with patient case mix more likely to use PHMs.
Topics: Antipsychotic Agents; Cholinergic Antagonists; Drug Prescriptions; Female; Humans; Inappropriate Prescribing; Male; Nursing Homes; United States
PubMed: 35868350
DOI: 10.1016/j.jamda.2022.06.008