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Clinical Oral Investigations Jun 2023The present systematic review and network meta-analysis of randomized control trials (RCTs) aimed to establish whether there are evidence-based differences in the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The present systematic review and network meta-analysis of randomized control trials (RCTs) aimed to establish whether there are evidence-based differences in the pharmacological agents used to manage sialorrhea in patients with Parkinson's disease (PD).
MATERIAL AND METHODS
The authors searched the databases: MEDLINE via PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library for clinical trials. Unpublished trials were searched on clinicaltrials.gov and the Brazilian Clinical Trials Registry. Means and standard deviations of changes in the salivary flow or drooling reported by participants due to the interventions were recorded.
RESULTS
The authors analyzed 13 RCTs. Compared to the placebo, types A and B of the botulinum toxin effectively reduced the salivary flow and the severity or frequency of drooling. However, the network meta-analysis did not differentiate between the botulinum toxin types. Ipratropium bromide and glycopyrrolate did not differ from the placebo. Indirect evidence showed that ipratropium had similar results to those obtained with both types of botulinum toxin. The CINeMA approach estimated the quality of the evidence as very low for all comparisons.
CONCLUSION
The best treatment for sialorrhea in patients with PD is not fully elucidated yet. Therefore, more well-conducted randomized clinical trials are required to increase the level of evidence.
CLINICAL RELEVANCE
There needs to be more evidence defining the best intervention to treat sialorrhea in patients with PD. However, botulinum toxin types A and B seem to reduce sialorrhea in patients effectively.
Topics: Humans; Sialorrhea; Parkinson Disease; Network Meta-Analysis; Botulinum Toxins, Type A; Glycopyrrolate
PubMed: 37036514
DOI: 10.1007/s00784-023-04981-9 -
BMC Pharmacology & Toxicology Oct 2023Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD).
METHODS
We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I tests. We used the GRADE tool to assess the certainty of evidence (COE).
RESULTS
Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low).
CONCLUSIONS
The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function.
TRIAL REGISTRATION
Our review protocol was registered on PROSPERO (42021288334).
Topics: Humans; Botulinum Toxins, Type A; Sialorrhea; Parkinson Disease; Dental Caries; Treatment Outcome
PubMed: 37828600
DOI: 10.1186/s40360-023-00694-7 -
Frontiers in Neurology 2022The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic...
BACKGROUND
The prevalence and associated factors of dysphagia in Parkinson's disease (PD) are different in studies conducted in different countries. The purpose of our systematic review and meta-analysis was to evaluate the prevalence of dysphagia in PD and to clarify its associated factors.
METHODS
Two researchers systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, SinoMed and VIP databases and manually searched references in the retrieved articles to identify potential research subjects. The last search was conducted on June 28, 2022. Finally, a total of 58 studies including 60 observations with 20,530 PD patients were included in our meta-analysis.
RESULTS
The meta-analysis estimated that the pooled prevalence rate of dysphagia in PD was 36.9% (95% CI: 30.7-43.6%) and instrumental examination showed a higher prevalence (57.3%, 95% CI: 44.3-69.1%). Oceania showed the highest prevalence of dysphagia in PD (56.3%) compared to Africa (39.5%), Asia (38.6%), Europe (36.1%) and America (28.9%). Dysphagia in PD was associated with older age, lower body mass index, longer disease duration, higher Hoehn and Yahr stage and levodopa equivalent daily dose, PIGD subtype, severe motor symptoms, drooling and higher levels of depression, and lower quality of life.
CONCLUSIONS
In conclusion, our meta-analysis showed that dysphagia occurs in more than one-third of PD patients and was associated with several demographic characteristics and PD-related characteristics, motor symptoms, non-motor symptoms, as well as decreased quality of life. It deserves early screening, diagnosis, and treatment in clinical practice to prevent serious complications from dysphagia.
PubMed: 36277913
DOI: 10.3389/fneur.2022.1000527 -
Cureus Jan 2024Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that... (Review)
Review
Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that drastically affect the patient's quality of life (QoL). Although there is no cure for PD, its symptoms can be significantly improved and even resolved through different treatments. Mainstay treatments for PD include levodopa combined with carbidopa, dopamine agonists, and even deep brain stimulation (DBS) of the subthalamic nucleus. New treatment methods have emerged, such as botulinum toxin (BoNT), which further improve symptoms and, thus, the QoL of patients with PD. Botulinum toxin is a potent neurotoxin produced by that typically causes descending paralysis by suppressing acetylcholine secretion. Serotypes used to treat various disorders include serotype A (BoNT-A) and serotype B (BoNT-B). This paper aims to evaluate the outcomes of BoNT injection on different symptoms associated with PD. An extensive review using PubMed, ScienceDirect, and ProQuest articles concerning 'botulinum toxin and Parkinson's disease' was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in 23,803 articles. After applying strict inclusion and exclusion criteria, the total number of articles was finally 41. The results showed that movement disorders were a common occurrence in PD, consisting of tremors, dystonia, and freezing of gait (FOG), with tremors being the most common symptom. Tremors and dystonia were significantly improved following BoNT-A, correlating with significant improvements in various scales subjectively and objectively evaluating the symptoms and QoL. In contrast, FOG was not significantly improved by either BoNT-A or BoNT-B. Pain is associated with movement disorders such as PD and was the primary indication for the administration of BoNT; studies found pain and QoL were significantly improved following BoNT injection. Quality of life can also be affected by sialorrhea and overactive bladder, which often occur as the disease progresses. Injections of BoNT-A and BoNT-B were shown to significantly improve saliva production, flow rate, drooling frequency, voiding frequency, and urinary urge incontinence. Across all studies analyzed, it is evident that BoNT may have a significant effect on improving the QoL of patients suffering from PD. While research continues to find a cure or stop the progression of PD, it remains critical to continue focusing on improving patients' QoL. Future research should evaluate whether BoNT can be used to successfully treat other symptoms of PD, such as epiphora or constipation.
PubMed: 38435899
DOI: 10.7759/cureus.53309 -
The Annals of Otology, Rhinology, and... Feb 2023Botulinum toxin A is known to be effective and safe in managing sialorrhea in pediatric patients; however, there is no consensus on a protocol for optimal injection... (Review)
Review
OBJECTIVE
Botulinum toxin A is known to be effective and safe in managing sialorrhea in pediatric patients; however, there is no consensus on a protocol for optimal injection sites and appropriate dosing for injection.
METHODS
This review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. PubMed, EMBASE, and other databases were queried to identify articles that evaluated botulinum toxin type A for the treatment of sialorrhea in the pediatric population. A total of 405 studies were identified. After applying inclusion and exclusion criteria, 31 articles were included for review.
RESULTS
A total of 14 studies evaluated 2-gland injections, and 17 studies evaluated 4-gland injections. Of the 31 studies included, one study assessed incobotulinumtoxinA (Xeomin) the remaining all used onabotulinumtoxinA (Botox). For 2-gland injection studies, a combined total of 899 participants were reviewed, where 602 participants received 50 units into their submandibular glands, while 262 participants received 30 to 50 units. Among 4-gland injection studies, there was a combined total of 388 participants, with the most prevalent dosage utilized being 60 to 100 units in 230 participants, followed by 100 units total in 77 participants. The most common adverse event was dysphagia which resolved in nearly all cases. Three studies aimed to examine 2-gland versus 4-gland injections, with 2 of the studies concluding 4-gland injection was superior.
CONCLUSIONS
The strength of evidence suggests that the dosing of 50 units total of onabotulinumtoxinA to the submandibular glands is safe and effective in the pediatric population. For 4-gland injections, bilateral submandibular and parotid gland injections of 60 to 100 units total is the safe and effective dosage. There is no substantial evidence comparing 4-gland injections to 2-gland injections, but research thus far suggests 4-gland injections to be superior. Future study is needed to evaluate incobotulinumtoxinA and abobotulinumtoxinA dosages in the pediatric population.
Topics: Humans; Child; Botulinum Toxins, Type A; Sialorrhea; Parotid Gland; Submandibular Gland; Injections; Treatment Outcome
PubMed: 35176902
DOI: 10.1177/00034894221078365 -
Pharmaceuticals (Basel, Switzerland) Jul 2022Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and... (Review)
Review
Clozapine is the gold standard for treatment-resistant schizophrenia. Serious and even life-threatening adverse effects, mostly granulocytopenia, myocarditis, and constipation, are of great clinical concern and constitute a barrier to prescribing clozapine, thus depriving many eligible patients of a lifesaving treatment option. Interestingly, clozapine presents variable pharmacokinetics affected by numerous parameters, leading to significant inter- and intra-individual variation. Therefore, therapeutic drug monitoring of plasma clozapine levels confers a significant benefit in everyday clinical practice by increasing the confidence of the prescribing doctor to the drug and the adherence of the patient to the treatment, mainly by ensuring effective treatment and limited dose-related side effects. In the present systematic review, we aimed at identifying how a full range of adverse effects relates to plasma clozapine levels, using the Jadad grading system for assessing the quality of the available clinical evidence. Our findings indicate that EEG slowing, obsessive-compulsive symptoms, heart rate variability, hyperinsulinemia, metabolic syndrome, and constipation correlate to plasma clozapine levels, whereas QTc, myocarditis, sudden death, leucopenia, neutropenia, sialorrhea, are rather unrelated. Rapid dose escalation at the initiation of treatment might contribute to the emergence of myocarditis, or leucopenia. Strategies for managing adverse effects are different in these conditions and are discussed accordingly.
PubMed: 35890117
DOI: 10.3390/ph15070817 -
Schizophrenia Research Jun 2024To synthesize the information relevant for clinical practice on clozapine-antidepressant co-prescription concerning pharmacokinetic drug-drug interactions (DDI), adverse...
OBJECTIVES
To synthesize the information relevant for clinical practice on clozapine-antidepressant co-prescription concerning pharmacokinetic drug-drug interactions (DDI), adverse drug reactions (ADRs) associated with the co-prescription, antidepressant add-on for clozapine-resistant symptoms and antidepressant add-on for clozapine-induced ADRs.
METHODS
Articles were identified with MEDLINE, Web of Sciences and PsycINFO search from inception through April 2023. Data were synthesized narratively.
RESULTS
ADRs are most often induced by the co-prescription of antidepressants that inhibit CYP enzymes (fluvoxamine, fluoxetine, paroxetine). Fluvoxamine add-on is hazardous because of its potent inhibition of clozapine metabolism and has few indications (lowering daily number of clozapine tablets, reducing norclozapine-induced metabolic disturbances and other dose-dependent clozapine-induced ADRs). ADR frequency may be reduced by therapeutic drug monitoring and knowledge of other factors impacting clozapine metabolism (pneumonia, inflammation, smoking, etc.). Improvement of negative symptoms is the most documented beneficial effect of antidepressant add-on for clozapine-resistant psychotic symptoms. The add-on antidepressant should be chosen according to its safety profile regarding DDI with clozapine: antidepressants inhibiting clozapine metabolism or increasing the anticholinergic load should be avoided. Other indications of antidepressant add-on (affective or obsessive compulsive symptoms, sialorrhea, and enuresis) are poorly documented.
CONCLUSION
Antidepressant add-on to clozapine is associated with potential benefits in clozapine users as this strategy may contribute to reduce the burden of clozapine-resistant symptoms or of clozapine-induced ADRs. Further studies are needed to determine whether antidepressant add-on can reduce the risk of clozapine discontinuation.
Topics: Clozapine; Humans; Drug Interactions; Antidepressive Agents; Antipsychotic Agents; Drug Therapy, Combination; Schizophrenia
PubMed: 37852856
DOI: 10.1016/j.schres.2023.10.003 -
Paediatrics & Child Health May 2022Sialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic...
BACKGROUND
Sialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic relief, but there is no consensus regarding which treatment is the most efficacious.
OBJECTIVE
To examine the effectiveness of anticholinergic medications for sialorrhea in children.
METHODS
A systematic review was carried out in Medline, EMBASE, Cochrane, Scopus, and the Web of Science from inception until April 29, 2020. Studies reporting original data on the efficacy of anticholinergic medications in the management of sialorrhea in children aged 0 to 17 years of age were included. This review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Data on study design, setting, population, pharmacologic intervention(s), comparator(s), outcomes, and results were extracted and summarized.
RESULTS
The search strategy identified 2,800 studies of which 27 articles were included in the synthesis, including five randomized controlled trials. Each anticholinergic undergoing experimental study (glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine) showed evidence of efficacy. Adverse side effects were common. Significant heterogeneity exists in the studies' methodology and the variability of outcome measures used between studies precluded a meta-analysis.
CONCLUSIONS
Glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine have all shown efficacy in the treatment of sialorrhea in children. The small number of reports and the variability in study design precluded a meta-analysis. More studies are needed with uniformity in outcome measures to help guide evidence-based decision making. A guidance table is presented.
PubMed: 35599670
DOI: 10.1093/pch/pxab051 -
International Journal of Clinical... Jun 2024To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To describe the efficacy of atropine in controlling salivary flow in patients with sialorrhea or drooling.
MATERIALS AND METHODS
We included randomized controlled studies, quasi-randomized trials, case reports, clinical trials, systematic reviews, and meta-analyses assessing the use of atropine in patients with sialorrhea or drooling. The endpoints were reduction in salivary flow rate, amount of saliva secreted, reduction in clinical symptoms of sialorrhea, death rattle intensity, or reduction in drooling intensity as measured by an objective scale such as the drooling intensity scale.
RESULTS
A total of 56 studies with 2,378 patients were included in the systematic review. The underlying disease states included brain injury, amyotrophic lateral sclerosis, cerebral palsy, clozapine- and perphenazine-induced sialorrhea, Parkinson's disease, and terminal illness. The routes of atropine administration included sublingual, intravenous, subcutaneous, oral tablet or solution, and direct injection of atropine into parotid glands or at the base of the tongue. The generalized estimated equation regression models showed that sublingual administration is superior to oral and subcutaneous routes.
CONCLUSION
Atropine is efficacious in managing sialorrhea in most disease states. Sublingual administration of atropine is superior to other routes of administration in reducing salivary flow in patients with sialorrhea.
Topics: Sialorrhea; Humans; Atropine; Treatment Outcome; Salivation
PubMed: 38577753
DOI: 10.5414/CP204538 -
Children (Basel, Switzerland) Nov 2022Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food... (Review)
Review
Evaluation of the Effectiveness of Functional Chewing Training Compared with Standard Treatment in a Population of Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials.
BACKGROUND
Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. The aim of this systematic review was to evaluate the effectiveness of FuCT in improving chewing function and the severity of tongue thrust and drooling in children with cerebral palsy as compared with standard treatment.
METHODS
We conducted a systematic review of randomized controlled trials. The search was performed between October 2021 and January 2022 using the following databases: PubMed, Scopus, Web of Science, and CINAHL. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
The initial search yielded 56 articles. After reading the studies in full, 3 articles were chosen based on the inclusion criteria. Included participants were people with PCI; the studies reported a sample size ranging from 40-80 individuals, one study was on a pediatric population, while the others on adults. The selected studies were then evaluated using Jadad and PEDro scales.
CONCLUSION
Our study confirmed the value of FuCT in improving chewing function and the severity of tongue thrust and drooling. Our results may be useful in optimizing appropriate therapeutic management.
PubMed: 36553319
DOI: 10.3390/children9121876