Meta-analysis Of Clinical Trials Research Articles

Effect of gut microbiota modulation on sleep: a systematic review and meta-analysis of clinical trials.

A bidirectional relationship between gut microbiota (GM) and circadian rhythms has been proposed. The aim of this study was to analyze the efficacy of probiotic or prebiotic intervention on sleep quality and quantity. A systematic review and meta-analysis were conducted using the databases PubMed (MEDLINE), Embase, CINAHL, and Web of Science. Only randomized clinical trials written in English or Spanish were considered. The initial search resulted in 219 articles. Following the removal of duplicates and consideration of the selection criteria, 25 articles were selected for the systematic review and 18 articles for the meta-analysis. Microbiota modulation was not demonstrated to be associated with significant improvement in sleep quality in the present meta-analysis (P = 0.31). In terms of sleep duration, the meta-analysis found no improvement due to GM modulation (P = 0.43). The results of this meta-analysis indicate that there is still insufficient evidence to support the relationship between GM modulation and improved sleep quality. While several studies assume that including probiotics in the diet will undoubtedly improve sleep quality, more research is needed to fully understand this phenomenon. PROSPERO registration no. CRD42021245118.

Veklury®(remdesivir) formulations inhibit initial membrane-coupled events of SARS-CoV-2 infection due to their sulfobutylether-β-cyclodextrin content.

Despite its contradictory clinical performance, remdesivir (Veklury®) has a pivotal role in COVID-19 therapy. Possible contributions of the vehicle, sulfobutylether-β-cyclodextrin (SBECD) toVeklury® effects have been overlooked. The powder and solution formulations of Veklury® are treated equivalently despite their different vehicle content. Our objective was to study Veklury® effects on initial membrane-coupled events of SARS-CoV-2 infection focusing on the cholesterol depletion-mediated role of SBECD. Using time-correlated flow cytometry and quantitative three-dimensional confocal microscopy, we studied early molecular events of SARS-CoV-2-host cell membrane interactions. Veklury® and different cholesterol-depleting cyclodextrins (CDs) reduced binding of the spike receptor-binding domain (RBD) to ACE2 and spike trimer internalization for Wuhan-Hu-1, Delta and Omicron variants. Correlations of these effects with cholesterol-dependent changes in membrane structure and decreased lipid raft-dependent ACE2-TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector along with remdesivir due to its cholesterol-depleting potential. Veklury® solution inhibited RBD binding more efficiently due to its twice higher SBECD content. The CD-induced inhibitory effects were more prominent at lower RBD concentrations and in cells with lower endogenous ACE2 expression, indicating that the supportive CD actions can be even more pronounced during in vivo infection when viral load and ACE expression are typically low. Our findings call for the differentiation of Veklury® formulations in meta-analyses of clinical trials, potentially revealing neglected benefits of the solution formulation, and also raise the possibility of adjuvant cyclodextrin (CD) therapy, even at higher doses, in COVID-19.

Systematic Reviews on the Effectiveness of Multidisciplinary Rehabilitation

Systematic reviews and meta-analyses of clinical trials are considered to represent the highest level of scientific evidence in clinical medicine provided internationally accepted guidelines and checklists are followed.In systematic reviews and meta-analyses all clinical studies focussing a specific predefined clinical question are collected and evaluated. The results of systematic reviews strongly depend on the study protocol, including the exact definition of the population of interest, the therapeutic intervention under consideration and, last not least, the time period of observation. Moreover, evaluating multidisciplinary rehabilitation, its specifications with regard to therapeutic content, intensity and duration, supervision and general framework must be considered for correctly estimating determinants that control therapeutic success or failure.The range of potential risks of bias arising during planning, realization and publication of clinical studies is considerable and needs to be carefully estimated with regard to each single study included in meta-analysis.Taking together, the incremental scientific value of systematic reviews and meta-analyses cannot be taken for granted, but strongly depends on the methodological quality of the clinical studies being included as well as on the systematic process of the meta-analysis and the critical interpretation of the results.

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Efficacy and Safety of Fluvoxamine as Outpatient Treatment for Patients With Covid-19: A Systematic Review and Meta-analysis of Clinical Trials

Fluvoxamine may be beneficial for the management of coronavirus disease 2019 (Covid-19) because of its effect on the sigma-1 receptor. Available evidence from randomized clinical trials (RCTs) has shown conflicting results. This study sought to analyze the efficacy and safety of fluvoxamine as an outpatient treatment for Covid-19. Using specific keywords, we comprehensively go through the potential articles on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until February 1, 2023. We collected all published clinical trials on fluvoxamine and Covid-19. We were using Review Manager 5.4 to conduct statistical analysis. We include a total of 6 trials. Our pooled analysis revealed that fluvoxamine did not offer any significant benefit when compared with placebo in reducing the risk of clinical deterioration (risk ratio [RR] = 0.83; 95% CI: 0.65-1.06, P = 0.14, I2 = 29%), and hospitalization (RR = 0.80; 95% CI: 0.62-1.04, P = 0.09, I2 = 0%) of Covid-19 outpatients. The serious adverse events did not differ significantly between the 2 groups. This study indicates that although safe, fluvoxamine was not effective for outpatient treatment of Covid-19. Until more evidence can be obtained from larger RCTs, our study did not encourage the use of fluvoxamine as routine management for patients with Covid-19.

Effects of Probiotics on Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis of Clinical Trials.

Many studies have explored the efficacy of probiotics on autism spectrum disorder (ASD) in children, but there is no consensus on the curative effect. This systematic review and meta-analysis aimed to comprehensively investigate whether probiotics could improve behavioral symptoms in children with ASD. A systematic database search was conducted and a total of seven studies were included in the meta-analysis. We found a nonsignificant overall effect size of probiotics on behavioral symptoms in children with ASD (SMD = -0.24, 95% CI: -0.60 to 0.11, p = 0.18). However, a significant overall effect size was found in the subgroup of the probiotic blend (SMD = -0.42, 95% CI: -0.83 to -0.02, p = 0.04). Additionally, these studies provided limited evidence for the efficacy of probiotics due to their small sample sizes, a shorter intervention duration, different probiotics used, different scales used, and poor research quality. Thus, randomized, double-blind, and placebo-controlled studies following strict trial guidelines are needed to precisely demonstrate the therapeutic effects of probiotics on ASD in children.

Commentary on cardiovascular safety of DPP4Is: Focus on Alogliptin

DPP-4 inhibitors are present in the market for almost more than a decade. In Management of T2DM, DPP-4 inhibitors are established therapy option. The precise guidance for the pre- and post-approval and also CV safety of the newer antidiabetic agents was released by the USFDA in 2008. A neutral effect of Pooled safety analyses, as well as retrospective meta-analyses of clinical trials, have consistently demonstrated that DPP-4 inhibitors are not associated with any increase in cardiovascular adverse events, and have even pointed towards a risk reduction. The combination therapy of Alogliptin with other agents like metformin and pioglitazone have been shown to provide better and superior efficacy as compared to individual monotherapy. The hypoglycemic risk is less with Alogliptin. Alogliptin has been shown to be associated with less risk of hepatotoxicity, weight gain, and acute pancreatitis. Alogliptin does not worsen outcomes in patients with a history of heart failure (HF), neither does it increase rate of new hospitalization for heart failure (HF), as per the data from EXAMINE trial.

How Instructions, Learning, and Expectations Shape Pain and Neurobiological Responses.

Treatment outcomes are strongly influenced by expectations, as evidenced by the placebo effect. Meta-analyses of clinical trials reveal that placebo effects are strongest in pain, indicating that psychosocial factors directly influence pain. In this review, I focus on the neural and psychological mechanisms by which instructions, learning, and expectations shape subjective pain. I address new experimental designs that help researchers tease apart the impact of these distinct processes and evaluate the evidence regarding the neural mechanisms by which these cognitive factors shape subjective pain. Studies reveal that expectations modulate pain through parallel circuits that include both pain-specific and domain-general circuits such as those involved in affect and learning. I then review how expectations, learning, and verbal instructions impact clinical outcomes, including placebo analgesia and responses to pharmacological treatments, and discuss implications for future work.

Meta analysis of clinical trials of transcranial magnetic stimulation for chronic pelvic pain syndrome

In recent years, repeated transcranial magnetic stimulation has been used in clinical trials for the treatment of chronic pelvic pain syndrome, but its efficacy needs to be further verified. We aimed to summarize and discuss randomized controlled studies to provide clinical reference evidence for the future use of repeated transcranial magnetic stimulation in the treatment of chronic pelvic pain syndrome.

Effectiveness and Cost-Effectiveness of Team-Based Care for Hypertension: A Meta-Analysis and Simulation Study.

Team-based care (TBC), a team of ≥2 healthcare professionals working collaboratively toward a shared clinical goal, is a recommended strategy to manage blood pressure (BP). However, the most effective and cost-effective TBC strategy is unknown. A meta-analysis of clinical trials in US adults (aged ≥20 years) with uncontrolled hypertension (≥140/90 mm Hg) was performed to estimate the systolic BP reduction for TBC strategies versus usual care at 12 months. TBC strategies were stratified by the inclusion of a nonphysician team member who could titrate antihypertensive medications. The validated BP Control Model-Cardiovascular Disease Policy Model was used to project the expected BP reductions out to 10 years and simulate cardiovascular disease events, direct healthcare costs, quality-adjusted life years, and cost-effectiveness of TBC with physician and nonphysician titration. Among 19 studies comprising 5993 participants, the 12-month systolic BP change versus usual care was -5.0 (95% CI, -7.9 to -2.2) mm Hg for TBC with physician titration and -10.5 (-16.2 to -4.8) mm Hg for TBC with nonphysician titration. Relative to usual care at 10 years, TBC with nonphysician titration was estimated to cost $95 (95% uncertainty interval, -$563 to $664) more per patient and gain 0.022 (0.003-0.042) quality-adjusted life years, costing $4400/quality-adjusted life year gained. TBC with physician titration was estimated to cost more and gain fewer quality-adjusted life years than TBC with nonphysician titration. TBC with nonphysician titration yields superior hypertension outcomes compared with other strategies and is a cost-effective way to reduce hypertension-related morbidity and mortality in the United States.

Unrestricted weighted least squares represent medical research better than random effects in 67,308 Cochrane meta-analyses

ObjectivesTo evaluate how well meta-analysis mean estimators represent reported medical research and establish which meta-analysis method is better using widely accepted model selection measures: Akaike information criterion (AIC) and Bayesian information criterion (BIC). Study Design and SettingWe compiled 67,308 meta-analyses from the Cochrane Database of Systematic Reviews (CDSR) published between 1997 and 2020, collectively encompassing nearly 600,000 medical findings. We compared unrestricted weighted least squares (UWLS) vs. random effects (RE); fixed effect was also secondarily considered. ResultsThe probability that a randomly selected systematic review from the CDSR would favor UWLS over RE is 79.4% (95% confidence interval [CI95%]: 79.1; 79.7). The odds ratio that a Cochrane systematic review would substantially favor UWLS over RE is 9.33 (CI95%: 8.94; 9.73) using the conventional criterion that a difference in AIC (or BIC) of two or larger represents a ‘substantial’ improvement. UWLS's advantage over RE is most prominent in the presence of low heterogeneity. However, UWLS also has a notable advantage in high heterogeneity research, across different sizes of meta-analyses and types of outcomes. ConclusionUWLS frequently dominates RE in medical research, often substantially. Thus, the UWLS should be reported routinely in the meta-analysis of clinical trials.

Block Quality Of Dexmedetomidine-Based Spinal Anaesthesia In Orthopaedic Surgeries: A Meta-Analysis Of Clinical Trials

Background: Dexmedetomidine is used as an adjuvant to local anesthetic agents in spinal anesthesia and is believed to increase quality of sensory and motor blocks. Our aim was to assess the effects of dexmedetomidine as an adjunct on block quality of spinal anesthesia in orthopedic procedures.
 Methodology: A systematic review of randomized control trials was conducted to assess the effect of intrathecal dexmedetomidine added to local anesthetic agents on the block quality of spinal anesthesia in orthopedic surgeries. PubMed, Google scholar, and Medline databases were searched for randomized controlled clinical trials. Studies met our inclusion criteria, if they used intrathecal 5 µg dexmedetomidine as an additive to 2.5−3 ml (12.5−15 mg) bupivacaine or ropivacaine, and these were included in our meta-analysis.
 Results: Eight trials comprising 510 patients matched our inclusion criteria. Time to one sensory segment block regression (mean difference 139.72 min; 95% confidence interval (CI) 35.18−244.26; P = 0.009), two sensory segments block regression (mean difference 54.8 min; 95% CI [31.36−78.24]; P < 0.001), and Bromage score of zero (mean difference 93.66 min; 95%CI [30.20−157.12]; P = 0.004 ) were significantly prolonged in dexmedetomidine group. There were no significant differences between dexmedetomidine group and control group in duration of surgery (P = 0.33) or time till block reaches T10 dermatomal level (P = 0.30). Finally, time to reach Bromage score of III following injection was significantly shorter in dexmedetomidine group (mean difference 2.62 min; 95%CI [−5.12−−0.13]; P = 0.04).
 Conclusion: Dexmedetomidine was found to achieve extended motor and sensory block when needed, bearing in mind higher cost and potential side effects.
 Key words: Dexmedetomidine, Spinal Anesthesia, Orthopedic surgery, Meta-analysis.
 Citation: Alhajahjeh AA, Suleiman A, Almustafa HM, Mesmar TM, Hamdan A, Almustafa MM. Neuraxial block quality of dexmedetomidine-containing regimens in orthopedic surgeries: a meta-analysis. Anaesth. pain intensive care 2022;27(1):43−52.
 DOI: 10.35975/apic.v27i1.1876
 Received: May 22, 2022; Reviewed: August 14, 2022; Accepted: December 28, 2022

Cardiovascular and thromboembolic events associated with intense neoadjuvant androgen deprivation therapy followed by prostatectomy in patients with localized prostate cancer: A meta-analysis of clinical trials.

341 Background: Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients (pts). However, data regarding complications of the intense hormone therapy and surgical complications are scarce. The phase III trial PROTEUS testing ARSIs plus ADT added an amendment for thrombotic prophylaxis in the perioperative setting. We conducted a systematic review and meta-analysis to evaluate cardiovascular (CV) and thromboembolic (TE) adverse events (AEs) during neoadjuvant and perioperative intervals. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42022344104). A comprehensive search of PubMed, Embase, and Scopus databases and conference abstracts was performed from January 2010 to June 2022. Eligible studies include randomized and single-arm trials testing ARSIs prior to prostatectomy which adequately reported safety data regarding TE and CV AEs, peri-operative complications, and mortality during therapy. DerSimon and Laird method for random effects model was performed to estimate the pooled incidence (PI) of events with 95% confidence interval (95% CI). Heterogeneity was tested with I2 value. Results: 8 RCTs and 3 single-arm phase II trials comprising 674 pts were included (674 pts for CV and TE AEs and 499 for perioperative complications). Neoadjuvant regimen was classified as monotherapy with ADT (21 pts), ARSIs (100 pts), combination therapy with ADT + ARSI (338 pts), or ADT + ARSI + ARSI (215 pts). PI of all grade TE was 3.2% (95% CI, 1.6% – 4.8%, I2 = 0.0%, p = 0.92); TE incidence during perioperative period was 3.9% (95% CI, 1.6 – 6.1%, I2 = 0.0%, p = 0.67). 7 deaths were reported, with a PI of 3.0% (95% CI, 0.7–5.3%, I2 = 0.0%, p = 0.98). 2 of the mortality AE were considered treatment-related within perioperative interval. Incidence of hypertension grade 3-5 was 8.9% (95% CI, 5.2–12.7%, I2= 51.6%, p = 0.02). Incidence measures per regimen are described. Conclusions: CV and TE events associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 3.9% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting. [Table: see text]

Effects of Resistance Training on Pain Control and Physical Function in Older Adults With Low Back Pain: A Systematic Review With Meta-analysis.

Low back pain (LBP) has a high prevalence in older adults and is associated with elevated health care costs. This systematic review and meta-analysis examines the effects of progressive resistance training (PRT) interventions on physical function (PF) and pain control in community-dwelling older adults with chronic LBP. A meta-analysis applying the quality effect method was performed by calculating the effect sizes (ESs) using the Cohen d with a 95% CI. A subgroup analysis was performed according to the participant and intervention characteristics. The statistical significance of differences between subgroups was calculated using a Z -test. Study bias was estimated using the version 2 of the Cochrane risk of bias tool for randomized trials (RoB 2.0) and quality of evidence (Qi) index. Small study effect/publication bias was estimated using the Doi plot and Luis Furuya-Kanamori (LFK) index. The systematic search was conducted in major databases for clinical trials published between January 1, 1990, and January 9, 2021. The inclusion criteria were articles that (1) were peer-reviewed; (2) had participants' mean age of more than 60 years; (3) studied PRT interventions; (4) had participants with LBP; (5) measured LBP or PF outcomes; (6) measured PF in terms of functionality; (7) were randomized controlled trials; (8) and non-randomized controlled trials. The exclusion criteria were (1) articles not written in English, (2) nonexperimental studies, and (3) repeated publications. Twenty-one studies were included (n = 1661). Clear improvements were found in PF (ES = 0.32 [95% CI, 0.05-0.58]; I2 = 75.1%; P < .001), but results on LBP decrease were inconclusive (ES = 0.24 [95% CI, -0.05 to 1.10]; I2 = 75.7%; P < .001). The overall evidence of this aggregated data meta-analysis of clinical trials is level C+. Main limitations are the use of aggregated data and the large heterogeneity between studies. The Qi of this meta-analysis is level I (C+). We concluded that PRT interventions are useful for PF improvement in older adults with generalized LBP, LBP not arising from lumbar spinal stenosis, and having body mass index less than 27. In older adults with LBP not arising from lumbar spine stenosis, PRT interventions also decrease LBP. Interventions should have a frequency of at least 3 sessions per week. In addition, at a lower level of evidence IV (C+), we recommend that interventions with a duration of more than 12 weeks should be considered, whenever possible.

Effectiveness and Safety of Different Treatment Modalities for Patients Older Than 60 Years with Distal Radius Fracture: A Network Meta-Analysis of Clinical Trials.

We performed a network meta-analysis (NMA) of randomized clinical trials (RCTs). Eight databases were searched. The eligibility criteria for selecting studies were RCTs that compared different treatment modalities (surgical or nonoperative) in patients older than 60 years with displaced or unstable intra-articular and/or extra-articular DRFs. Twenty-three RCTs met the eligibility criteria (2020 patients). For indirect comparisons, the main findings of the NMA were in volar locking plate (VLP) versus cast immobilization, with the mean differences for the patient-rated wrist evaluation (PRWE) questionnaire at -4.45 points (p < 0.05) and grip strength at 6.11% (p < 0.05). Additionally, VLP showed a lower risk ratio (RR) of minor complications than dorsal plate fixation (RR: 0.02) and bridging external fixation (RR: 0.25). Conversely, VLP and dorsal plate fixation showed higher rates of major complications. Compared with other treatment modalities, VLP showed statistically significant differences for some functional outcomes; however, most differences were not clinically relevant. For complications, although most differences were not statistically significant, VLP was the treatment modality that reported the lowest rate of minor and overall complications but also showed one of the highest rates of major complications in these patients. PROSPERO Registration: CRD42022315562.

Efficacy of therapies targeting TGF-β in solid tumors: a systematic review and meta-analysis of clinical trials.

Aims: A comprehensive meta-analysis was conducted to explore the efficacy of TGF-β blockade therapies in solid tumors. Patients & methods: Results of overall survival (OS), progression-free survival (PFS), time to progression (TTP) and overall response rate (ORR) with their 95% CI were calculated. Also, subgroup analyses were conducted according to the categories of TGF-β blocker alone or combined with chemotherapy or radiotherapy. Results: Overall OS, PFS, TTPand ORR were 10.5months (95% CI: 7.76-13.25), 2.54months (95% CI: 1.66-3.43), 4.69months (95% CI: 3.18-6.21) and 0.83% (95% CI: 0.82-0.85), respectively. Conclusion: Collectively, TGF-β blockade combined with chemotherapy or radiotherapy showed more favorable clinical outcomes than monotherapy using TGF-β blockade.

Residual Bone Height and New Bone Formation after Maxillary Sinus Augmentation Procedure Using Biomaterials: A Network Meta-Analysis of Clinical Trials.

Different factors may affect new bone formation following maxillary sinus floor augmentation for the rehabilitation of posterior edentulous maxilla. The purpose of this study was to determine the influence of residual bone height (RBH) on new bone formation after lateral sinus augmentation utilizing different biomaterials, through a network meta-analysis (NMA). PUBMED, Scopus, and Web of Science electronic databases were searched until 31 December 2022 to obtain relevant articles. A hand search was also conducted. Randomised controlled studies on maxillary sinus augmentation comparing different grafting materials in patients with atrophic posterior maxilla, in need of prosthetic rehabilitation, were included. The risk of bias was assessed following the guidelines of the Cochrane Collaboration. The primary outcome was new bone formation (NBF), assessed histomorphometrically. The statistical analysis was performed by splitting the data according to RBH (<4 mm and ≥4 mm). A total of 67 studies were eligible for conducting NMA. Overall, in the included studies, 1955 patients were treated and 2405 sinus augmentation procedures were performed. The biomaterials used were grouped into: autogenous bone (Auto), xenografts (XG), allografts (AG), alloplasts (AP), bioactive agents (Bio), hyaluronic acid (HA), and combinations of these. An inconsistency factor (IF) seen in the entire loop of the XG, AP, and Bio+AP was found to be statistically significant. The highest-ranked biomaterials for the <4 mm RBH outcome were XG+AG, XG+AP, and Auto. Similarly, the surface under the cumulative ranking curve (SUCRA) of biomaterials for ≥4 mm RBH was Auto, Bio+XG, and XG+Auto. There is no grafting biomaterial that is consistently performing better than others. The performance of the materials in terms of NBF may depend on the RBH. While choosing a biomaterial, practitioners should consider both patient-specific aspects and sinus clinical characteristics.

Efficacy and safety of herbal medicine on dementia and cognitive function: An umbrella review of systematic reviews and meta-analysis.

This study aims to summarize the effects of herbs on dementia and assess the strength of evidence. Six international and local databases were searched from inception to October 2021 for systematic reviews and meta-analyses of clinical trials investigated the effects of herbal medicine on dementia or cognitive function. Two researchers independently extracted data, assessed the methodological quality, and rated the credibility of evidence according to established criteria. Thirty-seven articles evaluating 13 herbal medicines were included. Of these, 65% were rated critically low using AMSTAR2. Of 90 unique outcomes, 41 (45.6%) were statistically significant based on random effects model (p ≤ .05). Only 3 herbs were supported by suggestive evidence whereas the others were supported by weak evidence. The suggestive evidence supported benefits of Chinese herbal medicine (CHM) plus pharmacotherapy (WMD:1.84; 95% CI: 1.34, 2.35) and Vinpocetine (WMD: -0.94; 95%CI: -1.50, -0.38) on improving cognitive function assessing by Montreal Cognitive Assessment and Syndrom-Kurz-Test, respectively. Moreover, suggestive evidence supported benefit of Huperzia serrata on improving Activities of Daily Living (WMD:-7.18; 95%CI: -9.12, -5.23). No SAE was reported. In conclusion, several herbs were used for improving dementia and cognitive function but recent evidence were limited by the small sample size and poor methodological quality. Therefore, further large and well-designed studies are needed to support the evidence.

Towards Automated Meta-Analysis of Clinical Trials: An Overview

Background: Nowadays, much research deals with the application of the automated meta-analysis of clinical trials through appropriate machine learning tools to extract the results that can then be applied in daily clinical practice. Methods: The author performed a systematic search of the literature from 27 September 2022–22 November 2022 in PUBMED, in the first 6 pages of Google Scholar and in the online catalog, the Systematic Review Toolbox. Moreover, a second search of the literature was performed from 7 January 2023–20 January 2023 in the first 10 pages of Google Scholar and in the Semantic Google Scholar. Results: 38 approaches in 39 articles met the criteria and were included in this overview. These articles describe in detail machine learning approaches, methods, and tools that have been or can potentially be applied to the meta-analysis of clinical trials. Nevertheless, while the other tasks of a systematic review have significantly developed, the automation of meta-analyses is still far from being able to significantly support and facilitate the work of researchers, freeing them from manual, difficult and time-consuming work. Conclusions: The evaluation of automated meta-analysis results is presented in some studies. Their approaches show positive and promising results.

Effectiveness of clown therapy on procedural pain in children with cerebral palsy. A meta-analysis

BACKGROUND:Nearly 10% of the pain that affects children with cerebral palsy (CP) results from a medical procedure. Clown therapy is a popular distraction technique to reduce pain; some systematic reviews evaluate the efficacy of this intervention in the pediatric setting, but none on children with CP. AIM:To evaluate the effect of clown therapy on procedural pain in children with CP. METHODS:Systematic review with meta-analysis of clinical trials with control group. Retrieval of studies by querying biomedical databases, online resources and trial registers. Clown therapy was compared with standard care. The primary outcome was the pain level after surgery. The risk of bias was assessed with RoB 2. Effect size was calculated with a random effects model. RESULTS:Three studies with 164 patients were included. The risk of bias is high for two studies and raises some concerns for one. All studies analyzed the effect of clown therapy on procedural pain after botulinum toxin injection. There was a statistically non significant reduction in pain in the intervention group compared to the control group (SMD: -0.20, 95% CI: -0.56, 0.17). The heterogeneity between studies is high. CONCLUSION:Clown therapy for procedural pain from botulinum toxin injections in children with CP seems effective but the methodological limitations of the studies do not allow a definitive judgment. There is a lack of studies evaluating the effect of the intervention on other procedures that children with CP undergo periodically.