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Investigative and Clinical Urology May 2024To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction.
MATERIALS AND METHODS
According to a protocol (CRD42022350079), we searched multiple data sources for published and unpublished randomized controlled trials (RCTs) up to 2nd August 2022. Two review authors independently screened studies and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence (CoE).
RESULTS
We found data to inform two comparisons: beta-3 adrenergic agonists versus placebo (4 RCTs) and anticholinergics (2 RCTs). Only mirabegron was used for intervention in all included studies. Compared to placebo, beta-3 adrenergic agonists may have a clinically unimportant effect on urinary symptoms score (mean difference [MD] -2.50, 95% confidence interval [CI] -4.78 to -0.22; ²=92%; 2 RCTs; 192 participants; low CoE) based on minimal clinically important difference of 3. We are very uncertain of the effects of beta-3 adrenergic agonists on quality of life (MD 10.86, 95% CI 1.21 to 20.50; ²=41%; 2 RCTs; 98 participants; very low CoE). Beta-3 adrenergic agonists may result in little to no difference in major adverse events (cardiovascular adverse events) (risk ratio 0.57, 95% CI 0.14 to 2.37; ²=0%; 4 RCTs; 310 participants; low CoE). Compared to anticholinergics, no study reported urinary symptom scores and quality of life. There were no major adverse events (cardiovascular adverse events) in either study group (1 study; 60 participants; very low CoE).
CONCLUSIONS
Compared to placebo, beta-3 adrenergic agonists may have similar effects on urinary symptom scores and major adverse events. There were uncertainties about their effects on quality of life. Compared to anticholinergics, we are either very uncertain or have no evidence about urinary symptom scores, quality of life, and major adverse events.
Topics: Humans; Adrenergic beta-3 Receptor Agonists; Urinary Bladder, Neurogenic; Treatment Outcome; Lower Urinary Tract Symptoms; Randomized Controlled Trials as Topic
PubMed: 38714512
DOI: 10.4111/icu.20230271 -
British Journal of Anaesthesia Jun 2014Undergoing general anaesthesia is distressing for children, with up to two-thirds demonstrating abnormal behaviours after their procedure, such as emergence delirium... (Meta-Analysis)
Meta-Analysis Review
Undergoing general anaesthesia is distressing for children, with up to two-thirds demonstrating abnormal behaviours after their procedure, such as emergence delirium (ED) and post-hospitalization behaviour change. The aim of this systematic review was to determine the effect of intraoperative i.v. α₂-adrenergic agonists on postoperative behaviour in children. We included published full-text reports of randomized controlled trials involving children who received i.v. clonidine or dexmedetomidine after induction of general anaesthesia, who were assessed for postoperative behavioural disturbance. After screening of references identified by the search strategy, a data collection form was developed and piloted. Data extraction was performed by one reviewer and checked by a second. Twelve randomized trials met the inclusion criteria. Ten studies (n=669) reported dichotomous data that were included in the pooled analysis of α₂-adrenergic agonists vs placebo. There was strong evidence that i.v. α₂-adrenergic agonists reduced postoperative ED (overall summary odds ratio 0.28, 95% confidence interval 0.19-0.40, P<0.001). No studies examined post-hospitalization negative behaviour changes. There was evidence that α₂-adrenergic agonists prolonged time in the recovery room. No adverse haemodynamic events were reported in any arm of any study. This meta-analysis provides evidence that intraoperative i.v. α₂-adrenergic agonists reduce the incidence of emergency delirium in children. The prolongation of time in recovery is unlikely to be clinically relevant. The absence of data regarding the effect on post-hospitalization behavioural changes provides an opportunity for future research.
Topics: Administration, Intravenous; Adrenergic alpha-2 Receptor Agonists; Anesthesia Recovery Period; Anesthesia, General; Child; Child Behavior; Child, Preschool; Clonidine; Delirium; Dexmedetomidine; Female; Humans; Infant; Intraoperative Care; Male; Postoperative Complications; Postoperative Period; Randomized Controlled Trials as Topic; Time Factors
PubMed: 24727829
DOI: 10.1093/bja/aeu093 -
Respiratory Research Nov 2017Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD. The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD. The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD. This article analyses the evidence of efficacy and safety of the TIO/OLO combination.
METHODS
A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator.
RESULTS
A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918). TIO/OLO significantly improved trough FEV from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively). TIO/OLO improved transitional dyspnea index (TDI) and St. George's Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR: 1.28, 95%CI: [1.18, 1.40] versus OLO). Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components.
CONCLUSIONS
Treatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status. No differences in adverse events were observed compared with other active treatments.
CLINICAL TRIAL REGISTRATION
PROSPERO register of systematic reviews ( CRD42016040162 ).
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Benzoxazines; Bronchodilator Agents; Drug Combinations; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Spirometry; Tiotropium Bromide; Treatment Outcome
PubMed: 29178871
DOI: 10.1186/s12931-017-0683-x -
Neuroscience and Biobehavioral Reviews Sep 2021Activation of the HPA-axis and SNS are widely accepted to link chronic stress with elevated levels of peripheral pro-inflammatory markers in blood. Yet, empirical...
Glucocorticoid resistance and β2-adrenergic receptor signaling pathways promote peripheral pro-inflammatory conditions associated with chronic psychological stress: A systematic review across species.
Activation of the HPA-axis and SNS are widely accepted to link chronic stress with elevated levels of peripheral pro-inflammatory markers in blood. Yet, empirical evidence showing that peripheral levels of glucocorticoids and/or catecholamines mediate this effect is equivocal. Recent attention has turned to the possibility that cellular sensitivity to these ligands may contribute to inflammatory mediators that accompany chronic stress. We review current evidence for the association of chronic stress with glucocorticoid receptor (GR) and β-adrenergic receptor (β-AR) signaling sensitivity. Across 15 mouse, 7 primate, and 19 human studies, we found that chronic stress reliably associates with downregulation in cellular GR sensitivity, alterations in intracellular β-AR signaling, and upregulation in pro-inflammatory biomarkers in peripheral blood. We also present evidence that alterations in GR and β-AR signaling may be specific to myeloid progenitor cells such that stress-related signaling promotes release of cells that are inherently less sensitive to glucocorticoids and differentially sensitive to catecholamines. Our findings have broad implications for understanding mechanisms by which chronic stress may contribute to pro-inflammatory phenotypes.
Topics: Animals; Glucocorticoids; Hypothalamo-Hypophyseal System; Mice; Pituitary-Adrenal System; Receptors, Adrenergic; Receptors, Glucocorticoid; Stress, Psychological
PubMed: 34116126
DOI: 10.1016/j.neubiorev.2021.06.013 -
Frontiers in Psychiatry 2017Norepinephrine (NE) is recognized as having a key role in the pathophysiology of major depressive disorder (MDD) and schizophrenia, although its distinct actions... (Review)
Review
Norepinephrine (NE) is recognized as having a key role in the pathophysiology of major depressive disorder (MDD) and schizophrenia, although its distinct actions α-adrenergic receptors (α-ARs) are not well defined. We performed a systematic review examining the roles of NE and α-ARs in MDD and schizophrenia. PubMed and ProQuest database searches were performed to identify English language papers published between 2008 and 2015. In total, 2,427 publications (PubMed, = 669; ProQuest, = 1,758) were identified. Duplicates, articles deemed not relevant, case studies, reviews, meta-analyses, preclinical reports, or articles on non-target indications were excluded. To limit the review to the most recent data representative of the literature, the review further focused on publications from 2010 to 2015, which were screened independently by all authors. A total of 16 research reports were identified: six clinical trial reports, six genetic studies, two biomarker studies, and two receptor studies. Overall, the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition, arousal, and valence systems associated with MDD and schizophrenia. Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases. Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases, in particular with relation to specific valence systems. Clinical studies that attempt to define associations between specific receptor binding profiles of psychotropics and particular clinical outcomes are needed.
PubMed: 28367128
DOI: 10.3389/fpsyt.2017.00042 -
Sports Medicine (Auckland, N.Z.) May 2015'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic... (Review)
Review
BACKGROUND AND OBJECTIVE
'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations.
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW
All studies of the association of genetic factors with human hypoxic exercise performance, whether at sea level using 'nitrogen dilution of oxygen' (normobaric hypoxia), or at altitude or in low-pressure chambers (field or chamber hypobaric hypoxia, respectively) were sought for review.
SEARCH STRATEGY FOR IDENTIFICATION OF STUDIES
Two electronic databases were searched (Ovid MEDLINE, Embase) up to 31 January 2014. We also searched the reference lists of relevant articles for eligible studies. All studies published in English were included, as were studies in any language for which the abstract was available in English.
DATA COLLECTION AND ANALYSIS
Studies were selected and data extracted independently by two reviewers. Differences regarding study inclusion were resolved through discussion. The quality of each study was assessed using a scoring system based on published guidelines for conducting and reporting genetic association studies.
RESULTS
A total of 11 studies met all inclusion criteria and were included in the review. Subject numbers ranged from 20 to 1,931 and consisted of healthy individuals in all cases. The maximum altitude of exposure ranged from 2,690 to 8,848 m. The exercise performance phenotypes assessed were mountaineering performance (n = 5), running performance (n = 2), and maximum oxygen consumption ([Formula: see text]O2max) (n = 4). In total, 13 genetic polymorphisms were studied, four of which were associated with hypoxic exercise performance. The adenosine monophosphate deaminase (AMPD1) C34T (rs17602729), beta2-adrenergic receptor (ADRB2) Gly16Arg single nucleotide polymorphism (SNP) (rs1042713), and androgen receptor CAG repeat polymorphisms were associated with altitude performance in one study, and the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) (rs4646994) polymorphism was associated with performance in three studies. The median score achieved in the study quality analysis was 6 out of 10 for case-control studies, 8 out of 10 for cohort studies with a discrete outcome, 6 out of 9 for cohort studies with a continuous outcome, and 4.5 out of 8 for genetic admixture studies.
CONCLUSION
The small number of articles identified in the current review and the limited number of polymorphisms studied in total highlights that the influence of genetic factors on exercise performance in hypoxia has not been studied in depth, which precludes firm conclusions being drawn. Support for the association between the ACE-I allele and improved high-altitude performance was the strongest, with three studies identifying a relationship. Analysis of study quality highlights the need for future studies in this field to improve the conduct and reporting of genetic association studies.
Topics: AMP Deaminase; Actinin; Altitude Sickness; Athletic Performance; Exercise; Genetic Variation; Genotype; Humans; INDEL Mutation; Oxygen Consumption; Peptidyl-Dipeptidase A
PubMed: 25682119
DOI: 10.1007/s40279-015-0309-8 -
Medicina (Kaunas, Lithuania) Dec 2022Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles... (Review)
Review
Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles of silodosin and tamsulosin for medical expulsive therapy (MET) of ureteral stones. Materials and Methods: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science to identify articles published before July 2022 that described randomized controlled trials comparing silodosin and tamsulosin for MET of ureteral stones. Endpoints were stone expulsion rate, stone expulsion time, and total complication rate. Results: In total, 14 studies were included in our analysis. The size of ureteral stones was <1 cm. Compared with tamsulosin, silodosin resulted in a significantly higher stone expulsion rate (p < 0.01, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.91 to 3.06, I2 = 0%) and significantly shorter stone expulsion time (p < 0.01, mean difference = −3.04, 95% CI = −4.46 to −1.63, I2 = 89%). The total complication rate did not significantly differ between silodosin and tamsulosin (p = 0.33, OR = 1.15, 95% CI = 0.87 to 1.52, I2 = 7%). Conclusions: Compared with tamsulosin, silodosin resulted in significantly better expulsion of ureteral stones <1 cm. The total complication rate did not significantly differ between silodosin and tamsulosin. Thus, silodosin may be superior to tamsulosin for MET of ureter stones <1 cm.
Topics: Humans; Tamsulosin; Ureteral Calculi; Adrenergic alpha-1 Receptor Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36556996
DOI: 10.3390/medicina58121794 -
Frontiers in Genetics 2022Some studies have been carried out to investigate the association between Trp64Arg polymorphism in beta-3 adrenergic receptor gene () and susceptibility to overactive...
Some studies have been carried out to investigate the association between Trp64Arg polymorphism in beta-3 adrenergic receptor gene () and susceptibility to overactive bladder (OAB), but the results remain inconsistent. We carried out a meta-analysis to acquire a more accurate estimation. All eligible studies were searched in PubMed, Web of Science, Embase, and Cochrane Library. Pooled odds ratios, with 95% confidence intervals, were assessed for the association using fixed and random effects models. The overall results of this meta-analysis demonstrated that there might be an association between Trp64Arg polymorphism and susceptibility to OAB in allele model, dominant model, and heterozygote comparison with a relative risk of 2.00 (95% CI 1.36-2.93), 2.13 (95% CI 1.20-3.76), and 2.07 (95% CI: 1.13-3.79), respectively. However, in the recessive model and homozygote comparison, no significant association between Trp64Arg polymorphism and susceptibility to OAB was observed, with a relative risk of 2.47 (95% CI 0.63-9.73) and 3.12 (95% CI: 0.79-12.35), respectively. Based on trail sequential analysis, the results turned out to be true positive in the allele model, false positive in the dominant model and heterozygote comparison, and negative in the recessive model and homozygote comparison, respectively. Our analysis indicated that Trp64Arg polymorphisms in might increase the risk of OAB twice in the allele model, but further well-designed studies with large sample sizes are required to confirm the present findings in other modes and comparisons.
PubMed: 35903356
DOI: 10.3389/fgene.2022.930084 -
Drugs in Context 2022Few randomized controlled trials evaluate the long-term efficacy and safety of pharmacotherapy for overactive bladder (OAB). This network meta- analysis compares the...
BACKGROUND
Few randomized controlled trials evaluate the long-term efficacy and safety of pharmacotherapy for overactive bladder (OAB). This network meta- analysis compares the long-term (52-week) efficacy and safety of vibegron, mirabegron and anticholinergics for the treatment of OAB.
METHODS
A systematic literature review and network meta-analysis were conducted following PRISMA guidelines using MEDLINE, Embase and Cochrane Central Register of Controlled Trials and terms related to OAB. Efficacy outcomes included change from baseline to week 48-52 in mean daily total urinary incontinence (UI) episodes, mean daily number of micturitions and volume voided/micturition. Efficacy outcomes were analysed using Bayesian models. Commonly reported adverse events (AEs) are described.
RESULTS
Of 2098 hits retrieved, 5 publications and 1 study report describing 5 unique randomized controlled trials were included in the analyses. Mean (95% credible interval) change from baseline in total UI episodes for vibegron 75 mg (-2.2; -2.9 to -1.5) showed a significantly greater reduction than mirabegron 50 mg (-1.3; -1.9 to -0.8) and tolterodine 4 mg extended release (-1.6; -2.1 to -1.1). No significant differences were observed between vibegron and comparators for daily micturitions or volume voided/micturition. Within the manuscripts, the 4 most common AEs (range) for anticholinergics included dry mouth (5.2-90.0%), constipation (7.7-65.0%), blurred vision (3.8-35.0%) and hypertension (8.6-9.6%); the 4 most commonly reported AEs for β-adrenergic agonists included hypertension (8.8-9.2%), urinary tract infection (5.9-6.6%), headache (5.5%) and nasopharyngitis (4.8-5.2%).
CONCLUSION
Vibegron was associated with significantly greater improvement in daily total UI episodes at 52 weeks than mirabegron and tolterodine. When reported, the most common AE for anticholinergics was dry mouth and for β-adrenergic agonists was hypertension. Hypertension incidence was similar between drug classes.
PubMed: 36303599
DOI: 10.7573/dic.2022-4-2 -
Clinical Journal of the American... Oct 2021AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed.
RESULTS
Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap.
CONCLUSIONS
Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.
Topics: Acute Kidney Injury; Adrenergic alpha-2 Receptor Agonists; Age Factors; Bayes Theorem; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Dexmedetomidine; Female; Humans; Infant; Infant, Newborn; Ischemic Preconditioning; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 34620647
DOI: 10.2215/CJN.05800421