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BMC Musculoskeletal Disorders Dec 2016The aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly... (Review)
Review
BACKGROUND
The aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly diagnosed lumbar radicular pain (LRP) patients.
METHODS
The search was performed in Medline OVID, Embase, PsycInfo and Web of Science (2004 to 2015). Only prospective studies of patients with LRP addressing the role of genetic factors (genetic susceptibility) and pain biomarkers (proteins in serum) were included. Two independent reviewers extracted the data and assessed methodological quality.
RESULTS
The search identified 880 citations of which 15 fulfilled the inclusion criteria. Five genetic variants; i.e., OPRM1 rs1799971 G allele, COMT rs4680 G allele, MMP1 rs1799750 2G allele, IL1α rs1800587 T allele, IL1RN rs2234677 A allele, were associated with reduced recovery of LRP. Three biomarkers; i.e., TNFα, IL6 and IFNα, were associated with persistent LRP.
CONCLUSION
The present results indicate that several genetic factors and biomarkers may predict slow recovery in LRP. Still, there is a need for replication of the findings. A stricter use of nomenclature is also highly necessary.
TRIAL REGISTRATION
The review is registered PROSPERO 20 of November 2015. Registration number is CRD42015029125 .
Topics: Alleles; Biomarkers; Catechol O-Methyltransferase; Disabled Persons; Genetic Predisposition to Disease; Humans; Interferon-alpha; Interleukin 1 Receptor Antagonist Protein; Interleukin-1alpha; Interleukin-6; Low Back Pain; Lumbosacral Region; Matrix Metalloproteinase 1; Polymorphism, Single Nucleotide; Prevalence; Receptors, Opioid, mu; Sciatica; Tumor Necrosis Factor-alpha
PubMed: 27964712
DOI: 10.1186/s12891-016-1356-5 -
The Cochrane Database of Systematic... Jul 2014This is an updated version of the original Cochrane review published in Issue 4, 2012. Myofascial pain syndrome (MPS) is a regional muscular pain syndrome characterised... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 4, 2012. Myofascial pain syndrome (MPS) is a regional muscular pain syndrome characterised by the presence of trigger points, which are painful points in one or more muscles. The pain can be felt at the site where the trigger point is located or it can be felt away from that place when the muscle is pressed (referred pain). Botulinum toxin is a protein produced by the bacterium Clostridium botulinum and is a potent neurotoxin that eventually inhibits muscle contractions. It is capable of selectively weakening painful muscles and interrupting the pain cycle.
OBJECTIVES
To assess the effectiveness and safety of botulinum toxin A (BTXA) in the treatment of myofascial pain syndrome (MPS), excluding MPS in neck and head muscles.
SEARCH METHODS
This is an updated version of the original Cochrane review published in Issue 4, 2012. The search strategy for the update was the same as in the original review and we searched CENTRAL in The Cochrane Library (2013, Issue 11 of 12), MEDLINE (Ovid) (2012 to 29 November 2013) and EMBASE (Ovid) (2012 to 27 November 2013). The search strategy was composed of terms for myofascial pain and botulinum toxin. For the original review, we also searched the Cochrane Pain, Palliative and Supportive Care (PaPaS) Review Group Specialised Register until December 2011, PubMed (from 1966 to 2011) and LILACS (from 1982 to 2011). There was no language restriction.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving botulinum toxin for treating participants with MPS. We excluded studies with MPS of the neck and head from this review as they have already been assessed in existing systematic reviews. We considered a diagnosis of MPS to be based on the identification of trigger points in the taut band through palpation of sensitive nodules, local twitch response and specific patterns of referred pain associated with each trigger point.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened identified studies, extracted data, assessed trial quality and analysed results using the Cochrane PaPaS Review Group criteria.
MAIN RESULTS
Four studies with a total of 233 participants, comparing BTXA with placebo, met the inclusion criteria. In one study with 145 participants, significant improvement rates of pain intensity scores and duration of daily pain were demonstrated when comparing BTXA with placebo. The three other studies showed that there was no statistically significant difference between BTXA and placebo in pain intensity.
AUTHORS' CONCLUSIONS
Since the first publication of this review, no new studies were found. There is inconclusive evidence to support the use of botulinum toxin in the treatment of MPS based on data from four studies with a total of 233 participants, which we considered were of sufficient quality to be included in this review. Meta-analyses were not possible due to the heterogeneity between studies. We suggest that in future studies the same methodology to assess pain, a standardised dose of treatment, follow-up of at least four months (to observe the maximum and minimum curve of the drug effect) and appropriate data presentation should be used. More high-quality RCTs of botulinum toxin for treating MPS need to be conducted before firm conclusions on its effectiveness and safety can be drawn.
Topics: Adult; Botulinum Toxins, Type A; Humans; Myofascial Pain Syndromes; Neuromuscular Agents; Pain Measurement; Pain, Referred; Randomized Controlled Trials as Topic; Trigger Points
PubMed: 25062018
DOI: 10.1002/14651858.CD007533.pub3 -
Chinese Medical Journal Apr 2015OnabotulinumtoxinA is widely used in treating neurogenic detrusor overactivity (NDO). We carried out a systematic review and meta-analysis to assess the efficacy and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
OnabotulinumtoxinA is widely used in treating neurogenic detrusor overactivity (NDO). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating NDO.
METHODS
We searched the following databases: Medline, EMBASE, and the Cochrane Controlled Trials Register. All published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for the treatment of NDO were identified in the analysis. The reference lists of the retrieved studies were also investigated.
RESULTS
Four publications involving a total of 807 patients were identified in the analysis, which compared onabotulinumtoxinA with placebo. The changes of the mean number of urinary incontinence per week (the standardized mean difference [SMD] = -10.91, 95% confidence intervals [CIs] = -14.18--7.63, P < 0.0001); maximum cystometric capacity (SMD = 146.09, 95% CI = 126.19-165.99, P < 0.0001) and maximum detrusor pressure (SMD = -32.65, 95% CI = -37.83--27.48, P < 0.0001) indicated that onabotulinumtoxinA was more effective than the placebo, despite the doses of onabotulinumtoxinA. Safety assessments primarily localized to the urinary tract indicated onabotulinumtoxinA were often associated with more complications. Urinary tract infections (relative risk [RR] =1.48, 95% CI = 1.20-1.81, P = 0.0002); hematuria (RR = 1.81, 95% CI = 1.00-3.24, P = 0.05) and urinary retention (RR = 5.87, 95% CI = 3.61-9.56, P < 0.0001).
CONCLUSIONS
This meta-analysis indicates that onabotulinumtoxinA to be an effective treatment for NDO with side effects primarily localized to urinary tract.
Topics: Botulinum Toxins, Type A; Humans; Urinary Bladder, Overactive
PubMed: 25836619
DOI: 10.4103/0366-6999.154318 -
Clinical Rehabilitation Jun 2016A systematic review and meta analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. The aim was to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis Review
The efficacy of Botulinum Toxin A for limb spasticity on improving activity restriction and quality of life: a systematic review and meta-analysis using the GRADE approach.
OBJECTIVES
A systematic review and meta analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. The aim was to evaluate the efficacy of Botulinum Toxin type A for limb spasticity on improving activity restriction and quality of life outcomes.
DATA SOURCES
Pubmed, Cinahl, Amed, Embase and Cochrane databases. English Language. Search to January 2015.
REVIEW METHODS
All randomized, placebo controlled trials on adults with active function or quality of life measures for the arm and leg relating to spasticity of any origin and treated with a single dose of Botulinum Toxin A. Evidence quality was assessed by GRADE.
RESULTS
Twenty-five studies were reviewed. Meta analysis was carried out on six upper limb and six lower limb studies. Evidence quality for the upper limb was low/very low. A significant result for Botulinum Toxin A was found at four to twelve weeks for the upper limb for active function (SMD 0.32 CI 0.01, 0.62, P=0.04) These effects were maintained for up to six months for Active Research Arm Test (ARAT) only (MD 1.87 CI 0.53, 3.21, P=0.006).Evidence quality was very low for the lower limb. No significant effect was found. Meta analysis was not possible for quality of life measures.
CONCLUSION
Botulinum Toxin A may improve active outcomes in the upper limb but further evidence is needed. No conclusion can be drawn about the effect on active outcomes for the lower limb or for quality of life measures in either limb.
Topics: Adult; Botulinum Toxins, Type A; Extremities; Humans; Muscle Spasticity; Neuromuscular Agents; Outcome Assessment, Health Care; Quality of Life
PubMed: 26150020
DOI: 10.1177/0269215515593609 -
PloS One 2024The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary objective of this study was to determine the effectiveness of BTX in pain reduction for TMDs compared to placebo and other treatments. The secondary outcomes evaluated were adverse events, maximum mouth opening, bruxism events, and maximum occlusal force.
MATERIALS AND METHODS
A literature search was performed on PubMed, Dimension Publication, Scopus, and Google Scholar. The RoB 2 tool was used for quality assessment. The mean differences in pain scores were estimated to measure the effect of BTX on pain reduction. For adverse events, the risk ratio for the incidence of side effects was calculated.
RESULTS
Two hundred and sixty non-duplicate articles were identified; however, only 14 RCTS were included in this review. The total study population included 395 patients. The overall risk of bias showed a low to moderate quality of evidence. Results from 6 studies were reported only narratively; four studies were used for meta-analysis on pain reduction, and five were used for meta-analysis on adverse events. The control used in the meta-analysis was placebo injections. Results of the meta-analysis for pain reduction were statistically insignificant for the BTX group with mean differences at MD = -1.71 (95% CI, -2.87 to -0.5) at one month, -1.53 (95% CI, -2.80 to -0.27) at three months, and -1.33 (95% CI, -2.74 to 0.77) at six months. This showed that BTX treatment was not significantly better than placebo for a reduction in pain scores at 1, 3, and 6 months. Regarding safety, the placebo group showed a relative risk of 1.34 (95%CI, 0.48-6.78) and 1.17 (95%CI, 0.54-3.88) at 1 and 3 months respectively. However, the risks were not statistically significant. There was also no difference in the effectiveness of BTX compared to placebo and other treatments for maximum mouth opening, bruxism events, and maximum occlusal force.
CONCLUSION
BTX was not associated with better outcomes in terms of pain reduction, adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. More high-quality RCTs are needed to better understand this topic.
Topics: Humans; Botulinum Toxins, Type A; Bruxism; Pain; Temporomandibular Joint Disorders; Bite Force
PubMed: 38483856
DOI: 10.1371/journal.pone.0300157 -
The Cochrane Database of Systematic... May 2016This is an update of a Cochrane review first published in 2004, and previously updated in 2009 (no change in conclusions). Cervical dystonia is a frequent and disabling... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in 2004, and previously updated in 2009 (no change in conclusions). Cervical dystonia is a frequent and disabling disorder characterised by painful involuntary head posturing. Botulinum toxin type A (BtA) is usually considered the first line therapy for this condition, although botulinum toxin type B (BtB) is an alternative option.
OBJECTIVES
To compare the efficacy, safety and tolerability of botulinum toxin type B (BtB) versus placebo in people with cervical dystonia.
SEARCH METHODS
We identified studies for inclusion in the review using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles and conference proceedings, last run in October 2015. We ran the search from 1977 to 2015. The search was unrestricted by language.
SELECTION CRITERIA
Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtB versus placebo in adults with cervical dystonia.
DATA COLLECTION AND ANALYSIS
Two independent authors assessed records, selected included studies, extracted data using a paper pro forma and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third author. We performed one meta-analysis for the comparison BtB versus placebo. We used random-effects models when there was heterogeneity and fixed-effect models when there was no heterogeneity. In addition, we performed pre-specified subgroup analyses according to BtB doses and BtA previous clinical responsiveness. The primary efficacy outcome was overall improvement on any validated symptomatic rating scale. The primary safety outcome was the number of participants with any adverse event.
MAIN RESULTS
We included four RCTs of moderate overall methodological quality, including 441 participants with cervical dystonia. Three studies excluded participants known to have poorer response to Bt treatment, therefore including an enriched population with a higher probability of benefiting from Bt treatment. None of the trials were independently funded. All RCTs evaluated the effect of a single Bt treatment session using doses between 2500 U and 10,000 U. BtB was associated with an improvement of 14.7% (95% CI 9.8% to 19.5) in the patients' baseline clinical status as assessed by investigators, with reduction of 6.8 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-total score) at week 4 after injection (95% CI 4.54 to 9.01). Mean difference (MD) in TWSTRS-pain score at week 4 was 2.20 (95% CI 1.25 to 3.15). Overall, both participants and clinicians reported an improvement of subjective clinical status. There were no differences between groups in the withdrawals rate due to adverse events or in the proportion of participants with adverse events. However, BtB-treated patients had a 7.65 (95% CI 2.75 to 21.32) and a 6.78 (95% CI 2.42 to 19.05) increased risk of treatment-related dry mouth and dysphagia, respectively. Statistical heterogeneity between studies was low to moderate for most outcomes. All tested dosages were efficacious against placebo without clear-cut evidence of a dose-response gradient. However, duration of effect (time until return to baseline TWSTRS-total score) and risk of dry mouth and dysphagia were greater in the subgroup of participants treated with higher BtB doses. Subgroup analysis showed a higher improvement with BtB among BtA-non-responsive participants, although there were no differences in the effect size between the BtA-responsive and non-responsive subgroups.
AUTHORS' CONCLUSIONS
A single BtB-treatment session is associated with a significant and clinically relevant reduction of cervical dystonia impairment including severity, disability and pain, and is well tolerated, when compared with placebo. However, BtB-treated patients are at an increased risk of dry mouth and dysphagia. There are no data from RCTs evaluating the effectiveness and safety of repeated BtB injection cycles. There are no RCT data to allow us to draw definitive conclusions on the optimal treatment intervals and doses, usefulness of guidance techniques for injection, and impact on quality of life.
Topics: Botulinum Toxins; Botulinum Toxins, Type A; Female; Humans; Male; Middle Aged; Neuromuscular Agents; Randomized Controlled Trials as Topic; Torticollis; Treatment Outcome
PubMed: 27176573
DOI: 10.1002/14651858.CD004315.pub3 -
Clinics (Sao Paulo, Brazil) Apr 2007To carry out a systematic review and meta-analysis of the efficacy of chemonucleolysis in the treatment of lumbar disc herniation. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To carry out a systematic review and meta-analysis of the efficacy of chemonucleolysis in the treatment of lumbar disc herniation.
METHODS
Clinical trials were selected from 3 electronic databases (The Cochrane Controlled Trials Register, MEDLINE, and EMBASE). Data were analyzed with the software STATA, using the meta command.
RESULTS
Twenty-two clinical trials were eligible. For chemonucleolysis versus placebo, the summary risk ratio estimate for pain relief as outcome was 1.51 (95% CI: 1.27-1.80). The summary estimate was 1.07 (95% CI: 0.95-1.20) for the comparison between chymopapain and collagenase. Regarding chemonucleolysis with chymopapain versus surgery, the fixed-effect summary estimate of effect for pain relief was 0.93 (95% CI: 0.88-0.98) with surgery as the reference group. In this case, heterogeneity was statistically significant.
CONCLUSIONS
Chemonucleolysis with chymopapain was superior to placebo and was as effective as collagenase in the treatment of lumbar disc prolapse. Results for studies comparing chemonucleolysis with surgery were heterogeneous, making it difficult to interpret the summary measure of effect.
Topics: Chymopapain; Collagenases; Controlled Clinical Trials as Topic; Databases, Bibliographic; Humans; Intervertebral Disc Chemolysis; Intervertebral Disc Displacement; Placebos; Randomized Controlled Trials as Topic
PubMed: 17505703
DOI: 10.1590/s1807-59322007000200013 -
Toxins Jan 2022We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum... (Meta-Analysis)
Meta-Analysis
We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: -1.71, 3.90), 1.41 (95% CI: -0.61, 3.43), -0.16 (95% CI: -1.95, 1.63), 0.85 (95% CI: -1.85, 3.56), and -0.71 (95% CI: -3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent.
Topics: Adult; Aged; Aged, 80 and over; Botulinum Toxins, Type A; Female; Humans; Male; Middle Aged; Neuralgia; Patient Satisfaction; Quality of Life; Treatment Outcome
PubMed: 35051013
DOI: 10.3390/toxins14010036 -
International Journal of Molecular... Jun 2023Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to... (Meta-Analysis)
Meta-Analysis Review
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to differentiate MCL from other NHL types; however, recently, there has been an increase in the number of reported cases of CD10-positive MCL. This warrants further investigation into this rarer immunophenotype and its clinical significance. BCL6, which is a master transcription factor for the regulation of cell proliferation and key oncogene in B cell lymphomagenesis, has been reported to have co-expression with CD10 in MCL. The clinical significance of this aberrant antigen expression remains unknown. We conducted a systematic review by searching four databases and selected five retrospective analyses and five case series. Two survival analyses were conducted to determine if BCL6 positivity conferred a survival difference: 1. BCL6+ vs. BCL6- MCL. 2. BCL6+/CD10+ vs. BCL6-/CD10+ MCL. Correlation analysis was conducted to determine if BCL6 positivity correlated with the Ki67 proliferation index (PI). Overall survival (OS) rates were performed by the Kaplan-Meier method and log-rank test. Our analyses revealed that BCL6+ MCL had significantly shorter overall survival (median OS: 14 months vs. 43 months; = 0.01), BCL6+/CD10+ MCL had an inferior outcome vs. BCL6+/CD10- MCL (median OS: 20 months vs. 55 months = 0.1828), BCL6+ MCL had significantly higher percentages of Ki67% (Ki67% difference: 24.29; = 0.0094), and BCL6 positivity had a positive correlation with CD10+ status with an odds ratio 5.11 (2.49, 10.46; = 0.0000286). Our analysis showed that BCL6 expression is correlated with CD10 positivity in MCL, and BCL6 expression demonstrated an inferior overall survival. The higher Ki67 PI in BCL6+ MCL compared to BCL6- MCL further supports the idea that the BCL6+ immunophenotype may have prognostic value in MCL. MCL management should consider incorporating prognostic scoring systems adjusted for BCL6 expression. Targeted therapies against BCL6 may offer potential therapeutic options for managing MCL with aberrant immunophenotypes.
Topics: Humans; Adult; Lymphoma, Mantle-Cell; Neprilysin; Proto-Oncogene Proteins c-bcl-6; Retrospective Studies; Prognosis; Ki-67 Antigen
PubMed: 37373354
DOI: 10.3390/ijms241210207 -
Cerebrovascular Diseases (Basel,... 2022Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS.
METHODS
The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2).
RESULTS
The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality.
CONCLUSION
Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.
Topics: Biomarkers; Brain Ischemia; Ferritins; Hemorrhage; Humans; Ischemic Stroke; Matrix Metalloproteinase 9; Prognosis; Reproducibility of Results; Stroke
PubMed: 34569521
DOI: 10.1159/000518570