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Cells Jan 2024Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine... (Review)
Review
Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine receptor agonists using Clinicaltrial (CT) and EudraCT databases. Structured searches identified 39 trials, which used 15 different drugs designed to increase the function of the nAChRs. Most of the identified clinical trials were phase II trials, with some of them classified as ongoing for several years. The systematic screening of the literature led to the selection of 14 studies out of the 8261 bibliographic records retrieved. Six trials reported detailed data on adverse events associated with the intervention, while twelve trials reported data on efficacy measures, such as attention, behavior and cognition. Overall, smost of the physical side effects of cholinergic agonists were reported to be well tolerated. Some trials also reported improvements in attention. However, the efficacy of these drugs in other cognitive and behavioral outcomes remains highly controversial.
Topics: Humans; Alzheimer Disease; Receptors, Nicotinic; Brain; Nicotinic Agonists; Cognition
PubMed: 38334629
DOI: 10.3390/cells13030237 -
Food and Chemical Toxicology : An... Mar 2024This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on... (Review)
Review
BACKGROUND
This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on the subject to provide a comprehensive analysis of potential health risks associated with both smoking methods.
METHODS
The systematic review, incorporating searches in PubMed, Scopus, Web of Science, and the Cochrane Library up to July 2023, examines the results obtained in relevant studies, and provides a critical discussion of the results.
RESULTS
E-cigarettes exhibit reduced exposure to harmful toxins compared to traditional cigarettes.
CONCLUSION
However, concerns persist regarding respiratory irritation and potential health risks, especially among youth, emphasizing the need for comprehensive, long-term research and protective legislation.
Topics: Adolescent; Humans; Nicotine; Electronic Nicotine Delivery Systems; Tobacco Products; Smoking
PubMed: 38331086
DOI: 10.1016/j.fct.2024.114507 -
The American Journal of Psychiatry Mar 2024The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function.
METHODS
A systematic review and meta-analysis of prospective studies of antidepressant pharmacotherapy for adults age 50 or older (or mean age of 65 or older) with LLD was conducted. MEDLINE, EMBASE, and PsycInfo were searched through December 31, 2022. The primary outcome was a change on cognitive test scores from baseline to after treatment. Secondary outcomes included the effects of specific medications and the associations between changes in depressive symptoms and cognitive test scores. Participants with bipolar disorder, psychotic depression, dementia, or neurological disease were excluded. Findings from all eligible studies were synthesized at a descriptive level, and a random-effects model was used to pool the results for meta-analysis.
RESULTS
Twenty-two studies were included. Thirteen of 19 studies showed an improvement on at least one cognitive test after antidepressant pharmacotherapy, with the most robust evidence for the memory and learning (nine of 16 studies) and processing speed (seven of 10 studies) domains and for sertraline (all five studies). Improvements in depressive symptoms were associated with improvement in cognitive test scores in six of seven relevant studies. The meta-analysis (eight studies; N=493) revealed a statistically significant overall improvement in memory and learning (five studies: effect size=0.254, 95% CI=0.103-0.404, SE=0.077); no statistically significant changes were seen in other cognitive domains. The evaluated risk of publication bias was low.
CONCLUSION
Antidepressant pharmacotherapy of LLD appears to improve certain domains of cognitive function, particularly memory and learning. This effect may be mediated by an improvement in depressive symptoms. Studies comparing individuals receiving pharmacotherapy with untreated control participants are needed.
Topics: Aged; Humans; Middle Aged; Antidepressive Agents; Cognition; Depression; Depressive Disorder, Major; Prospective Studies
PubMed: 38321915
DOI: 10.1176/appi.ajp.20230392 -
Ophthalmic Plastic and Reconstructive...This meta-analysis aimed to evaluate the safety and efficacy of abobotulinumtoxinA (ABO) and ABO solution for injection (ASI) for treating moderate-to-severe glabellar... (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis aimed to evaluate the safety and efficacy of abobotulinumtoxinA (ABO) and ABO solution for injection (ASI) for treating moderate-to-severe glabellar lines.
METHODS
The EMBASE, PubMed, and web of science databases were systematically searched. Methodological quality was checked using the Cochrane Risk of Bias tool. We also performed statistical analyses using Stata software to examine the efficacy and safety of ABO.
RESULTS
Nine randomized controlled trials were included in the meta-analysis. The results showed that at maximum frown, the proportion of responders as measured by the investigator's live assessment and subject's self-assessment of moderate-to-severe glabellar lines were significantly higher in the ABO and ASI treatment groups than in the placebo group. In addition, from baseline to maximum frown, the ≥1-grade improvement rate in moderate-to-severe glabellar lines severity was also significantly higher in the ABO and ASI treatment groups than in the placebo group. No significant differences in adverse events were found between ABO, ASI and placebo groups, indicating that ABO and ASI have good safety.
CONCLUSIONS
ABO and ASI are effective and safe options for the treatment of moderate-to-severe glabellar lines. More high-quality studies are needed to verify these conclusions.
Topics: Humans; Botulinum Toxins, Type A; Databases, Factual; Software
PubMed: 38319153
DOI: 10.1097/IOP.0000000000002491 -
BMC Neurology Feb 2024Cervical dystonia is a movement disorder typically characterized by a patterned and twisting movement of sustained or intermittent muscle contractions. Recently, new... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cervical dystonia is a movement disorder typically characterized by a patterned and twisting movement of sustained or intermittent muscle contractions. Recently, new clinical trials are emerging, highlighting the potential benefit of physiotherapy (PT) on disease outcomes. Thus, the objective of this review is to update the effectiveness of PT on cervical dystonia disease outcomes and subsequently perform a meta-analysis.
METHODS
Interventional studies published in English with adult patients with isolated cervical dystonia following a physiotherapy program were included. Relevant articles were searched in PubMed (MEDLINE), Web of Science, and Scopus. Cochrane and Joanna Briggs Institute risk of bias checklists were used for quality reporting. Meta-analysis was done using Review Manager 5.3 statistical software and a pooled mean difference for pain was presented.
RESULTS
Fourteen articles were included in the review and two articles were included in the meta-analysis. The meta-analysis revealed that PT intervention had a significant effect on pain reduction scale (-5.00, 95% CI -6.26, -3.74) when used as an additional therapy with botulinum toxin (BoNT) injection. Additionally, findings indicate a possible positive effect of PT disease severity, disability, and quality of life.
CONCLUSIONS
Physiotherapy in addition to BoNT is recommended to decrease pain. The findings suggest a reduction of disease severity, disability, and improvement in quality of life. The variety in the type and duration of PT interventions did not allow a clear recommendation of a specific type of PT.
Topics: Adult; Humans; Torticollis; Quality of Life; Botulinum Toxins; Dystonic Disorders; Pain; Physical Therapy Modalities
PubMed: 38302911
DOI: 10.1186/s12883-023-03473-3 -
The Laryngoscope Jul 2024Sialorrhea, also known as drooling, hypersalivation, or ptyalism, has a significant impact on the medical and psychosocial well-being of children. Onabotulinum toxin A... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Sialorrhea, also known as drooling, hypersalivation, or ptyalism, has a significant impact on the medical and psychosocial well-being of children. Onabotulinum toxin A (BoNT-A) is the most commonly used botulinum toxin worldwide for the treatment of sialorrhea in children.
OBJECTIVES
To conduct a comprehensive systematic review and meta-analysis to assess the clinical efficacy and potential adverse effects of BoNT-A as a treatment for drooling in children.
METHODS
Cochrane, Embase, and Medline databases were systematically searched (up to May 2023). Out of 535 identified publications, 20 were found eligible for inclusion. A systematic review and meta-analysis were performed to determine the efficacy of BoNT-A treatment in children in reducing the frequency and severity of drooling.
RESULTS
Out of the 20 studies included, a meta-analysis was conducted on the complete dataset of eight studies involving 131 patients. BoNT-A was found to significantly decrease the severity of drooling in patients with sialorrhea (standardized mean difference [SMD], -2.07; 95% confidence interval [CI], -2.91 to -1.23; p < 0.0001) when compared with the conditions before injections using random-effects models. Six studies out of 20 reported dysphagia as an adverse effect after injection. Other side effects included thickness of saliva and pain at the site of injection.
CONCLUSION
BoNT-A is a clinically effective therapy that improves drooling severity in children with sialorrhea. Although there were some adverse side effects reported, they were transient and not severe. Future studies are needed to further evaluate the best techniques and to identify the ideal dosages required to achieve the optimal outcomes. Laryngoscope, 134:3012-3017, 2024.
Topics: Humans; Sialorrhea; Botulinum Toxins, Type A; Child; Neuromuscular Agents; Treatment Outcome; Child, Preschool; Adolescent; Male; Female
PubMed: 38294288
DOI: 10.1002/lary.31277 -
Neurourology and Urodynamics Mar 2024Antimuscarinics and the β3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α -adrenoreceptor antagonists... (Meta-Analysis)
Meta-Analysis Review
Safety and efficacy of an α -blocker plus mirabegron compared with an α -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis.
AIM
Antimuscarinics and the β3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α -adrenoreceptor antagonists (α -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α -blocker plus mirabegron with an α -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations.
METHODS
Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α -blocker plus OAB agent with an α -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Q ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis.
RESULTS
Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α -blocker plus mirabegron and α -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α -blocker plus mirabegron group compared with the α -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Q . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation.
CONCLUSION
This systematic review and meta-analysis showed that an α -blocker plus mirabegron and an α -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.
Topics: Humans; Male; Female; Urinary Bladder, Overactive; Muscarinic Antagonists; Prostatic Hyperplasia; Urinary Retention; Bayes Theorem; Network Meta-Analysis; Treatment Outcome; Drug Therapy, Combination; Acetanilides; Lower Urinary Tract Symptoms; Adrenergic beta-3 Receptor Agonists; Randomized Controlled Trials as Topic; Thiazoles
PubMed: 38291827
DOI: 10.1002/nau.25399 -
Annals of Plastic Surgery Jan 2024Keloids are common benign skin lesions originating from a disorganized fibroproliferative collagen response; these lesions often lead to both physical and psychological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Keloids are common benign skin lesions originating from a disorganized fibroproliferative collagen response; these lesions often lead to both physical and psychological problems. The optimal treatment for keloids is yet to be standardized. Intralesional injection, which is simple and nontraumatic, is one of the most commonly used treatment modalities for these lesions. In this study, we compared 5 different drugs (intralesional injections) for the treatment of keloids in terms of efficacy.
METHODS
We systemically searched relevant studies on PubMed, EMBASE, and Cochrane Library. Randomized clinical trials on the safety and efficacy of triamcinolone acetonide (TAC), 5-fluorouracil (5-FU), botulinum toxin A (BTA), verapamil, and bleomycin were included in this study.
RESULTS
This network meta-analysis included a total of 1114 patients from 20 randomized controlled trials. Botulinum toxin A alone and TAC plus 5-FU exhibited significantly better efficacy than did 5-FU, TAC, and verapamil. No significant difference in efficacy between BTA alone and TAC combined with 5-FU was observed. No significant differences were noted in the adverse event rate between BTA, TAC plus 5-FU, 5-FU, and TAC. Furthermore, we performed surface under the cumulative ranking curve analyses to predict the rank of each intervention (by efficacy and adverse event rate). The predicted ranking by efficacy was as follows: TAC plus 5-FU, BTA, bleomycin, TAC, 5-FU, and verapamil; the predicted ranking by adverse events was as follows: TAC, 5-FU, TAC plus 5-FU, and BTA. Funnel plot analysis revealed no publication bias.
CONCLUSIONS
Botulinum toxin A and TAC plus 5-FU appear to have outstanding therapeutic efficacy for keloids. The rate of adverse events was similar among BTA, TAC, 5-FU, and TAC plus 5-FU. Nonetheless, additional reviews of rigorous, large-scale randomized controlled trials are warranted for further validation of our findings.
Topics: Humans; Keloid; Botulinum Toxins, Type A; Network Meta-Analysis; Drug Therapy, Combination; Treatment Outcome; Fluorouracil; Injections, Intralesional; Bleomycin; Verapamil; Randomized Controlled Trials as Topic
PubMed: 38285997
DOI: 10.1097/SAP.0000000000003759 -
Biomolecules Dec 2023The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically... (Review)
Review
The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria named 6-hydroxy-L-nicotine (6HLN) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those published between 1992 and 2023, was conducted. The search focused specifically on articles about nicotine metabolites, memory, oxidative stress, and cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 212 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6HLN.
Topics: Bacteria; Brain; Cholinergic Agents; Databases, Factual; Nicotine; Humans
PubMed: 38254623
DOI: 10.3390/biom14010023 -
Toxins Dec 2023Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided... (Review)
Review
Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson's disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory-motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD.
Topics: Animals; Humans; Parkinson Disease; Central Nervous System; Disease Models, Animal; Tremor; Botulinum Toxins
PubMed: 38251226
DOI: 10.3390/toxins16010009