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Medicine Feb 2021Vibegron is a new β3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vibegron is a new β3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the efficiency of vibegron vs antimuscarinic monotherapy for treating OAB.
METHODS
Randomized controlled trials (RCTs) of Vibegron vs antimuscarinic monotherapy for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The RevMan version 5.3.0. was used to analysis the data.
RESULTS
Three RCTs involving a total of 1751 patients were studied in the Systematic review and Meta-analysis. Efficacy end points: the mean number of micturitions episodes/d (P = .16); the mean number of urgency episodes/d (P = .05); mean number of urgency incontinence episodes/d (P = .11) and mean number of incontinence episodes/d (P = .14) indicated that vibegron and antimuscarinic had no significant differences in terms of OAB treatment. Mean volume voided/micturition showed a distinct difference in the two groups (P = .009). With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic. Serious adverse event (SAE) and discontinuations due to adverse event (AE) did not show a significant difference between the two groups.
CONCLUSIONS
The therapeutic effect of vibegron is similar to that of antimuscarinic, but vibegron does not increase the risk of AE.
Topics: Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive
PubMed: 33592817
DOI: 10.1097/MD.0000000000023171 -
The International Journal of... Jul 2021Hyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet...
Hyponatremia Following Antipsychotic Treatment: In Silico Pharmacodynamics Analysis of Spontaneous Reports From the US Food and Drug Administration Adverse Event Reporting System Database and an Updated Systematic Review.
BACKGROUND
Hyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet been explained.
METHODS
We investigated the relationship between pharmacological targets of antipsychotic drugs and the occurrence of hyponatremia by conducting a nested case-control study using the Food and Drug Administration Adverse Event Reporting System database. Multiple logistic regression was used to determine the associations between antipsychotics receptor occupancy and hyponatremia. We also performed a systematic review of clinical studies on this association.
RESULTS
Of 139 816 reports involving at least 1 antipsychotic, 1.1% reported hyponatremia. Olanzapine was the most frequently suspected drug (27%). A significant positive association was found between dopamine D3, D4, and hyponatremia, while adrenergic α 1, serotonin 5-HT1A, and 5-HT2A receptor occupancies were negatively associated. A multivariable stepwise regression model showed that dopamine D3 (adj. odds ratio = 1.21; 95% CI = 1.09-1.34; P < .05) predicted the risk for hyponatremia (P < .05), while serotonin 5-HT2A occupancy (Adj. odds ratio = 0.78; 95% CI = 0.68-0.90; P < .01) exhibited a protective effect against hyponatremia. Among the 11 studies included in the systematic review, incidence rates of hyponatremia diverged between 0.003% and 86%, whereas the odds of developing hyponatremia from effect studies ranged between 0.83 and 3.47.
CONCLUSIONS
Antipsychotic drugs having a combined modest occupancy for D3 and 5-HT2A receptors and higher levels of D3 receptor occupancy correspond to different degrees of risk for hyponatremia. Based on the few, relatively large-scale available studies, atypical antipsychotics have a more attenuated risk profile for hyponatremia.
Topics: Antipsychotic Agents; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Hyponatremia; Pharmacovigilance; United States; United States Food and Drug Administration
PubMed: 33575781
DOI: 10.1093/ijnp/pyab005 -
The Cochrane Database of Systematic... Feb 2021Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Although transient tachypnea of the newborn is usually a self-limited condition, it is associated with wheezing syndromes in late childhood. The rationale for the use of salbutamol (albuterol) for transient tachypnea of the newborn is based on studies showing that β-agonists can accelerate the rate of alveolar fluid clearance. This review was originally published in 2016 and updated in 2020.
OBJECTIVES
To assess whether salbutamol compared to placebo, no treatment or any other drugs administered to treat transient tachypnea of the newborn, is effective and safe for infants born at 34 weeks' gestational age with this diagnosis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2020, Issue 4) in the Cochrane Library; PubMed (1996 to April 2020), Embase (1980 to April 2020); and CINAHL (1982 to April 2020). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia New Zealand and Pediatric Academic Societies) from 2000 to 2020 and clinical trial registries.
SELECTION CRITERIA
Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing salbutamol versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology for data collection and analysis. The primary outcomes considered in this review were duration of oxygen therapy, need for continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Seven trials, which included 498 infants, met the inclusion criteria. All trials compared a nebulized dose of salbutamol with normal saline. Four studies used one single dose of salbutamol; in two studies, three to four doses were provided; in one study, additional doses were administered if needed. The certainty of the evidence was low for duration of hospital stay and very low for the other outcomes. Among the primary outcomes of this review, four trials (338 infants) reported the duration of oxygen therapy, (mean difference (MD) -19.24 hours, 95% confidence interval (CI) -23.76 to -14.72); one trial (46 infants) reported the need for continuous positive airway pressure (risk ratio (RR) 0.73, 95% CI 0.38 to 1.39; risk difference (RD) -0.15, 95% CI -0.45 to 0.16), and three trials (254 infants) reported the need for mechanical ventilation (RR 0.60, 95% CI 0.13 to 2.86; RD -0.01, 95% CI -0.05 to 0.03). Both duration of hospital stay (4 trials; 338 infants) and duration of respiratory support (2 trials, 228 infants) were shorter in the salbutamol group (MD -1.48, 95% CI -1.8 to -1.16; MD -9.24, 95% CI -14.24 to -4.23, respectively). One trial (80 infants) reported duration of mechanical ventilation and pneumothorax but data could not be extracted due to the reporting of these outcomes (type of units of effect measure and unclear number of events, respectively). Five trials are ongoing.
AUTHORS' CONCLUSIONS
There was limited evidence to establish the benefits and harms of salbutamol in the management of transient tachypnea of the newborn. We are uncertain whether salbutamol administration reduces the duration of oxygen therapy, duration of tachypnea, need for continuous positive airway pressure and for mechanical ventilation. Salbutamol may slightly reduce hospital stay. Five trials are ongoing. Given the limited and low certainty of the evidence available, we could not determine whether salbutamol was safe or effective for the treatment of transient tachypnea of the newborn.
Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Continuous Positive Airway Pressure; Humans; Infant, Newborn; Intermittent Positive-Pressure Ventilation; Length of Stay; Nebulizers and Vaporizers; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Time Factors; Transient Tachypnea of the Newborn
PubMed: 33543473
DOI: 10.1002/14651858.CD011878.pub3 -
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 -
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 -
Respiratory Research Nov 2020Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs)... (Comparative Study)
Comparative Study Meta-Analysis
Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.
BACKGROUND
Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA).
METHODS
We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753.
RESULTS
We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia.
CONCLUSIONS
The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more.
TRIAL REGISTRATION
This study was prospectively registered in PROSPERO; CRD42019126753.
Topics: Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Bronchodilator Agents; Delayed-Action Preparations; Disease Progression; Follow-Up Studies; Humans; Mortality; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 33238986
DOI: 10.1186/s12931-020-01540-8 -
International Journal of Chronic... 2020Inhaled corticosteroids (ICS) are widely used and recommended to treat chronic obstructive pulmonary disease (COPD). While generally considered safe, several studies... (Review)
Review
BACKGROUND
Inhaled corticosteroids (ICS) are widely used and recommended to treat chronic obstructive pulmonary disease (COPD). While generally considered safe, several studies demonstrated an increased risk of pneumonia with the use of ICS in COPD patients. Although all ICS indicated for COPD carry the class labeling warning of increased pneumonia risk, evidence suggests an intraclass difference in the risk of pneumonia between inhaled budesonide and fluticasone. To date, systematic reviews of direct-comparison studies have not been performed to assess if an intraclass difference exists.
RESEARCH QUESTION
This review investigated whether there is an intraclass difference in risk of pneumonia between inhaled fluticasone and budesonide, the 2 most commonly used ICS in COPD.
STUDY DESIGN AND METHODS
A search of the medical literature was conducted in PubMed and Embase for the time period of 01/01/69-05/31/19. The search strategy combined terms that defined the patient/disease type, exposures, outcome, and the study/publication type. Descriptive and comparative statistics reported for fluticasone- and budesonide-containing products in each study, including data for pneumonia event subgroups, were extracted and reported by dose, seriousness, or practice setting. Controlled clinical trials and observational studies meeting the inclusion criteria were assessed for methodologic quality by using the appropriate tool from the list of study quality assessment tools developed by the National Institutes of Health.
RESULTS
The summary relative risk (RR) ratio across 5 included studies (57,199 patients) was 1.13 (95% CI: 1.09-1.19), representing a 13.5% increased risk of pneumonia among fluticasone users compared to budesonide users. Similarly, summary RR ratio for serious pneumonia implied a 14.4% increased risk of serious pneumonia among fluticasone users compared to budesonide users (pooled RR: 1.14; 95% CI: 1.09-1.20).
INTERPRETATION
There is likely a clinically important intraclass difference in the risk of pneumonia between fluticasone- and budesonide-containing inhaled medications in COPD.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Budesonide; Fluticasone; Humans; Pneumonia; Pulmonary Disease, Chronic Obstructive
PubMed: 33204085
DOI: 10.2147/COPD.S269637 -
The Cochrane Database of Systematic... Nov 2020Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously down the ureter and into the bladder. Alpha-blockers may assist in promoting the passage of stone fragments, but their effectiveness remains uncertain. OBJECTIVES: To assess the effects of alpha-blockers as adjuvant medical expulsive therapy plus usual care compared to placebo and usual care or usual care alone in adults undergoing shock wave lithotripsy for renal or ureteral stones.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Library, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, several clinical trial registries and grey literature for published and unpublished studies irrespective of language. The date of the most recent search was 27 February 2020.
SELECTION CRITERIA
We included randomized controlled trials of adults undergoing SWL. Participants in the intervention group had to have received an alpha-blocker as adjuvant medical expulsive therapy plus usual care. For the comparator group, we considered studies in which participants received placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion/exclusion, and performed data abstraction and risk of bias assessment. We conducted meta-analysis for the identified dichotomous and continuous outcomes using RevManWeb according to Cochrane methods using a random-effects model. We judged the certainty of evidence on a per outcome basis using GRADE.
MAIN RESULTS
We included 40 studies with 4793 participants randomized to usual care and an alpha-blocker versus usual care alone. Only four studies were placebo controlled. The mean age of participants was 28.6 to 56.8 years and the mean stone size prior to SWL was 7.1 mm to 13.2 mm. The most widely used alpha-blocker was tamsulosin; others were silodosin, doxazosin, terazosin and alfuzosin. Alpha-blockers may improve clearance of stone fragments after SWL (risk ratio (RR) 1.16, 95% confidence interval (CI) 1.09 to 1.23; I² = 78%; studies = 36; participants = 4084; low certainty evidence). Based on the stone clearance rate of 69.3% observed in the control arm, an alpha-blocker may increase stone clearance to 80.4%. This corresponds to 111 more (62 more to 159 more) participants per 1000 clearing their stone fragments. Alpha-blockers may reduce the need for auxiliary treatments after SWL (RR 0.67, 95% CI 0.45 to 1.00; I² = 16%; studies = 12; participants = 1251; low certainty evidence), but also includes the possibility of no effect. Based on a rate of auxiliary treatments in the usual care arm of 9.7%, alpha-blockers may reduce the rate to 6.5%. This corresponds 32 fewer (53 fewer to 0 fewer) participants per 1000 undergoing auxiliary treatments. Alpha-blockers may reduce major adverse events (RR 0.60, 95% CI 0.46 to 0.80; I² = 0%; studies = 7; participants = 747; low certainty evidence). Major adverse events occurred in 25.8% of participants in the usual care group; alpha-blockers would reduce this to 15.5%. This corresponds to 103 fewer (139 fewer to 52 fewer) major adverse events per 1000 with alpha-blocker treatment. None of the reported major adverse events appeared drug-related; most were emergency room visits or rehospitalizations. Alpha-blockers may reduce stone clearance time in days (mean difference (MD) -3.74, 95% CI -5.25 to -2.23; I² = 86%; studies = 14; participants = 1790; low certainty evidence). We found no evidence for the outcome of quality of life. For those outcomes for which we were able to perform subgroup analyses, we found no evidence of interaction with stone location, stone size or type of alpha-blocker. We were unable to conduct an analysis by lithotripter type. The results were also largely unchanged when the analyses were limited to placebo controlled studies and those in which participants explicitly only received a single SWL session.
AUTHORS' CONCLUSIONS
Based on low certainty evidence, adjuvant alpha-blocker therapy following SWL in addition to usual care may result in improved stone clearance, less need for auxiliary treatments, fewer major adverse events and a reduced stone clearance time compared to usual care alone. We did not find evidence for quality of life. The low certainty of evidence means that our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxazosin; Humans; Indoles; Kidney Calculi; Lithotripsy; Middle Aged; Prazosin; Quinazolines; Randomized Controlled Trials as Topic; Tamsulosin; Ureteral Calculi
PubMed: 33179245
DOI: 10.1002/14651858.CD013393.pub2 -
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 -
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