Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis

Network meta-analysis of antidepressants

Pharmacological treatments for generalised anxiety disorder

Performing and evaluating meta-analyses

Background:Primary dysmenorrhea (PD), one of the most common diseases in women, is known to be effective with object-separated moxibustion. However, because there is no large sample size for comparison, it is difficult to choose the best method for the clinical treatment of these different treatments. Therefore, our aim was to compare and rank different moxibustion methods to determine the most effective treatment method for PD.Materials and methods:A systematic search was carried out in PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature, to identify the randomized controlled trials (RCTs) investigated the object-separated moxibustion is associated with dysmenorrhea, as well as we also manually checked the bibliographies of eligible studies and topic-related reviews, RCTs from their inception to May 1, 2020. Three investigators read the citations and excluded quasi-randomized trials and trials that were incomplete. We extracted data following a predefined hierarchy. We assessed the studies’ risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The primary outcomes were efficacy (response rate) and dysmenorrhea scores. We estimated the summary odds ratio (OR) and mean difference (MD) using pairwise and network meta-analyses with random effects. STATA software version 16.0, ADDIS software version 1.16.5, and R software version 3.6.1 were used to statistically analyze all data.Results:Fifty-six RCTs with 5550 patients were included, comparing 6 object-separated moxibustion therapies with acupuncture or oral medicine. All moxibustions were more effective than ibuprofen, with OR ranging between 6.75 (95%CI: 3.58 to 13.22) for moxibustion at the navel. For relieving pain which uses dysmenorrhea score to evaluate, mild moxibustion (MD = −1.42, −4.24 to 0.85) was more effective than others. A total of 24 (42.8%) of 56 trials were rated as having a high risk of bias, 31(55.4%) as moderate, and 1(1.8%) as low, and the certainty of the evidence was moderate.Conclusions:Mild moxibustion cannot only effectively treat PD but also relieve pain in comparison with ibuprofen. Although GRADE evidence indicate low to moderate for most comparisons, mild moxibustion seems to be an advisable option for PD treatment to relieve symptoms.

The objective of our study was to assess the benefits and harms of tramadol vs placebo in adults with chronic pain. The research method was a systematic review of randomised clinical trials with meta-analysis. The review followed the Trial Sequential Analysis and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The Cochrane Library, MEDLINE, Embase, Science Citation Index and BIOSIS were searched for trials published from inception to 6 February 2025. Studies were eligible for inclusion if they were published and unpublished randomised clinical trials comparing tramadol vs placebo in adults with any type of chronic pain. Risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. The main outcome measures were pain level, adverse events, quality of life, dependence, abuse and depressive symptoms. We included 19 randomised placebo-controlled clinical trials enrolling 6506 participants. All outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed evidence of a beneficial effect of tramadol on chronic pain (mean difference numerical rating scale (NRS) -0.93 points; 97.5% CI -1.26 to -0.60; p<0.0001; low certainty of evidence). However, the effect size was below our predefined minimal important difference of 1.0 point on NRS. Beta binomial regression showed evidence of a harmful effect of tramadol on serious adverse events (OR 2.13; 97.5% CI 1.29 to 3.51; p=0.001; moderate certainty of evidence), mainly driven by a higher proportion of cardiac events and neoplasms. It was not possible to conduct a meta-analysis of the quality of life due to a lack of data. Meta-analysis and Trial Sequential Analysis showed that tramadol increased the risk of several non-serious adverse events including nausea (number needed to harm (NNH) 7), dizziness (NNH 8), constipation (NNH 9), and somnolence (NNH 13) (all very low certainty of evidence). Tramadol may have a slight effect on reducing chronic pain levels (low certainty of evidence) while likely increasing the risk of both serious (moderate certainty of evidence) and non-serious adverse events (very low certainty of evidence). The potential harms associated with tramadol use for pain management likely outweigh its limited benefits.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

279Clinical outcome after coronary bifurcation stenting: a systematic review and network meta-Analysis of PCI bifurcation techniques comprising 5572 patients

Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD. We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model. 56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low. Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.

Comparative efficacy and acceptability of different intensity levels of extracorporeal shock wave therapy in adults with plantar heel pain: A systematic review and network meta-analysis.

Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: a systematic review and Bayesian network meta-analysis

Conservative treatments for De Quervain's tenosynovitis: A systematic review and network meta-analysis.

Sustaining independence is important for older people, but there is insufficient guidance about which community health and care services to implement. To synthesise evidence of the effectiveness of community services to sustain independence for older people grouped according to their intervention components, and to examine if frailty moderates the effect. Systematic review and network meta-analysis. Studies: Randomised controlled trials or cluster-randomised controlled trials. Participants: Older people (mean age 65+) living at home. Interventions: community-based complex interventions for sustaining independence. Comparators: usual care, placebo or another complex intervention. Living at home, instrumental activities of daily living, personal activities of daily living, care-home placement and service/economic outcomes at 1 year. We searched MEDLINE (1946-), Embase (1947-), CINAHL (1972-), PsycINFO (1806-), CENTRAL and trial registries from inception to August 2021, without restrictions, and scanned reference lists. Interventions were coded, summarised and grouped. Study populations were classified by frailty. A random-effects network meta-analysis was used. We assessed trial-result risk of bias (Cochrane RoB 2), network meta-analysis inconsistency and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation for network meta-analysis). We included 129 studies (74,946 participants). Nineteen intervention components, including 'multifactorial-action' (multidomain assessment and management/individualised care planning), were identified in 63 combinations. The following results were of low certainty unless otherwise stated. For living at home, compared to no intervention/placebo, evidence favoured: multifactorial-action and review with medication-review (odds ratio 1.22, 95% confidence interval 0.93 to 1.59; moderate certainty) multifactorial-action with medication-review (odds ratio 2.55, 95% confidence interval 0.61 to 10.60) cognitive training, medication-review, nutrition and exercise (odds ratio 1.93, 95% confidence interval 0.79 to 4.77) and activities of daily living training, nutrition and exercise (odds ratio 1.79, 95% confidence interval 0.67 to 4.76). Four intervention combinations may reduce living at home. For instrumental activities of daily living, evidence favoured multifactorial-action and review with medication-review (standardised mean difference 0.11, 95% confidence interval 0.00 to 0.21; moderate certainty). Two interventions may reduce instrumental activities of daily living. For personal activities of daily living, evidence favoured exercise, multifactorial-action and review with medication-review and self-management (standardised mean difference 0.16, 95% confidence interval -0.51 to 0.82). For homecare recipients, evidence favoured the addition of multifactorial-action and review with medication-review (standardised mean difference 0.60, 95% confidence interval 0.32 to 0.88). Care-home placement and service/economic findings were inconclusive. High risk of bias in most results and imprecise estimates meant that most evidence was low or very low certainty. Few studies contributed to each comparison, impeding evaluation of inconsistency and frailty. Studies were diverse; findings may not apply to all contexts. Findings for the many intervention combinations evaluated were largely small and uncertain. However, the combinations most likely to sustain independence include multifactorial-action, medication-review and ongoing review of patients. Some combinations may reduce independence. Further research is required to explore mechanisms of action and interaction with context. Different methods for evidence synthesis may illuminate further. This study is registered as PROSPERO CRD42019162195. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128862) and is published in full in Health Technology Assessment; Vol. 28, No. 48. See the NIHR Funding and Awards website for further award information.

Evidence Evaluation Process and Management of Potential Conflicts of Interest: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs.Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low.Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Background There are currently no sex-specific recommendations for antipsychotic prescribing in schizophrenia, although women may be more susceptible to certain side-effects and may require lower doses to achieve comparable efficacy to men. However, sex differences remain insufficiently studied to inform treatment decisions. Methods We plan a systematic review and individual-participant-data meta-analysis of randomized trials comparing different antipsychotic drugs, doses, formulations with each other or with placebo in adults with acute schizophrenia. Eligible studies will be identified through the Vivli platform, and their individual-participant-data will be harmonized into a common dataset. Two independent reviewers will screen search results and assess risk of bias using the Risk of Bias 2 tool. The primary outcome will be overall symptoms of schizophrenia, and secondary outcomes will include a broad range of efficacy, tolerability, acceptability, and dosing measures. A stepwise approach to data synthesis will be adopted, depending on individual-participant-data availability, aiming to examine sex differences in the effects of antipsychotic drugs compared to placebo. If sufficient data are available, we will conduct random-effects meta-analyses using regression models to evaluate biological sex, typically categorised as male or female, as both a prognostic factor and an effect modifier, network meta-analyses to synthesize direct and indirect evidence, and dose-response meta-analyses using restricted cubic splines to explore dose-effect relationships. The robustness of the findings will be assessed through sensitivity analyses adjusting for additional covariates. The certainty of evidence on sex differences will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for subgroup analysis. If the certainty is judged to be moderate or high, sex-specific treatment effects will be further assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This study will examine sex differences in the efficacy, tolerability, and dosing of antipsychotics in acute schizophrenia, potentially contributing to evidence-based, sex-specific treatment recommendations for antipsychotic prescribing. Protocol registration PROSPERO-ID: CRD420251022957