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Journal of Oral Rehabilitation May 2024Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear.
OBJECTIVE
To assess the efficacy, safety and optimal dose of BTX-A for treating TMD.
METHODS
We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model.
RESULTS
Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (μV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo.
CONCLUSIONS
BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.
Topics: Humans; Botulinum Toxins, Type A; Randomized Controlled Trials as Topic; Pain; Temporomandibular Joint Disorders; Treatment Outcome
PubMed: 38151884
DOI: 10.1111/joor.13648 -
Journal of Pediatric Urology Apr 2024Dysfunctional voiding (DV) is a habitual voiding disorder caused by involuntary contraction or non-relaxation of the external urethral sphincter (EUS) during voiding.... (Review)
Review
INTRODUCTION
Dysfunctional voiding (DV) is a habitual voiding disorder caused by involuntary contraction or non-relaxation of the external urethral sphincter (EUS) during voiding. This contraction causes high post-void residuals (PVR), urinary incontinence and urinary tract infections (UTIs). Various treatments for DV are available, but some children do not respond. Intersphincteric botulinum toxin-A (BTX-A) may be a possible treatment for therapy-refractory children with DV.
OBJECTIVE
The aim of this systematic review is to summarize the effects and safety of intersphincteric BTX-A as a treatment for therapy-refractory DV in children.
METHODS
A systematic search in Embase, MEDLINE, Cochrane, and Web of Science databases was performed. Studies reporting on the usage of intersphincteric BTX-A as a treatment for DV in children were included. Data on PVR, maximum flow rate (Qmax), repeat injections and complications were extracted.
RESULTS
From a total of 277 articles, five cohort studies were identified, reporting on 78 children with DV of whom 53 were female (68 %) and 25 were male (32 %). Sample sizes ranged from ten to twenty patients. Mean or median age at the time of intervention ranged from 8 to 10.5 years. Meta-analysis could not be performed due to lack of data. The narrative synthesis approach was therefore used to summarize the results. All studies showed significant decrease in PVR after BTX-A injection. Three studies showed a 33-69 % improvement on incontinence after BTX-A injection. Less UTIs were reported after treatment. A temporary increase in incontinence, UTIs and transitory numbness to the gluteus muscle were reported as side-effects.
CONCLUSIONS
BTX-A could be a safe and effective treatment option for therapy-refractory DV in children by reducing PVR, UTIs and incontinence. Hereby, the synergistic effect of BTX-A and urotherapy should be emphasized in future management. Furthermore, this study identified gaps in current knowledge that are of interest for future research.
Topics: Child; Humans; Male; Female; Botulinum Toxins, Type A; Urinary Bladder Diseases; Urinary Incontinence; Urination Disorders; Urethra; Treatment Outcome
PubMed: 38135586
DOI: 10.1016/j.jpurol.2023.10.034 -
Toxins Dec 2023This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT's... (Review)
Review
This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT's effect on pain at the site of surgery or radiation. All 13 published studies on this issue indicated reduction or cessation of pain at these sites after local injection of BoNTs. Twelve studies addressed the effect of BoNT injection into the pylorus (sphincter between the stomach and the first part of the gut) for the prevention of gastroparesis after local resection of esophageal cancer. In eight studies, BoNT injection was superior to no intervention; three studies found no difference between the two approaches. One study compared the result of intra-pyloric BoNT injection with preventive pyloromyotomy (resection of pyloric muscle fibers). Both approaches reduced gastroparesis, but the surgical approach had more serious side effects. BoNT injection was superior to saline injection in the prevention of esophageal stricture after surgery (34% versus 6%, respectively, = 0.02) and produced better results (30% versus 40% stricture) compared to steroid (triamcinolone) injection close to the surgical region. All 12 reported studies on the effect of BoNT injection into the parotid region for the reduction in facial sweating during eating (gustatory hyperhidrosis) found that BoNT injections stopped or significantly reduced facial sweating that developed after parotid gland surgery. Six studies showed that BoNT injection into the parotid region prevented the development of or healed the fistulas that developed after parotid gland resection-parotidectomy gustatory hyperhidrosis (Frey syndrome), post-surgical parotid fistula, and sialocele. Eight studies suggested that BoNT injection into masseter muscle reduced or stopped severe jaw pain after the first bite (first bite syndrome) that may develop as a complication of parotidectomy.
Topics: Humans; Botulinum Toxins, Type A; Sweating, Gustatory; Gastroparesis; Pain; Neoplasms
PubMed: 38133193
DOI: 10.3390/toxins15120689 -
Journal of Evidence-based Medicine Dec 2023To investigate the most effective and best-tolerated drugs for treating diseased smokers. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the most effective and best-tolerated drugs for treating diseased smokers.
METHODS
Eight databases were searched for randomized controlled trials (RCTs) involving different pharmacological interventions for smoking cessation in disease patients (January 2023). Network meta-analysis was performed using STATA 15.1 software. The Cochrane Risk of Bias Tool assessed the risk of bias, and confidence in evidence was assessed using CINeMA.
RESULTS
A total of 60 RCTs involving 13,009 patients of 12 disease categories were included. All trials reported 13 interventions, resulting in 78 comparisons. Network meta-analysis showed that varenicline (OR = 2.30, 95% CI (1.77, 3.00)) and bupropion (OR = 1.65, 95% CI (1.29, 2.11)) showed favorable abstinence effects compared to placebo in the cardiovascular disease population. Nicotine replacement therapy (NRT) had better withdrawal advantages than placebo (OR = 11.18, 95% CI (2.25, 55.54)) in the chronic obstructive pulmonary disease (COPD) population. Some combination treatments showed better results than monotherapy, such as bupropion + NRT was superior to bupropion (OR = 8.45, 95% CI (1.84, 38.89)) and NRT (OR = 4.98, 95% CI (1.25, 19.78)) in mental illness population. The final surface under the cumulative ranking curve indicated that bupropion + NRT achieved the best smoking cessation effect. Overall confidence in the evidence was low. In a comparison of drugs, the results showed that bupropion + NRT had the best safety.
CONCLUSIONS
Most interventions show the benefit of quitting smoking compared with placebo, including monotherapy and combination therapy. Moreover, varenicline or bupropion combined with NRT is superior to some monotherapies.
Topics: Humans; Smoking Cessation; Bupropion; Varenicline; Nicotinic Agonists; Smokers; Network Meta-Analysis
PubMed: 38102895
DOI: 10.1111/jebm.12570 -
European Archives of... Mar 2024This study aims to aggregate and analyze existing clinical evidence to compare the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for... (Meta-Analysis)
Meta-Analysis
Comparison of the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for adductor spasmodic dysphonia: a systematic review and meta-analysis.
PURPOSE
This study aims to aggregate and analyze existing clinical evidence to compare the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for the treatment of adductor spasmodic dysphonia (ADSD).
METHODS
Reports from non-randomized controlled trials and cohort studies pertaining to the efficacy and adverse effects of unilateral and bilateral botulinum toxin injections for ADSD were identified and retrieved from four electronic databases from inception to July 2023. The meta-analysis employed fixed or random effects models to assess pooled relative risks (RR), mean differences (MDs), and standard mean differences (SMDs) with their corresponding 95% confidence intervals (CIs).
RESULTS
We included two non-randomized controlled trials and seven cohort studies comprising 854 total patients. Meta-analysis of the included studies showed that bilateral botulinum toxin injections associated with a longer duration of vocal improvement (MD = - 2.89, 95% CI - 3.13 to - 2.65, I = 0%, P < 0.00001). However, bilateral botulinum toxin injections associated with an increase in adverse effects, including a longer duration of breathy voice quality (SMD = - 0.51, 95% CI - 0.79 to - 0.22, I = 35%, P = 0.0005) and a higher occurrence of swallowing difficulties (RR = 0.46, 95% CI 0.35 to 0.11, I = 0%, P < 0.00001).
CONCLUSION
Bilateral botulinum toxin injections for ADSD showed a longer duration of vocal improvement, a longer breathy voice duration and a higher dysphagia occurrence and duration than unilateral injections.
Topics: Humans; Dysphonia; Botulinum Toxins, Type A; Injections; Drug-Related Side Effects and Adverse Reactions; Treatment Outcome; Laryngeal Muscles; Injections, Intramuscular; Voice Disorders
PubMed: 38095707
DOI: 10.1007/s00405-023-08366-2 -
Digestive Surgery 2024Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is...
INTRODUCTION
Postoperative ileus (POI) is a significant complication following abdominal surgery, increasing morbidity and mortality. The cholinergic anti-inflammatory response is one of the major pathways involved in developing POI, but current recommendations to prevent POI do not target this. This review aims to summarise evidence for the use of acetylcholinesterase inhibitors, neostigmine and pyridostigmine, to reduce the time to return of gastrointestinal function (GI) following abdominal surgery.
METHODS
A systematic search of various databases was performed from 1946 to May 2023. Randomised controlled trials (RCTs) on acetylcholinesterase inhibitors in intra-abdominal surgery were included. Data on time to flatus and/or stool and side effects were extracted.
RESULTS
Among 776 screened manuscripts, 8 RCTs (703 patients) investigating acetylcholinesterase inhibitors in intra-abdominal surgery were analysed. Five studies showed a significant reduction in time to flatus and/or stool by 17-47.6 h. Methodological variations, differing procedure types, and potential bias were observed. Limited studies reported side effects or length of stay.
CONCLUSION
Acetylcholinesterase inhibitors may reduce the time for GI to return. However, current evidence is limited and biased. Further studies incorporating acetylcholinesterase inhibitors in an enhanced recovery protocol are required to address this question, especially for patients undergoing colorectal surgery.
Topics: Humans; Cholinesterase Inhibitors; Recovery of Function; Flatulence; Postoperative Complications; Ileus
PubMed: 38091957
DOI: 10.1159/000535753 -
Frontiers in Immunology 2023Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders,...
BACKGROUND
Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far.
OBJECTIVES
The aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release.
MATERIAL AND METHODS
This review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing studies on the direct impact of nicotine on specified human neutrophil functions.
RESULTS
Of the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase.
CONCLUSION
Nicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.
Topics: Humans; Extracellular Traps; Neutrophils; Nicotine; Reactive Oxygen Species; Granulocytes
PubMed: 38077313
DOI: 10.3389/fimmu.2023.1281685 -
Brain, Behavior, and Immunity Feb 2024Vagus nerve stimulation (VNS) has been identified as an innovative immunosuppressive treatment strategy in rodent studies. However, its' clinical potential is still... (Meta-Analysis)
Meta-Analysis
Vagus nerve stimulation (VNS) has been identified as an innovative immunosuppressive treatment strategy in rodent studies. However, its' clinical potential is still unclear. Therefore, we aimed to assess whether VNS can reduce inflammatory proteins and/or immune cells in humans, through a pre-registered systematic review and meta-analysis according to PRISMA guidelines. The databases Cochrane, Pubmed and World of Knowledge were searched in duplicate up to the 3rd of March 2022 and publications from identified clinical trial registrations were identified until 20th of August 2023. Studies were included if they provided peer-reviewed data for humans who received VNS as short-term (<=1 day) or long-term (>=2 days-365 days) stimulation and reported at least one cytokine or immune cell after treatment.Screening of title, abstract, full text, and data extraction was performed in duplicate by two independent reviewers. Data were pooled using a random-effects model and meta-regression was performed for moderating factors. Reporting bias was assessed. The standardized mean difference (Hedge's g) was used to indicate overall differences of cytokine data (mean and standard deviation or median and interquartile range at the study level) to test our a-priori hypothesis. The systematic review of 36 studies with 1135 participants (355 receiving a control/sham condition and 780 receiving VNS) revealed anti-inflammatory effects of VNS for cytokines in several reports, albeit often in subgroup analyses, but our meta-analyses of 26 studies did not confirm these findings. Although most cytokines were numerically reduced, the reduction did not reach statistical significance after VNS: not in the between-group comparisons (short-term: TNF-α: g = -0.21, p = 0.359; IL-6: g = -0.94, p = 0.112; long-term: TNF-α: g = -0.13, p = 0.196; IL-6: g = -0.67, p = 0.306); nor in the within-study designs (short-term: TNF-α: g = -0.45, p = 0.630; IL-6: g = 0.28, p = 0.840; TNF-α: g = -0.53, p = 0.297; IL-6:g = -0.02, p = 0.954). Only the subgroup analysis of 4 long-term studies with acute inflammation was significant: VNS decreased CRP significantly more than sham stimulation. Additional subgroup analyses including stimulation duration, stimulation method (invasive/non-invasive), immune stimulation, and study quality did not alter results. However, heterogeneity was high, and most studies had poor to fair quality. Given the low number of studies for each disease, a disease-specific analysis was not possible. In conclusion, while numeric effects were reported in individual studies, the current evidence does not substantiate the claim that VNS impacts inflammatory cytokines in humans. However, it may be beneficial during acute inflammatory events. To assess its full potential, high-quality studies and technological advances are required.
Topics: Humans; Vagus Nerve Stimulation; Tumor Necrosis Factor-alpha; Interleukin-6; Cytokines; Anti-Inflammatory Agents; Vagus Nerve
PubMed: 38070618
DOI: 10.1016/j.bbi.2023.12.008 -
Contact Lens & Anterior Eye : the... Feb 2024To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). (Review)
Review
PURPOSE
To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED).
METHODS
A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected.
RESULTS
A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 ± 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 ± 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %.
CONCLUSIONS
OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
Topics: Humans; Dry Eye Syndromes; Fluorescein; Nasal Sprays; Tears; Varenicline
PubMed: 38065797
DOI: 10.1016/j.clae.2023.102097 -
The Cochrane Database of Systematic... Dec 2023Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are... (Review)
Review
BACKGROUND
Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline.
OBJECTIVES
Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes.
SEARCH METHODS
We searched CENTRAL on 22 December 2022, and we searched MEDLINE, Embase, and three other databases from inception to 1 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed the risk of bias of included studies. The data were not suitable for meta-analysis, so we summarised them narratively. We used GRADE methods to rate our confidence in the review results.
MAIN RESULTS
We included three trials with a total of 299 participants. All three trials were conducted in a cognitively mixed population (some cognitively healthy participants, some participants with dementia). Outcomes were assessed after one to three months. One trial reported significantly improved performance on the Digit Symbol Substitution Test (DSST) in the intervention group (treatment difference 0.70, 95% confidence interval (CI) 0.11 to 1.30), although there was no difference between the groups in the proportion of participants with reduced anticholinergic burden. Two trials successfully reduced anticholinergic burden in the intervention group. Of these, one reported no significant difference between the intervention versus control in terms of their effect on cognitive performance measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate recall (mean between-group difference 0.54, 95% CI -0.91 to 2.05), CERAD delayed recall (mean between-group difference -0.23, 95% CI-0.85 to 0.38), CERAD recognition (mean between-group difference 0.77, 95% CI -0.39 to 1.94), and Mini-Mental State Examination (mean between-group difference 0.39, 95% CI -0.96 to 1.75). The other trial reported a significant correlation between anticholinergic burden and a test of working memory after the intervention (which suggested reducing the burden improved performance), but reported no effect on multiple other cognitive measures. In GRADE terms, the results were of very low certainty. There were no reported between-group differences for any other clinical outcome we investigated. It was not possible to investigate differences according to type of reduction intervention or type of anticholinergic scale, to measure the sustainability of interventions, or to establish lessons learnt for upscaling. No trials investigated safety outcomes.
AUTHORS' CONCLUSIONS
There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately.
Topics: Aged; Humans; Alzheimer Disease; Cardiovascular Diseases; Cholinergic Antagonists; Cognitive Dysfunction; Deprescriptions
PubMed: 38063254
DOI: 10.1002/14651858.CD015405.pub2