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Neurourology and Urodynamics Jan 2022Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no... (Meta-Analysis)
Meta-Analysis Review
AIMS
Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no systematic review with meta-analysis addressing potential benefits or adverse effects exists. The aim of this review was to assess the effectiveness, both benefits and harms, of using parasympathomimetics for the treatment of underactive bladder.
METHODS
The protocol was registered in PROSPERO, and searches undertaken in PubMed, Embase, and CENTRAL, including randomized and non-randomized controlled trials of patients with underactive bladder, comparing parasympathomimetic to placebo, no treatment, or other pharmaceuticals. Risk ratios, odds ratios, and mean differences were calculated.
RESULTS
Twelve trials with 3024 participants were included. There was a significant difference between parasympathomimetics and comparators (favoring parasympathomimetics) in the number of patients with urinary retention (risk ratio 0.55, 95% confidence interval [CI] 0.3-0.98, p = 0.04, low quality of evidence). There was no difference in mean postvoid volume overall (MD -41.4 ml, 95% CI -92.0 to 9.1, p = 0.11, low quality of evidence). There was a significant difference at up to 1 week post-intervention, favoring parasympathomimetics (MD -77.5 ml, 95% CI -90.9 to -64.1, p < 0.001, low quality of evidence), but no difference at 1 month post-intervention. There was no difference in adverse events (odds ratio 1.19, 95% CI 0.62-2.28, p = 0.6, moderate quality of evidence).
CONCLUSIONS
The evidence supporting the use of parasympathomimetics is of low quality, with relatively short follow-up durations. Overall, it is not possible to draw clear evidence-based conclusions from the current literature, presenting the use of parasympathomimetics for treating underactive bladder as a key area that requires future well-controlled clinical trials.
Topics: Humans; Parasympathomimetics; Urinary Bladder, Underactive; Urinary Retention
PubMed: 34816481
DOI: 10.1002/nau.24839 -
International Braz J Urol : Official... 2015To evaluate the efficacy and safety of onabotulinumtoxinA for patients with neurogenic detrusor overactivity (NDO). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy and safety of onabotulinumtoxinA for patients with neurogenic detrusor overactivity (NDO).
MATERIALS AND METHODS
We searched the Cochrane Library, PUBMED, EMBASE, Chinese Bio-medicine database, China Journal Full-text Database, VIP database, Wanfang database for randomized controlled trials (from inception to September 2012). Two authors independently selected studies, extracted data and assessed the methodological and evidence quality using the Cochrane Risk of Bias Table and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) respectively. Data analysis was performed by RevMan 5.1 and descriptive analysis was employed if necessary.
RESULTS
Eight studies were selected (n=1879 participants). OnabotulinumtoxinA was more related to urinary tract infection (UTI) (200 U: OR 1.72, CI: 1.18-2.52; 300 U: OR 1.88, CI: 1.31-2.69) versus placebo. Also, OnabotulinumtoxinA was superior to placebo in improving maximum cystometric capacity (MCC) (200 U: OR 138.80, CI: 112.45-165.15; 300 U: OR 152.09, CI: 125.25-178.93) and decreasing maximum detrusor pressure (MDP) (200 U: MD -29.61, CI: -36.52--22.69; 300 U: MD-28.92, CI: -39.59--18.25). However, there were no statistical differences between 200 U and 300 U onabotulinumtoxinA in UTI (OR 0.84, CI: 0.58-1.22), MCC (OR-12.72, CI: -43.36-17.92) and MDP (MD 2.21, CI: -6.80-11.22).
CONCLUSIONS
OnabotulinumtoxinA may provide superior clinical and urodynamic benefit for populations with NDO. High-quality studies are required for evaluating the optimal dose, long-term application and when to perform repeated injections.
Topics: Acetylcholine Release Inhibitors; Adult; Botulinum Toxins, Type A; Female; Humans; Publication Bias; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Young Adult
PubMed: 26005961
DOI: 10.1590/S1677-5538.IBJU.2015.02.05 -
Scandinavian Journal of Pain Oct 2021The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial nociceptors is suggested as a potential mechanism and injections of botulinum toxin (BONTA) have thus been used in the treatment for both headache conditions. BONTA inhibits the release of acetylcholine at the neuromuscular junction and inhibits contraction of skeletal muscles. If the pain is precipitated by increased tone in cervical muscles, local injections of BONTA could represent a prophylactic measure. However, the treatment is still controversial, and a thorough assessment of the current evidence is required. This review aims to assess the evidence of BONTA injection as a prophylactic treatment for CTTH and CEH by reviewing and examining the quality of placebo-controlled, randomized trials.
METHODS
Data sources: we searched in the following databases: PubMed (including Medline), Embase, Cochrane Central register of Controlled Trials, Cinahl, Amed, SCOPUS and Google Scholar including other repository sources. Both MeSH and free keywords were used in conducting the systematic search in the databases. The search covered publications from the root of the databases to November 2020.
STUDY ELIGIBILITY CRITERIA
The review included RCTs, comparing single treatment of BONTA with placebo on patients with CTTH or CEH above 18 years of age, by measuring pain severity/relief or headache frequency.
DATA EXTRACTION
The following data were extracted: year of publication, country, setting, trial design, number of participants, injection procedure, BONTA dosages, and clinical outcome measures.
STUDY APPRAISAL
To assess validity and quality, and risk of bias, the Oxford Pain Validity Scale, Modified Jadad Scale, last version of Cochrane Collaboration's tool for assessing risk of bias (RoB 2), and the CONSORT 2010 Checklist were used. The trials were assessed, and quality scored independently by two of the reviewers. A quantitative synthesis and meta-analyses of headache frequency and intensity were performed.
RESULTS
We extracted 16 trials, 12 on prophylactic BONTA treatment for CTTH and four on CEH. Of these 12 trials (8 on CTTH and 4 on CEH) were included in the quantitative synthesis. A majority of the trials found no significant difference on the primary outcome measure when BONTA treatment was compared with placebo. Three "positive" trials, reporting significant difference in favor of BONTA treatment, but two of these were hampered by low validity and quality scores and high risk of bias.
CONCLUSIONS
There is no clear clinical evidence supporting prophylactic treatment with BONTA for CTTH or CEH.
Topics: Botulinum Toxins, Type A; Headache; Headache Disorders; Humans; Post-Traumatic Headache; Randomized Controlled Trials as Topic; Tension-Type Headache
PubMed: 34090319
DOI: 10.1515/sjpain-2021-0038 -
Addiction (Abingdon, England) Jul 2024Cytisine (also known as cytisinicline) is a low-cost partial agonist of nicotinic acetylcholine receptors used to assist tobacco cessation. We aimed to review the... (Review)
Review
BACKGROUND AND AIMS
Cytisine (also known as cytisinicline) is a low-cost partial agonist of nicotinic acetylcholine receptors used to assist tobacco cessation. We aimed to review the effectiveness of cytisine for tobacco cessation and the effects of dose and co-use of behavioural or other pharmacological interventions on cessation outcomes.
METHODS
We searched seven databases, Google Scholar, and reference lists of included publications for randomised controlled trials investigating use of cytisine as a tobacco cessation aid. Studies were eligible if participants were ≥15 years old and used tobacco upon study enrolment. We conducted four random effects meta-analyses and sensitivity analyses with fixed effects models. We used the Cochrane risk-of-bias tool for randomised trials version 2 to assess risk of bias in included studies, with adjustments recommended by the Cochrane Tobacco Addiction Group.
RESULTS
Participants using cytisine were significantly more likely to quit tobacco than participants who received placebo/no intervention/usual care (risk ratio [RR] = 2.65, 95% confidence interval [CI] = 1.50-4.67, 6 trials, 5194 participants) or nicotine replacement therapy (RR = 1.36, 95% CI = 1.06-1.73, p = 0.0152, 2 trials, 1511 participants). The difference in cessation rates among participants receiving cytisine versus varenicline was not statistically significant (RR = 0.96, 95% CI 0.63-1.45, P = 0.8464, 3 trials, 2508 participants). Two trials examined longer versus shorter treatment duration, finding higher abstinence rates with longer treatment (RR = 1.29, 95% CI = 1.02-1.63, 2 trials, 1009 participants). The differences in the number of adverse events reported by participants who received cytisine versus placebo (RR = 1.19, 95% CI = 0.99-1.41, P = 0.0624; 6 trials; 4578 participants) or cytisine versus varenicline (RR = 1.37, 95% CI = 0.57-3.33, P = 0.4835; 2 trials; 1345 participants) were not statistically significant. Most adverse events were mild (e.g. abnormal dreams, nausea, headaches).
CONCLUSIONS
Cytisine is an effective aid for tobacco cessation and appears to be more effective for tobacco cessation than placebo, no intervention, usual care and nicotine replacement therapy.
PubMed: 38965792
DOI: 10.1111/add.16592 -
International Urology and Nephrology Nov 2015To assess the impact on safety and efficiency of onabotulinumtoxinA (BOTOX1, Allergan, Inc.) treatment in patients with an overactive bladder. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the impact on safety and efficiency of onabotulinumtoxinA (BOTOX1, Allergan, Inc.) treatment in patients with an overactive bladder.
MATERIALS AND METHODS
We searched the PubMed(®), Embase(®), and Cochrane Library Databases to identify all randomized controlled trials comparing the outcomes of onabotulinumtoxinA and placebo for overactive bladder. The outcomes included reductions in overactive bladder symptoms or improvements in the function of bladder and the side effects of two treatments. The Cochrane Collaboration Review Manager software (RevMan 5.1.4) was used for statistical analysis.
RESULTS
The study inclusion criteria were met by eight randomized controlled trials involving 1875 patients. The synthesized data from these randomized controlled trials indicated that onabotulinumtoxinA was better than placebo in decreasing most overactive bladder symptoms (p < 0.00001, p < 0.00001, p < 0.00001, p < 0.00001, p = 0.0003) in the micturition, urgency, urinary incontinence, urgency urinary incontinence (UUI), and nocturia per day change, respectively; however, the maximum cystometric capacity change from the baseline appeared not to be significantly different between two methods (p = 0.05). In addition, the side effects in the onabotulinumtoxinA group were more serious than the placebo group (p < 0.00001, p = 0.009, p = 0.07, p < 0.0001, p = 0.03 in the UTI, bacteriuria, dysuria, urinary retention, residual urine volume, respectively).
CONCLUSIONS
Compared with the placebo, onabotulinumtoxinA had significantly and clinically relevant reductions in overactive bladder symptoms, but it also leaded to more side effects.
Topics: Acetylcholine Release Inhibitors; Botulinum Toxins, Type A; Humans; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive
PubMed: 26433883
DOI: 10.1007/s11255-015-1125-7 -
International Urogynecology Journal Mar 2015Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION AND HYPOTHESIS
Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data assessing the effectiveness of trigonal BoNT-A are limited. This study evaluates adverse events (AEs) and short-term efficacy associated with trigonal and extratrigonal BoNT-A.
METHODS
Electronic databases (PubMed, EMBASE, and the Cochrane database) were searched for studies comparing trigonal and extratrigonal BoNT-A for DO. Meta-analyses were performed using the random effects model. Outcome measures included incidence of AEs and short-term efficacy.
RESULTS
Six studies describing 258 patients met the inclusion criteria. The meta-analysis did not show significant differences between trigonal and extratrigonal BoNT-A for acute urinary retention (AUR; 4.2 vs 3.7 %; odds ratio [OR]: 1.068, 95 % confidence interval [CI]: 0.239-4.773; P = 0.931) or high post-void residual (PVR; 25.8 vs 22.2 %; OR: 0.979; 95 % CI: 0.459-2.088; P = 0.956). The incidence of urinary tract infection (UTI; 7.5 vs 21.0 %; OR: 0.670; 95 % CI: 0.312-1.439; P = 0.305), haematuria (15.8 vs 25.9 %; OR: 0.547; 95 % CI: 0.264-1.134; P = 0.105) and post-operative muscle weakness (9.2 vs 11.3 %; OR: 0.587; 95 % CI: 0.205-1.680, P = 0.320) was similar in both groups. Finally, differences in short-term cure rates between two study arms were not statistically significant (52.9 vs 56.9 %; OR: 1.438; 95 % CI: 0.448-4.610; P = 0.542).
CONCLUSIONS
Although data are limited, no significant differences between trigonal and extratrigonal BoNT-A in terms of AEs and short-term efficacy were observed. Additional randomised controlled trials are required to define optimal injection techniques and sites for administering intra-vesical BoNT-A.
Topics: Acetylcholine Release Inhibitors; Administration, Intravesical; Botulinum Toxins, Type A; Humans; Urinary Bladder, Overactive
PubMed: 25216630
DOI: 10.1007/s00192-014-2499-2 -
Journal of Clinical Anesthesia Jun 2017Magnesium sulfate displays numerous characteristics that make it a useful drug in anesthesiology (N-methyl-d-aspartate receptor antagonist, vasodilator, antiarrhythmic,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Magnesium sulfate displays numerous characteristics that make it a useful drug in anesthesiology (N-methyl-d-aspartate receptor antagonist, vasodilator, antiarrhythmic, inhibitor of catecholamine release and of acetylcholine in the terminal motor plate). The perioperative use of this drug as an adjuvant capable of decreasing the required dose of anesthetics, has been proposed.
OBJECTIVES
To assess the influence of intravenous magnesium sulfate administration during general anesthesia on the overall dose of required anesthetics.
DESIGN
A systematic review of controlled randomized trials and meta-analysis.
DATA SOURCES
An electronic bibliography search in MEDLINE and in the Cochrane Database of Controlled trials (CENTRAL) up to 2015.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS
Randomized, double-blind trials relating to general anesthesia in elective surgery using intravenous magnesium sulfate that provide information about the anesthetic requirements in ASA I and II patients.
RESULTS
20 clinical trials were selected for the qualitative analysis and 19 for the quantitative one. The use of perioperative intravenous magnesium sulfate reduces the requirement of the anesthetic, propofol during induction (-28.52mg; CI 95% -35.22-1.82; p<0.001) and maintenance (-213.56mg; CI 95% -322.93, -104.18; p<0.001) of anesthesia. Additionally, magnesium sulfate reduces the requirement of neuromuscular non-despolarizing blocking agents (-2.99mg; CI 95% -44.47, -1.99; p<0.001) and the intraoperative consumption of fentanile(-53.57 mcg; CI 95% -75.01, -32.12; p<0.001).
CONCLUSIONS
We conclude that perioperative magnesium sulfate acts as a coadjuvant drug capable of reducing anesthetic requirements.
Topics: Anesthesia, General; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Humans; Magnesium Sulfate; Perioperative Care; Propofol; Randomized Controlled Trials as Topic
PubMed: 28494889
DOI: 10.1016/j.jclinane.2017.03.038 -
The Cochrane Database of Systematic... 2000Nicotine is a cholinergic agonist that acts, not only post-synaptically, but also releases pre-synaptic acetylcholine, and in animal models has been shown to reverse... (Review)
Review
BACKGROUND
Nicotine is a cholinergic agonist that acts, not only post-synaptically, but also releases pre-synaptic acetylcholine, and in animal models has been shown to reverse spatial memory decline in rats with lesion in the medial septal nucleus and to show recovery on memory in aged monkeys. Nicotine also has effects on other transmitters like serotonin (5HT), dopamine, or GABA. On the other hand, because nicotine has serious adverse effects, especially concerning cardiovascular risks in elderly people, and also on sleep and behavior, there are several important reasons to conduct a systematic review to assess the clinical efficacy and safety of nicotine in patients with AD.
OBJECTIVES
The aim of this review is to determine whether there is evidence of beneficial effect, and to assess its safety profile, when nicotine is used for Alzheimer's disease.
SEARCH STRATEGY
The Cochrane Controlled Trials Register (Issue 2, 99) was searched using the terms nicotin* and alzheimer*. Three references to trials were deemed suitable for inclusion but are awaiting consideration while the investigators are contacted.
SELECTION CRITERIA
All unconfounded, double-blind, randomized trials in which treatment with nicotine patches or administration of nicotine intravenously was administered for more than a day and compared to placebo in people with Alzheimer's disease.
DATA COLLECTION AND ANALYSIS
As no trials were suitable for inclusion, no data have been extracted or pooled in a meta-analysis. One trial is awaiting consideration, and if included in an update of this review, any available data will be incorporated.
MAIN RESULTS
The poor quality of the trials did not allow any synthesis of results across studies. However, the data available in trials considered are compatible with nicotine producing harm, no change or improvement.
REVIEWER'S CONCLUSIONS
This review is not able to provide reliable evidence that nicotine is a useful treatment for Alzheimer's disease.
Topics: Alzheimer Disease; Cognition Disorders; Humans; Nicotine; Nicotinic Agonists
PubMed: 10796667
DOI: 10.1002/14651858.CD001749 -
European Journal of Cardiovascular... Oct 2011The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease.
BACKGROUND
Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease.
METHODS AND RESULTS
The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009. Eligible studies were randomized controlled trials on the effects of statins compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Forty-six eligible trials enrolled a total of 2706 patients: 866 (32%) were women and 432 (16%) had established cardiovascular disease. Meta-analysis using random-effects models showed treatment with statins significantly improved endothelial function [standardized mean difference (SMD) 0.66, 95% CI 0.46-0.85, p < 0.001]. Subgroup analyses demonstrated statistically significant improvement in endothelial function assessed both peripherally by flow-mediated dilatation (SMD 0.68, 95% CI 0.46-0.90, p < 0.001) and venous occlusion plethysmography (SMD 0.59, 95% CI 0.06-1.13, p = 0.03) and centrally in the coronary circulation by infusion of acetylcholine (SMD 1.58, 95% CI 0.31-2.84, p = 0.01). Significant heterogeneity observed across studies was explained in part by the type of endothelial function measurement, statin type and dose, and study population differences. Exclusion of outlier studies did not significantly alter the results.
CONCLUSION
Statin therapy is associated with significant improvement in both peripheral and coronary endothelial function. The current study supports a role for statin therapy in patients with endothelial dysfunction.
Topics: Adult; Aged; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Evidence-Based Medicine; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Patient Selection; Peripheral Vascular Diseases; Predictive Value of Tests; Randomized Controlled Trials as Topic; Recovery of Function; Treatment Outcome
PubMed: 21450596
DOI: 10.1177/1741826711398430 -
European Respiratory Review : An... Jun 2022Patients suffering from chronic obstructive pulmonary disease (COPD) clinically manifest airway mucus hypersecretion as sputum expectoration and cough. Evidence... (Review)
Review
Patients suffering from chronic obstructive pulmonary disease (COPD) clinically manifest airway mucus hypersecretion as sputum expectoration and cough. Evidence accumulated in the past decade has shown that the cholinergic system not only regulates airway smooth muscle contraction but also the activity of inflammatory and airway epithelial cells, including goblet cells, and submucosal gland activity. Long-acting muscarinic antagonists (LAMAs) with the most favourable M/M muscarinic acetylcholine (ACh) receptors residency properties are not only excellent bronchodilators but potentially also mucus-modifying agents, able to positively impact on mucus hypersecretion and cough. The aim of this systematic review was to investigate the impact of LAMAs on mucus hypersecretion and cough in COPD patients. The evidence confirmed that LAMAs, mainly tiotropium and aclidinium, improved sputum production and cough in moderate to severe COPD. Thus, LAMAs not only antagonise the ACh-induced bronchoconstriction of the airways but also appear to limit the production of mucus secreted in response to ACh by airway goblet cells and/or submucosal glands. Further clinical studies are necessary to evaluate the impact of LAMAs exclusively on sputum symptoms and cough as primary end-points and to investigate whether LAMAs have a modulatory action on the rheological properties of mucus.
Topics: Cough; Humans; Mucus; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide
PubMed: 35508331
DOI: 10.1183/16000617.0196-2021