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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 -
Respiratory Research Jun 2021Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial.
METHODS
We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest.
RESULTS
We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64-0.83) and improved the QOL score and trough FEV compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18-0.48) and mortality (odds ratio 0.66, 95% CI 0.50-0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16-2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV than LAMA/LABA. Concerning the trough FEV, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference.
CONCLUSION
Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations.
CLINICAL TRIAL REGISTRATION
PROSPERO; CRD42020191978.
Topics: Adrenergic beta-2 Receptor Agonists; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 34154582
DOI: 10.1186/s12931-021-01777-x -
Anesthesia and Pain Medicine Apr 2020Alpha-2 agonists have sedative, analgesic, and opioid-sparing effects. Moreover, intraoperative or postoperative systemic administration of alpha-2 adrenergic agonists...
BACKGROUND
Alpha-2 agonists have sedative, analgesic, and opioid-sparing effects. Moreover, intraoperative or postoperative systemic administration of alpha-2 adrenergic agonists is known to reduce postoperative pain and opioid consumption. This meta-analysis investigated whether preoperative administration of alpha-2 agonists can affect postoperative pain and opioid consumption.
METHODS
We searched the MEDLINE, EMBASE, Cochrane Library (CENTRAL), KoreaMed, and KMbase databases through March 2019 to identify relevant randomized controlled trials (RCTs) on the effect of preoperative systemic administration of alpha-2 agonists on postoperative pain and opioid consumption. We conducted a meta-analysis according to the Cochrane Collaboration guidelines. Standardized mean differences (SMDs) of postoperative pain intensity or dose of opioid consumption in the alpha-2 agonist group were extracted and combined using a random-effect model and were compared to those of the control group.
RESULTS
Eleven RCTs involving 748 participants were included in this meta-analysis. Preoperative administration of systemic alpha-2 agonists significantly reduced cumulative opioid consumption up to 6 h (SMD, -0.52; 95% confidence interval [-0.90 to -0.14]) and 24 h (SMD, -0.68 [-1.27 to -0.09]) after surgery. Moreover, preoperative administration of alpha-2 agonists significantly reduced postoperative pain intensity at 6 h (SMD, -0.50 [-0.78 to -0.21]) and 24 h (SMD, -0.44 [-0.86 to -0.03]).
CONCLUSIONS
In this meta-analysis, high degree of heterogeneity limits the preoperative administration of alpha-2 agonists in reducing postoperative opioid consumption and pain intensity. Future powered large RCTs are required to increase the certainty of evidence on the effect in reducing postoperative opioid consumption and pain intensity.
PubMed: 33329808
DOI: 10.17085/apm.2020.15.2.157 -
Cells Nov 2020As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is...
As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α-ARs in HF using 5 databases for our search. All three α-AR subtypes (α, α and α) are expressed in human and animal hearts and blood vessels in a tissue-dependent manner. We summarize the changes observed in HF regarding the density, signaling and responses of α-ARs. Conflicting findings arise from different studies concerning the influence that HF has on α-AR expression and function; in contrast to β-ARs there is no consistent evidence for down-regulation or desensitization of cardiac or vascular α-ARs. Whether α-ARs are a therapeutic target in HF remains a matter of debate.
Topics: Blood Vessels; Heart Failure; Humans; Models, Biological; Myocardium; Receptors, Adrenergic, alpha-1; Signal Transduction
PubMed: 33158106
DOI: 10.3390/cells9112412 -
International Journal of Chronic... 2020This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in...
Efficacy and Safety of LAMA/LABA Fixed-Dose Combination Therapies in Chronic Obstructive Pulmonary Disease: A Systematic Review of Direct and Indirect Treatment Comparisons.
BACKGROUND
This literature review assessed comparative efficacy and safety of long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) fixed-dose combinations (FDCs) in patients with COPD and moderate-to-very severe airflow limitation, using evidence from direct (head-to-head) and indirect treatment comparisons.
METHODS
Two systematic literature reviews were conducted to identify direct comparisons (head-to-head randomized controlled trials [RCTs]) and indirect comparisons (network meta-analyses [NMAs]; indirect treatment comparisons; meta-analyses) in patients with COPD with moderate-to-very severe airflow limitation. Study/Analysis characteristics, eligibility criteria, patient characteristics, and overall conclusions were extracted from relevant publications. The review of indirect comparisons focused on NMAs reporting efficacy outcomes at 12 and 24 weeks of treatment (established durations of symptomatic studies in COPD recommended by regulators).
RESULTS
Four RCTs that provided head-to-head comparisons of LAMA/LABA FDCs were identified, and these varied in their study design, included patient population and reported endpoints. While some differences in lung function outcomes were noted, where assessed, LAMA/LABA FDCs had comparable efficacy in improving symptoms, health status, exacerbations, and comparable safety profiles. However, the differences in study methodology and patient characteristics between these studies made it difficult to draw generalizable conclusions regarding the comparative effectiveness of LAMA/LABA FDCs from the direct comparisons alone. Six NMAs were identified that reported indirect comparisons between LAMA/LABA FDCs; five of these were within the pre-defined scope of this review. Although the scope of each NMA varied, all five concluded that LAMA/LABA FDCs were generally comparable in terms of lung function improvements, patient-reported outcomes, and safety (where assessed).
CONCLUSION
Although there were some inconsistencies between the outcomes of RCTs and NMAs for lung function, the totality of lung function, symptoms, exacerbations, and safety data suggests that currently available LAMA/LABA FDCs have comparable efficacy and safety in patients with COPD and moderate-to-very severe airflow limitation.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Combinations; Humans; Lung; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 32669839
DOI: 10.2147/COPD.S230955 -
Chest Jun 2021Although clinical studies have evaluated dexmedetomidine as a strategy to improve noninvasive ventilation (NIV) comfort and tolerance in patients with acute respiratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although clinical studies have evaluated dexmedetomidine as a strategy to improve noninvasive ventilation (NIV) comfort and tolerance in patients with acute respiratory failure (ARF), their results have not been summarized.
RESEARCH QUESTION
Does dexmedetomidine, when compared with another sedative or placebo, reduce the risk of delirium, mortality, need for intubation and mechanical ventilation, or ICU length of stay (LOS) in adults with ARF initiated on NIV in the ICU?
STUDY DESIGN AND METHODS
We electronically searched MEDLINE, EMBASE, and the Cochrane Library from inception through July 31, 2020, for randomized clinical trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with the corresponding 95% CIs using a random-effect model.
RESULTS
Twelve RCTs were included in our final analysis (n = 738 patients). The use of dexmedetomidine, compared with other sedation strategies or placebo, reduced the risk of intubation (RR, 0.54; 95% CI, 0.41-0.71; moderate certainty), delirium (RR, 0.34; 95% CI, 0.22-0.54; moderate certainty), and ICU LOS (MD, -2.40 days; 95% CI, -3.51 to -1.29 days; low certainty). Use of dexmedetomidine was associated with an increased risk of bradycardia (RR, 2.80; 95% CI, 1.92-4.07; moderate certainty) and hypotension (RR, 1.98; 95% CI, 1.32-2.98; moderate certainty).
INTERPRETATION
Compared with any sedation strategy or placebo, dexmedetomidine reduced the risk of delirium and the need for mechanical ventilation while increasing the risk of bradycardia and hypotension. The results are limited by imprecision, and further large RCTs are needed.
TRIAL REGISTRY
PROSPERO; No.: 175086; URL: www.crd.york.ac.uk/prospero/.
Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Dexmedetomidine; Humans; Noninvasive Ventilation; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 33434496
DOI: 10.1016/j.chest.2020.12.052 -
Clinical Research in Cardiology :... Jun 2024Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials.
BACKGROUND
Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.
METHODS
A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.
RESULTS
Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference - 0.65 beats/minute compared to control, 95% CI - 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36-1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17-0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54-2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90-1.46; p = 0.28), hypotension (RR 1.85, 0.87-3.93; p = 0.11), bradycardia (RR 1.29, 0.25-6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49-2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).
CONCLUSIONS
Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.
Topics: Humans; Atrial Fibrillation; Atrial Flutter; Randomized Controlled Trials as Topic; Heart Rate; Treatment Outcome; Acute Disease; Adrenergic beta-Antagonists; Adrenergic beta-1 Receptor Antagonists; Administration, Intravenous; Anti-Arrhythmia Agents
PubMed: 37658166
DOI: 10.1007/s00392-023-02295-0 -
Frontiers in Medicine 2023To systematically review and quantitively evaluate the efficacy and safety of mirabegron as a medical expulsive therapy for ureteral stones.
OBJECTIVE
To systematically review and quantitively evaluate the efficacy and safety of mirabegron as a medical expulsive therapy for ureteral stones.
METHODS
We performed an extensive search of the EMBASE and PubMed databases for studies examining the use of mirabegron as a medical expulsive therapy for ureteral stones. The primary outcome measure assessed was the stone expulsion rate (SER), while the secondary outcomes evaluated were the stone expulsion interval (SEI) and the occurrence of pain episodes during follow-up. Risk ratios (RRs) and mean differences (MDs) with their respective 95% CIs were calculated.
RESULTS
We included a total of seven studies involving 728 participants. Our analysis revealed a significant increase in the stone expulsion rate (SER) with mirabegron (RR = 1.40; 95% CI = 1.17-1.67; < 0.001) and a reduction in the frequency of pain episodes (MD = -0.80; 95% CI = -0.39 to -0.21; = 0.008) compared to the control group. No significant difference was found in SEI between the two groups (MD = -3.04; 95% CI = -6.33 to 0.25; = 0.07). Subgroup analysis revealed that the increased SER was significant for distal ureteral stones, but not for proximal and middle ureter stones. Compared to tamsulosin or silodosin, mirabegron showed no significant difference in SER, SEI, or pain episode frequency. The adverse effects of mirabegron were relatively rare and mild.
CONCLUSION
Mirabegron appears to be a promising candidate for the MET of distal ureteral stones rather than proximal and middle ureteral stones, as it significantly increases SER and reduces pain episode frequency. Further well-designed randomised controlled trials are needed to validate and affirm these findings.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42022341603).
PubMed: 38249979
DOI: 10.3389/fmed.2023.1280487 -
BMC Pulmonary Medicine Nov 2019The published data on the association between β2-adrenergic receptor gene polymorphisms and asthma susceptibility are inconclusive. To derive a more precise estimation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The published data on the association between β2-adrenergic receptor gene polymorphisms and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed.
METHODS
A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and the China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to calculate the strength of the association. A sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger's tests were used for indications of publication bias.
RESULTS
Seventy three studies with three single nucleotide polymorphisms (SNP) (rs1042713, c.G46A, p.Gly16Arg; rs1042714, c.G79C, p.Gln27Glu; rs1042711, c.T-47C, p.Cys19Arg) were finally identified. For the rs1042713 polymorphism, no significant association with asthma risk was found in the overall population. However, a significant protective association was found in the Indian population in the dominant model comparison (OR = 0.72, 95% CI = 0.59-0.87, I = 25%, studies = 5, cases = 1190, controls = 1241). A significant risk association was found in the Arab population in the dominant model comparison (OR = 1.75, 95% CI = 1.14-2.70, I = 0%, studies = 2, cases = 307, controls = 361) and the homozygote model comparison (OR = 1.88, 95% CI = 1.17-3.02, I = 0%, studies = 2, cases = 307, controls = 361), and in the Hispanic-Latino population in the dominant model comparison (OR = 1.68, 95% CI = 1.10-2.55, I = 77%, studies = 5, cases = 1026, controls = 1412). For the rs1042714 polymorphism, we found a significant association in the recessive model comparison (OR = 0.83, 95% CI = 0.70-0.98, I = 44%, studies = 52, cases = 8242, controls = 16,832), the homozygote genotype comparison (OR = 0.84, 95% CI = 0.72-0.98, I = 25%, studies = 52, cases = 8242, controls = 16,832) and the allelic genetic model (OR = 0.91, 95% CI = 0.83-0.99, I = 59%, studies = 52, cases = 8242, controls = 16,832) in the overall population. When stratified by age, a significant association was also found in children in the recessive model comparison (OR = 0.59, 95% CI = 0.39-0.88, I = 58%, studies = 18, cases = 2498, controls = 2510) and the homozygote genotype comparison (OR = 0.63, 95% CI = 0.43-0.92, I = 46%, studies = 18, cases = 2498, controls = 2510), but not in adult. For the rs1042711 polymorphism, no significant associations were found in the any genetic model.
CONCLUSION
The meta-analysis suggests that the ADRB2 rs1042714 polymorphism has a protective association with asthma in the overall population and the pediatric subgroup.
Topics: Alleles; Asthma; Child; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2; Risk Factors
PubMed: 31699066
DOI: 10.1186/s12890-019-0962-z -
BMJ Open Sep 2020To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.
METHODS
Systematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortality and adverse events. Qualitative comparisons of efficacies between RCTs and observational studies.
RESULTS
212 RCTs and 19 observational studies were included. Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)). No differences in lung function (0.02 (95% CI: -0.10 to 0.14)), health-related quality of life (-1.12 (95% CI: -3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found. Most of the observational evidence trended in the same direction as pooled RCT data.
CONCLUSION
Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits.
PROSPERO REGISTRATION NUMBER
CRD42018088013.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Respiratory Therapy
PubMed: 32994234
DOI: 10.1136/bmjopen-2019-036455