-
Neurourology and Urodynamics Jun 2015We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating idiopathic OAB. (Meta-Analysis)
Meta-Analysis Review
AIM
We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating idiopathic OAB.
METHODS
A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for the treatment of idiopathic OAB. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated.
RESULTS
Eight publications involving a total of 1,320 patients were used in the analysis, including six RCTs that compared onabotulinumtoxinA with placebo. OnabotulinumtoxinA significantly decreased the mean number of urinary incontinence (UI) per day -2.77 versus -1.01 (the standardized mean difference (SMD) = -1.68, 95% CI = -2.06 to -1.31, P < 0.00001); the mean number of micturitions per day -1.61 versus -0.87 (SMD = -1.82, 95% CI = -2.61 to -1.02, P < 0.00001); maximum cystometric capacity (MCC) 91.39 versus 32.32 (SMD = 63.82, 95% CI = 38.14 to 89.50, P < 0.00001) and volume voided 44.29 versus 7.36 (SMD = 33.05, 95% CI = 22.45 to 43.66, P < 0.00001) versus placebo and 29.20% versus 7.95% of patients became incontinence-free (odds ratio [OR] = 4.89, 95% confidence interval [CI] = 3.11 to 7.70, P < 0.00001). Safety assessments primarily localized to the urinary tract indicated onabotulinumtoxinA were often associated with complications resulting from postvoid residuals (PVR; P < 0.00001), urinary tract infections (UTI; P < 0.00001) and clean intermittent catheterization (CIC; P < 0.00001).
CONCLUSION
This meta-analysis indicates that onabotulinumtoxinA to be an effective treatment for idiopathic overactive bladder symptoms with side effects primarily localized to urinary tract.
Topics: Acetylcholine Release Inhibitors; Botulinum Toxins, Type A; Humans; Treatment Outcome; Urinary Bladder, Overactive; Urinary Catheterization; Urinary Retention; Urinary Tract Infections
PubMed: 24676791
DOI: 10.1002/nau.22598 -
Drug and Alcohol Dependence Oct 2022Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting... (Review)
Review
BACKGROUND
Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation.
METHODS
A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized.
RESULTS
People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs.
CONCLUSION
Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.
Topics: Bupropion; Genetic Variation; Humans; Nicotine; Polymorphism, Single Nucleotide; Receptors, Nicotinic; Smoking Cessation; Tobacco Products; Tobacco Use Cessation Devices
PubMed: 35981468
DOI: 10.1016/j.drugalcdep.2022.109596 -
International Urogynecology Journal May 2016Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness.
METHODS
A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale.
RESULTS
Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary-Sant questionnaire.
CONCLUSION
Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed.
Topics: Acetylcholine Release Inhibitors; Adjuvants, Immunologic; Administration, Intravesical; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Botulinum Toxins, Type A; Cystitis, Interstitial; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Hyperbaric Oxygenation; Lidocaine; Pentosan Sulfuric Polyester; Physical Therapy Modalities; Sodium Chloride
PubMed: 26272202
DOI: 10.1007/s00192-015-2815-5 -
Frontiers in Cellular Neuroscience 2016Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination... (Review)
Review
Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination of axons. Cells of the oligodendrocyte lineage are generated in the germinal zone from migratory bipolar oligodendrocyte precursor cells (OPCs), and acquire cell surface markers as they mature and respond specifically to factors which regulate proliferation, migration, differentiation, and survival. Loss of myelin underlies a wide range of neurological disorders, some of an autoimmune nature-multiple sclerosis probably being the most prominent. Current therapies are based on the use of immunomodulatory agents which are likely to promote myelin repair (remyelination) indirectly by subverting the inflammatory response, aspects of which impair the differentiation of OPCs. Cells of the oligodendrocyte lineage express and are capable of responding to a diverse array of ligand-receptor pairs, including neurotransmitters and nuclear receptors such as γ-aminobutyric acid, glutamate, adenosine triphosphate, serotonin, acetylcholine, nitric oxide, opioids, prostaglandins, prolactin, and cannabinoids. The intent of this review is to provide the reader with a synopsis of our present state of knowledge concerning the pharmacological properties of the oligodendrocyte lineage, with particular attention to these receptor-ligand (i.e., neurotransmitters and nuclear receptor) interactions that can influence oligodendrocyte migration, proliferation, differentiation, and myelination, and an appraisal of their therapeutic potential. For example, many promising mediators work through Ca(2+) signaling, and the balance between Ca(2+) influx and efflux can determine the temporal and spatial properties of oligodendrocytes (OLs). Moreover, Ca(2+) signaling in OPCs can influence not only differentiation and myelination, but also process extension and migration, as well as cell death in mature mouse OLs. There is also evidence that oligodendroglia exhibit Ca(2+) transients in response to electrical activity of axons for activity-dependent myelination. Cholinergic antagonists, as well as endocannabinoid-related lipid-signaling molecules target OLs. An understanding of such pharmacological pathways may thus lay the foundation to allow its leverage for therapeutic benefit in diseases of demyelination.
PubMed: 26903812
DOI: 10.3389/fncel.2016.00027 -
Acta Psychiatrica Scandinavica Apr 2022The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT.
METHODS
Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random-effects models were used. PROSPERO registration number was CRD42021212773.
RESULTS
Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention-types. Quantitative synthesis (meta-analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention-types. Low-quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low-quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low-quality), herbal preparations with anti-inflammatory properties (very low to low-quality) and opioid receptor agonists (low-quality).
CONCLUSION
Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT.
Topics: Cognition; Electroconvulsive Therapy; Humans; Ketamine; Memantine; Triiodothyronine
PubMed: 35075641
DOI: 10.1111/acps.13397 -
The Cochrane Database of Systematic... Sep 2015Alzheimer's disease is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of... (Review)
Review
BACKGROUND
Alzheimer's disease is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by the use of cholinesterase inhibitors to delay the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. Other cholinesterase inhibitors, including rivastigmine, with superior properties in terms of specificity of action and lower risk of adverse effects have since been introduced. Rivastigmine has received approval for use in 60 countries including all member states of the European Union and the USA.
OBJECTIVES
To determine the clinical efficacy and safety of rivastigmine for patients with dementia of Alzheimer's type.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 2 March 2015 using the terms: Rivastigmine OR exelon OR ENA OR "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries and grey literature sources.
SELECTION CRITERIA
We included all unconfounded, double-blind, randomised, controlled trials in which treatment with rivastigmine was administered to patients with dementia of the Alzheimer's type for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two formulations of rivastigmine were compared.
DATA COLLECTION AND ANALYSIS
One review author (JSB) applied the study selection criteria, assessed the quality of studies and extracted data.
MAIN RESULTS
A total of 13 trials met the inclusion criteria of the review. The trials had a duration of between 12 and 52 weeks. The older trials tested a capsule form with a dose of up to 12 mg/day. Trials reported since 2007 have tested continuous dose transdermal patch formulations delivering 4.6, 9.5 and 17.7 mg/day.Our main analysis compared the safety and efficacy of rivastigmine 6 to 12 mg/day orally or 9.5 mg/day transdermally with placebo.Seven trials contributed data from 3450 patients to this analysis. Data from another two studies were not included because of a lack of information and methodological concerns. All the included trials were multicentre trials and recruited patients with mild to moderate Alzheimer's disease with a mean age of about 75 years. All had low risk of bias for randomisation and allocation but the risk of bias due to attrition was unclear in four studies, low in one study and high in two studies.After 26 weeks of treatment rivastigmine compared to placebo was associated with better outcomes for cognitive function measured with the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score (mean difference (MD) -1.79; 95% confidence interval (CI) -2.21 to -1.37, n = 3232, 6 studies) and the Mini-Mental State Examination (MMSE) score (MD 0.74; 95% CI 0.52 to 0.97, n = 3205, 6 studies), activities of daily living (SMD 0.20; 95% CI 0.13 to 0.27, n = 3230, 6 studies) and clinician rated global impression of changes, with a smaller proportion of patients treated with rivastigmine experiencing no change or a deterioration (OR 0.68; 95% CI 0.58 to 0.80, n = 3338, 7 studies).Three studies reported behavioural change, and there were no differences compared to placebo (standardised mean difference (SMD) -0.04; 95% CI -0.14 to 0.06, n = 1529, 3 studies). Only one study measured the impact on caregivers using the Neuropsychiatric Inventory-Caregiver Distress (NPI-D) scale and this found no difference between the groups (MD 0.10; 95% CI -0.91 to 1.11, n = 529, 1 study). Overall, participants who received rivastigmine were about twice as likely to withdraw from the trials (odds ratio (OR) 2.01, 95% CI 1.71 to 2.37, n = 3569, 7 studies) or to experience an adverse event during the trials (OR 2.16, 95% CI 1.82 to 2.57, n = 3587, 7 studies).
AUTHORS' CONCLUSIONS
Rivastigmine (6 to 12 mg daily orally or 9.5 mg daily transdermally) appears to be beneficial for people with mild to moderate Alzheimer's disease. In comparisons with placebo, better outcomes were observed for rate of decline of cognitive function and activities of daily living, although the effects were small and of uncertain clinical importance. There was also a benefit from rivastigmine on the outcome of clinician's global assessment. There were no differences between the rivastigmine group and placebo group in behavioural change or impact on carers. At these doses the transdermal patch may have fewer side effects than the capsules but has comparable efficacy. The quality of evidence is only moderate for all of the outcomes reviewed because of a risk of bias due to dropouts. All the studies with usable data were industry funded or sponsored. This review has not examined economic data.
PubMed: 26393402
DOI: 10.1002/14651858.CD001191.pub4 -
Chemical Biology & Drug Design Dec 2023Alzheimer's disease (AD) is a chronic age-related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability... (Review)
Review
Alzheimer's disease (AD) is a chronic age-related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability of an individual. The exact pathophysiology of AD is not fully understood. However low level of the neurotransmitter named acetylcholine (ACh), aggregation of Aβ peptide into toxic Aβ plaque, hyperphosphorylation of tau, bio-metal imbalance, and oxidative stress are the main hallmarks of this disease. Due to the complex pathophysiology of AD, no specific treatment is available in the market, and treatment is only limited to the symptomatic relief. So, there is an urgent need for the development of new drug candidate, which can have disease-modifying effect and improve learning and memory in AD patient. Therefore, berberine-based multifunction compounds with potential cholinesterase inhibitory properties were reviewed in this article. Structure-activity relationship (SAR) and biological activity provide highlights on the new derivatives used for the management of AD.
Topics: Humans; Amyloid beta-Peptides; Acetylcholinesterase; Berberine; Alzheimer Disease; Oxidative Stress; Cholinesterase Inhibitors
PubMed: 37665093
DOI: 10.1111/cbdd.14337 -
International Journal of Cardiology Oct 2017Systematic review of literature to evaluate safety of intracoronary (i.c.) pharmacologic testing with acetylcholine (ACh), or ergonovine (ERGO), to induce coronary... (Review)
Review
AIMS
Systematic review of literature to evaluate safety of intracoronary (i.c.) pharmacologic testing with acetylcholine (ACh), or ergonovine (ERGO), to induce coronary artery spasm.
METHODS AND RESULTS
Review of all relevant publications using MEDLINE and EMBASE databases yielded 10 publications, totalling 9,444 patients. Prevalence of provoked spasm varied from 2.3% to 54.7% of patients tested in the selected studies. The wide variability in prevalence was due to heterogeneity of study populations and provocation protocols. No deaths were reported. Overall occurrence of major (0.8%) and minor (4.7%) complications for i.c. pharmacologic testing was low. Compared to ERGO, ACh showed significantly higher rate of major (1.09% vs 0.15%; p<0.001) and minor complications (5.87% vs 2.36%; p<0.001).
CONCLUSION
Provocative testing with i.c. ACh or ERGO are safe and can facilitate the diagnosis of inducible coronary artery spasm during diagnostic coronary angiography. These tests should be part of the routine armamentarium of interventional cardiologists.
Topics: Acetylcholine; Coronary Angiography; Coronary Vasospasm; Ergonovine; Humans; Injections, Intra-Arterial; Oxytocics; Vasodilator Agents
PubMed: 28622945
DOI: 10.1016/j.ijcard.2017.05.109 -
Nutrition Reviews Aug 2015Choline is a precursor of both betaine and acetylcholine and might, therefore, influence cardiovascular and cognitive outcomes. There has been concern, however, that it... (Review)
Review
CONTEXT
Choline is a precursor of both betaine and acetylcholine and might, therefore, influence cardiovascular and cognitive outcomes. There has been concern, however, that it may influence blood lipid levels because it is an essential component of very-low-density lipoproteins.
OBJECTIVE
The aim was to systematically review, using PRISMA guidelines, the literature pertaining to the effects of choline on body composition and on metabolic, cardiovascular, respiratory, and neurological outcomes in different life stages.
DATA SOURCES
The MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar databases were searched up to July 2014.
DATA EXTRACTION
Fifty relevant articles were identified. These comprised trials and cohort, case-control, and cross-sectional studies that assessed blood levels of choline, dietary intake of choline, and supplementation with choline in a population free of diseases at baseline.
DATA SYNTHESIS
There is some observational evidence that choline during pregnancy may be beneficial for the neurological health of the child. In adults, choline may have beneficial effects on cognition, but high-quality (intervention) studies are lacking. Results on the effects of choline on body composition, blood lipids, and cardiovascular health were inconsistent.
CONCLUSIONS
Evidence to confirm the suggested effects of choline on health in different stages of life is scarce. Potential effects of choline need to be confirmed by intervention studies. Possible harmful effects on cardiometabolic health need careful evaluation.
Topics: Body Composition; Choline; Dietary Supplements; Health Status; Humans; Lipids
PubMed: 26108618
DOI: 10.1093/nutrit/nuv010 -
Frontiers in Pharmacology 2023Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the...
Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the migrating myoelectric complex component of GI motility. Changes in MLN availability are associated with GI diseases such as gastroesophageal reflux disease and functional dyspepsia. Furthermore, herbal medicines have been used for several years to treat various GI disorders. We systematically reviewed clinical and animal studies on how herbal medicine affects the modulation of MLN and subsequently brings the therapeutic effects mainly focused on GI function. We searched the PubMed, Embase, Cochrane, and Web of Science databases to collect all articles published until 30 July 2023, that reported the measurement of plasma MLN levels in human randomized controlled trials and herbal medicine studies. The collected characteristics of the articles included the name and ingredients of the herbal medicine, physiological and symptomatic changes after administering the herbal medicine, changes in plasma MLN levels, key findings, and mechanisms of action. The frequency patterns (FPs) of botanical drug use and their correlations were investigated using an FP growth algorithm. Nine clinical studies with 1,308 participants and 20 animal studies were included in the final analyses. Herbal medicines in clinical studies have shown therapeutic effects in association with increased levels of MLN, including GI motility regulation and symptom improvement. Herbal medicines have also shown anti-stress, anti-tumor, and anti-inflammatory effects . Various biochemical markers may correlate with MLN levels. Markers may have a positive correlation with plasma MLN levels included ghrelin, acetylcholine, and secretin, whereas a negative correlation included triglycerides and prostaglandin E. Markers, such as gastrin and somatostatin, did not show any correlation with plasma MLN levels. Based on the FP growth algorithm, and were the most frequently used species. Herbal medicine may have therapeutic effects mainly on GI symptoms with involvement of MLN regulation and may be considered as an alternative option for the treatment of GI diseases. Further studies with more solid evidence are needed to confirm the efficacy and mechanisms of action of herbal medicines. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=443244, identifier CRD42023443244.
PubMed: 38161695
DOI: 10.3389/fphar.2023.1286333