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International Journal of Surgery... May 2023Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of... (Meta-Analysis)
Meta-Analysis
The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.
BACKGROUND
Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy.
OBJECTIVE
The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO.
METHODS
The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual.
RESULTS
A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and β3-adrenoceptor-agonists possessed good effectiveness and safety.
CONCLUSION
OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and β3-adrenoceptor-agonists have good effectiveness and safety.
Topics: Humans; Adult; Female; Botulinum Toxins, Type A; Quality of Life; Network Meta-Analysis; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Treatment Outcome; Receptors, Adrenergic; Tibial Nerve
PubMed: 36974676
DOI: 10.1097/JS9.0000000000000338 -
Chronic Respiratory Disease 2023The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of additional treatment with short-acting muscarinic antagonist combined with long-acting beta-2 agonist in stable patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.
BACKGROUND
The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied.
METHODS
We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest.
RESULTS
We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV (mean difference (MD) 98.70 mL, < .00001), transitional dyspnea index score (MD .85, = .02), and St George's Respiratory Questionnaire score (MD -2.00, = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD ( = .20) and only a slight trend of increased severe adverse events (OR: 2.16, = .08) and cardiovascular events (OR: 2.38, = .06).
CONCLUSION
Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.
Topics: Humans; Muscarinic Antagonists; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Administration, Inhalation; Dyspnea
PubMed: 36967224
DOI: 10.1177/14799731231166008 -
Lower Urinary Tract Symptoms May 2023The aim of this study was to indirectly compare the efficacy and safety of mirabegron and vibegron in patients with overactive bladder. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of this study was to indirectly compare the efficacy and safety of mirabegron and vibegron in patients with overactive bladder.
METHODS
A systematic search was performed on Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases to identify studies from the date of database inception to January 1, 2022. All randomized controlled trials comparing mirabegron or vibegron with tolterodine, imidafenacin, or placebo were eligible. One reviewer extracted data, and a second reviewer checked. Included trials were assessed for similarity, and networks were developed using Stata 16.0 software. Mean differences for continuous variables and odds ratios for dichotomous variables together with their 95% confidence intervals (CIs) were used to rank treatments and compare the differences, respectively.
RESULTS
A total of 11 randomized controlled trials and 10 806 patients were included. For each outcome, results for all licensed treatment doses were included. Both vibegron and mirabegron were more efficacious than placebo at reducing the frequency of micturition, incontinence, urgency, urgency incontinence, and nocturia. Vibegron was more efficacious than mirabegron in reducing mean voided volume/micturition (95% CI [5.15, 14.98]). Safety outcomes for vibegron and mirabegron were similar to those in the placebo group, except for mirabegron, which had a higher risk of nasopharyngitis and cardiovascular adverse events than placebo.
CONCLUSIONS
Both drugs seem to be comparable and well tolerated, particularly as direct comparisons are not available. However, vibegron may be more effective than mirabegron in reducing mean voided volume.
Topics: Humans; Urinary Bladder, Overactive; Network Meta-Analysis; Treatment Outcome; Double-Blind Method; Acetanilides; Adrenergic beta-3 Receptor Agonists; Randomized Controlled Trials as Topic
PubMed: 36863312
DOI: 10.1111/luts.12475 -
The Journal of Urology Apr 2023The aim of this meta-analysis was to investigate the effect of pharmacotherapy for overactive bladder on the pathogenesis of urinary tract infection. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aim of this meta-analysis was to investigate the effect of pharmacotherapy for overactive bladder on the pathogenesis of urinary tract infection.
MATERIALS AND METHODS
A comprehensive search was performed in MEDLINE and the Cochrane Library using terms for overactive bladder, antimuscarinic agents, and beta 3-adrenoceptor agonists. The primary end point was the emergence of urinary tract infection after pharmacotherapy for overactive bladder. The secondary end point was the emergence of urinary retention, dysuria, and/or increased residual urine volume after overactive bladder treatment. Meta-analyses were conducted using random-effects models.
RESULTS
A total of 35,939 patients in 33 trials (29 trials of antimuscarinic agents vs placebo, and 9 trials of beta 3-adrenoceptor agonists vs placebo) that included patients with overactive bladder were identified. At 1-3 months after treatment, the incidence of urinary tract infections was statistically significantly higher in the patients treated with antimuscarinic agents (RR: 1.23, 95% CI: 1.04, 1.45; = .013) than in the placebo control group. The incidence of urinary tract infections was not increased in the patients treated with beta 3-adrenoceptor agonists (RR: 1.04, 95% CI: 0.76, 1.42; = .796). Antimuscarinic agents also statistically significantly increased the risks of urinary retention, dysuria, and/or increased residual urine volume (RR: 2.88, 95% CI: 1.79, 4.63; < .001), whereas beta 3-adrenoceptor agonists did not (RR: 1.26, 95% CI: 0.38, 4.14; = .708).
CONCLUSIONS
This meta-analysis showed that antimuscarinic agents statistically significantly increased the incidences of urinary tract infection and lower urinary tract symptoms and dysfunction, but beta 3-adrenoceptor agonists did not. To prevent urinary tract infection emergence, beta 3-adrenoceptor agonists might be safer than antimuscarinic agents.
Topics: Humans; Urinary Bladder, Overactive; Muscarinic Antagonists; Incidence; Urinary Retention; Dysuria; Adrenergic beta-3 Receptor Agonists; Urinary Tract Infections; Receptors, Adrenergic
PubMed: 36787147
DOI: 10.1097/JU.0000000000003209 -
World Journal of Critical Care Medicine Jan 2023Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use...
BACKGROUND
Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation. As clonidine is an enterally available alpha-2A adrenergic agonist, it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes. The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known. The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms.
AIM
To systematically review the practice, dosing schema, and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults.
METHODS
This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults (≥ 18 years). Randomized controlled trials, prospective cohorts, and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included. The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal. Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use, re-initiation of dexmedetomidine, duration of mechanical ventilation, and ICU length of stay.
RESULTS
A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients. All three studies were observational, two being prospective and one retrospective. In all included studies, the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician. Weaning time ranged from 13 to 167 h on average. Enteral clonidine was started in the prospective studies in a similar protocolized method, with 0.3 mg every 6 h. After starting clonidine, patients remained on dexmedetomidine for a median of 1-28 h. Following the termination of dexmedetomidine, two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h, 12h, and 24 h, followed by clonidine discontinuation. For indicators of enteral clonidine withdrawal, the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol. The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation. The re-initiation of dexmedetomidine was not documented in any study. Only 17 (37%) patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies. ICU lengths of stay were similar.
CONCLUSION
Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine. There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.
PubMed: 36683967
DOI: 10.5492/wjccm.v12.i1.18 -
Archivio Italiano Di Urologia,... Dec 2022Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS),... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke.
OBJECTIVE
The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder.
MATERIALS AND METHODS
We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022.
RESULTS
A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups.
CONCLUSIONS
The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.
Topics: Humans; Cholinergic Antagonists; Nocturia; Pelvic Floor; Randomized Controlled Trials as Topic; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence
PubMed: 36576454
DOI: 10.4081/aiua.2022.4.492 -
The Lancet. Child & Adolescent Health Feb 2023In clinical practice guidelines there is no consensus about the medications that should be initially offered to children and young people with Tourette's syndrome. To... (Meta-Analysis)
Meta-Analysis
Comparative efficacy, tolerability, and acceptability of pharmacological interventions for the treatment of children, adolescents, and young adults with Tourette's syndrome: a systematic review and network meta-analysis.
BACKGROUND
In clinical practice guidelines there is no consensus about the medications that should be initially offered to children and young people with Tourette's syndrome. To provide a rigorous evidence base that could help guide decision making and guideline development, we aimed to compare the efficacy, tolerability, and acceptability of pharmacological interventions for Tourette's syndrome.
METHODS
For this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, PubMed, Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov, for published and unpublished studies from database inception to Nov 19, 2021. We included double-blind randomised controlled trials of any medication administered as a monotherapy for at least 1 week against another medication or placebo in children and adolescents (aged ≥4 years and ≤18 years), adults (>18 years), or both, diagnosed with Tourette's syndrome according to standardised criteria. We excluded studies that exclusively recruited participants with comorbid attention-deficit hyperactivity disorder or obsessive-compulsive disorder. The primary outcome was change in severity of tic symptoms (efficacy). Secondary outcomes were treatment discontinuations due to adverse events (tolerability) and for any reason (acceptability). Pharmacological interventions were examined considering medication categories and medications individually in separate analyses. Summary data were extracted and pooled with a random-effects network meta-analysis to calculate standardised mean differences for efficacy and odds ratios for tolerability and acceptability, with 95% CIs. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was pre-registered in PROSPERO (CRD42022296975).
FINDINGS
Of the 12 088 records identified through the database search, 88 records representing 39 randomised controlled trials were included in the network meta-analysis; these 39 randomised controlled trials comprised 4578 participants (mean age 11·8 [SD 4·5] years; 3676 [80·8%] male participants) and evaluated 23 individual medications distributed across six medication categories. When considering medication categories, first-generation (standardised mean difference [SMD] -0·65 [95% CI -0·79 to -0·51]; low certainty of evidence) and second-generation (-0·71 [-0·88 to -0·54]; moderate certainty of evidence) antipsychotic drugs, as well as α-2 agonists (-0·21 [-0·39 to -0·03]; moderate certainty of evidence), were more efficacious than placebo. First-generation and second-generation antipsychotic drugs did not differ from each other (SMD 0·06 [95% CI -0·14 to 0·25]; low certainty of evidence). However, both first-generation (SMD 0·44 [95% CI 0·21 to 0·66]) and second-generation (0·49 [0·25 to 0·74]) antipsychotic drugs outperformed α-2 agonists, with moderate certainty of evidence. Similar findings were observed when individual medications were considered: aripiprazole (SMD -0·60 [95% CI -0·83 to -0·38]), haloperidol (-0·51 [-0·88 to -0·14]), olanzapine (-0·83 [-1·49 to -0·18]), pimozide (-0·48 [-0·84 to -0·12]), risperidone (-0·66 [-0·98 to -0·34]), and clonidine (-0·20 [-0·37 to -0·02]) all outperformed placebo, with moderate certainty of evidence. Antipsychotic medications did not differ from each other, but there was low to very low certainty of evidence for these comparisons. However, aripiprazole (SMD -0·40 [95% CI -0·69 to -0·12]) and risperidone (-0·46 [-0·82 to -0·11]) outperformed clonidine, with moderate certainty of evidence. Heterogeneity or inconsistency only emerged for a few comparisons. In terms of tolerability and acceptability, there were no relevant findings for any of the efficacious medication categories or individual medications against each other or placebo, but there was low to very low certainty of evidence associated with these comparisons.
INTERPRETATION
Our analyses show that antipsychotic drugs are the most efficacious intervention for Tourette's syndrome, while α-2 agonists are also more efficacious than placebo and could be chosen by those who elect not to take antipsychotic drugs. Shared decision making about the degree of tic-related severity and distress or impairment, the trade-offs of efficacy and safety between antipsychotic drugs and α-2 agonists, and other highly relevant individual factors that could not be addressed in the present analysis, should guide the choice of medication for children and young people with Tourette's syndrome.
FUNDING
None.
Topics: Male; Adolescent; Child; Young Adult; Humans; Female; Tourette Syndrome; Antipsychotic Agents; Clonidine; Aripiprazole; Risperidone; Network Meta-Analysis; Tics; Adrenergic alpha-2 Receptor Agonists; Randomized Controlled Trials as Topic
PubMed: 36528030
DOI: 10.1016/S2352-4642(22)00316-9 -
Respiratory Research Dec 2022Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes.
METHODS
A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted.
RESULTS
Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0-1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities.
CONCLUSIONS
LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes.
Topics: Humans; Adrenergic beta-2 Receptor Agonists; Exercise Tolerance; Quality of Life; Administration, Inhalation; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Exercise; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36522735
DOI: 10.1186/s12931-022-02268-3 -
The Cochrane Database of Systematic... Dec 2022Current guidelines recommend a higher-dose inhaled corticosteroids (ICS) or adding a long-acting muscarinic antagonist (LAMA) when asthma is not controlled with... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis.
BACKGROUND
Current guidelines recommend a higher-dose inhaled corticosteroids (ICS) or adding a long-acting muscarinic antagonist (LAMA) when asthma is not controlled with medium-dose (MD) ICS/long-acting beta2-agonist (LABA) combination therapy.
OBJECTIVES
To assess the effectiveness and safety of dual (ICS/LABA) and triple therapies (ICS/LABA/LAMA) compared with each other and with varying doses of ICS in adolescents and adults with uncontrolled asthma.
SEARCH METHODS
We searched multiple databases for pre-registered randomised controlled trials (RCTs) of at least 12 weeks of study duration from 2008 to 18 February 2022.
SELECTION CRITERIA
We searched studies, including adolescents and adults with uncontrolled asthma who had been treated with, or were eligible for, MD-ICS/LABA, comparing dual and triple therapies. We excluded cluster- and cross-over RCTs.
DATA COLLECTION AND ANALYSIS
We conducted a systematic review and network meta-analysis according to the previously published protocol. We used Cochrane's Screen4ME workflow to assess search results and Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. The primary outcome was steroid-requiring asthma exacerbations and asthma-related hospitalisations (moderate to severe and severe exacerbations).
MAIN RESULTS
We included 17,161 patients with uncontrolled asthma from 17 studies (median duration 26 weeks; mean age 49.1 years; male 40%; white 81%; mean forced expiratory volume in 1 second (MEF 1)1.9 litres and 61% predicted). The quality of included studies was generally good except for some outcomes in a few studies due to high attrition rates. Medium-dose (MD) and high-dose (HD) triple therapies reduce steroid-requiring asthma exacerbations (hazard ratio (HR) 0.84 [95% credible interval (CrI) 0.71 to 0.99] and 0.69 [0.58 to 0.82], respectively) (high-certainty evidence), but not asthma-related hospitalisations, compared to MD-ICS/LABA. High-dose triple therapy likely reduces steroid-requiring asthma exacerbations compared to MD triple therapy (HR 0.83 [95% CrI 0.69 to 0.996], [moderate certainty]). Subgroup analyses suggest the reduction in steroid-requiring exacerbations associated with triple therapies may be only for those with a history of asthma exacerbations in the previous year but not for those without. High-dose triple therapy, but not MD triple, results in a reduction in all-cause adverse events (AEs) and likely reduces dropouts due to AEs compared to MD-ICS/LABA (odds ratio (OR) 0.79 [95% CrI 0.69 to 0.90], [high certainty] and 0.50 [95% CrI 0.30 to 0.84], [moderate certainty], respectively). Triple therapy results in little to no difference in all-cause or asthma-related serious adverse events (SAEs) compared to dual therapy (high certainty). The evidence suggests triple therapy results in little or no clinically important difference in symptoms or quality of life compared to dual therapy considering the minimal clinically important differences (MCIDs) and HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA.
AUTHORS' CONCLUSIONS
Medium-dose and HD triple therapies reduce steroid-requiring asthma exacerbations, but not asthma-related hospitalisations, compared to MD-ICS/LABA especially in those with a history of asthma exacerbations in the previous year. High-dose triple therapy is likely superior to MD triple therapy in reducing steroid-requiring asthma exacerbations. Triple therapy is unlikely to result in clinically meaningful improvement in symptoms or quality of life compared to dual therapy considering the MCIDs. High-dose triple therapy, but not MD triple, results in a reduction in all-cause AEs and likely reduces dropouts due to AEs compared to MD-ICS/LABA. Triple therapy results in little to no difference in all-cause or asthma-related SAEs compared to dual therapy. HD-ICS/LABA is unlikely to result in any significant benefit or harm compared to MD-ICS/LABA, although long-term safety of higher rather than MD- ICS remains to be demonstrated given the median duration of included studies was six months. The above findings may assist deciding on a treatment option when asthma is not controlled with MD-ICS/LABA.
Topics: Adult; Male; Adolescent; Humans; Middle Aged; Adrenergic beta-2 Receptor Agonists; Network Meta-Analysis; Drug Therapy, Combination; Adrenal Cortex Hormones; Asthma; Muscarinic Antagonists; Nebulizers and Vaporizers; Administration, Inhalation
PubMed: 36472162
DOI: 10.1002/14651858.CD013799.pub2 -
Minerva Anestesiologica May 2023Elective cesarean section (CS) is usually performed using spinal anesthesia (SA), which requires the use of local anesthetic (LA) agents, commonly combined with adjuvant... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Elective cesarean section (CS) is usually performed using spinal anesthesia (SA), which requires the use of local anesthetic (LA) agents, commonly combined with adjuvant drugs. We performed a systematic review and meta-analysis aimed at studying the advantages of α-2 agonists as compared to fentanyl during SA for CS.
EVIDENCE ACQUISITION
We screened PubMed and EMBASE for randomized controlled trials (RCTs). We calculated the mean difference (MD) for continuous outcomes, and the relative risk for dichotomous outcomes, using a random-effect model with 95% confidence interval (CI). We performed a Trial Sequential Analysis (TSA) assuming an alpha risk of 5%. The primary outcome was the time to first rescue analgesia.
EVIDENCE SYNTHESIS
Eight RCTs were included. Time to first rescue analgesia was significantly longer when the α-2 agonists were used (MD 85.9 min [95% CI: 23.8, 147.9]; P=0.007). Duration of sensory block was also longer in the α-2 group (MD 40.5 [95% CI: 20.21,60.7]; P<0.0001), while no differences were found for onset of sensory block and onset and duration of motor block. Rates of shivering and nausea or vomiting were significantly lower in the α-2 agonist group, while risk of hypotension or respiratory depression were not different. The TSA on the primary outcome suggests the need of further research before drawing conclusions.
CONCLUSIONS
α2-agonists seem to increase the time to first rescue analgesia and to prolong the duration of sensory block when used as adjuvants to LA in CS patients compared to fentanyl. Also, α2-agonists may reduce the incidence of shivering and nausea or vomiting.
Topics: Pregnancy; Female; Humans; Anesthesia, Spinal; Fentanyl; Anesthetics, Local; Pain; Adrenergic alpha-2 Receptor Agonists; Vomiting; Nausea; Adjuvants, Pharmaceutic; Cesarean Section; Adjuvants, Anesthesia
PubMed: 36448990
DOI: 10.23736/S0375-9393.22.16969-5