-
BMJ Open Jun 2023To evaluate the efficacy and safety of botulinum toxin (BTX) for motor dysfunction in Parkinson's disease (PD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of botulinum toxin (BTX) for motor dysfunction in Parkinson's disease (PD).
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Searches of PubMed, EMBASE and the Cochrane Library, from database inception to 20 October 2022.
ELIGIBILITY CRITERIA
Studies reported in English with adult PD patients treated with BTX.
DATA EXTRACTION AND SYNTHESIS
Primary outcomes were United Parkinson's Disease Rate Scale Section (UPDRS) III (or its items) and Visual Analogue Scale (VAS). Secondary outcomes were UPDRS-II (or its items), Freezing of Gait Questionnaire (FOG-Q), Timed Up and Go test (TUG) and treatment-related adverse events (TRAEs). Mean difference (MD) or standardised MD (SMD) before and after treatment with 95% CIs were used for continuous variables and risk ratios (RRs) with 95% CIs was used for TRAEs.
RESULTS
Six randomised controlled trials (RCTs) and six non-RCTs (case series) were included (n=224 participants, n=165). No significant difference was found in pooled results of UPDRS-III (available in four RCTs and two non-RCTs, SMD=-0.19, 95% CI -0.98 to 0.60), UPDRS-II (four RCTs and one non-RCT, SMD=-0.55, 95% CI -1.22 to 0.13), FOG-Q (one RCT and one non-RCT, SMD=0.53, 95% CI -1.93 to 2.98) or the risk of TRAEs (five RCTs, RR 0.87, 95% CI 0.37 to 2.01). Significant decreases were found in pooled VAS score (three RCTs and five non-RCTs, MD=-2.14, 95% CI -3.05 to -1.23) and TUG (MD=-2.06, 95% CI -2.91 to -1.20) after BTX treatment.
CONCLUSIONS
BTX may not be associated with motor symptoms alleviation, although it benefits pain alleviation and functional mobility improvement.
Topics: Adult; Humans; Parkinson Disease; Botulinum Toxins
PubMed: 37328181
DOI: 10.1136/bmjopen-2021-060274 -
Farmacia Hospitalaria : Organo Oficial... 2023Post-stroke spasticity (PSS) is a common complication in stroke survivors, causing severe burden to patients living with it. The aim of this review was to conduct a...
OBJECTIVE
Post-stroke spasticity (PSS) is a common complication in stroke survivors, causing severe burden to patients living with it. The aim of this review was to conduct a cost-effectiveness analysis (CEA) of the treatment of post-stroke spasticity, in adults, with abobotulinumtoxinA compared to the best supportive care, based on results from a systematic literature review. Given that abobotulinumtoxinA (aboBoNT-A) is always accompanied by the best supportive care treatment, the CEA compared aboBoNT-A plus the best supportive care with the best supportive care alone.
METHODS
A systematic literature review in EMBASE (including Medline and PubMed), Scopus, and other sources (Google Scholar) was conducted. Articles of all types, providing information on the costs and/or effectiveness measures for the current treatments of PSS in adults were included. The synthesis of information from the review provided the parameters for the design of a cost-effectiveness analysis of the mentioned treatment of interest. The societal perspective was compared to a perspective where only direct costs were observed.
RESULTS
In total, 532 abstracts were screened. Full information was revised from 40 papers and 13 of these were selected as core papers for full data extraction. Data from the core publications formed the basis for the development of a cost-effectiveness model. In all the included papers physiotherapy was the best supportive care treatment (SoC). The cost-effectiveness analysis showed that even in the most conservative scenario, assuming the worst case scenario, the probability of a cost per quality-adjusted life-year (QALY) gained below €40,000, for aboBoNT-A together with physiotherapy is above 0.8, and with certainty below €50,000/QALY when either a direct costs, or a societal perspective was taken. On average, the probabilistic model obtains a negative mean incremental cost-effectiveness ratio of around -15,000 €/QALY.
CONCLUSION
The cost-effectiveness analyses show that aboBoNT-A together with physiotherapy would be a cost-effective treatment compared with physiotherapy alone, independently of the perspective considered.
Topics: Adult; Humans; Cost-Effectiveness Analysis; Cost-Benefit Analysis; Botulinum Toxins, Type A; Stroke; Physical Therapy Modalities; Quality-Adjusted Life Years
PubMed: 37244845
DOI: 10.1016/j.farma.2023.04.006 -
Annals of Vascular Surgery Oct 2023The optimal diagnostic and treatment algorithm for patients with suspected thoracic outlet syndrome (TOS) remains challenging. Botulinum toxin (BTX) muscle injections... (Review)
Review
BACKGROUND
The optimal diagnostic and treatment algorithm for patients with suspected thoracic outlet syndrome (TOS) remains challenging. Botulinum toxin (BTX) muscle injections have been suggested to shrink muscles in the thoracic outlet reducing neurovascular compression. This systematic review evaluates the diagnostic and therapeutic value of BTX injections in TOS.
METHODS
A systematic review of studies reporting BTX as a diagnostic or therapeutic tool in TOS (or pectoralis minor syndrome as TOS subtype) was conducted in PubMed, Embase, and CENTRAL databases on May 26, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Primary end point was symptom reduction after primary procedure. Secondary end points were symptom reduction after repeated procedures, the degree of symptom reduction, complications, and duration of clinical effect.
RESULTS
Eight studies (1 randomized controlled trial [RCT], 1 prospective cohort study, and 6 retrospective cohort studies) were included reporting 716 procedures in at least 497 patients (at minimum 350 primary and 25 repeated procedures, residual unclear) diagnosed with presumably only neurogenic TOS. Except for the RCT, the methodological quality was fair to poor. All studies were designed on an intention to treat basis, one also investigated BTX as a diagnostic tool to differentiate pectoralis minor syndrome from costoclavicular compression. Reduction of symptoms was reported in 46-63% of primary procedures; no significant difference was found in the RCT. The effect of repeated procedures could not be determined. Degree of symptom reduction was reported by up to 30-42% on the Short-form McGill Pain scale and up to 40 mm on a visual analog scale. Complication rates varied among studies, no major complications were reported. Symptom relief ranged from 1 to 6 months.
CONCLUSIONS
Based on limited quality evidence, BTX may provide short-lasting symptom relief in some neurogenic TOS patients but remains overall undecided. The role of BTX for treatment of vascular TOS and as a diagnostic tool in TOS is currently unexploited.
Topics: Humans; Treatment Outcome; Thoracic Outlet Syndrome; Algorithms; Databases, Factual; Botulinum Toxins
PubMed: 37236533
DOI: 10.1016/j.avsg.2023.05.009 -
Toxins May 2023Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15... (Meta-Analysis)
Meta-Analysis Review
Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the machinery for exocytosis of neurotransmitters and neuropeptides, has been approved for use in chronic migraine since 2010. This systematic review and meta-analysis appraises the safety of onabotulinumtoxin A treatment for chronic migraine and the occurrence of treatment-related adverse events (TRAEs) in randomized, clinical studies in comparison with placebo or other comparators and preventative treatments according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieved 888 total records. Nine studies are included and seven were eligible for meta-analysis. The present study demonstrates that toxin produces more TRAEs than placebo, but less than oral topiramate, supporting the safety of onabotulinumtoxin A, and highlights the heterogeneity of the studies present in the literature (I = 96%; < 0.00001). This points to the need for further, adequately powered, randomized clinical trials assessing the safety of onabotulinumtoxin A in combination with the newest treatment options.
Topics: Humans; Botulinum Toxins, Type A; Randomized Controlled Trials as Topic; Migraine Disorders; Headache
PubMed: 37235366
DOI: 10.3390/toxins15050332 -
Biomolecules Apr 2023Hypertrophic cardiomyopathy (HCM) is a genetic condition determined by an altered collagen turnover of the extracellular matrix. Matrix metalloproteinases (MMPs) and... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a genetic condition determined by an altered collagen turnover of the extracellular matrix. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are abnormally released in patients with HCM. The purpose of this systematic review was to thoroughly summarize and discuss the existing knowledge of MMPs profile in patients with HCM. All studies meeting the inclusion criteria (detailed data regarding MMPs in patients with HCM) were selected, after screening the literature from July 1975 to November 2022. Sixteen trials that enrolled a total of 892 participants were included. MMPs-particularly MMP2-levels were found higher in HCM patients compared to healthy subjects. MMPs were used as biomarkers after surgical and percutaneous treatments. Understanding the molecular processes that control the cardiac ECM's collagen turnover allows for a non-invasive evaluation of HCM patients through the monitoring of MMPs and TIMPs.
Topics: Humans; Cardiomyopathy, Hypertrophic; Heart; Collagen; Matrix Metalloproteinases
PubMed: 37189412
DOI: 10.3390/biom13040665 -
International Journal of Molecular... Apr 2023Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is... (Meta-Analysis)
Meta-Analysis Review
Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls ( < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts ( = 0.006, < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Matrix Metalloproteinase 7; Prognosis; Cystectomy; Cohort Studies; Lymph Nodes
PubMed: 37175566
DOI: 10.3390/ijms24097859 -
Toxins Mar 2023Accurate targeting of overactive muscles is fundamental for successful botulinum neurotoxin (BoNT) injections in the treatment of spasticity. The necessity of... (Meta-Analysis)
Meta-Analysis Review
Accurate targeting of overactive muscles is fundamental for successful botulinum neurotoxin (BoNT) injections in the treatment of spasticity. The necessity of instrumented guidance and the superiority of one or more guidance techniques are ambiguous. Here, we sought to investigate if guided BoNT injections lead to a better clinical outcome in adults with limb spasticity compared to non-guided injections. We also aimed to elucidate the hierarchy of common guidance techniques including electromyography, electrostimulation, manual needle placement and ultrasound. To this end, we conducted a Bayesian network meta-analysis and systematic review with 245 patients using the MetaInsight software, R and the Cochrane Review Manager. Our study provided, for the first time, quantitative evidence supporting the superiority of guided BoNT injections over the non-guided ones. The hierarchy comprised ultrasound on the first level, electrostimulation on the second, electromyography on the third and manual needle placement on the last level. The difference between ultrasound and electrostimulation was minor and, thus, appropriate contextualization is essential for decision making. Taken together, guided BoNT injections based on ultrasound and electrostimulation performed by experienced practitioners lead to a better clinical outcome within the first month post-injection in adults with limb spasticity. In the present study, ultrasound performed slightly better, but large-scale trials should shed more light on which modality is superior.
Topics: Adult; Humans; Bayes Theorem; Botulinum Toxins, Type A; Injections, Intramuscular; Muscle Spasticity; Network Meta-Analysis; Neuromuscular Agents; Neurotoxins; Stroke; Treatment Outcome
PubMed: 37104194
DOI: 10.3390/toxins15040256 -
International Journal of Medical... 2023Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The... (Meta-Analysis)
Meta-Analysis Review
Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.
Topics: Humans; Coronary Artery Disease; Acute Coronary Syndrome; Matrix Metalloproteinase 3; Plaque, Atherosclerotic; Smoking
PubMed: 37057211
DOI: 10.7150/ijms.79889 -
International Journal of Molecular... Mar 2023Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is... (Review)
Review
Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.
Topics: Female; Humans; Uterine Cervical Neoplasms; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Extracellular Matrix; Matrix Metalloproteinases; Endometrial Neoplasms; Tumor Microenvironment
PubMed: 36982551
DOI: 10.3390/ijms24065463 -
International Journal of Surgery... May 2023Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of... (Meta-Analysis)
Meta-Analysis
The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis.
BACKGROUND
Oral medications, onabotulinumtoxinA injections, and transcutaneous tibial nerve stimulation (TTNS) are recommended by the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction guidelines as non or minimally invasive treatments for patients with neurogenic detrusor overactivity (NDO) without treatment hierarchy.
OBJECTIVE
The objective was to compare and rank the effectiveness and safety of oral medications, three doses of onabotulinumtoxinA, and TTNS on improving urodynamic outcomes in patient-reported outcomes and safety outcomes in patients with NDO.
METHODS
The authors searched PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov, from their inception to October 2022 and included randomized controlled studies on the drug, onabotulinumtoxinA, and TTNS for the treatment of patients with NDO. Outcomes included urodynamic parameters, voiding diary, quality of life changes, adverse event rate and postvoid residual.
RESULTS
A total of 26 articles and 2938 patients were included in the statistics. Regarding effectiveness, all interventions except TTNS and α-blockers were statistically different for the placebo group. The urodynamic outcome and patient-reported outcome suggested that onabotulinumtoxinA injection (urodynamic outcome: onabotulinumtoxinA 200 U, the mean surface under the cumulative ranking curve (SUCRA): 87.4; patient-reported outcome: onabotulinumtoxinA 100 U, mean SUCRA: 89.8) was the most effective treatment, and the safety outcome suggested that TTNS (SUCRA: 83.3) was the safest. Cluster analysis found that antimuscarinics and β3-adrenoceptor-agonists possessed good effectiveness and safety.
CONCLUSION
OnabotulinumtoxinA injection is probably the most effective way to treat patients with NDO, with increasing effectiveness but decreasing safety as the dose rises. The effectiveness of α-blockers and TTNS was not statistically different from the placebo group. Antimuscarinics and β3-adrenoceptor-agonists have good effectiveness and safety.
Topics: Humans; Adult; Female; Botulinum Toxins, Type A; Quality of Life; Network Meta-Analysis; Muscarinic Antagonists; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Treatment Outcome; Receptors, Adrenergic; Tibial Nerve
PubMed: 36974676
DOI: 10.1097/JS9.0000000000000338