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Ageing Research Reviews Nov 2022The aim of the present systematic review (SR) was to provide an overview of all published and unpublished clinical trials investigating the safety and efficacy of... (Review)
Review
The aim of the present systematic review (SR) was to provide an overview of all published and unpublished clinical trials investigating the safety and efficacy of disease-modifying drugs targeting synaptic plasticity in dementia. Searches on CT.gov and EuCT identified 27 trials (4 phase-1, 1 phase-1/2, 18 phase-2, 1 phase-2/3, 1 phase-3, 1 phase-4, and 1 not reported). Twenty of them completed, and seven are currently active or enrolling. The structured bibliographic searches yielded 3585 records. A total of 12 studies were selected on Levetiracetam, Masitinib, Saracatinib, BI 40930, Bryostatin 1, PF-04447943 and Edonerpic drugs. We used RoB tool for quality analysis of randomized studies. Efficacy was assessed as a primary outcome in all studies except one and the main scale used was ADAS-Cog (7 studies), MMSE and CDR (4 studies). Safety and tolerability were reported in eleven studies. The incidence of SAEs was similar between treatment and placebo. At the moment, only one molecule reached phase-3. This could suggest that research on these drugs is still preliminary. Of all, three studies reported promising results on Levetiracetam, Bryostatin 1 and Masitinib.
Topics: Alzheimer Disease; Benzamides; Bryostatins; Humans; Levetiracetam; Neuronal Plasticity; Piperidines; Pyridines; Thiazoles
PubMed: 36031056
DOI: 10.1016/j.arr.2022.101726 -
CNS Drugs Jan 2024Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was reported in patients with amnestic mild cognitive impairment, schizophrenia, and Alzheimer's disease. However, the specific cognitive domains affected and the degree of evidence supporting these effects remain unclear. This systematic review and meta-analysis aimed to explore the effects of levetiracetam on different cognitive domains.
METHODS
This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We defined our inclusion criteria for the systematic review as: (1) randomized placebo-controlled trials (RCTs) involving human subjects, (2) double-blinded RCTs, and (3) RCTs evaluating the quantitative differences in cognitive function between levetiracetam and placebo. We excluded: (1) non-RCT studies, (2) open-label studies, and (3) RCTs lacking cognitive assessments for either intervention. Two authors independently searched electronic databases, including PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until 2 July 2023. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Meta-analytic techniques were applied to examine the impact of levetiracetam on cognitive domain tests, with Hedges' g facilitating the comparison with placebo. The domains analyzed comprised multi-domain, executive function, processing speed, working memory, verbal memory/learning (verbal ML), visuospatial memory/learning (visuospatial ML), and language. We used odds ratios to compare the incidence of treatment-emergent adverse events between the groups, including somnolence, fatigue, dizziness, headache, irritability, and cognitive adverse events.
RESULTS
A random-effects model was utilized to perform a meta-analysis of 16 RCTs including 545 participants. Compared with a placebo, levetiracetam was associated with improved executive function [Hedges'g = - 0.390, 95% confidence interval (CI) = - 0.609 to - 0.172, p < 0.001, I = 24.0%]. Subgroup analysis showed that levetiracetam outperformed placebo in patients without epilepsy (Hedges' g = - 0.419, 95% CI = - 0.647 to - 0.191, p < 0.001, I = 26.2%). Meanwhile, low-dose levetiracetam showed a moderate favorable effect over placebo (Hedges' g = -0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). In patients without epilepsy, low-dose levetiracetam was associated with improved executive function (Hedges'g = - 0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). Concurrently, levetiracetam was associated with more frequent somnolence than a placebo (odds ratio = 4.654, 95% CI = 1.533 to 14.124, p = 0.007, I = 32.9%). Potential publication bias was observed in the executive function domain.
CONCLUSIONS
This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution.
Topics: Humans; Cognition; Cognitive Dysfunction; Epilepsy; Levetiracetam; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 38102532
DOI: 10.1007/s40263-023-01058-9 -
Journal of Evidence-based Medicine Nov 2020The effects of topical azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid (alpha-hydroxy acid) for acne are unclear. We aimed to assess the effects...
Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review.
OBJECTIVE
The effects of topical azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid (alpha-hydroxy acid) for acne are unclear. We aimed to assess the effects of these topical treatments by collecting randomized controlled trials.
METHODS
We searched The Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS up to May 2019. We also searched five trials registers. Two review authors independently extracted data and assessed risk of bias. Meta analyses were performed by using Review Manager 5 software.
RESULTS
We included a total of 49 trials involving 3880 participants. In terms of treatment response (measured using participants' global self-assessment of acne improvement, PGA), azelaic acid was probably less effective than benzoyl peroxide (RR = 0.82, 95% CI 0.72-0.95). However, there was probably little or no difference in PGA when comparing azelaic acid to tretinoin (RR = 0.94, 95% CI 0.78-1.14). There may be little or no difference when comparing salicylic acid to tretinoin (RR = 1.00, 95% CI 0.92-1.09). There were no studies measured PGA when evaluating nicotinamide. With respect to alpha-hydroxy acid, there may be no difference in PGA when comparing glycolic acid to salicylic-mandelic acid (RR = 1.06, 95% CI 0.88-1.26). We were uncertain about the effects of sulfur and zinc. Adverse events associated with these topical treatments were always mild and transient.
CONCLUSIONS
Moderate-quality evidence was available for azelaic acid and low- to very-low-quality evidence for other topical treatments. Risk of bias and imprecision limit our confidence in the evidence.
Topics: Acne Vulgaris; Administration, Cutaneous; Dermatologic Agents; Dicarboxylic Acids; Fruit; Glycolates; Humans; Niacinamide; Salicylic Acid; Sulfur; Treatment Outcome; Zinc
PubMed: 33034949
DOI: 10.1111/jebm.12411 -
Phytomedicine : International Journal... Dec 2022Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of... (Review)
Review
BACKGROUND
Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products.
METHODS
A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria.
RESULTS
Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin.
CONCLUSION
Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9‑methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, β-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.
Topics: Acetates; Acrolein; Animals; Arbutin; Bleaching Agents; Cell Line, Tumor; Curcumin; Emodin; Flavonoids; Ginsenosides; Glucosides; Humans; Hydroxybenzoates; Melanins; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Phytochemicals; Plant Extracts; Pterocarpans; Stilbenes; Transcription Factors
PubMed: 36126406
DOI: 10.1016/j.phymed.2022.154449 -
The Cochrane Database of Systematic... Aug 2021Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of... (Review)
Review
BACKGROUND
Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout.
SEARCH METHODS
We updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020.
SELECTION CRITERIA
We included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol. Two trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias. Moderate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16). More participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal. Moderate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded for indirectness and imprecision). Participants on lesinurad in the original study continued (CONT) on the same dose. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution; 43/65 in the lesinurad 400 mg CONT arm compared to 38/64 in the lesinurad 200 mg CONT arm had tophi resolution (RR 1.11, 95% CI 0.85 to 1.46). Lesinurad 400 mg plus febuxostat may result in no difference in adverse events; 57/65 in the lesinurad 400 mg CONT arm had an adverse event compared to 50/64 in lesinurad 200 mg CONT arm (RR 1.12, 95% CI 0.96 to 1.32). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events; 10/65 participants in the lesinurad 400 mg CONT arm withdrew due to an adverse event compared to 10/64 participants in the lesinurad 200 mg CONT arm (RR 0.98, 95% CI 0.44 to 2.20). Lesinurad 400 mg plus febuxostat may result in no difference in mean serum uric acid (sUA), which was 3 mg/dl in the lesinurad 400 mg CONT group compared to 3.9 mg/dl in the lesinurad 200 mg CONT group (mean difference -0.90, 95% CI -1.51 to -0.29). Participants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. Low-certainty evidence downgraded for indirectness and imprecision showed that lesinurad 400 mg (CROSS) may result in tophi resolution (17/34) compared to lesinurad 200 mg (CROSS) (14/33) (RR 1.18, 95% CI 0.70 to 1.98). Lesinurad 400 mg in combination with febuxostat may result in no difference in adverse events (33/34 in the lesinurad 400 mg CROSS arm compared to 27/33 in the lesinurad 200 mg (CROSS); RR 1.19, 95% CI 1.00 to 1.41). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events, 5/34 in the lesinurad 400 mg CROSS arm withdrew compared to 2/33 in the lesinurad 200 mg CROSS arm (RR 2.43, 95% CI 0.51 to 11.64). Lesinurad 400 mg plus febuxostat results in no difference in sUA (4.2 mg/dl in lesinurad 400 mg CROSS) compared to lesinurad 200 mg (3.8 mg/dl in lesinurad 200 mg CROSS), mean difference 0.40 mg/dl, 95% CI -0.75 to 1.55.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.
Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Polyethylene Glycols; Randomized Controlled Trials as Topic; Thioglycolates; Triazoles; Urate Oxidase
PubMed: 34379791
DOI: 10.1002/14651858.CD010069.pub3 -
The American Journal of Geriatric... Dec 2023The neuropsychiatric symptoms of frontotemporal dementia (FTD) have a profound negative impact on disease outcomes and care burden. Available pharmacotherapies might be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The neuropsychiatric symptoms of frontotemporal dementia (FTD) have a profound negative impact on disease outcomes and care burden. Available pharmacotherapies might be supported by small-scale randomized controlled trials (RCTs); however, clinical recommendations might not be conclusive.
METHODS
We systematically searched several databases from inception to April 30, 2022, for RCTs of drug therapy in patients with FTD and neuropsychiatric symptoms (primary outcome). Secondary outcomes included changes in caregiver stress, daily interactive activities, cognitive function, and acceptability (adverse event or dropout rates). The network meta-analysis (NMA) procedure was performed under the frequency model, showing effect sizes as standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (95% CIs).
RESULTS
Seven RCTs with 243 participants were included. Compared with placebo, high-dose oxytocin (72 international units) was associated with the greatest improvement in patients' neuropsychiatric symptoms (SMD = -1.17, 95% CIs = -2.25 to -0.08, z = -2.10, p = 0.035). Piracetam significantly worsened neuropsychiatric symptoms (SMD = 3.48, 95% CIs = 1.58 to 5.37, z = 3.60, p < 0.001) and caregiver stress (SMD = 2.40, 95% CIs = 0.80-4.01, z = 2.94, p = 0.003). Trazodone had significantly higher rates of adverse events (OR = 9.53, 95% CIs = 1.85-49.20, z = 2.69, p = 0.007). No pharmacological intervention significantly benefited cognitive function.
CONCLUSIONS
This study provides the first NMA for clinical recommendation to support the use of high-dose oxytocin and caution regarding the use of piracetam for neuropsychiatric symptoms in patients with FTD.
Topics: Humans; Frontotemporal Dementia; Network Meta-Analysis; Piracetam; Oxytocin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 37633762
DOI: 10.1016/j.jagp.2023.06.013 -
International Endodontic Journal Oct 2023Sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic acid (EDTA) and/or calcium hydroxide (Ca(OH) ) are commonly used during root canal treatment. Evaluation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic acid (EDTA) and/or calcium hydroxide (Ca(OH) ) are commonly used during root canal treatment. Evaluation of their effectiveness regarding clinical and patient-related outcomes requires further understanding.
OBJECTIVES
To assess the effectiveness of root canal irrigation and dressing for the treatment of teeth with apical periodontitis (AP).
METHODS
A search was conducted in the PubMed-MEDLINE, Scopus, EMBASE, Google scholar databases and available repositories, followed by hand searches, until July 2021. Eligibility criteria followed the a priori formulated Population, Intervention, Comparator, Outcomes, Timing, and Study design (PICOTS) framework. Clinical studies restricted to English language were included. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess the quality of included studies. Meta-analyses were performed using the fixed-effect model to obtain Risk Ratio (RR) and 95% Confidence Interval (CI), with sensitivity analysis. Overall quality of evidence of meta-analyses was assessed through the Grading of Recommendations Assessment, Development, and Evaluation tool.
RESULTS
The search identified 1357 records of which six fulfilled the inclusion criteria, providing data for 'irrigation' from 212 teeth and for 'dressings' from 438 teeth. Two studies reported no significant difference regarding the outcome 'pain at 7 days' using 2% chlorhexidine vs. 5.25% NaOCl and EDTA or after using different concentrations of NaOCl (1% vs. 5%). No significant difference was detected between different NaOCl concentrations regarding the reduction of AP. A meta-analysis was possible for the comparison of single-visit (SV) versus multiple-visits including the use of Ca(OH) demonstrating a significant effect in favour of SV (RR: 1.10; 95% CI: 1.03-1.19; p = .007; I = 0). RoB of included studies was moderate to low.
DISCUSSION
The use of Ca(OH) for the treatment of AP may not be beneficial. There is scarce or no evidence fulfilling the proposed PICOTS regarding irrigants and dressings.
CONCLUSIONS
There is moderate certainty that SV treatment is associated with better radiographic evidence of normal periodontal ligament space (strict criteria) compared with the use of Ca(OH) Reduction of AP is comparable after irrigation with 1% and 5% NaOCl, whereas postoperative pain at 7 days for the irrigants assessed is similar.
REGISTRATION
PROSPERO database CRD42021260271.
Topics: Humans; Dental Pulp Cavity; Edetic Acid; Root Canal Therapy; Periapical Periodontitis; Bandages; Root Canal Irrigants
PubMed: 35579074
DOI: 10.1111/iej.13777 -
European Journal of Clinical... Oct 2023The incidence of linezolid-induced thrombocytopenia (LIT) has been reported to vary widely across studies. We performed a meta-analysis to identify the risk factors for... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The incidence of linezolid-induced thrombocytopenia (LIT) has been reported to vary widely across studies. We performed a meta-analysis to identify the risk factors for thrombocytopenia among patients who received linezolid treatment.
METHODS
The PubMed, Embase and Cochrane Library databases were searched from inception to November 2022 to identify eligible studies. Data on the potential predictors of incidence in LIT were pooled using a random effects model. Sensitivity analyses were performed to determine the robustness of the results when significant heterogeneity was observed.
RESULTS
Forty observational studies involving 6454 patients treated with linezolid were included in the analysis. LIT was estimated to occur in 37% of patients. The following important factors were associated with the incidence of LIT: advanced age, body mass index, concurrent renal impairment or liver disease, abnormal laboratory parameters (including white blood cell count, serum creatinine, baseline platelet count, albumin, creatinine clearance rate, and estimated glomerular filtration rate), treatment duration and renal replacement therapy.
CONCLUSIONS
A variety of risk factors related to the occurrence of LIT were revealed in our analysis. Early identification of these factors could help patients improve clinical outcomes.
Topics: Humans; Linezolid; Thrombocytopenia; Platelet Count; Renal Insufficiency; Risk Factors; Anemia; Anti-Bacterial Agents
PubMed: 37578552
DOI: 10.1007/s00228-023-03542-z -
International Endodontic Journal Jun 2022The effects of ethylenediaminetetraacetic acid (EDTA) on regenerative endodontic procedures (REPs) are controversial, because, despite releasing growth factors from... (Review)
Review
BACKGROUND
The effects of ethylenediaminetetraacetic acid (EDTA) on regenerative endodontic procedures (REPs) are controversial, because, despite releasing growth factors from dentine, some studies show negative effects on cell behaviour.
OBJECTIVES
The aim of the study was to investigate the influence of the use of EDTA in REP on the growth factors' release, cell behaviour and tissue regeneration.
METHODS
A systematic search was conducted (PubMed/Medline, Scopus, Cochrane Library, Web of Science, Embase, OpenGrey and reference lists) up to February 2021. Only in vivo and in vitro studies evaluating the effects of EDTA on the biological factors of dentine, pulp/periapical tissues and cell behaviour were eligible. Studies without a control group or available full text were excluded. The growth factors' release was the primary outcome. Risk of bias in the in vitro and in vivo studies was performed according to Joanna Briggs Institute's Checklist and SYRCLE's RoB tool, respectively.
RESULTS
Of the 1848 articles retrieved, 36 were selected. Amongst these, 32 were in vitro, three animal studies and one with both models. The EDTA concentrations ranged from 3% to 15%, at different times. Regarding growth factors' release (17 studies), 15 studies found significant transforming growth factor (TGF)-β release after dentine conditioning with EDTA, and most found no influence on vascular endothelial growth factor release. Regarding cell behaviour (26 studies), eight studies showed no influence of EDTA-treated dentine on cell viability, whereas, five, nine and six studies showed higher cell migration, adhesion and differentiation respectively. No influence of EDTA conditioning was observed in animal studies. In vitro studies had a low risk of bias, whereas animal studies had high risk of bias. Meta-analysis was unfeasible.
DISCUSSION
This review found that EDTA increased TGF-β release and improved cell activity. However, well-designed histological analyses using immature teeth models are needed.
CONCLUSIONS
High-quality in vitro evidence suggests that EDTA-treated dentine positively influences TGF-β release, cell migration, attachment and differentiation; further research to evaluate its influence on tissue regeneration is necessary due to low methodological quality of the animal studies.
Topics: Dental Pulp; Edetic Acid; Regenerative Endodontics; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A
PubMed: 35305029
DOI: 10.1111/iej.13728 -
Journal of Clinical Pharmacology Mar 2024Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by... (Meta-Analysis)
Meta-Analysis Review
Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by performing a network meta-analysis of randomized and non-randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of "all muscle injuries." A random-effects model was used to perform a frequentist network meta-analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) "all muscle injuries" were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate-lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63-1.73), febuxostat (RR 1.10, 95%CI 0.71-1.70), lesinurad (RR 7.00, 95%CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55-7.03), and topiroxostat (RR 0.99, 95%CI 0.37-2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate-lowering drugs in the clinical setting.
Topics: Humans; Allopurinol; Febuxostat; Muscles; Network Meta-Analysis; Thioglycolates; Triazoles; Uric Acid; Controlled Clinical Trials as Topic
PubMed: 37840156
DOI: 10.1002/jcph.2369