-
International Journal of Clinical... 2022This study aimed to assess the efficacy of mirabegron (50 mg daily) as a medical expulsive therapy for ureteral stones in adults. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to assess the efficacy of mirabegron (50 mg daily) as a medical expulsive therapy for ureteral stones in adults.
MATERIALS AND METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 2021 to collect the clinical trials. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for the meta-analysis.
RESULTS
A total of four studies were included, involving 398 patients: 197 patients in mirabegron group and 201 patients in control group. The meta-analysis showed that the stone expulsion rate was higher in the mirabegron group than in the control group (OR: 2.12; 95% CI: 1.33 to 3.40; =0.002). Subgroup analysis identified that the stone expulsion rate of patients with stone size <5/6 mm was significantly higher than that of patients with stone size ≥5/6 mm (OR: 0.31; 95% CI: 0.13 to 0.72; =0.006). But no significant difference was identified between the mirabegron group and the control group for the stone expulsion interval (MD: -1.16, 95% CI: -3.56 to 1.24; =0.35). In terms of pain episodes, the mirabegron group was significantly lower than that of the control group (MD: -0.34, 95% CI: -0.50 to 0.19; < 0.0001).
CONCLUSIONS
The medical expulsive therapy with mirabegron had a significant effect in improving the stone expulsion rate for patients with ureteral stones, especially in those whose stone size <5/6 mm. Mirabegron had no effect on the stone expulsion interval but did decrease the pain episodes.
Topics: Acetanilides; Adult; Humans; Pain; Thiazoles; Ureteral Calculi
PubMed: 35685505
DOI: 10.1155/2022/2293182 -
The Cochrane Database of Systematic... May 2022Clonidine is a presynaptic alpha-2-adrenergic receptor agonist that has been used for many years to treat hypertension and other conditions, including chronic pain.... (Review)
Review
BACKGROUND
Clonidine is a presynaptic alpha-2-adrenergic receptor agonist that has been used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs has been gaining interest since the beginning of the century, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated for almost 20 years in clinical trials. This is an update of the original Cochrane Review published in Issue 8, 2015.
OBJECTIVES
The objective of this review was to assess the analgesic efficacy and safety of TC compared with placebo or other drugs in adults aged 18 years or above with chronic neuropathic pain.
SEARCH METHODS
For this update we searched the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid), and Embase (Ovid) databases, and reference lists of retrieved papers and trial registries. We also contacted experts in the field. The most recent search was performed on 27 October 2021.
SELECTION CRITERIA
We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in adults with chronic neuropathic pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. Any discrepancies were resolved by discussion or by consulting a third review author if necessary. Where required, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) with P values. We used Review Manager Web software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model. The review primary outcomes were: participant-reported pain relief of 50% or greater; participant-reported pain relief of 30% or greater; much or very much improved on Patient Global Impression of Change scale (PGIC); and very much improved on PGIC. Secondary outcomes included withdrawals due to adverse events; participants experiencing at least one adverse event; and withdrawals due to lack of efficacy. All outcomes were measured at the longest follow-up period. We assessed the certainty of evidence using GRADE and created two summary of findings tables.
MAIN RESULTS
We included four studies in the review (two new in this update), with a total of 743 participants with painful diabetic neuropathy (PDN). TC (0.1% or 0.2%) was applied in gel form to the painful area two to three times daily. The double-blind treatment phase of three studies lasted 8 weeks to 85 days and compared TC versus placebo. In the fourth study, the double-blind treatment phase lasted 12 weeks and compared TC versus topical capsaicin. We assessed the studies as at unclear or high risk of bias for most domains; all studies were at unclear risk of bias for allocation concealment and blinding of outcome assessment; one study was at high risk of bias for blinding of participants and personnel; two studies were at high risk of attrition bias; and three studies were at high risk of bias due to notable funding concerns. We judged the certainty of evidence (GRADE) to be moderate to very low, downgrading for study limitations, imprecision of results, and publication bias. TC compared to placebo There was no evidence of a difference in number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.78 to 1.86; 179 participants; 1 study; low certainty evidence). However, the number of participants with participant-reported pain relief of 30% or greater during longest follow-up period (8 to 12 weeks) was higher in the TC group compared with placebo (RR 1.35, 95% CI 1.03 to 1.77; 344 participants; 2 studies, very low certainty evidence). The number needed to treat for an additional beneficial outcome (NNTB) for this comparison was 8.33 (95% CI 4.3 to 50.0). Also, there was no evidence of a difference between groups for the outcomes much or very much improved on the PGIC during longest follow-up period (12 weeks) or very much improved on PGIC during the longest follow-up period (12 weeks) (RR 1.06, 95% CI 0.76 to 1.49 and RR 1.82, 95% CI 0.89 to 3.72, respectively; 179 participants; 1 study; low certainty evidence). We observed no evidence of a difference between groups in withdrawals due to adverse events and withdrawals due to lack of efficacy during the longest follow-up period (12 weeks) (RR 0.34, 95% CI 0.04 to 3.18 and RR 1.01, 95% CI 0.06 to 15.92, respectively; 179 participants; 1 study; low certainty evidence) and participants experiencing at least one adverse event during longest follow-up period (12 weeks) (RR 0.65, 95% CI 0.14 to 3.05; 344 participants; 2 studies; low certainty evidence). TC compared to active comparator There was no evidence of a difference in the number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (RR 1.41, 95% CI 0.99 to 2.0; 139 participants; 1 study; low certainty evidence). Other outcomes were not reported.
AUTHORS' CONCLUSIONS
This is an update of a review published in 2015, for which our conclusions remain unchanged. Topical clonidine may provide some benefit to adults with painful diabetic neuropathy; however, the evidence is very uncertain. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine whether it is possible to predict who or which groups of people will benefit from TC.
Topics: Adult; Analgesics; Chronic Pain; Clonidine; Diabetic Neuropathies; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 35587172
DOI: 10.1002/14651858.CD010967.pub3 -
International Journal of Chronic... 2022Several large randomized clinical trials (RCTs) have assessed the efficacy and safety of inhaled corticosteroid (ICS) combination regimens versus non-ICS therapy in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several large randomized clinical trials (RCTs) have assessed the efficacy and safety of inhaled corticosteroid (ICS) combination regimens versus non-ICS therapy in patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbation risk with mixed results.
METHODS
We performed a systematic literature review and meta-analysis of RCTs comparing the effect of ICS-containing combination therapy and non-ICS regimen in patients with COPD.
RESULTS
A total of 54 RCTs (N = 57,333) reported treatment effects on various outcomes and were eligible for inclusion. Overall, the number of patients experiencing moderate/severe exacerbations was significantly lower for ICS-containing combination therapy versus non-ICS therapy (RR: 0.86 [95% CI: 0.80-0.93]). The annual rate of exacerbations was also significantly reduced by 22% (0.78 [0.72-0.86]) with ICS-containing versus non-ICS therapy. The annual rate of exacerbations requiring hospitalisation was reduced by 31% versus non-ICS therapy (0.69 [0.54-0.88]); similar reduction was observed for exacerbations requiring oral steroids (0.69 [0.66-0.73]). Overall, the effect on trough FEV1 was comparable between ICS-containing and non-ICS therapies (follow-up: 6-52 weeks); however, a significant improvement in lung function (trough FEV1) was observed for ICS/LABA versus LABA (MD: +0.04 L [0.03-0.05]) and ICS/LABA/LAMA versus LAMA (MD: +0.09 L [0.05-0.13]) regimens. In addition, a significant improvement in QoL was observed with ICS-containing versus non-ICS therapy (MD in SGRQ score: -0.90 [-1.50, -0.31]).
CONCLUSION
This meta-analysis demonstrated that a wide range of patients with COPD could benefit from dual and triple ICS-containing therapy.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 35547781
DOI: 10.2147/COPD.S347588 -
Europace : European Pacing,... Jul 2022Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines... (Meta-Analysis)
Meta-Analysis
AIMS
Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that midodrine, a prodrug for an α1-adrenergic receptor agonist, might suppress VVS but supporting studies have utilized heterogeneous methods and yielded inconsistent results. To evaluate the efficacy of midodrine to prevent syncope in patients with recurrent VVS by conducting a systematic review and meta-analysis of published studies.
METHODS AND RESULTS
Relevant randomized controlled trials were identified from the MEDLINE, Embase, CENTRAL, and CINAHL databases without language restriction from inception to June 2021. All studies were conducted in clinical syncope populations and compared the benefit of midodrine vs. placebo or non-pharmacological standard care. Weighted relative risks (RRs) were estimated using random effects meta-analysis techniques. Seven studies (n = 315) met inclusion criteria. Patients were 33 ± 17 years of age and 31% male. Midodrine was found to substantially reduce the likelihood of positive head-up-tilt (HUT) test outcomes [RR = 0.37 (0.23-0.59), P < 0.001]. In contrast, the pooled results of single- and double-blind clinical trials (I2 = 54%) suggested a more modest benefit from midodrine for the prevention of clinical syncope [RR = 0.51 (0.33-0.79), P = 0.003]. The two rigorous double-blind, randomized, placebo-controlled clinical trials included 179 VVS patients with minimal between-study heterogeneity (I2 = 0%) and reported a risk reduction with midodrine [RR = 0.71 (0.53-0.95), P = 0.02].
CONCLUSIONS
Midodrine is effective in preventing syncope induced by HUT testing and less, but still significant, RR reduction in randomized, double-blinded clinical trials.
Topics: Double-Blind Method; Female; Humans; Male; Midodrine; Randomized Controlled Trials as Topic; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35025999
DOI: 10.1093/europace/euab323 -
Brazilian Journal of Anesthesiology... 2023Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist used for its sedative, analgesic, and anxiolytic effects. Non-Operating Room Anesthesia (NORA) is a modality... (Review)
Review
BACKGROUND
Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist used for its sedative, analgesic, and anxiolytic effects. Non-Operating Room Anesthesia (NORA) is a modality of anesthesia that can be done under general anesthesia or procedural sedation or/and analgesia. In this particular setting, a level-2 sedation, such as the one provided by DEX, is beneficial. We aimed to study the effects and safety of DEX in the different NORA settings in the adult population.
METHODS
A systematic review with meta-analysis of randomized controlled trials was conducted. Interventions using DEX only or DEX associated with other sedative agents, in adults (18 years old or more), were included. Procedures outside the NORA setting and/or without a control group without DEX were excluded. MEDLINE, ClinicalTrials.gov, Scopus, LILACS, and SciELO were searched. The primary outcome was time until full recovery. Secondary outcomes included hemodynamic and respiratory complications and other adverse events, among others.
RESULTS
A total of 97 studies were included with a total of 6,706 participants. The meta-analysis demonstrated that DEX had a higher time until full recovery (95% CI = [0.34, 3.13] minutes, a higher incidence of hypotension (OR = 1.95 [1.25, 3.05], p = 0.003, I = 39%) and bradycardia (OR = 3.60 [2.29, 5.67], p < 0.00001, I = 0%), and a lower incidence of desaturation (OR = 0.40 [0.25, 0.66], p = 0.0003, I² = 60%).
CONCLUSION
DEX in NORA procedures in adults was associated with a lower incidence of amnesia and respiratory effects but had a long time to recovery and more hemodynamic complications.
PubMed: 34933035
DOI: 10.1016/j.bjane.2021.12.002 -
Medicine Oct 2021We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of anticholinergic agents.
MATERIALS AND METHODS
A comprehensive search for all randomized controlled trials that evaluated the safety of mirabegron and anticholinergic agents on overactive bladder was performed, and we searched the Cochrane Central Register of Controlled trials databases, Pubmed, Embase, and relevant trials from 2013.02 to 2019.10.
RESULTS
Eight studies included 5500 patients with treatment of monotherapy on overactive bladder were identified. The total number of treatment-emergent adverse events had no significantly difference between two monotherapies (RR = 0.88 95%CI: 0.76-1.01; P = .08); however, patients would have a better tolerance with mirabegron (50 mg) in adverse events of dry mouth (RR = 0.42; 95%CI: 0.33-0.53; P < .01) and tachycardia (RR = 0.52; 95%CI: 0.29-0.94; P = .03); and there were no significant differences between two groups in hypertension (RR = 1.02; 95%CI: 0.80-1.30; P = .90), constipation (RR = 0.91; 95%CI: 0.65-1.26; P = 0.57), blurred vision (RR = 1.03; 95%CI: 0.60-1.77; P = 0.92), and urinary tract infection (RR = 0.90; 95%CI: 0.70-1.16; P = .41).
CONCLUSIONS
Treatment-emergent adverse events in patients with overactive bladder who underwent monotherapy of mirabegron (50 mg) or the anticholinergic agents had no significant differences, but mirabegron has a better tolerance in the aspect of dry mouth and tachycardia.
Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholinergic Antagonists; Constipation; Female; Humans; Hypertension; Male; Middle Aged; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Safety; Tachycardia; Thiazoles; Urinary Bladder, Overactive; Urinary Tract Infections; Vision, Low; Xerostomia
PubMed: 34731124
DOI: 10.1097/MD.0000000000027469 -
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 -
International Neurourology Journal Sep 2021Beta-3 adrenoceptor (B3AR) agonist which mediate detrusor relaxation has been tried as a new treatment modality for men with benign prostatic hyperplasia (BPH). However,...
Beta-3 adrenoceptor (B3AR) agonist which mediate detrusor relaxation has been tried as a new treatment modality for men with benign prostatic hyperplasia (BPH). However, it remains unclear whether the B3AR agonist has more clinical benefits and fewer adverse effects in men with BPH than in women. We performed a comprehensive search using multiple databases, trials registries, other sources of grey literature, and conference proceedings regardless of language or publication status and included randomized controlled trials. Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. Primary outcomes were urologic symptom scores, quality of life (QoL), and overall adverse events. We found 4 randomized controlled trials with 1,105 participants in 3 comparisons. All studies reported short-term outcomes (ranged from 8 weeks to 12 weeks). Mirabegron, tamsulosin, silodosin, fesoterodine, and tadalafil were administrated as intervention. While B3AR agonist can improve the patient-important outcomes within group (before and after treatment), B3AR agonist combination therapy with current standard BPH treatment such as alpha blocker or anticholinergic may not have additional effects on urological symptom scores and QoL compared to alpha blocker or anticholinergic monotherapy. B3AR agonist therapy with phosphodiesterase 5 inhibitor (PDE5I) showed statistical improvement on urological symptom scores or QoL compared to PDE5I monotherapy. For safety profile, B3AR agonist in all 3 comparisons may not increase adverse event rate. While B3AR agonists may be used for the treatment of lower urinary tract symptoms in men with BPH if storage symptoms with standard BPH treatment are insufficient, B3AR agonists appear to have trivial or similar effects compared to current standard BPH treatment.
PubMed: 34610712
DOI: 10.5213/inj.2142068.034 -
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 -
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