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Advances in Therapy Sep 2022Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β-agonist [LABA], and long-acting muscarinic antagonist... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.
METHODS
This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).
RESULTS
The NMA was informed by five trials reporting FEV at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).
CONCLUSION
The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Benzyl Alcohols; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Drug Combinations; Fluticasone; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines
PubMed: 35849317
DOI: 10.1007/s12325-022-02231-0 -
JAMA Jun 2021The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.
OBJECTIVE
To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.
DATA SOURCES
MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.
STUDY SELECTION
Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.
MAIN OUTCOMES AND MEASURES
Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.
RESULTS
Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).
CONCLUSIONS AND RELEVANCE
Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Child; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Muscarinic Antagonists; Nebulizers and Vaporizers; Quality of Life; Severity of Illness Index; Symptom Flare Up; Xerostomia
PubMed: 34009257
DOI: 10.1001/jama.2021.7872 -
The Cochrane Database of Systematic... Feb 2023Myopia is a common refractive error, where elongation of the eyeball causes distant objects to appear blurred. The increasing prevalence of myopia is a growing global... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myopia is a common refractive error, where elongation of the eyeball causes distant objects to appear blurred. The increasing prevalence of myopia is a growing global public health problem, in terms of rates of uncorrected refractive error and significantly, an increased risk of visual impairment due to myopia-related ocular morbidity. Since myopia is usually detected in children before 10 years of age and can progress rapidly, interventions to slow its progression need to be delivered in childhood.
OBJECTIVES
To assess the comparative efficacy of optical, pharmacological and environmental interventions for slowing myopia progression in children using network meta-analysis (NMA). To generate a relative ranking of myopia control interventions according to their efficacy. To produce a brief economic commentary, summarising the economic evaluations assessing myopia control interventions in children. To maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE; Embase; and three trials registers. The search date was 26 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of optical, pharmacological and environmental interventions for slowing myopia progression in children aged 18 years or younger. Critical outcomes were progression of myopia (defined as the difference in the change in spherical equivalent refraction (SER, dioptres (D)) and axial length (mm) in the intervention and control groups at one year or longer) and difference in the change in SER and axial length following cessation of treatment ('rebound'). DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. We assessed bias using RoB 2 for parallel RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes: change in SER and axial length at one and two years. Most comparisons were with inactive controls.
MAIN RESULTS
We included 64 studies that randomised 11,617 children, aged 4 to 18 years. Studies were mostly conducted in China or other Asian countries (39 studies, 60.9%) and North America (13 studies, 20.3%). Fifty-seven studies (89%) compared myopia control interventions (multifocal spectacles, peripheral plus spectacles (PPSL), undercorrected single vision spectacles (SVLs), multifocal soft contact lenses (MFSCL), orthokeratology, rigid gas-permeable contact lenses (RGP); or pharmacological interventions (including high- (HDA), moderate- (MDA) and low-dose (LDA) atropine, pirenzipine or 7-methylxanthine) against an inactive control. Study duration was 12 to 36 months. The overall certainty of the evidence ranged from very low to moderate. Since the networks in the NMA were poorly connected, most estimates versus control were as, or more, imprecise than the corresponding direct estimates. Consequently, we mostly report estimates based on direct (pairwise) comparisons below. At one year, in 38 studies (6525 participants analysed), the median change in SER for controls was -0.65 D. The following interventions may reduce SER progression compared to controls: HDA (mean difference (MD) 0.90 D, 95% confidence interval (CI) 0.62 to 1.18), MDA (MD 0.65 D, 95% CI 0.27 to 1.03), LDA (MD 0.38 D, 95% CI 0.10 to 0.66), pirenzipine (MD 0.32 D, 95% CI 0.15 to 0.49), MFSCL (MD 0.26 D, 95% CI 0.17 to 0.35), PPSLs (MD 0.51 D, 95% CI 0.19 to 0.82), and multifocal spectacles (MD 0.14 D, 95% CI 0.08 to 0.21). By contrast, there was little or no evidence that RGP (MD 0.02 D, 95% CI -0.05 to 0.10), 7-methylxanthine (MD 0.07 D, 95% CI -0.09 to 0.24) or undercorrected SVLs (MD -0.15 D, 95% CI -0.29 to 0.00) reduce progression. At two years, in 26 studies (4949 participants), the median change in SER for controls was -1.02 D. The following interventions may reduce SER progression compared to controls: HDA (MD 1.26 D, 95% CI 1.17 to 1.36), MDA (MD 0.45 D, 95% CI 0.08 to 0.83), LDA (MD 0.24 D, 95% CI 0.17 to 0.31), pirenzipine (MD 0.41 D, 95% CI 0.13 to 0.69), MFSCL (MD 0.30 D, 95% CI 0.19 to 0.41), and multifocal spectacles (MD 0.19 D, 95% CI 0.08 to 0.30). PPSLs (MD 0.34 D, 95% CI -0.08 to 0.76) may also reduce progression, but the results were inconsistent. For RGP, one study found a benefit and another found no difference with control. We found no difference in SER change for undercorrected SVLs (MD 0.02 D, 95% CI -0.05 to 0.09). At one year, in 36 studies (6263 participants), the median change in axial length for controls was 0.31 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD -0.33 mm, 95% CI -0.35 to 0.30), MDA (MD -0.28 mm, 95% CI -0.38 to -0.17), LDA (MD -0.13 mm, 95% CI -0.21 to -0.05), orthokeratology (MD -0.19 mm, 95% CI -0.23 to -0.15), MFSCL (MD -0.11 mm, 95% CI -0.13 to -0.09), pirenzipine (MD -0.10 mm, 95% CI -0.18 to -0.02), PPSLs (MD -0.13 mm, 95% CI -0.24 to -0.03), and multifocal spectacles (MD -0.06 mm, 95% CI -0.09 to -0.04). We found little or no evidence that RGP (MD 0.02 mm, 95% CI -0.05 to 0.10), 7-methylxanthine (MD 0.03 mm, 95% CI -0.10 to 0.03) or undercorrected SVLs (MD 0.05 mm, 95% CI -0.01 to 0.11) reduce axial length. At two years, in 21 studies (4169 participants), the median change in axial length for controls was 0.56 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD -0.47mm, 95% CI -0.61 to -0.34), MDA (MD -0.33 mm, 95% CI -0.46 to -0.20), orthokeratology (MD -0.28 mm, (95% CI -0.38 to -0.19), LDA (MD -0.16 mm, 95% CI -0.20 to -0.12), MFSCL (MD -0.15 mm, 95% CI -0.19 to -0.12), and multifocal spectacles (MD -0.07 mm, 95% CI -0.12 to -0.03). PPSL may reduce progression (MD -0.20 mm, 95% CI -0.45 to 0.05) but results were inconsistent. We found little or no evidence that undercorrected SVLs (MD -0.01 mm, 95% CI -0.06 to 0.03) or RGP (MD 0.03 mm, 95% CI -0.05 to 0.12) reduce axial length. There was inconclusive evidence on whether treatment cessation increases myopia progression. Adverse events and treatment adherence were not consistently reported, and only one study reported quality of life. No studies reported environmental interventions reporting progression in children with myopia, and no economic evaluations assessed interventions for myopia control in children.
AUTHORS' CONCLUSIONS
Studies mostly compared pharmacological and optical treatments to slow the progression of myopia with an inactive comparator. Effects at one year provided evidence that these interventions may slow refractive change and reduce axial elongation, although results were often heterogeneous. A smaller body of evidence is available at two or three years, and uncertainty remains about the sustained effect of these interventions. Longer-term and better-quality studies comparing myopia control interventions used alone or in combination are needed, and improved methods for monitoring and reporting adverse effects.
Topics: Humans; Child; Network Meta-Analysis; Myopia; Refractive Errors; Atropine; Refraction, Ocular
PubMed: 36809645
DOI: 10.1002/14651858.CD014758.pub2 -
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 -
Advances in Therapy Nov 2022Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD.
METHODS
A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented.
RESULTS
The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation.
CONCLUSION
UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Dyspnea; Forced Expiratory Volume; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome
PubMed: 35857184
DOI: 10.1007/s12325-022-02234-x -
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 -
Advances in Therapy Jun 2021In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic... (Meta-Analysis)
Meta-Analysis
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 33929661
DOI: 10.1007/s12325-021-01703-z -
The Cochrane Database of Systematic... Jan 2020Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses, and pharmaceutical agents.
OBJECTIVES
To assess the effects of interventions, including spectacles, contact lenses, and pharmaceutical agents in slowing myopia progression in children.
SEARCH METHODS
We searched CENTRAL; Ovid MEDLINE; Embase.com; PubMed; the LILACS Database; and two trial registrations up to February 2018. A top up search was done in February 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs). We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than -0.25 diopters (D) spherical equivalent myopia.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods.
MAIN RESULTS
We included 41 studies (6772 participants). Twenty-one studies contributed data to at least one meta-analysis. Interventions included spectacles, contact lenses, pharmaceutical agents, and combination treatments. Most studies were conducted in Asia or in the United States. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average -0.15 D (95% confidence interval [CI] -0.29 to 0.00; n = 142; low-certainty evidence) more than those wearing fully corrected single vision lenses (SVLs). In one study, axial length increased 0.05 mm (95% CI -0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low-certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95% CI 0.08 to 0.21; n = 1463; moderate-certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (-0.06 mm, 95% CI -0.09 to -0.04; n = 896; moderate-certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low-certainty evidence). Contact lenses: there may be little or no difference between vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95% CI -0.06 to 0.47; n = 300; low-certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD -0.11 mm, 95% CI -0.14 to -0.08; n = 300; low-certainty evidence). Two studies investigating rigid gas permeable contact lenses (RGPCLs) showed inconsistent results in myopia progression; these two studies also found no evidence of difference in axial elongation (MD 0.02mm, 95% CI -0.05 to 0.10; n = 415; very low-certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD -0.28 mm, 95% CI -0.38 to -0.19; n = 106; moderate-certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor in axial length (n = 209; low-certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95% CI 0.93 to 1.07), 0.31 D (95% CI 0.17 to 0.44), and 0.34 (95% CI 0.08 to 0.60), respectively (moderate-certainty evidence). Axial elongation was less for children treated with atropine (MD -0.35 mm, 95% CI -0.38 to -0.31; n = 502) and pirenzepine (MD -0.13 mm, 95% CI -0.14 to -0.12; n = 326) than for those treated with placebo (moderate-certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95% CI 0.49 to 1.07 for 0.1% atropine; MD 0.81 D, 95% CI 0.57 to 1.05 for 0.25% atropine; and MD 1.01 D, 95% CI 0.74 to 1.28 for 0.5% atropine; n = 196; low-certainty evidence) but did not report axial length. Systemic 7-methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95% CI -0.09 to 0.24) nor on axial elongation (MD -0.03 mm, 95% CI -0.10 to 0.03) compared with placebo in one study (n = 77; moderate-certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD -0.05 D, 95% CI -0.21 to 0.11; n = 95; low-certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95% CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate-certainty evidence). One study reported -0.37 mm (95% CI -0.47 to -0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate-certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95% CI 0.11 to 0.61; n = 64; moderate-certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95% CI 0.06 to 0.32; n = 97; moderate-certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95% CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95% CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low-certainty evidence to support RGPCLs and sperical aberration SCLs.
Topics: Atropine; Child; Contact Lenses; Cyclopentolate; Humans; Muscarinic Antagonists; Myopia, Degenerative; Ophthalmic Solutions; Pirenzepine; Randomized Controlled Trials as Topic
PubMed: 31930781
DOI: 10.1002/14651858.CD004916.pub4 -
Developmental Medicine and Child... Sep 2021To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and... (Meta-Analysis)
Meta-Analysis
AIM
To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia.
METHOD
Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE.
RESULTS
Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis.
INTERPRETATION
Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.
Topics: Baclofen; Botulinum Toxins; Cerebral Palsy; Clonidine; Deep Brain Stimulation; Dystonia; Humans; Injections, Spinal; Levodopa; Neurosurgical Procedures; Trihexyphenidyl
PubMed: 33772789
DOI: 10.1111/dmcn.14874 -
International Braz J Urol : Official... 2023bladder based on a systematic review and network meta-analysis approach. (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
bladder based on a systematic review and network meta-analysis approach.
METHODS
Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software.
RESULT
A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache.
CONCLUSION
Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.
Topics: Humans; Urinary Bladder, Overactive; Solifenacin Succinate; Tolterodine Tartrate; Network Meta-Analysis; Double-Blind Method; Constipation; Xerostomia; Treatment Outcome; Muscarinic Antagonists; Randomized Controlled Trials as Topic
PubMed: 37506033
DOI: 10.1590/S1677-5538.IBJU.2023.0158