-
Advances in Therapy Nov 2021In the absence of head-to-head trials, we performed an indirect treatment comparison of the β-adrenergic agonists vibegron and mirabegron in the treatment of overactive...
BACKGROUND
In the absence of head-to-head trials, we performed an indirect treatment comparison of the β-adrenergic agonists vibegron and mirabegron in the treatment of overactive bladder (OAB).
METHODS
PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively.
RESULTS
After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) (P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) (P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials.
CONCLUSIONS
Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between vibegron and mirabegron.
Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive
PubMed: 34537953
DOI: 10.1007/s12325-021-01902-8 -
Frontiers in Endocrinology 2021Insulin resistance is a metabolic disorder that occurs in type 2 diabetes mellitus and obesity. Genetic factors such as β3-adrenoceptor polymorphism (Trp64Arg) may be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Insulin resistance is a metabolic disorder that occurs in type 2 diabetes mellitus and obesity. Genetic factors such as β3-adrenoceptor polymorphism (Trp64Arg) may be involved in IR and insulin secretion. However, their association is controversial. Therefore, the current meta-analysis was conducted to clarify the relationship between the Trp64Arg and IR.
METHODS
The literature search was performed in PubMed, Embase, and Web of Science using the keywords "Receptors, Adrenergic, beta-3, Receptors, Adrenergic, Insulin Resistance, Protein-Coupled Receptor Kinase 3" from 2005 to February 7, 2021. We used a random-effects model to calculate the pooled effect size. We conducted subgroup analysis and regression analysis to identify sources of heterogeneity; and Egger's test and funnel plot were used to test publication bias. Finally, we conducted a sensitivity analysis.
RESULTS
We included eight papers with 1,586 subjects. There was a positive correlation between Trp64Arg mutation and insulin level (standardized mean difference = 0.20, 95% confidence intervals: 0.00 to 0.39, = 57.6%, = 0.016). However, there was no association between Trp64Arg and the homeostasis model (HOMA-IR) assessment. Egger's tests showed no publication bias; the sensitivity analysis showed that our results were stable. Regression analysis revealed no source of heterogeneity.
CONCLUSION
Trp64Arg may be associated with IR. European ancestry, obesity, plasma insulin level, and test status may be potential factors affecting the relationship between Trp64Arg and IR.
Topics: Genetic Predisposition to Disease; Glucose Intolerance; Humans; Insulin Resistance; Polymorphism, Genetic; Prognosis; Receptors, Adrenergic, beta
PubMed: 34512548
DOI: 10.3389/fendo.2021.708139 -
Allergy Apr 2022A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators... (Review)
Review
A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators (LABA). The addition of long-acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single-inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS-LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive
PubMed: 34478578
DOI: 10.1111/all.15076 -
PloS One 2021Airway inflammation in asthma involves not only the central airways but extends to peripheral airways. Lung deposition may be key for an appropriate treatment of asthma.... (Comparative Study)
Comparative Study Meta-Analysis
Extrafine HFA-beclomethasone-formoterol vs. nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist in patients with persistent asthma: A systematic review and meta-analysis.
OBJECTIVE
Airway inflammation in asthma involves not only the central airways but extends to peripheral airways. Lung deposition may be key for an appropriate treatment of asthma. We compared the clinical effects of extrafine hydrofluoroalkane (HFA)-beclomethasone-formoterol (BDP-F) versus equipotent doses of nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist (ICS-LABA) in asthma.
METHODS
We identified eligible studies by a comprehensive literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Data analysis was performed with the Review Manager 5.3.5 software (Cochrane IMS, 2014).
RESULTS
A total of 2326 patients with asthma from ten published randomized controlled trials (RCTs) were enrolled for analysis. Change from baseline in morning pre-dose peak expiratory flow (PEF), evening pre-dose PEF and forced expiratory volume in one second (FEV1) were detected no significant differences between extrafine HFA-BDP-F and nonextrafine ICS-LABAs (p = 0.23, p = 0.99 and p = 0.23, respectively). Extrafine HFA-BDP-F did not show any greater benefit in forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%), the parameter concerning peripheral airways (MD 0.03L/s, p = 0.65; n = 877). There were no substantial differences between interventions in fractional exhaled nitric oxide (FeNO) levels or in its alveolar fraction. The overall analysis showed no significant benefit of extrafine HFA-BDP-F over nonextrafine ICS-LABA in improving Asthma Control Test (ACT) score (p = 0.30) or decreasing the number of puffs of rescue medication use (p = 0.16). Extrafine HFA-BDP-F did not lead to less exacerbations than nonextrafine ICS-LABA (RR 0.61, 95% CI: 0.31 to 1.20; I2 = 0; p = 0.15).
CONCLUSION
Enrolled RCTs of extrafine HFA-BDP-F have demonstrated no significant advantages over the equivalent combination of nonextrafine ICS-LABA in improving pulmonary function concerning central airways or peripheral airways, improving asthma symptom control or reducing exacerbation rate.
Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Beclomethasone; Female; Formoterol Fumarate; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Outcome Assessment, Health Care; Publication Bias; Risk; Young Adult
PubMed: 34478483
DOI: 10.1371/journal.pone.0257075 -
Biomedicine & Pharmacotherapy =... Oct 2021β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical... (Meta-Analysis)
Meta-Analysis
β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical practice. Interindividual variability in response to β-blockers may be explained by genetic differences. In fact, pharmacogenetic interactions for some of these drugs have been widely studied, such as metoprolol. But studies that explore genetic variants affecting bisoprolol response are inconclusive, limited or confusing because of mixed results with other β-Blockers, different genetic polymorphisms observed, endpoint studied etc. Because of this, we performed a systematic review in order to find relevant genetic variants affecting bisoprolol response. We have found genetic polymorphism in several genes, but most of the studies focused in ADRB variants. The ADRB1 Arg389Gly (rs1801253) was the most studied genetic polymorphism and it seems to influence the response to bisoprolol, although studies are inconclusive. Even, we performed a meta-analysis about its influence on systolic/diastolic blood pressure in patients treated with bisoprolol, but this did not show statistically significant results. In conclusion, many genetic polymorphisms have been assessed about their influence on patients´ response to bisoprolol and the ADRB1 Arg389Gly (rs1801253) seems the most relevant genetic polymorphism in this regard but results have not been confirmed with a meta-analysis. Our results support the need of further studies about the impact of genetic variants on bisoprolol response, considering different genetic polymorphisms and conducting single and multiple SNPs analysis, including other clinical parameters related to bisoprolol response in a multivariate study.
Topics: Adrenergic beta-1 Receptor Antagonists; Bisoprolol; Blood Pressure; Cardiovascular Diseases; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-1; Treatment Outcome
PubMed: 34470728
DOI: 10.1016/j.biopha.2021.112069 -
Medicine Aug 2021Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB).
METHODS
We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796.
RESULTS
After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05).
CONCLUSIONS
This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.
Topics: Adjuvants, Anesthesia; Adrenergic alpha-2 Receptor Agonists; Anesthesia, Local; Dexamethasone; Dexmedetomidine; Glucocorticoids; Humans; Nerve Block; Peripheral Nerves; Randomized Controlled Trials as Topic
PubMed: 34449500
DOI: 10.1097/MD.0000000000027064 -
Journal of Investigative Medicine : the... Dec 2021Chronic obstructive pulmonary disease (COPD) is at present the third leading cause of death in the world. Long-acting muscarinic antagonist (LAMA) is widely used as a... (Meta-Analysis)
Meta-Analysis
Chronic obstructive pulmonary disease (COPD) is at present the third leading cause of death in the world. Long-acting muscarinic antagonist (LAMA) is widely used as a bronchodilator in patients with COPD. However, there is controversy concerning their cardiovascular safety. This meta-analysis aims to assess the efficacy and cardiovascular safety of LAMAs versus placebo in patients with COPD. We searched Pub Med, Embase, Cochrane Library, and Web of Science to identify studies that compared LAMA with placebo in patients with COPD. Twenty-one studies involving 24,987 participants were finally included in the analysis. There was no significant difference in the incidence of all adverse events (risk ratio (RR)=1.01, 95% CI 1.00 to 1.02, I=15.2%) and cardiovascular events (RR=0.98, 95% CI 0.88 to 1.09, I=4.9%) in patients treated with LAMAs versus placebo. LAMAs significantly improved trough forced expiratory volume in 1 s (weighted mean difference (WMD)=0.12, 95% CI 0.10 to 0.14, I=86.6%), Transitional Dyspnea Index (WMD=0.75, 95% CI 0.56 to 0.94, I=0%), and St. George's Respiratory Questionnaire (WMD=‒2.50, 95% CI ‒3.32 to ‒1.69, I=39.8%). Moreover, LAMAs significantly reduced the incidence of exacerbation in patients with COPD (RR=0.85, 95% CI 0.79 to 0.91, I=69.9%). LAMAs are safe therapy and play a pivotal role in improving lung function, dyspnea, and health status, and reducing the exacerbation in patients with COPD.
Topics: Adrenergic beta-2 Receptor Agonists; Dyspnea; Humans; Lung; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 34362778
DOI: 10.1136/jim-2021-001931 -
PloS One 20212021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS/LAMA/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD.
METHODS AND ANALYSES
Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods.
ETHICS AND DISSEMINATION
No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients.
PROTOCOL REGISTRATION NUMBER
CRD42021240823.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Disease Progression; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Prognosis; Pulmonary Disease, Chronic Obstructive
PubMed: 34351996
DOI: 10.1371/journal.pone.0255545 -
Jornal de Pediatria 2022Dexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Dexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery.
SOURCES
Databases such as PubMed, Cochrane, Web of Science, WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb. 2021. Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation (SMD), odds ratio (OR) and 95% confidence interval (CI).
SUMMARY OF THE FINDINGS
Fifteen articles were included for this meta-analysis, and 9 articles for qualitative analysis. The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and reducing heart rate (HR) (SBP: SMD = -0.35,95% CI: -0.72, 0.01; MAP: SMD = -0.83, 95% CI: -1.87,0.21; DBP: SMD = -0.79,95% CI: -1.66,0.08; HR: SMD = -1.71,95% CI: -2.29, -1.13). In addition, the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group.
CONCLUSIONS
The application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability, and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences.
Topics: Blood Pressure; Cardiac Surgical Procedures; Child; Dexmedetomidine; Hemodynamics; Humans; Hypnotics and Sedatives
PubMed: 34252370
DOI: 10.1016/j.jped.2021.05.008 -
Pharmacology 2021Patients who undergo surgery of femur fracture suffer the excruciating pain. Dexmedetomidine (DEX) is a unique α2-adrenergic receptor agonist with sedative and... (Meta-Analysis)
Meta-Analysis
Patients who undergo surgery of femur fracture suffer the excruciating pain. Dexmedetomidine (DEX) is a unique α2-adrenergic receptor agonist with sedative and analgesic properties, whose efficacy and safety are still unclear for surgery of femur fracture. Randomized controlled trials comparing the effects of addition of DEX to general or local anesthesia in surgery of femur fracture were searched from MEDLINE, EMBASE, and the Cochrane Library database. Patients who received DEX infusion had a significant longer time to rescue analgesia compared with those without DEX coadministration. DEX treatment seemed to reduce the visual analog score; however, the significance did not reach any statistical difference. DEX as an analgesic adjuvant did not reduce the onset of sensory block time, shorten the time to achieve maximum sensory block level, and provide a longer duration of sensory block. The difference in mean sedation scores between 2 groups was not statistically significant. As for adverse effects, DEX therapy significantly increased the rate of hypotension. In conclusion, dexmedetomidine as a local anesthetic adjuvant in femur fracture surgery had a longer duration of rescue analgesia. However, the incidence of hypotension was markedly increased in these patients. It was worth noting that the evidence was of low to moderate quality.
Topics: Analgesics, Non-Narcotic; Blood Pressure; Chemotherapy, Adjuvant; Dexmedetomidine; Femoral Neck Fractures; Humans; Infusions, Intravenous; Randomized Controlled Trials as Topic
PubMed: 34167123
DOI: 10.1159/000515788