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The Cochrane Database of Systematic... Oct 2023This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the... (Review)
Review
BACKGROUND
This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the population. Pharmacological treatment remains the first choice to control epilepsy. However, up to 30% of people do not respond to drug treatment, and therefore do not achieve seizure remission. Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy.
OBJECTIVES
To assess the efficacy and tolerability of immunomodulatory interventions on seizures, adverse effect profile, cognition, and quality of life, compared to placebo controls, when used as additional therapy for focal epilepsy in children and adults.
SEARCH METHODS
For the latest update, we searched the following databases on 11 November 2021: Cochrane Register of Studies (CRS Web) and Medline (Ovid) 1946 to 10 November 2021. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. We placed no language restrictions. We reviewed the bibliographies of retrieved studies to search for additional reports of relevant studies.
SELECTION CRITERIA
Randomised placebo-controlled trials of add-on immunomodulatory drug interventions, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. Eligible participants were children (aged over 2 years) and adults with focal epilepsy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration. We assessed the following outcomes. 1. 50% or greater reduction in seizure frequency. 2. Seizure freedom. 3. Treatment withdrawal for any reason. 4. Quality of life. 5.
ADVERSE EFFECTS
We used an intention-to-treat (ITT) population for all primary analyses, and we presented results as risk ratios (RRs) with 95% confidence intervals (95% Cl).
MAIN RESULTS
We included three randomised, double-blind, placebo-controlled trials on a total of 172 participants. All trials included children and adults over two years of age with focal epilepsy. Treatment phases lasted six weeks and follow-up from six weeks to six months. One of the three included trials described an adequate method of concealment of randomisation, whilst the other two trials were rated as having an unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in all three trials. All analyses were by ITT. One trial was sponsored by the manufacturer of an immunomodulatory agent and therefore was at high risk of funding bias. Immunomodulatory interventions were significantly more effective than placebo in reducing seizure frequency (risk ratio (RR) 2.30, 95% confidence interval (CI) 1.15 to 4.60; 3 studies, 172 participants; moderate-certainty evidence). For treatment withdrawal, there was insufficient evidence to conclude that people were more likely to discontinue immunomodulatory intervention than placebo (RR 1.04, 95% CI 0.28 to 3.80; 3 studies, 172 participants; low-certainty evidence). The RR for adverse effects was 1.16 (95% CI 0.84 to 1.59; 1 study, 66 participants; low-certainty evidence). Certain adverse effects such as dizziness, headache, fatigue, and gastrointestinal disorders were more often associated with immunomodulatory interventions. There were little to no data on cognitive effects and quality of life. No important heterogeneity between studies was found for any of the outcomes. We judged the overall certainty of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals.
AUTHORS' CONCLUSIONS
Immunomodulatory interventions as add-on treatment for children and adults with focal epilepsy appear to be effective in reducing seizure frequency. It is not possible to draw any conclusions about the tolerability of these agents in children and adults with epilepsy. Further randomised controlled trials are needed.
Topics: Adult; Child; Humans; Aged; Anticonvulsants; Quality of Life; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Seizures; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic
PubMed: 37842826
DOI: 10.1002/14651858.CD009945.pub3 -
European Journal of Clinical... Feb 2024To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal... (Meta-Analysis)
Meta-Analysis
PURPOSE
To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI).
METHODS
We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes.
RESULTS
A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups.
CONCLUSION
This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.
Topics: Humans; Ketamine; Suicidal Ideation; Depression; Administration, Intranasal; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 38117332
DOI: 10.1007/s00228-023-03605-1 -
International Journal of Sport... Nov 2022The aim of this study was to conduct a systematic review and meta-analysis of the effects of short-term creatine supplementation on repeated sprint ability. Fourteen... (Meta-Analysis)
Meta-Analysis
The aim of this study was to conduct a systematic review and meta-analysis of the effects of short-term creatine supplementation on repeated sprint ability. Fourteen studies met the inclusion criteria of adopting double-blind randomized placebo-controlled designs in which participants (age: 18-60 years) completed a repeated sprint test (number of sprints: 4 < n ≤ 20; sprint duration: ≤10 s; recovery duration: ≤90 s) before and after supplementing with creatine or placebo for 3-7 days in a dose of ∼20 g/day. No exclusion restrictions were placed on the mode of exercise. Meta-analyses were completed using random-effects models, with effects on measures of peak power output, mean power output, and fatigue (performance decline) during each repeated sprint test presented as standardized mean difference (δ), and with effects on body mass and posttest blood lactate concentration presented as raw mean difference (D). Relative to placebo, creatine resulted in a significant increase in body mass (D = 0.79 kg; p < .00001) and mean power output (δ = 0.61; p = .002). However, there was no effect of creatine on measures of peak power (δ = 0.41; p = .10), fatigue (δ = 0.08; p = .61), or posttest blood lactate concentration (D = 0.22 L/min; p = .60). In conclusion, creatine supplementation may increase mean power output during repeated sprint tests, although the absence of corresponding effects on peak power and fatigue means that more research, with measurements of intramuscular creatine content, is necessary to confirm.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Creatine; Exercise Test; Lactic Acid; Fatigue; Dietary Supplements; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36041731
DOI: 10.1123/ijsnem.2022-0072 -
American Journal of Obstetrics &... Jul 2022This study aimed to assess the changes in the acceptance rates between double- and single-blind peer review systems. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to assess the changes in the acceptance rates between double- and single-blind peer review systems.
DATA SOURCES
The search was conducted using Medline, Embase, and ClinicalTrials.gov databases as electronic databases from the inception of each database to June 2021. No restriction for language or geographic location was applied.
STUDY ELIGIBILITY CRITERIA
The selection criteria included randomized controlled trials comparing the double-blind peer review process vs the single-blind peer review process.
METHODS
The primary outcome was manuscripts acceptance rates. The summary measures were reported as relative risk with 95% confidence intervals using the random-effects model meta-analyses. Between-study heterogeneity was explored using the I statistic.
RESULTS
A total of 11 randomized controlled trials, including 3477 reviewers and 3784 manuscripts, were identified. The manuscript acceptance rates were significantly lower in the double-blind (200/1413 [14.2%]) peer review processes than in the single-blind (194/1019 [19.0%]) peer review processes (relative risk, 0.82; 95% confidence interval, 0.70-0.97; n=5 randomized controlled trials). Only 1 randomized controlled trial assessed the authors' and/or institutions' prestige on acceptance rates with results not statistically significant. Only 2 randomized controlled trials assessed the manuscript origin (US or non-US) effect on acceptance rates with results not statistically significant. Gender of the manuscript authors was assessed by only 1 randomized controlled trial, and although blinding or not female author names made no statistical difference, blinding of male author names was associated with a significant decrease in acceptance rate (139/1266 [11.0%] vs 190/1266 [15.0%]; relative risk, 0.73; 95% confidence interval, 0.59-0.90). Double-blind peer review was deemed successful by reviewers in only approximately 52% of the cases (n=5 randomized controlled trials).
CONCLUSION
The double-blind peer review process seemed to be associated with an 18% lower manuscript acceptance rate than the single-blind peer review process. However, given the large heterogeneity among the included studies, more research is needed to confirm these findings and elucidate those factors that can affect the acceptance rate in double- and single-blind peer reviews.
Topics: Double-Blind Method; Humans; Male; Peer Review; Randomized Controlled Trials as Topic; Single-Blind Method
PubMed: 35430413
DOI: 10.1016/j.ajogmf.2022.100645 -
Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis.Archives of Osteoporosis May 2023Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis medication, was stopped in the Long-term Odanacatib Fracture Trial (LOFT) phase III study because it increased the risk of stroke. Herein, we conducted a systematic review and meta-analysis to further assess the efficacy and safety of ODN in osteoporosis treatment.
METHODS
We searched the PubMed, EMBASE, Cochrane Library, and Web of Science, using the core search terms "osteoporosis" and "odanacatib." The primary outcomes were the percentage change in markers of bone turnover and bone formation as well as that in the bone mineral density (BMD) of the lumbar spine, hip, femoral neck, and greater trochanter. The secondary outcome was the risk of adverse events (AEs), used to explore the safety of ODN.
RESULTS
Ten articles-all double-blinded, randomized, placebo-controlled trials-were included. All trials were considered to be of high quality if they met the inclusion and exclusion criteria. We found that ODN increases BMD in the lumbar spine, total hip, and femoral neck, whereas it decreases the concentration of serum C-telopeptides of type I collagen (sCTx) and urinary N-telopeptide/creatinine ratio (uNTx/Cr). We found no significant differences in total, drug-related, serious, or skin AEs between the ODN and control groups. However, significant differences in fracture and stroke AEs were found between the ODN and control groups.
CONCLUSION
ODN is an appealing long-term osteoporosis treatment method; however, further research should focus on the potential increased risk of fracture and stroke.
Topics: Aged; Female; Middle Aged; Humans; Bone Density Conservation Agents; Osteoporosis, Postmenopausal; Double-Blind Method; Osteoporosis; Bone Density; Fractures, Bone; Stroke
PubMed: 37169994
DOI: 10.1007/s11657-023-01261-7 -
Journal of the Medical Association of... Jul 2016To determine the efficacy of chicken essence for improving cognitive performance. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determine the efficacy of chicken essence for improving cognitive performance.
MATERIAL AND METHOD
English language database including Embase, Medline, PsychINFO and Global Health (up to May 2014) were searched. Inclusion criteria were randomized double-blind controlled studies (RCT) or cross-over studies comparing chicken essence with placebo.
RESULTS
Four trials were included. Three studies measured cognitive performance, while the remaining study assessed cognitive performance after fatigue-inducing tasks. When compared to placebo, chicken essence improved arithmetic (SMD -1.23, 95% CI -2.51 to -0.31) and memory (SMD -3.94, 95% CI -4.59 to -3.29). There were no ascertainable positive effects on attention/concentration (SMD -1.55, 95% CI -4.77 to 1.67), anti-fatigue (SMD 1.20, 95% CI 0.53 to 1.88), and recovery from mental fatigue (SMD -0.38, 95% CI -1.0 to 0.25). However, the levels of evidence with respect to each cognitive domain was rated as ‘very low’ using the GRADE system because of low sample size, inconsistency and high risk of bias.
CONCLUSION
There are few trials examining the efficacy of chicken essence to cognitive performance. Furthermore, the level of evidence was very low. Using it for this indication is not suggested at present. Additional high quality RCT designs are needed to arrive at a stronger conclusion.
Topics: Affect; Animals; Chickens; Cognition; Cognitive Dysfunction; Cooking; Dietary Supplements; Fatigue; Humans; Poultry Products
PubMed: 29919993
DOI: No ID Found -
Schizophrenia Bulletin Jul 2023Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND HYPOTHESIS
Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention research. We sought to systematically determine the incidence and persistence of PEs in the general population.
STUDY DESIGN
A double-blind search of databases (Embase, Pubmed PMC, Psychinfo, Medline, and Web of Science) from inception to January 2023 and data extraction, were conducted. Study quality was assessed using the NIH assessment tool. Random effects models were conducted to calculate pooled incidence rate per person-year and proportion of persistent PEs per year. Age and study design were all examined using subgroup analyses. Demographic, risk factors, and outcomes for incidence and persistence of PEs were reported in a narrative synthesis.
STUDY RESULTS
Using a double-blind screening method for abstract (k = 5763) and full text (k = 250) were screened. In total 91 samples from 71 studies were included, of which 39 were included in a meta-analysis (incidence: k = 17, n = 56 089; persistence: k = 22, n = 81 847). Incidence rate was 0.023 per person-year (95% CI [0.0129;0.0322]). That is, for every 100 people, 2 reported first onset PEs in a year. This was highest in adolescence at 5 per 100(13-17 years). The pooled persistence rate for PEs was 31.0% (95% CI [26.65,35.35]) This was highest in adolescence at 35.8%. Cannabis was particularly associated with incidence of PEs, and persistence of PEs were associated with multiple mental disorders.
CONCLUSIONS
Each year incidence of PEs is 2 of every 100 people, and persists each year in 31% of cases, this risk is highest in adolescents.
Topics: Adolescent; Humans; Psychotic Disorders; Incidence; Mental Disorders; Risk Factors; Randomized Controlled Trials as Topic
PubMed: 37402250
DOI: 10.1093/schbul/sbad056 -
Journal of Orthopaedic Surgery and... Apr 2016Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and... (Review)
Review
Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.
Topics: Cartilage, Articular; Humans; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Regeneration; Tissue and Organ Harvesting
PubMed: 27072345
DOI: 10.1186/s13018-016-0378-x -
Pediatric Dermatology 2023Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored the effectiveness and safety of dupilumab in adults with AD. However, the underlying mechanisms of AD can vary among different age groups, emphasizing the need for separate investigation into the use of dupilumab in children and adolescents with AD.
OBJECTIVE
To evaluate the efficacy and safety of dupilumab in children and adolescents with AD based on evidence from clinical trials and observational studies.
METHODS
The process of meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines.
RESULTS
Seven clinical trials and 11 observational studies involving 1275 children and adolescents with AD were eligible for quantitative analysis. Overall, the pooled percentages of eczema area and severity index (EASI) 50, EASI 75, EASI 90, EASI 100, and investigator's global assessment (IGA) 0/1 were 72.9% (95% CI: 61.6%-81.9%), 57.4% (48.1%-66.2%), 31.3% (24.0%-39.7%), 29.7% (23.3%-37.0%), and 35.2% (29.3%-41.5%). With prolonged treatment time, an increase was seen in the pooled rate of EASI response, indicating that dupilumab may provide sustained benefits for children and adolescents over the long term. The reported adverse events were primarily mild and manageable, with an overall incidence rate of 7.2% across clinical trials and 7.6% across observational studies.
CONCLUSION
Dupilumab was an effective and safe treatment option for children and adolescents with AD, with positive results observed from long-term use and an acceptable safety profile. More long-term, high-quality, controlled studies in different regions are needed for further verification.
Topics: Adult; Humans; Adolescent; Child; Dermatitis, Atopic; Injections, Subcutaneous; Treatment Outcome; Severity of Illness Index; Double-Blind Method
PubMed: 37529963
DOI: 10.1111/pde.15398 -
The impact of double-blind peer review on gender bias in scientific publishing: a systematic review.American Journal of Obstetrics and... Jul 2022Gender-based bias during journal peer review can lead to publication biases and perpetuate gender inequality in science. Double-blind peer review, in which the names of... (Review)
Review
OBJECTIVE
Gender-based bias during journal peer review can lead to publication biases and perpetuate gender inequality in science. Double-blind peer review, in which the names of authors and reviewers are masked, may present an opportunity for scientific literature to increase equity and reduce gender-based biases. This systematic review of studies evaluates the impact of double-blind vs single-blind peer review on the publication rates by perceived author gender.
DATA SOURCES
The PubMed, Embase, Web of Science, and Scopus electronic databases were searched using the terms "blind," "peer review," "gender," "woman," and "author." All published literature in the English language from database inception through 2020 was queried.
STUDY ELIGIBILITY CRITERIA
Prospective experimental and observational studies comparing double-blind to single-blind peer review strategies examining impact on publication decisions by author gender were included.
STUDY APPRAISAL AND SYNTHESIS METHODS
The extracted data were primarily descriptive and included information on study design, sample size, primary outcome, major findings, and scientific discipline. The studies were characterized on the basis of design and whether the results demonstrated an impact of double-blind peer review on review scores and publication decision by perceived author gender. This study was registered with the International Prospective Register of Systematic Reviews or PROSPERO.
RESULTS
In total, 1717 articles were identified, 123 were reviewed, and 8 were included, encompassing 5 prospective experimental studies and 3 observational studies. Four studies demonstrated a difference in the acceptance rate or review score on the basis of perceived author gender, whereas the other 4 studies demonstrated no differences when the author gender was anonymized.
CONCLUSION
Studies evaluating the impact of double-blind peer review on author gender demonstrate mixed results, but there is reasonable evidence that gender bias may exist in scientific publishing and that double-blinding can mitigate its impact. Further evaluation of the processes in place to create the body of evidence that clinicians and researchers rely on is essential to reduce bias, particularly in female-majority fields such as obstetrics and gynecology.
Topics: Female; Humans; Male; Double-Blind Method; Peer Review; Publishing; Sexism; Single-Blind Method
PubMed: 35120887
DOI: 10.1016/j.ajog.2022.01.030