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The International Journal of... Dec 2022Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.
METHODS
We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.
RESULTS
Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.
CONCLUSIONS
Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.
Topics: Humans; Vortioxetine; Depressive Disorder, Major; Piperazines; Sulfides; Randomized Controlled Trials as Topic; Cognitive Dysfunction; Treatment Outcome; Double-Blind Method
PubMed: 35981958
DOI: 10.1093/ijnp/pyac054 -
The Cochrane Database of Systematic... Aug 2022This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder,... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs.
OBJECTIVES
To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 13 July 2021) on 15 July 2021. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.
SELECTION CRITERIA
We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, a third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life.
MAIN RESULTS
We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data. Only one study reported the outcome of 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate whilst another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants. We assessed the evidence for all outcomes using GRADE and rated the evidence as very low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update.
AUTHORS' CONCLUSIONS
In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.
Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsies, Partial; Felbamate; Humans; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Single-Blind Method
PubMed: 35914010
DOI: 10.1002/14651858.CD008295.pub6 -
Journal of Clinical Hypertension... Aug 2022Hypertension is a prevalent risk factor for cardiovascular disease. Angiotensin II receptor blockers are widely prescribed to patients with hypertension, while new drugs... (Meta-Analysis)
Meta-Analysis
Hypertension is a prevalent risk factor for cardiovascular disease. Angiotensin II receptor blockers are widely prescribed to patients with hypertension, while new drugs are continuously developed. However, data on comparative efficacy and safety of novel agents, such as fimasartan, are scarce. Here, we aimed to collect clinical evidence on different angiotensin II receptor blockers using a network meta-analysis. Randomized controlled trials whose follow-up time is within 12 weeks were identified from eight databases via a systematic literature review. Of the 7909 possibly relevant studies, 61 studies with 14,249 adult patients were included in the analysis. These studies were further subjected to quality appraisal using Cochran's Risk of Bias, and sitting systolic blood pressure was considered the primary endpoint. A Bayesian random effect generalized linear model was used for the network meta-analysis, and the treatment rank probability was determined. Olmesartan (standardized mean difference -0.987 [-1.29, -0.729]) and fimasartan (standardized mean difference -0.966 [-1.21, -0.745]) showed the highest rank probabilities (37% and 35%) in the 4-week group, considering the primary endpoint. Furthermore, the odds ratio of adverse events for all agents did not differ significantly from that of the placebo. The treatment rank of angiotensin II receptor blockers varied depending on the outcome type and follow-up period considerably. Fimasartan rapidly lowered blood pressure in 4 weeks, which was further maintained until 12 weeks, indicating its competent efficacy and tolerability. Our findings may help medical practitioners and patients to select the best angiotensin II receptor blocker against hypertension.
Topics: Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Bayes Theorem; Biphenyl Compounds; Blood Pressure; Double-Blind Method; Humans; Hypertension; Network Meta-Analysis; Pyrimidines; Randomized Controlled Trials as Topic; Tetrazoles
PubMed: 35819029
DOI: 10.1111/jch.14536 -
Acta Dermato-venereologica Aug 2022The aim of this study was to compare the efficacies of systemic treatments with dupilumab, tralokinumab and Janus kinase inhibitors for moderate-to-severe atopic... (Meta-Analysis)
Meta-Analysis
The aim of this study was to compare the efficacies of systemic treatments with dupilumab, tralokinumab and Janus kinase inhibitors for moderate-to-severe atopic dermatitis. A systematic review following Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All randomized controlled trials investigating the efficacy of systemic treatments for moderate-to-severe atopic dermatitis in adults were included. Primary outcomes were the proportion of patients with atopic dermatitis achieving 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI) score after dupilumab, tralokinumab or Janus kinase inhibitors. Nineteen studies totalling 6,444 patients were included. In monotherapy studies, upadacitinib 30 mg once daily had the numerically highest efficacy regarding EASI-50, EASI-75 and EASI-90. In combination therapy studies with topical corticosteroids, dupilumab 300 mg once every other week had highest efficacy regarding EASI-50, and abrocitinib 200 mg once daily had the highest score regarding EASI-75 and EASI-90. Analysis provided evidence that dupilumab, tralokinumab and Janus kinase inhibitors all had an acceptable efficacy profile and resulted in clinically relevant improvements in EASI score. Furthermore, upadacitinib and abrocitinib seem to have great potential to treat patients with atopic dermatitis. However, further studies are needed to determine the long-term efficacy of Janus kinase inhibitors in adults with moderate-to-severe atopic dermatitis.
Topics: Adult; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Dermatitis, Atopic; Double-Blind Method; Humans; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 35818735
DOI: 10.2340/actadv.v102.2075 -
The Journal of Headache and Pain Jul 2022In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).
METHODS
Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.
RESULTS
Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.
CONCLUSIONS
The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.
Topics: Adult; Benzamides; Double-Blind Method; Female; Humans; Middle Aged; Migraine Disorders; Network Meta-Analysis; Piperidines; Pyridines; Pyrroles; Randomized Controlled Trials as Topic
PubMed: 35790906
DOI: 10.1186/s10194-022-01440-w -
Translational Psychiatry Jun 2022It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive-compulsive and related disorders. Thus, in an attempt to answer... (Meta-Analysis)
Meta-Analysis
It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive-compulsive and related disorders. Thus, in an attempt to answer this clinical question, we performed a systematic review and a random-effects meta-analysis of double-blind, randomized, placebo-controlled trials. The primary outcome was change in overall symptoms as measured using standardized rating scales. Other outcomes were response to treatment; improvement in anxiety-related scales scores, depression-related scale scores, Clinical Global Impression Severity Scale (CGI-S) scores, and Sheehan Disability Scale (SDS) scores; all-cause discontinuation; and individual adverse events. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. We reviewed 17 studies (n = 629, 72.62% female; duration = 2-20 weeks; mean age = 30.47 years) of MMs: eicosapentaenoic acid (K = 1), folic acid (K = 1), lithium (K = 1), N-acetylcysteine (K = 10), inositol (K = 3), and silymarin (K = 1). MMs outperformed placebo in overall improvement in symptoms (p < 0.01) and in improving anxiety-related scale scores (p = 0.05). Subgroup analysis of individual MMs revealed that although overall symptoms were better improved by N-acetylcysteine (p < 0.01) and lithium (p = 0.04), no MMs outperformed placebo in terms of improving anxiety-related scale scores. Neither pooled nor individual MMs outperformed placebo in improving response to treatment, depression-related scale scores, CGI-S scores, SDS scores, or all-cause discontinuation. N-acetylcysteine was no more associated with a higher incidence of individual adverse events including gastrointestinal symptoms, than placebo. In conclusion, N-acetylcysteine was beneficial in the treatment of obsessive-compulsive and related disorders. However, further study with larger samples is necessary to confirm this finding.
Topics: Acetylcysteine; Adult; Double-Blind Method; Female; Humans; Inositol; Lithium; Male; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic
PubMed: 35764619
DOI: 10.1038/s41398-022-02026-5 -
Journal of Comparative Effectiveness... Aug 2022To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A... (Meta-Analysis)
Meta-Analysis Review
To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A systematic review and meta-analysis were conducted. Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving opicapone increased the frequency of dyskinesia. Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.
Topics: Adult; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Double-Blind Method; Humans; Levodopa; Oxadiazoles; Parkinson Disease
PubMed: 35758044
DOI: 10.2217/cer-2022-0031 -
BMC Medical Research Methodology Jun 2022To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates.
BACKGROUND
To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates.
METHODS
A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots.
RESULTS
Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results).
CONCLUSIONS
Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.
Topics: Bias; Double-Blind Method; Epidemiologic Studies; Humans; Outcome Assessment, Health Care; Sample Size
PubMed: 35705904
DOI: 10.1186/s12874-022-01650-5 -
Journal of Prosthodontic Research Jan 2023The efficacy of etch-and-rinse, selective enamel-etching, and self-etching protocols for universal adhesives in follow-ups of over 12 months was compared in a network... (Meta-Analysis)
Meta-Analysis
Efficacy of adhesive strategies for restorative dentistry: A systematic review and network meta-analysis of double-blind randomized controlled trials over 12 months of follow-up.
PURPOSE
The efficacy of etch-and-rinse, selective enamel-etching, and self-etching protocols for universal adhesives in follow-ups of over 12 months was compared in a network meta-analysis.
STUDY SELECTION
Randomized controlled trials (RCTs) published from 1998 to 2022 that compared marginal staining, marginal adaptation, retention and fractures, post-operative sensitivity, or recurrence of caries that took place over 12-months post-restoration were selected. A network meta-analysis determined the performance of each adhesive protocol.
RESULTS
After screening 981 articles, 16 RCTs were subjected to data extraction. Of which, 674 patients with 2816 restorations, were included in the network meta-analysis. The pooled risk of marginal discoloration following self-etching was significantly higher than that following etch-and-rinse at over 12, 24, and 36 months, which was time-dependent. The pooled risks of unfavorable marginal adaptation and unfavorable retention and fractures following self-etching were also significantly higher than that following etch-and-rinse, with the rates of unfavorable retention and fractures in non-carious cervical lesions increasing in a time-dependent manner. The pooled risks of marginal discoloration, unfavorable marginal adaptation, retention and fractures were similar between etch-and-rinse and selective enamel-etching protocols. Post-operative hypersensitivity and recurrence of caries were not significantly different among etch-and-rinse, selective enamel-etching, and self-etching protocols.
CONCLUSIONS
In follow-ups over 12 months, esthetic and functional outcomes of restorations completed with an etch-and-rinse adhesive protocol were superior to the ones achieved with a self-etching strategy without selective enamel-etching. Selective enamel etching is recommended for self-etching systems. Biological responses were similar for all three adhesive strategies.
Topics: Humans; Dental Caries; Dental Marginal Adaptation; Dental Restoration, Permanent; Follow-Up Studies; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Adhesives; Denture Retention; Double-Blind Method; Dental Etching
PubMed: 35691823
DOI: 10.2186/jpr.JPR_D_21_00279 -
Translational Pediatrics Apr 2022Oxygen therapy is one of the most common treatments for bronchiolitis, But traditional standard oxygen therapy is poorly tolerated by patients. Nasal continuous positive...
BACKGROUND
Oxygen therapy is one of the most common treatments for bronchiolitis, But traditional standard oxygen therapy is poorly tolerated by patients. Nasal continuous positive airway pressure (nCPAP) also has many contraindications. High-flow nasal cannula (HFNC), as a new method of adjunctive respiratory support, has received extensive attention in oxygen therapy in pediatric. In this meta-analysis, we evaluated the efficacy and safety of HFNC in the treatment of infant bronchiolitis.
METHODS
We searched PubMed, Web of Science, CNKI, GeenMedical, Wanfang, and Weipu using the following keywords: children with respiratory diseases, infant bronchiolitis, bronchiolitis treatment, HFNCs, warming and humidifying high-flow, nasal catheter oxygen inhalation, and conventional oxygen therapy. The publication time was set from the establishment of the database to October 2021. Selected articles were randomized controlled trial (RCT) studies in which the patients were less than 16 years old and the experimental group was treated with HFNCs, and the control group was treated with nCPAP or conventional oxygen. After extracting the data, the study subjects were divided into HFNC treatment and control groups. The Cochrane risk of bias tool was used to assess the quality of the included literature, and RevMan 5.30 was used for meta-analysis.
RESULTS
Seven articles met the inclusion criteria. All articles described random sequence generation, four articles reported on allocation concealment, only two articles reported on the double-blind method. All articles described the complete blinding of outcome evaluation bias, outcome data bias, selective reporting bias, and other risk biases. The HFNC treatment group included 436 children, 405 children treated with nCPAP or standard oxygen therapy were included in the control. The results showed that the failure rate [relative risk (RR) is 0.57, 95% CI: 0.43-0.76], respiratory rate [mean difference (MD) is -7.43, 95% CI: -8.42 to -6.43], and social function (MD is 0.76, 95% CI: -0.32 to 1.83) of HFNC-treated children with bronchiolitis were significantly different to that of the control group patients.
DISCUSSION
HFNC treatment provides the same improvement in arterial oxygen partial pressure as standard oxygen therapy or transnasal positive airway pressure treatment, but it is significantly better at improving the respiratory rate of children with bronchiolitis.
PubMed: 35558971
DOI: 10.21037/tp-22-73