This study aimed to evaluate and rank the effectiveness of pharmacological and non-pharmacological interventions for managing dyspnea severity, anxiety, exercise capacity, and health-related quality of life (HRQoL) in patients with advanced cancer.

A comprehensive search of PUBMED, HINARI, CENTRAL, and ResearchGate was conducted to identify randomized controlled trials (RCTs) published up to March 2024. Network meta-analysis was performed to compare interventions, calculating mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CI). P-scores were used to rank the interventions. Risk of bias was assessed using the Cochrane tool, and the quality of evidence (QOE) was evaluated using the GRADE framework.

A total of 42 RCTs, encompassing 3,832 patients, were included in the analysis. Among the evaluated interventions, high-flow nasal cannula (HFNC) demonstrated the most significant improvement in dyspnea relief (SMD = -1.91; 95% CI: -3.32 to -0.49; QOE: moderate), followed by acupressure/reflexology (SMD = -1.04; 95% CI: -2.02 to -0.06; QOE: very low). Activity rehabilitation was the only intervention that significantly reduced anxiety compared to the control group (SMD = -0.64; 95% CI: -0.97 to -0.32; QOE: very low). While all interventions showed trends of improving exercise capacity, none reached statistical significance. Notably, acupressure/reflexology significantly enhanced HRQoL (SMD = 1.55; 95% CI: 0.22 to 2.88; QOE: moderate).

Non-pharmacological interventions, particularly HFNC and acupressure/reflexology, were more effective than pharmacological approaches in improving dyspnea relief and HRQoL. However, the low quality of evidence underscores the need for high-quality, large-scale trials to confirm these findings and refine treatment strategies for dyspnea management in advanced cancer patients.

PROSPERO CRD42023479041.

Janus kinase (JAK) inhibitors (JAKinibs) are effective for inflammatory bowel disease (IBD), but their cardiovascular safety is inconclusive. We aim to assess the cardiovascular risks associated with JAKinibs in IBD patients.

Systematic searches of seven databases and ClinicalTrials.gov from inception to February 2024 were conducted. Outcomes included major adverse cardiovascular events (MACE), venous thromboembolism events (VTE) and cardiovascular events (CVE), which were separately evaluated based on whether or not the dose was considered. P-score was applied to rank interventions.

A total of 26 trials involving 10,537 IBD patients were included, and results showed no significantly increased risk of MACE, VTE and CVE was associated with JAKinibs. However, when the dose was considered, Tofacitinib 5 mg BID (versus placebo) showed a trend towards an increased risk of MACE [odds ratio (OR)=1.05, 95% confidence interval (CI): 0.23-4.82], as well as Upadacitinib 30 mg QD (versus placebo) showed a trend towards increased risks of VTE (OR=1.36, 95% CI: 0.23-8.03) and CVE (OR=1.08, 95% CI: 0.24-4.85), and ranked higher than placebo for the risk of VTE [P-score=0.766 (versus 0.722)]. Notably, Deucravacitinib ranked lowest for all cardiovascular risks, and significantly decreased the risks of VTE (OR=0.03, 95% CI: 0.00-0.87) and CVE (OR=0.03, 95% CI: 0.00-0.87) compared with placebo.

Although a trend of increased cardiovascular risks was found considering dose, no significantly increased cardiovascular risk was associated with JAKinibs in IBD patients, and Deucravacitinib significantly decreased the risks of VTE and CVE.

We performed a comprehensive systematic review and network meta-analysis (NMA) to assess the efficacy of pharmacological agents for the treatment of proliferative vitreoretinopathy (PVR) following retinal detachment (RD) surgery. A systematic search was performed across PubMed, Scopus, Web of Science, and Embase. Randomized and non-randomized controlled trials and comparative observational studies evaluating the effect of pharmacological agents in a clinical setting were included. The primary outcome was retinal reattachment rate, and secondary outcomes were PVR recurrence, reoperation, intraocular pressure (IOP), epiretinal membrane (ERM), and macular edema. A total of 23 studies with 1749 eyes were included. Twelve different drugs or drug combinations were assessed. The NMA was performed for retinal reattachment, PVR recurrence, and reoperation rate outcomes. Among the pharmacological agents analyzed, adjunctive therapy with 13-cis-retinoic acid (13-cis-RA) demonstrated a statistically significant improvement in retinal reattachment rates (RR=1.36, 95 % CI: 1-1.84) and a reduction in reoperation rates (RR=0.23, 95 % CI: 0.07-0.69) compared to the control group, while none of the other drugs had statistically significant results. Additionally, adjunctive therapy did not yield significant improvements in IOP, ERM, or macular edema, except for a reduction in macular edema associated with dexamethasone in one study. This systematic review and NMA indicate that most pharmacological agents could not significantly improve retinal reattachment, reduce PVR recurrence, or lower reoperation rates following RD surgery. 13-cis-RA was the only drug that showed a significant impact on lowering retinal detachment and reoperation rates. Further high-quality clinical trials are warranted to confirm these findings.

This study aimed to evaluate the effectiveness of various formulas and the ability of breastfeeding with the exclusion of cow milk protein to reduce the Scoring Atopic Dermatitis (SCORAD) index and promote growth in infants with cow milk protein allergy.

We conducted a systematic search of PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, China National Knowledge Infrastructure, WanFang Data, Weipu, and the China Biomedical Literature Database. The search period ranged from the inception of each database to December 2023 (with an update until January 15, 2025). We included randomized controlled trials (RCTs) comparing formulas and breastfeeding for cow's milk protein allergy in infants. Two independent reviewers extracted data via standardized methods and assessed the risk of bias via the revised Cochrane risk-of-bias 2.0 tool. We performed a network meta-analysis (NMA) via a Bayesian fixed-effects model in RStudio and assessed the certainty of the evidence via the Confidence in Network Meta-Analysis (CINeMA) online application. The protocol for this NMA was preregistered in PROSPERO (No. CRD42024504707).

This analysis included 23 RCTs involving 1997 children and assessed 12 interventions. Compared with the regular formula, the pectin-thickened amino acid formula (TAAF) might reduce the SCORAD index (-12.49, 95% confidence interval [CI] -20.38 to -4.48, low certainty). At ≤6 months of follow-up, compared with rice-hydrolyzed formula (RHF), breastfeeding might improve the length-for-age Z score (LAZ) (0.47, 95% CI 0.13-0.81, moderate certainty), and breastfeeding (0.39, 95% CI 0.02-0.77, low certainty) and extensively hydrolyzed formula (EHF) with probiotics (0.38, 95% CI 0.00-0.77, low certainty) might respectively improve the weight-for-age Z score (WAZ) and weight-for-length Z score (WLZ). At the 12-month follow-up, EHF might improve the LAZ (0.41, 95% CI 0.11-0.71, low certainty) and WLZ (0.37, 95% CI 0.18-0.56, low certainty) compared with RHF, whereas the amino acid formula (AAF) may improve the WAZ (0.33, 95% CI 0.02-0.63, low certainty).

Low-certainty evidence suggested that TAAF might reduce the SCORAD index. Moderate or low certainty evidence indicated that, at ≤6 months of follow-up, breastfeeding might improve the LAZ and WAZ, whereas EHF with probiotics might improve the WLZ. At the 12-month follow-up, EHF might improve the LAZ and WLZ, whereas AAF might improve the WAZ. However, further high-quality studies would be needed to confirm these findings and assess their safety and cost-effectiveness.

There has been an increase in randomized controlled trials (RCTs) comparing probiotics with various maintenance therapies, such as polyethylene glycol, lactulose, and mineral oil, to treat functional constipation in children.

The aim was to compare probiotics with all other oral maintenance therapies for functional constipation in children and rank all treatments in terms of effectiveness in a network meta-analysis.

RCTs were identified through systematically searching the MEDLINE, Scopus, EMBASE, and Cochrane Library databases, trial registries, and forward and backward citation searching. Within-study risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and confidence in the estimates was assessed using the CINeMA (Confidence in Network Meta-Analysis) framework. Random-effects network meta-analyses were conducted.

Data were pooled from 41 and 29 RCTs for network meta-analysis of defecation frequency and treatment success, respectively. Probiotics did not significantly increase the number of bowel movements per week when compared with any conventional treatment or placebo. A combination of mineral oil and probiotics was the most effective treatment for increasing defecation frequency (mean difference: 3.13; 95% confidence interval [CI]: 0.64, 5.63). The most effective treatments for increasing the risk of treatment success as compared with placebo were mineral oil (relative risk [RR]: 2.41; 95% CI: 1.53, 3.81) and a combined treatment of polyethylene glycol and lactulose (RR: 2.45; 95% CI: 1.21, 4.97). Confidence in the estimates ranged from very low to moderate.

Currently, there is no evidence to suggest that probiotics should be used as a standalone treatment for functional constipation in children. More high-quality studies are needed to evaluate different strains of probiotics and their potential benefit as an additional treatment component to conventional treatments. Mineral oil and polyethylene glycol were the most effective treatments to increase defecation frequency and treatment success rates and should remain the first line of treatment for children with functional constipation.

PROSPERO registration no.

CRD42022360977 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=360977).

We conducted a systematic review with pairwise (PMA) and network meta-analyses (NMA) to evaluate sodium-glucose transport protein 2 inhibitor (SGLT2i) effects in patients with both heart failure (HF) and type 2 diabetes mellitus (T2DM). Five databases were searched up to April 15, 2025. Primary outcomes were all-cause mortality (ACM), cardiovascular death (CVD), all-cause hospitalization (ACH), and hospitalization for heart failure (HHF). SGLT2i class effects versus control were assessed via PMA and individual SGLT2i comparative efficacy via NMA plus ranking using p-scores. Seventeen randomized controlled trials (n = 17,809) were included. Arms included canagliflozin (n = 2), dapagliflozin (n = 6), empagliflozin (n = 6), ertugliflozin (n = 1), ipragliflozin (n = 1), sotagliflozin (n = 1), placebo (n = 13), and standard of care (n = 4). Compared to control, SGLT2i significantly reduced ACM (HR 0.87, 95 %CI 0.78 to 0.98, low quality of evidence [QoE]), ACH (HR 0.74, 95 %CI 0.62 to 0.88, high QoE), and HHF (HR 0.70, 95 %CI 0.63 to 0.77, low QoE); but not CVD (HR 0.87, 95 %CI 0.76 to 1.00, very low QoE). Canagliflozin ranked highest in decreasing ACM (p-score = 0.86), CVD (p-score = 0.82), and HHF (p-score = 0.88). In patients with HF and T2DM, SGLT2i class effects include ACM, ACH, and HHF reduction. Among SGLT2i, canagliflozin showed greatest ACM, CVD, and HHF benefit.

Various digital therapeutics (DTx), which utilize computerized cognitive training (CCT) to improve cognitive functioning, have been tested and released. However, the efficacy of these DTx approaches may be diverse. This study aims to meta-synthesize the associations between mobile applications and cognitive functioning outcomes in older adults with mild cognitive impairment (MCI) or dementia from randomized controlled trials (RCTs). We searched PubMed, EMBASE, Scopus, and Cochrane Library from the inception through the end of June 2024. We selected RCTs using mobile application interventions in older adults with MCI or dementia. Interventions and comparisons included: CCT, intensive CCT (CCT2x), computerized cognitive engagement, progressive resistance training (PRT), CCT plus medication, CCT plus PRT, and medications only. Outcomes of interest included cognitive functioning and other measures of functioning (e.g., activities of daily living [ADLs]). Network meta-analysis was conducted to estimate pooled standardized mean differences (SMDs) with corresponding 95 % confidence intervals (CIs). Of 1,189 studies extracted, 10 RCTs were included in our analysis. CCT2x demonstrated statistically significant improvements in global cognitive function (SMD, 1.21 [95 % CI, 0.69-1.73]), episodic memory (SMD, 0.87 [0.47-1.27]), and working memory (SMD, 0.93 [0.44-1.42]) when compared with controls. For ADLs, CCT significantly reduced functional impairment (SMD, -0.80 [-1.40 to -0.21]). In depressive symptoms, CCT2x was the most effective in reducing symptoms (SMD, -0.77 [-1.08 to -0.45]). Overall, the DTx may be effective in improving cognitive and other functioning outcomes in older adults with MCI or dementia.

Patients with irritable bowel syndrome (IBS) are often interested in dietary interventions as a means of managing their symptoms. However, the relative efficacy of available diets for the management of IBS is unclear. We aimed to examine the relative efficacy of various dietary interventions in IBS.

For this systematic review and network meta-analysis we searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials from database inception to Feb 7, 2025, to identify randomised controlled trials comparing an active dietary intervention requiring changes to the intake of more than one food in IBS with either a control intervention, such as a habitual diet, sham diet, a high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, or alternative miscellaneous dietary advice, or any other active dietary intervention requiring changes to the intake of more than one food. We assessed efficacy using dichotomous assessments of improvement in global IBS symptoms or improvement in individual IBS symptoms, including abdominal pain, abdominal bloating or distension, and bowel habit. We pooled data using a random-effects model, with the efficacy of each intervention reported as pooled relative risks (RRs) with 95% CIs. We ranked interventions according to their P-score, which measures the mean extent of certainty that one intervention is better than another, averaged over all competing interventions.

We identified 28 eligible randomised controlled trials (comprising 2338 patients) of 11 different dietary interventions compared with four control interventions, of which six (low FODMAP diet, British Dietetic Association/National Institute for Health and Care Excellence [BDA/NICE] diet, lactose-reduced diet, starch-reduced and sucrose-reduced diet, a personalised diet, and a Mediterranean diet) were studied in more than one trial. For global IBS symptoms, assessed in 28 randomised controlled trials and when considering only the dietary interventions studied in more than one trial, a starch-reduced and sucrose-reduced diet ranked first (RR of global IBS symptoms not improving 0·41 [95% CI 0·26-0·67]; P-score 0·84; two trials), a low FODMAP diet ranked fourth (0·51 [0·37-0·70]; P-score 0·71; 24 trials), and a BDA/NICE diet ranked tenth (0·62 [0·43-0·90]; P-score 0·44; eight trials), versus a habitual diet. For abdominal pain, assessed in 26 trials and when considering only the dietary interventions studied in more than one randomised controlled trial, a starch-reduced and sucrose-reduced diet ranked second (RR of abdominal pain not improving 0·54 [95% CI 0·33-0·90]; P-score 0·73; two trials), and a low FODMAP diet ranked fifth (0·61 [0·42-0·89]; P-score 0·64; 23 trials), versus a habitual diet. For abdominal bloating or distension, assessed in 26 trials and when considering only the dietary interventions studied in more than one randomised trial, only a low FODMAP diet (RR of abdominal bloating or distension not improving 0·55 [95% CI 0·37-0·80]; P-score 0·64; 23 trials) was superior to a habitual diet and ranked fourth. For bowel habit, assessed in 23 randomised trials, none of the dietary interventions was superior to any of the control interventions, but a low FODMAP diet was superior to a BDA/NICE diet (RR of bowel habit not improving 0·79 [95% CI 0·63-0·99]). All comparisons across the network were rated as low or very low confidence, except for direct comparisons between a low FODMAP diet or a starch-reduced and sucrose-reduced diet and habitual diet, both of which were rated as moderate confidence.

In terms of dietary interventions for IBS, the most evidence exists for a low FODMAP diet, but other promising therapies are emerging and should be the subject of further study.

None.

Psoriatic arthritis (PsA) constitutes a heterogeneous disease. Diagnosis is commonly made by identifying joint inflammation, dactylitis, enthesitis, or axial spine involvement in cutaneous or nail psoriasis. Janus kinases (JAKs) are intracellular kinases that mediate cytokine signaling. The present network meta-analysis aimed to provide a comprehensive summary regarding the use of JAK inhibitors (JAKis) in PsA. We systematically searched MEDLINE, CENTRAL, Web of Science databases, and the clinicaltrials.gov registry until October 2023 and included randomized controlled trials (RCTs). Examined outcomes consisted of the proportion of participants achieving ACR20, ACR50, ACR70, PASI75, resolution of enthesitis, resolution of dactylitis, and experiencing serious adverse events (SAEs). Changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) from the baseline were also recorded. The revised Cochrane Risk of Bias 2.0 tool determined the risk of bias. Networks were constructed, and random-effects frequentist analyses were employed utilizing the placebo arms from each study. Most JAKis were superior to placebo for all examined outcomes. Statistical advantages of one JAKi over another were recorded, and all concerned upadacitinib. However, the safety profile of upadacitinib did not differ significantly from that of other JAKis. Our network meta-analysis is the first to concentrate on comparable, current outcome data of JAKis in PsA on clinical efficacy. It reveals statistically significant variations in the advantages and disadvantages among JAKis in PsA, which require further meticulous assessment.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To undertake network meta-analysis (NMA) and component network meta-analysis (CNMA) to explore the comparative effectiveness of different community-based interventions, and the components within the interventions used singly or in combination, for the prevention or management of dental caries in children.  .

Atypical depression is a highly prevalent subtype that includes mood reactivity, hypersomnia, and leaden paralysis, necessitating different therapeutic approaches than melancholic depression. No network meta-analysis has been conducted on pharmacological treatments for atypical depression.

We performed a PRISMA-compliant systematic review and network meta-analysis searching PubMed/Central, Clinicaltrials.gov, Embase, PsycINFO, Scopus, WebOfScience for randomized controlled trials (RCTs) testing pharmacological interventions for atypical depression until 04/24/24 (PROSPERO: CRD42024540262). Depressive symptom change (standardized mean difference/SMD), response, and all-cause discontinuation (acceptability) (risk ratio/RR) were co-primary outcomes; tolerability was the secondary outcome. Risk-of-bias and global/local inconsistencies were measured, and Confidence in Network Meta-Analysis (CINeMA) was used to assess the confidence in the evidence.

Out of 2214 hits, we included 21 eligible RCTs, 20 entering the NMA. For efficacy (k = 16, N = 903, treatments=12), only phenelzine outperformed placebo (SMD=-1.31, 95 %C.I.=[-2.14;-0.49]). Phenelzine, moclobemide, isocarboxazid, imipramine, selegiline, sertraline, and fluoxetine all outperformed nortriptyline (from SMD=-4.54, 95 %C.I.=[-8.02;-1.07] to SMD=-3.08, 95 %C.I.=[-5.42; -0.75]). Regarding response (k = 13, N = 1442, treatments=7), phenelzine (RR=2.58, 95 %C.I.=[2.02-3.31]), sertraline (RR=2.25, 95 %C.I.=[1.01-4.99]), moclobemide (RR=2.16, 95 %C.I.=[1.12-4.19]), fluoxetine (RR=1.89, 95 %C.I.=[1.30-2.76]) and imipramine (RR=1.76, 95 %C.I.=[1.35-2.28]) outperformed placebo, and phenelzine also outperformed imipramine (RR=1.56, 95 %C.I.=[1.25-1.96]). No treatment was significantly different from placebo for acceptability. No intervention outperformed placebo on any outcome in sensitivity analyses upon exclusion of high-risk-of-bias and intention-to-treat trials, likely due to a loss in power of the analysis, and overall CINeMA ratings were low/very low.

Phenelzine might perform better than other compounds, but several drugs outperformed placebo in response. Nortriptyline performed worse than other treatments. High-quality studies are needed.

The purpose of this network meta-analysis (NMA) of randomized controlled trials (RCT) was to examine the effects of different exercise intensities on inflammatory markers in women with overweight/obesity.

A systematic search for RCTs that met the inclusion criteria for the period up to October 2024. random effects NMA was performed within a frequency-based framework.

A total of 75 RCTs were included (3989 participants). High-intensity exercise significantly modulated leptin and adiponectin levels, but had a nonsignificant effect on TNF-α, CRP, and IL-6 levels. Moderate-intensity exercise significantly modulated TNF-α, CRP, IL-6, leptin, and adiponectin levels. Surface under the cumulative ranking curve (SUCRA) probability ranking showed that moderate-intensity exercise was the most recommended exercise intensity for reducing TNF-α, CRP, IL-6, and leptin levels, and for modulating adiponectin levels, moderate-intensity exercise also had a SUCRA value of 65.4%, so we believe that moderate-intensity exercise may be the most robust type of exercise intensity in terms of the breadth of effects. Subgroup analysis showed that moderate-intensity aerobic exercise (MAE) significantly reduced TNF-α levels. Moderate-intensity resistance training (MRT) is the most recommended type for decreasing IL-6 and leptin levels. Moderate-intensity combined exercise (MCE) is the best type of exercise for managing CRP and adiponectin levels.

There were significant differences in the effects of different exercise intensities on specific inflammatory markers in women living with overweight and obesity. Moderate-intensity exercise may be the most robust type of exercise intensity. Future studies should consider the importance of exercise duration and volume (e.g., in MET* minutes/week) to better understand the relationship between exercise intensity and inflammatory markers. The effects of combining exercise and diet on inflammatory markers in women with overweight and obesity should also be explored in greater depth.

Daratumumab (Dara)-based regimens have been investigated in randomized controlled trials (RCTs) involving patients with newly diagnosed and previously untreated multiple myeloma (NDMM), but the optimal daratumumab-based regimen remains unclear. This study compares the efficacy of daratumumab-containing regimens for NDMM patients and explores optimal combinations.

Databases were searched from inception until February 29, 2024. Trials comparing regimens with and without daratumumab, as well as their mutual comparisons, were included. Random effects models for serious adverse events (SAEs) and fixed effects models for other outcomes were utilized in both network meta-analysis (NMA) and component NMA (CNMA), with pooled effects estimated. The efficacy of all possible combinations of daratumumab with other drugs was assessed.

A total of 17 trials were included, enrolling 7261 patients, of whom 2083 were treated with daratumumab. The optimal regimens for different outcomes were identified as follows: Dara-bortezomib (V)-melphalan (M)-corticosteroids (D) (Dara-VMD) showed the best results for both overall response rate (ORR) [RR = 1.97; 95% CI: 1.42 to 2.75; I2 = 0.00%; 16 trials; 7136 participants; P = 0.00] and ≥ very good partial response (≥ VGPR) [RR = 7.46; 95% CI: 4.10 to 13.46; I2 = 23.96%; 16 trials; 7118 participants; P = 0.00]; Dara-V-thalidomide (T)-D (Dara-VTD) was optimal for achieving ≥ complete response (≥ CR) [RR = 14.15; 95% CI: 3.74 to 53.52; I2 = 0.00%; 17 trials; 7261 participants; P = 0.00]. The individual effects of daratumumab were calculated as follows: [ORR: RR = 1.14; 95% CI: 1.08 to 1.21; I2 = 0.00%; 16 trials; 7136 participants; P = 0.00; ≥ VGPR: RR = 1.46; 95% CI: 1.36 to 1.58; I2 = 23.96%; 16 trials; 7118 participants; P = 0.00; ≥ CR: RR = 1.77; 95% CI: 1.55 to 1.99; I2 = 0.00; 17 trials; 7261 participants; P = 0.00; progression-free survival (PFS): hazard ratio (HR) = 0.53; 95% CI: 0.43 to 0.65; I2 = 0.00%; 13 trials; 5977 participants; P = 0.00; overall survival (OS): HR = 0.68; 95% CI: 0.58 to 0.79; I2 = 28.97%; 12 trials; 5977 participants; P = 0.00]. Additionally, the optimal regimens for PFS and OS were Dara-lenalidomide (R)-D [HR = 0.37; 95% CI: 0.23 to 0.61; I2 = 0.00%; 13 trials; 5977 participants; P = 0.00] and Dara-VRD [HR = 0.40; 95% CI: 0.19 to 0.85; I2 = 28.97%; 12 trials; 5977 participants; P = 0.02], respectively. Finally, CNMA indicated that Dara-VRD, Dara-carfilzomib (K)-RD, Dara-RD, and Dara-cyclophosphamide (C)-RD were four regimens, which could improve remission rate, and reduce death or progression during induction and prolong lifetime.

Dara-VRD, Dara-KRD, Dara-RD, and Dara-CRD are optimal daratumumab-based regimens for patients with newly diagnosed and previously untreated multiple myeloma.

To conduct a network meta-analysis comparing the effects of various long-term non-pharmacological treatments on inhibitory control in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) to provide theoretical support for non-pharmacological interventions in ADHD management.

Randomized controlled trials (RCTs) on the effects of long-term non-pharmacological treatments on inhibitory control in children and adolescents with ADHD published up to November 11, 2024, were searched in databases such as CNKI, Web of Science, APA PsycInfo, Embase, PubMed and Cochrane Library.

A total of 42 studies, including seven non-pharmacological types, were included, involving 1981 children and adolescents with ADHD, with a mean age of 10.04 ± 1.82 years. Both traditional and network meta-analyses based on post-test data revealed that physical exercise, cognitive training, behavior therapy, and neurofeedback significantly improved inhibitory control (P < 0.05), with physical exercise showing the best improvement (SUCRA: 85.9 %). At the same time, board games, EMG feedback, and meditation had no significant effect (P > 0.05). Follow-up analysis showed that behavior therapy and cognitive training had a good maintenance effect (P < 0.05), with behavior therapy demonstrating the best sustained effect (SUCRA: 95.1 %). In contrast, physical exercise, board games, and neurofeedback showed diminishing effects over time and had no significant long-term effect (P > 0.05).

Existing evidence shows that physical exercise, cognitive training, behavior therapy, and neurofeedback all have a positive effect on improving inhibitory control in children and adolescents with ADHD, with physical exercise showing the best effect, though with poor maintenance, while cognitive training and behavior therapy had a slightly lower effect, but their maintenance was better.

This network meta-analysis aimed to assess the efficacy of different acupuncture-related therapies in improving pregnancy outcomes among women undergoing in vitro fertilization and embryo transfer (IVF-ET).

Randomized controlled trials (RCTs) examining acupuncture-related therapies as adjuncts to IVF-ET were systematically searched in eight databases from inception until January 15, 2025. Dichotomous outcomes concerning efficacy were evaluated as odds risk (OR) and continuous data as mean difference (MD) and 95% credible intervals (CrI) utilizing R 4.1.2 and Stata 16.1.

Through a comprehensive literature search, we ultimately identified 96 RCTs that involved 14,736 participants and 15 interventions in this systematic analysis. Based on the clinical pregnancy rate outcome, warm acupuncture for three menstrual cycles before oocyte retrieval (WA-TTP, OR 3.56, 95% CrI 2.05 to 6.25, low certainty, SUCRA = 89.54%), acupuncture combined with moxibustion for three menstrual cycles before oocyte retrieval (AC + M-TTP, OR 3.31, 95% CrI 1.05 to 11.77, low certainty, SUCRA = 78.70%), and acupuncture for one menstrual cycle before oocyte retrieval (AC-OTP, OR 2.69, 95% CrI 1.76 to 4.09, moderate certainty, SUCRA = 77.98%) demonstrated potential superiority compared to false acupuncture or no treatment (F/N). Significant subgroup differences between clinical pregnancy rates were observed by subgroup analysis.

Acupuncture-related therapies can potentially enhance clinical pregnancy rates among women undergoing IVF-ET, with WA-TTP, AC + M-TTP, and AC-OTP demonstrating potential superiority. AC-TTP demonstrated a greater efficacy in improving live birth rates, increasing endometrial thickness, and reducing pulsation index. Our findings emphasize that acupuncture-related therapies with a limited number of sessions before or after embryo transfer show minimal clinical benefit except auricular acupressure.

Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects over half of the world population, accountable for 89% of all gastric cancer cases. The efficacy of the proton-pump inhibitor (PPI) based-triple therapy is declining, while the novel potassium-competitive acid blocker (P-CAB) based therapy gets new attention. However, it remains unclear regarding the optimal duration and number of comedication(s) for P-CAB-based regimens, which P-CAB is the best-in-class, and whether P-CABs perform better than all PPIs.

To compare the efficacy on first-line H. pylori eradication between P-CAB-based therapies versus PPI-based therapies.

A systematic review on randomized controlled trials, with network meta-analysis conducted under the Frequentist approach. The P-score method was used to rank the probability of being the best intervention.

For the first-line treatment eradicating H. pylori infection, the 7-day vonoprazan-based triple therapy (VAC7) has the highest P-score for the probability of being the best intervention (0.96). VAC7 has a significantly higher eradication rate of H. pylori than most PPI-based therapies, including esomeprazole-based, lansoprazole-based, pantoprazole-based, and omeprazole-based regimens, as well as the other P-CAB based regimens, such as tegroprazan-based triple regimen (OR: 2.41, 95% CI: 1.13-5.15).

Vonoprazan-based triple therapy has a higher eradication rate than PPI-based triple therapies, as well as other P-CABs based regimens. It remains unclear whether VAC7 is superior over vonoprazan-based dual therapy (VA7). Overall, VAC7 should be recommended for clinical and public health interventions, with VA7 as a possible alternative considering the local antimicrobial resistance profiles.

The risk of stroke among patients with cancer is two times that of the general population due to a combination of cancer-, chemotherapy-, radiotherapy-, and surgery-related factors. There is a paucity of data regarding the optimal antithrombotic therapy for secondary stroke prevention in these patients.

Our goal was to review the stroke recurrence in patients treated with different antithrombotic therapies (antiplatelets, warfarin, heparin, and direct oral anticoagulants). Our secondary objective was to review the bleeding risk across different antithrombotic therapies.

A review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles that adequately assessed secondary prevention of stroke in patients with cancer were selected from the PubMed, Embase, and Scopus databases from inception until March 2, 2025. We performed a network meta-analysis for stroke recurrence, major bleeding, and mortality. The treatments were ranked by P-SCORE. Subgroup analyses were conducted based on median D-dimer levels, multiple territories of stroke, and exclusion of studies with high risk of bias.

We included 11 studies (four RCTs, six retrospective studies, and one case series) with a total of 1319 patients. In the primary analysis, antiplatelets were the highest-ranked treatment for reducing stroke recurrence (RR 0.44 [0.20; 0.96]), followed by LMWH (RR 0.50 [0.26; 0.96]), both significantly superior to no treatment. However, LMWH consistently ranked higher than antiplatelets in all subgroup analyses. There was no difference regarding major bleeding or mortality.

Antiplatelets can be considered an option for secondary prevention of stroke in patients with cancer, especially in patients with a higher bleeding risk. Future research with high-quality studies is needed to confirm our preliminary findings and should focus on identifying subgroups of patients with cancer who may benefit most from specific antithrombotic therapies.

This systematic review aimed to answer the question: In patients undergoing periodontal and peri-implant surgery, gingival augmentation, implant site development or placement, are pre-emptive analgesics effective in controlling post-operative pain compared with patients not receiving pre-emptive medications?

After comprehensive electronic and manual literature searches, randomised placebo-controlled clinical trials on adults undergoing the aforementioned surgeries were included. A meta-analysis was performed comparing pain (standardised mean difference) between pre-emptive medication and placebo at post-operative hours 1, 3, 6, 8, 24 and 72.

Two reviewers screened 1995 titles, included 18 studies in the systematic review (open flap debridement, osseous, mucogingival, unspecified periodontal surgery, implant placement; 1008 patients) and 7 studies in the meta-analysis. Non-steroidal anti-inflammatory drugs, acetaminophen and corticosteroids were prescribed 8 h to immediately pre-operatively and post-operatively until 12 h after the first dose. A clinically significant pain reduction peaked at 3 h (-0.81 [95% CI: -1.03, -0.58]; 9 study arms, n = 165 drug vs. n = 96 placebo patients) and was significant until 8 h (-0.54 [95% CI: -0.79, -0.28]; 7 study arms, n = 126 drug vs. n = 96 placebo patients), with moderate certainty of evidence (GRADE assessment).

Pre-emptive analgesia can reduce pain for up to 8 h following periodontal and implant placement surgery.

Therapeutic exercise (TE) is the only intervention with strong recommendation for fibromyalgia. However, there is controversy as to which type of exercise is the most beneficial.

To determine which TE approach is the most effective in reducing pain intensity in women with fibromyalgia.

A systematic review was performed with a network meta-analysis (NMA). Six databases were searched from inception until January 2024. Randomized controlled trials (RCTs) evaluating the effects of TE on pain intensity were included in women with fibromyalgia. Methodological quality was assessed using the Physiotherapy Evidence Database scale. The size of the effect and the clinically important difference were determined in the short-term (≤3 months) and long-term (>3 months).

Sixty-one studies were identified, of which 51 were included in the quantitative synthesis (n = 2873). Fifteen TE interventions and eight comparison interventions (comparators) were identified. Aquatic exercise (p-score: 0.8713) was found to provide best benefits in the short-term and resistance training in the long-term (p-score: 0.9749). Statistically significant differences were found in favor of aquatic exercise, Pilates, qigong, resistance training, virtual reality, mixed exercise, and aerobic exercise (in the short-term) and in favor of resistance training, dance, functional training, aquatic exercise, virtual reality, and aerobic exercise (in the long-term) compared to usual care.

With a moderate level of evidence, our NMA shows that, in the short-term, aquatic exercise is the most effective TE intervention to reduce pain intensity in women with fibromyalgia, while resistance training is the most effective in the long-term. More RCTs are needed to strengthen these findings.

Nutraceuticals have been taken as an alternative and add-on treatment for depressive disorders. Direct comparisons between different nutraceuticals and between nutraceuticals and placebo or antidepressants are limited. Thus, it is unclear which nutraceuticals are the most efficacious.

We conducted a network meta-analysis to estimate the comparative efficacy and tolerability of nutraceuticals for the treatment of depressive disorder in adults. The primary outcome was the change in depressive symptoms, as measured by the standard mean difference (SMD). Secondary outcomes included response rate, remission rate, and anxiety. Tolerability was defined as all-cause discontinuation and adverse events. Frequentist random-effect NMA was conducted.

Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion. Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response. Notable combinations were Eicosapentaenoic acid + Docosahexaenoic Acid plus ADT (EPA + DHA + ADT) (SMD 1.04, 95% confidence interval 0.64-1.44), S-Adenosyl Methionine (SAMe) + ADT (0.99, 0.31-1.68), curcumin + ADT (1.03, 0.55-1.51), Zinc + ADT (1.59, 0.63-2.55), tryptophan + ADT (1.24, 0.32-2.16), and folate + ADT (0.64, 0.17-1.10). Additionally, four nutraceutical monotherapies demonstrated superior efficacy compared to ADT: EPA + DHA (0.6, 0.32-0.88), SAMe (0.52, 0.18-0.87), curcumin (0.62, -0.17 to 1.40) and saffron (0.69, 0.34-1.04). It is noted that EPA + DHA, SAMe, and curcumin showed strong performance as either monotherapies or adjuncts to ADT. Most nutraceuticals showed comparable tolerability to placebo.

This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.

Several first-line therapeutic strategies have been evaluated alongside platinum-based chemotherapy in advanced or recurrent endometrial cancer (a/rEC). However, the optimal approach remains unclear.

A systematic review was conducted to identify randomized control trials (RCTs) that evaluate first-line therapeutic strategies in a/rEC involving immune checkpoint inhibitors (ICI) and PARP inhibitors (PARPi). A network meta-analysis with a frequentist framework using random-effects and an extracted individual patient data meta-analysis were performed. The primary endpoint was progression-free survival (PFS) by MMR status, p53 status within the MMRp population and PD-L1 status.

A total of 3210 patients with EC were included. In the MMRp population, the combination (ICI and PARPi) showed a not statistically significant PFS benefit compared with each agent alone. In MMRp p53-abnormal patients (n = 590), combining PARPi and ICI statistically improved PFS compared to ICI alone (HR=0.47, 95 %CI 0.40-0.94) with a numerically better outcome compared to PARPi alone (HR=0.63, 95 %CI 0.26-1.57). No benefit from PARPi was observed in the p53 wild-type MMRp population. PD-L1-positivity (n = 1121) appears to predict more benefit from the addition of ICI and PARPi, with a larger benefit of combination therapy. In the MMRd population (n = 769), the best outcomes were observed with ICI alone, with no additional benefit of PARPi. Grade 3 or greater treatment-related adverse events were seen in 75.1 % patients treated with the combination.

The addition of the combination of ICI and PARPi to platinum-based chemotherapy provides greatest benefit to p53-abnormal MMRp patients. PD-L1 is a potentially useful biomarker with PD-L1-positive tumors more likely to respond to ICI. Implementation of biomarkers is crucial to redefine the treatment paradigm in a/rEC.

A systematic evaluation and network meta-analysis (NMA) using randomized controlled trials (RCTs) was conducted to investigate the effects of different exercise intensities and dosages on the mental health of college students.

A systematic search of eight electronic databases of RCTs involving mental health exercise interventions for college students was conducted, which included data from the inception of the databases through July 2024. Two independent reviewers assessed the quality of the literature. Pairwise, network, and dose‒response meta-analyses were conducted via random-effects models to analyze the effects of exercise on college students' mental health.

A total of 48 RCTs (3951 patients) were included. Light, moderate, and vigorous exercise were all significantly effective at reducing symptoms of depression, anxiety and stress, whereas very light exercise was only effective at reducing symptoms of depression and stress. Surface under the cumulative ranking curve (SUCRA) probability ranking revealed that vigorous exercise had the highest probability of being the best intervention intensity to improve depression and stress symptoms, and the best exercise intensity to improve anxiety symptoms was moderate. The minimum threshold for overall exercise intervention for depressive symptoms was 150 METs-min per week, the benefits provided after doses above 1300 METs-min per week were less pronounced, and the predicted maximum significant response dose was 860 METs-min per week, which was the same as the predicted data for moderate exercise.

Very light, light, moderate, and vigorous exercise are all potentially effective exercise intensities for improving the mental health of college students, with no significant difference in effectiveness across the four exercise intensities. SUCRA rankings revealed that vigorous exercise is the most effective intervention for depression and stress and that moderate exercise is the most effective intervention for anxiety. Exercise interventions for depressive symptoms have a low dosage threshold, are simple and easy to administer, and are good treatments for psychological problems in college students.

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children.

We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes.

Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5 mg twice daily, fluticasone 3 mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3 mg daily, cendakimab 180 mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5 mg daily, OVB low dose, reslizumab 3 mg/kg, reslizumab 1 mg/kg, and reslizumab 2 mg/kg.

Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

To review and synthesize the effectiveness of exercise interventions on mobility, postural control, and falls in older adults with mild cognitive impairment (MCI).

This review was registered with PROSPERO (CRD42023453320) and adhered to the PRISMA guidelines. The PubMed, Embase, APA PsycInfo, Cochrane Library, Web of Science, CINAHL, and SPORTDiscus were searched from inception until September 2024.

Randomized controlled trials (RCTs) examining the effectiveness of exercise interventions on mobility, postural control, and falls in older adults with MCI.

Data extraction included author names, publication years, participant characteristics, intervention details, outcomes, key results, and attrition rates. Data accuracy was verified by 2 reviewers, with discrepancies resolved through consultation with a third reviewer.

Thirty-two RCTs met the criteria for qualitative systematic review, with 22 RCTs included in the pairwise meta-analysis and network meta-analysis. Aerobic exercise (AE) (SMD 1.07 [95% CI, 0.62-1.52]), multicomponent exercise (SMD 0.46 [95% CI, 0.18-0.74]), and simultaneous cognitive-motor training (SMD 0.56 [95% CI, 0.23-0.89]) significantly improved gait speed during single task (P<.05). AE was the most effective intervention for single-task walking performance (99.3%), whereas Exergaming was the most effective for timed Up and Go performance (100.0%) according to the surface under the cumulative ranking. Paddling exercise (SMD 0.42 [95% CI, 0.16-0.68]) effectively increased handgrip strength (P<.05). However, network meta-analyses revealed no intervention demonstrating significant effects on postural control performance (Berg Balance Scale and Functional Reach Test scores). The effect of exercise on falls remained inconclusive because of the limited number of studies.

AE, multicomponent exercise, and combined cognitive-motor training significantly enhance gait speed and functional performance in older adults with MCI. However, the effect of exercise on fall risk remains unclear. These findings underscore the potential of tailored exercise interventions to improve physical function in this vulnerable population.

Concerns about the cardiovascular safety of medications used for the treatment of attention-deficit hyperactivity disorder (ADHD) remain. We aimed to compare the effects of pharmacological treatments for ADHD on haemodynamic values and electrocardiogram (ECG) parameters in children, adolescents, and adults.

For this systematic review and network meta-analysis, we searched 12 electronic databases, including Cochrane CENTRAL, Embase, PubMed, and the WHO International Clinical Trials Registry Platform, from database inception to Jan 18, 2024, for published and unpublished randomised controlled trials comparing amphetamines, atomoxetine, bupropion, clonidine, guanfacine, lisdexamfetamine, methylphenidate, modafinil, or viloxazine against each other or placebo. Primary outcomes were change in systolic blood pressure (SBP) and diastolic blood pressure (DBP), measured in mm Hg, and pulse, measured in beats per minute, at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. Summary data were extracted and pooled in random-effects network meta-analyses. Certainty of evidence was assessed with the Confidence in Network Meta-Analysis (CINeMA) framework. This study was registered with PROSPERO, CRD42021295352. Before study initiation, we contacted representatives of a UK-based charity of people with lived experience of ADHD-the ADHD Foundation-regarding the relevance of the topic and the appropriateness of the outcomes chosen.

102 randomised controlled trials with short-term follow-up (median 7 weeks [IQR 5-9]) were included, encompassing 13 315 children and adolescents (aged ≥5 years and <18 years; mean age 11 years [SD 3]; of available data, 9635 [73%] were male and 3646 [27%] were female; of available data, 289 [2%] were Asian, 1719 [15%] were Black, and 8303 [71%] were White) and 9387 adults (≥18 years, mean age 35 years [11]; of available data, 5064 [57%] were male and 3809 [43%] were female; of available data, 488 [6%] were Asian, 457 [6%] were Black, and 6372 [79%] were White). Amphetamines, atomoxetine, lisdexamfetamine, methylphenidate, and viloxazine led to increments in haemodynamic values in children and adolescents, adults, or both. In children and adolescents, mean increase against placebo ranged from 1·07 (95% CI 0·36-1·79; moderate CINeMA confidence) with atomoxetine to 1·81 (1·05-2·57; moderate) with methylphenidate for SBP; from 1·93 (0·74-3·11; high) with amphetamines to 2·42 (1·69-3·15; low) with methylphenidate for DBP; and from 2·79 (1·05-4·53; moderate) with viloxazine to 5·58 (4·67-6·49; high) with atomoxetine for pulse. In adults, mean increase against placebo ranged from 1·66 (95% CI 0·38-2·93; very low) with methylphenidate to 2·3 (0·66-3·94; very low) with amphetamines for SBP; from 1·60 (0·29-2·91; very low) with methylphenidate to 3·07 (0·69-5·45; very low) with lisdexamfetamine for DBP; and from 4·37 (3·16-5·59; very low) with methylphenidate to 5·8 (2·3-9·3; very low) with viloxazine for pulse. Amphetamines, lisdexamfetamine, or methylphenidate were not associated with larger increments in haemodynamic values compared with atomoxetine or viloxazine in either children and adolescents or adults. Guanfacine was associated with decrements in haemodynamic values in children and adolescents (mean decrease against placebo of -2·83 [95% CI -3·8 to -1·85; low CINeMA confidence] in SBP, -2·08 [-3 to -1·17; low] in DBP, and -4·06 [-5·45 -2·68; moderate] in pulse) and adults (mean decrease against placebo of -10·1 [-13·76 to -6·44; very low] in SBP, -7·73 [-11·88 to -3·58; very low] in DBP, and -6·83 [-10·85 to -2·81; very low] in pulse). Only four RCTs informed on effects in the medium term and none on the long term.

Practitioners should monitor blood pressure and pulse in patients with ADHD treated with any pharmacological intervention, and not stimulants only. Given the short duration of available randomised controlled trials, new research providing insights on the causal effects of ADHD medications on cardiovascular parameters in the longer term should be funded.

National Institute for Health and Care Research.

Although acute minor stroke often presents with mild symptoms, such as unilateral limb weakness, mild aphasia, dizziness, or mild cognitive impairment, untreated outcomes could be poor, and optimal treatment methods are still debated.

We aimed to identify the optimum treatment for minor strokes with a network meta-analysis.

Studies from Embase, Ovid, and Cochrane Library were considered. Randomized controlled trials and prospective cohort studies on ischemic stroke with a National Institutes of Health Stroke Scale score no more than 5, explicit intravenous thrombolysis, or antiplatelet therapy were included. Efficacy outcome was measured by 3-month modified Rankin scale (mRS), with primary outcome defined as mRS score of 0 to 1 and secondary outcome defined as mRS score of 0 to 2. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 3 months.

Nine studies encompassing 10 665 patients were meta-analyzed. Aspirin plus clopidogrel (n = 4283) was more strongly associated with primary outcome than aspirin (n = 2128; odds ratio [OR], 1.26; 95% CI, 1.04∼1.54) and recombinant tissue plasminogen activator (rt-PA; n = 1840; OR, 1.23; 95% CI, 1.00∼1.50). Aspirin plus clopidogrel (n = 3933) also had a lower sICH risk than rt-PA (n = 2538; OR, 0.11; 95% CI, 0.04∼0.30) and tenecteplase (n = 194; OR, 0.15; 95% CI, 0.03∼0.68), as well as a lower mortality than aspirin alone (n = 830; OR, 0.27; 95% CI, 0.10∼0.71). Patients treated with aspirin (n = 815) also had a lower sICH risk than rt-PA (n = 2538; OR, 0.20; 95% CI, 0.04∼0.95).

Dual antiplatelet therapy based on aspirin and clopidogrel offers balanced efficacy and safety, positioning it as a potentially optimal treatment for minor stroke. rt-PA showed comparable efficacy, while its associated risks were more pronounced.

Although CBT has been found to be effective in the treatment of eating disorders, it is not clear if there are differences between treatment formats. We conducted a network meta-analysis (NMA) of randomized trials of broadly defined CBT comparing individual, group, guided self-help (GSH) and unguided self-help (USH) with each other or with a control condition. The NMA used a frequentist graph-theoretical approach and included 36 trials (53 comparisons; 3,136 participants). Only one trial was aimed at anorexia nervosa. All formats resulted in large, significant effects when compared to waitlists, with no significant difference between formats (group: g = 1.08, 95% CI: 0.84; 1.31; GSH: g = 0.94, 95% CI: 0.75; 1.13; individual: g = 1.06, 95% CI: 0.77; 1.36; USH: g = 0.62, 95% CI: 0.30; 0.93). No significant difference was found between any format and care-as-usual. Analyses limited to binge eating disorder supported the effects of individual, group and GSH formats, with no significant differences between them. Few trials with low risk of bias were available. CBT for eating disorders can probably be delivered effectively in any format, without significant differences between the formats. These results should be considered with caution because of the non-significant differences when compared to care-as-usual and the considerable risk of bias.

To evaluated the effectiveness and safety of single anti-seizure medication (ASM) when used as adjunctive therapy for drug-resistant focal epilepsy.

We conducted a comprehensive search of PubMed, EMbase, and the Cochrane Library from their inception until 12 February, 2025, to identify randomized controlled trials (RCTs) meeting our criteria. The trials were analyzed for their use of ASMs in treating drug-resistant focal epilepsy. Inclusion criteria comprised: 1) Participants aged 12 years or older with drug-resistant focal epilepsy; 2) Incorporation of an additional single ASM as an adjunct to the existing antiepileptic treatment regimen; 3) Comparison with placebo or continuation of the original antiepileptic regimen without a new ASM; 4) Primary outcome as a 50% response rate, with safety as a secondary outcome, encompassing dizziness, somnolence, headache, ataxia, diplopia, fatigue, and nausea; and 5) Study design limited to RCTs. The surface under the cumulative ranking curve (SUCRA) was employed to rank the effectiveness and safety of the ASMs.

A total of 53 RCTs involving 17 ASMs as adjunctive therapy and placebo were analyzed. Compared to placebo, the following ASMs demonstrated statistically significant effectiveness in achieving a 50% response rate: brivaracetam (RR = 2.07, 95% CI: 1.53-2.81), cenobamate (RR = 2.12, 95% CI: 1.56-2.88), eslicarbazepine acetate (RR = 1.95, 95% CI: 1.41-2.70), gabapentin (RR = 2.30, 95% CI: 1.76-3.02), lacosamide (RR = 2.22, 95% CI: 1.47-3.35), lamotrigine (RR = 1.55, 95% CI: 1.00-2.40), levetiracetam (RR = 2.43, 95% CI: 1.88-3.15), oxcarbazepine (RR = 3.03, 95% CI: 2.08-4.40), perampanel (RR = 1.72, 95% CI: 1.21-2.44), pregabalin (RR = 2.06, 95% CI: 1.70-2.50), rufinamide (RR = 2.28, 95% CI: 1.20-4.31), tiagabine (RR = 4.07, 95% CI: 2.03-8.18), topiramate (RR = 3.10, 95% CI: 2.44-3.95), vigabatrin (RR = 2.34, 95% CI: 1.58-3.46), and zonisamide (RR = 2.40, 95% CI: 1.76-3.27). Based on SUCRA rankings, tiagabine (92.7%) exhibited the most favorable therapeutic outcome, followed by topiramate (87.3%), oxcarbazepine (83%), and levetiracetam (62.8%). The ASMs with the least favorable therapeutic effects were placebo (1.1%), lamotrigine (17.8%), and perampanel (24.7%).

The network meta-analysis revealed topiramate, tiagabine, oxcarbazepine, and levetiracetam as the four most effective adjuvant ASM treatments for drug-resistant focal epilepsy. However, it is noteworthy that topiramate and oxcarbazepine were associated with a higher incidence of somnolence. Additionally, comprehensive safety data for tiagabine and levetiracetam are lacking, necessitating further research. Larger studies are required to solidify these findings and better understand the safety profiles of all involved ASMs.

When conducting network meta-analysis (NMA), researchers need to make several methodological and analytical decisions, which can influence the results of NMAs. Our objective was to evaluate the impact of different methodological choices on the conclusions from the analyses of a network of 20 active treatments in patients with psoriasis.

We re-analysed the available data of a living Cochrane NMA evaluating the systemic treatments in psoriasis under various analytical scenarios defined by the combination of pre-specified methodological choices. We performed NMAs on three outcomes: Psoriasis Area Severity Index (PASI) 90, PASI 100 and serious adverse events (SAEs). Variability of the effect estimates across NMAs was summarized using ratio of relative risks (RRR) and ratio of odds ratio (ROR). We estimated the level of agreement between the treatment hierarchies using the Average Overlap (AO).

Overall, 560 NMAs were conducted. The median number of included interventions was 18 (IQR 17-19), for a median number of included studies of 68 (IQR 57-93). The median RRR was 1.06 (IQR 1.06-1.08) for PASI 90, 1.07 (IQR 1.06-1.10) for early PASI 90, 1.14 (IQR 1.06-1.15) for late PASI 90, 1.04 (IQR 1.01-1.05) for PASI 100, and 1.02 (IQR 1.02-1.06) for SAEs. The criteria with the greatest impact on the effect estimates were the inclusion or exclusion of studies with biological-naïve patients, inclusion or exclusion of phase II trials, and the inclusion or exclusion of studies evaluating conventional treatments. The analysis choice with the greatest impact was the use of the Mantel-Haenszel method instead of the inverse variance method. There was a high agreement of treatment hierarchies between analyses. For the top 6 ranking treatments, the median AO across all scenarios for PASI 90 was 0.84 (IQR 0.72-0.97). For early PASI 90, late PASI 90, PASI 100, and SAE, the median AO were 0.94 (IQR 0.91-0.97), 0.75 (IQR 0.65-0.97), 0.94 (IQR 0.91-0.97), and 0.59 (IQR 0.59- 0.90), respectively.

We found that different methodological choices could influence NMAs' results. However, even though moderate variation in effect estimates could be observed across the analyses, treatment hierarchies remained stable for the top-ranking drugs.

Knee osteoarthritis (KOA) is a prevalent chronic joint disease. Due to the risks of opioid use and limited pharmacological effectiveness, mind-body exercise (MBE) therapy and other non-pharmacological interventions have emerged as first-line treatments for this condition. However, the optimal MBE modes for KOA remain undetermined. This systematic review and network meta-analysis (NMA) aims to compare the efficacy of different MBE modes, including Pilates, Tai Chi, Yoga, and Qigong, in managing KOA.

We searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Database from inception to 25 April 2024. Randomized clinical trials comparing MBE interventions for pain, physical function and quality of life (QoL) in KOA patients were eligible. The Cochrane Risk-of-Bias Tool 2.0 and Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach were used to assess literature quality and evidence certainty for each outcome.

A total of 38 studies (N = 2561) were included, with 38 for pain, 36 for physical function, and 12 for QoL in the NMA. With moderate-certainty, both Pilates and TC showed significant improvements in pain reduction [Pilates: standardized mean difference (SMD) =  - 1.19, 95% confidence intervals (95% CI): - 1.92 to - 0.46; TC: SMD =  - 0.78, 95% CI - 0.97 to - 0.59] and physical function (Pilates: SMD =  - 1.37, 95% CI - 2.13 to - 0.50; TC: SMD =  - 0.85, 95% CI - 1.08 to - 0.63) compared to the usual care group, while TC [SMD =  - 0.57, 95% CI = (- 1.07 to - 0.06)] showed statistically significant efficacy in improving QoL compared to the usual care group.

There is moderate-certainty evidence that Pilates and Tai Chi may be the most effective mind-body exercises for improving pain and physical function in knee osteoarthritis, while Tai Chi may be the best for improving quality of life. These findings may help clinicians guide their prescription of exercise types with respect to treatment outcomes. The limited number of large sample studies and the few studies with low bias risk are limitations. Trial registration The protocol for NMA has been registered with PROSPERO (CRD42024531878).

This systematic review and network meta-analysis aims to investigate the comparative effectiveness of six biophysical agents, including Transcutaneous electrical nerve stimulation (TENS), interferential current (IFC), extracorporeal shockwave therapy (ESWT), therapeutic ultrasound, low-level laser therapy (LLLT), and high-intensity laser therapy (HILT) on neck pain rehabilitation.

Three bibliographic databases, PubMed, Embase, and Scopus were searched from inception to July 30, 2024. Randomized controlled trials comparing a single biophysical agent with placebo control or another biophysical agent on neck pain intensity as an outcome were selected. Two independent reviewers independently conducted study selection, data extraction, and quality assessment. The methodological quality of included randomized controlled trials was assessed using the Physiotherapy Evidence Database scale.

A total of 34 randomized controlled trials with 2141 patients with neck pain were included, and all included studies had good or above quality. A random-effects frequentist network meta-analysis, assuming a common random-effects standard deviation for all comparisons in the network. Effects of biophysical agents on neck pain intensity were estimated as mean differences with 95% confidence intervals. League tables were created to display the relative degree of neck pain for all comparisons among the six biophysical agents.

This study suggests that rehabilitation of neck pain using biophysical agents should be prioritized in the following ranks: HILT, ESWT, IFC, TENS, LLLT, and therapeutic ultrasound. The results clarified how different biophysical agents may influence neck pain outcomes and provided proper evidence to inform clinicians to select biophysical agents prudently for neck pain management.

Over the past decade, methylation has developed rapidly for the detection of multiple diseases, and several methylation assays have been studied and even applied in clinical practice. This study undertook diagnostic test accuracy (DTA) and network meta-analysis (NMA) to investigate the value of extensively validated methylation assays for use in clinical practice or research for triage of advanced cervical intraepithelial neoplasia (CIN) among high-risk human papillomavirus (HPV)-positive women. PubMed, Web of Science, the Cochrane Library and Scopus were searched for eligible studies. DTA and NMA were conducted using R Version 4.2.0 with a random-effects model. Twenty-eight studies with 16,256 patients were included. The DTA results showed that the pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of all methylation assays for CIN grade 3+ (CIN3+) were 0.708 [95 % confidence interval (CI) 0.676-0.738], 0.780 (95 % CI 0.736-0.819), 0.436 (95 % CI 0.348-0.528) and 0.920 (95 % CI 0.885-0.945), respectively. The diagnostic odds ratio of CIN3+ was 8.828 (95 % CI 7.109-10.962), which was higher compared with that for CIN2+ (6.115, 95 % CI 4.604-8.123). NMA revealed that most methylation assays included in this study performed similarly to cytology. Among the available methylation assays, S5 classifier has a balanced performance in sensitivity and specificity overall. In conclusion, methylation assays are an effective and accurate triage strategy for advanced CIN among high-risk HPV-positive women. S5 classifier seems to be promising due to its triage performance. Cervi-M and GynTect are suitable for application in developing countries due to their superior specificity and PPV. However, more studies are needed to confirm these conclusions.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To evaluate the relative benefits and harms of therapy with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), and their combination in adults with type 2 diabetes mellitus. Secondary objectives To determine the relative rankings of GLP-1RA, SGLT2i, and their combination, according to their comparative efficacy for the critical outcomes identified in this review through a network meta-analysis.

Remdesivir (RDV) and nirmatrelvir/ritonavir (NRM/RTV) are two antiviral agents for treating outpatient adults with mild to moderate symptomatic COVID-19 at high risk of developing a severe disease. The review objectives are to compare the efficacy and safety of these antivirals based on published RCT and real-world data, and to evaluate costs from a healthcare perspective.

This study provides a network meta-analysis of RDV and NRM/RTV for early treatment of COVID-19. The outcomes analysed were hospitalisation for any cause and serious adverse events. A cost-analysis was performed incorporating drug costs, administration, hospitalisations, and management of adverse events. A budget impact analysis was estimated for the University Hospital of Padua.

Our results indicated that RDV showed a trend towards a lower risk of hospitalisation compared to NRM/RTV (RR 1.59, 95% CI: 0.60-4.20), though this was not statistically significant. For safety, NRM/RTV demonstrated a slightly lower risk of serious adverse events compared to RDV (RR 0.92, 95% CI: 0.31-2.74), but without statistical significance. A cost analysis showed that NRM/RTV could save €550,854.46 per 1,000 patients. Finally, a budget impact analysis based on data from the University Hospital of Padua estimated annual savings of €210,977.25 if all early treatments were administered with NRM/RTV instead of RDV.

The comparison of the two antiviral therapies for the early treatment of COVID-19 did not yield statistically significant differences in the potential efficacy and safety to prevent hospitalisation or serious adverse events. However, the results of the cost-analysis showed a saving in favour of NRM/RTV.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age at diagnosis of 68 years. The outcomes in older or unfit AML patients on intensive chemotherapy are poor, and thus, it is necessary to explore alternative strategies. In recent years, non-intensive therapies have transformed the standard of care for this population. Despite the increasing number of randomized clinical trials (RCTs) and cohort studies in this area, the optimal treatment approach remains unclear.

We sourced four databases, PubMed, Embase, Cochrane, and Web of Science, until July 07, 2024, to identify all Phase II/III randomized controlled trials (RCTs) and cohort studies evaluating low-intensity treatments for older AML patients. Overall survival (OS), recurrence-free survival (RFS), complete remission (CR), complete remission with incomplete hematologic recovery (CRi), overall response rate (ORR), and adverse events (AEs) graded ≥ 3 were analyzed using a Bayesian fixed-effects network meta-analysis (NMA).

A total of 4920 patients across 26 trials were included. In terms of improving OS, AZA + VEN, LDAC + glasdegib, and LDAC + VEN (SUCRA = 0.936, 0.898, and 0.718, respectively) were the most effective treatments. For CR, ORR, and CRi, AZA + VEN ranked highest among all therapies (SUCRA = 0.836, 0.911, and 0.829, respectively).

This systematic review and network meta-analysis suggest that AZA + VEN is superior to the current standard of care, particularly in improving OS, CR, ORR, and CRi. LDAC + glasdegib also demonstrated promising efficacy and warrants further investigation.

Despite the increasing approval of antiamyloid antibodies for Alzheimer disease (AD), their clinical relevance and risk-benefit profile remain uncertain. The heterogeneity of AD and the limited availability of long-term clinical data make it difficult to establish a clear rationale for selecting one treatment over another.

The aim of this work was to assess and compare the efficacy and safety of antiamyloid antibodies through an interactive online meta-analytic approach by performing conventional pair-wise meta-analyses and frequentist and Bayesian network meta-analyses of phase II and III clinical trial results. To achieve this, we developed AlzMeta.app 2.0, a freely accessible web application that enables researchers and clinicians to evaluate the relative and absolute risks and benefits of these therapies in real time, incorporating different prior choices and assumptions of baseline risks of disease progression and adverse events.

We adhered to PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for reporting of systematic reviews with network meta-analysis) and GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) guidelines for reporting and rating the certainty of evidence. Clinical trial reports (until September 30, 2024) were retrieved from PubMed, Google Scholar, and clinical trial databases (including ClinicalTrials.gov). Studies with <20 sporadic AD patients and a modified Jadad score <3 were excluded. Risk of bias was assessed with the RoB-2 tool. Relative risks and benefits have been expressed as risk ratios and standardized mean differences, with confidence, credible, and prediction intervals calculated for all outcomes. For significant results, the intervention effects were ranked in frequentist and Bayesian frameworks, and their clinical relevance was determined by the absolute risk per 1000 people and number needed to treat (NNT) for a wide range of control responses.

Among 7 treatments tested in 21,236 patients (26 studies with low risk of bias or with some concerns), donanemab was the best-ranked treatment on cognitive and functional measures, and it was almost 2 times more effective than aducanumab and lecanemab and significantly more beneficial than other treatments on the global (cognitive and functional) Clinical Dementia Rating Scale-Sum of Boxes (NNT=10, 95% CI 8-16). Special caution is required regarding cerebral edema and microbleeding due to the clinically relevant risks of edema for donanemab (NNT=8, 95% CI 5-16), aducanumab (NNT=10, 95% CI 6-17), and lecanemab (NNT=14, 95% CI 7-31), which may outweigh the benefits.

Our results showed that donanemab is more effective and has a safety profile similar to aducanumab and lecanemab, highlighting the need for treatment options with improved safety. Potential bias may have been introduced in the included trials due to unblinding caused by frequent cerebral edema and microbleeds, as well as the impact of the COVID-19 pandemic.

Antidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.

To assess antidepressants' efficacy and tolerability in individuals with depression and comorbid physical conditions.

Systematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (https://osf.io/9cjhe/).

Of the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from -1.01 (imipramine) to -0.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was 'low' or 'very low' for most comparisons.

Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.

Epidural anesthesia stands out as the most commonly employed approach for labor analgesia, frequently complemented by various local anesthetics, and the analgesic effectiveness and safety profiles of distinct local anesthetic regimens are different. To compare the efficacy and adverse reactions of different local anesthetic regimens in relieving labor pain by performing a network meta-analysis.

We systematically searched four electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials from the inception of the databases up to March 3, 2025. Included in the study were patients aged 18 to 35 years who underwent painless delivery under epidural anesthesia.

The meta-analysis included a total of 59 studies involving 6972 patients. The combination of Ropivacaine_Dexmedetomidine_Sufentanil (Rop_Dex_Suf) was the most effective and fast in reducing Visual Analog Scale (VAS) scores at 30 min after block, compared to most other anesthesia schemes. Labor pain lasted for the longest time with Ropivacaine_Dexmedetomidine(Rop_Dex). Meanwhile, Bupivacaine_Pethidine(Bpv_Pet), Bupivacaine_Dexmedetomidine(Bpv_Dex), Fentanyl(Fen), and Bupivacaine_Diamorphine(Bpv_DiaMor) had the lowest incidence of nausea, vomiting, hypotension, and pruritus. Besides, Bupivacaine_Dexmedetomidine(Bpv_Dex), Ropivacaine_Dexmedetomidine(Rop_Dex), and Ropivacaine_Dexmedetomidine_Sufentanil (Rop_Dex_Suf) have demonstrated outstanding analgesic efficacy and safety.

Our study demonstrates that the combination of ropivacaine, dexmedetomidine, and sufentanil is the most effective regimen for alleviating labor pain. Nonetheless, given the limited number of studies on certain protocols, additional high-quality, large-scale randomized controlled trials (RCTs) are anticipated to substantiate our conclusion in the future.

CRD42023459538.

Not applicable.

The optimal pharmacological prophylaxis for venous thromboembolism (VTE) after hip or knee arthroplasty is uncertain. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of various medications. We searched multiple databases for randomized clinical trials (RCTs) comparing medications (including factor Xa inhibitors, factor IIa inhibitor, warfarin, unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], aspirin, pentasaccharide) for VTE prophylaxis post-arthroplasty. Outcomes included any postoperative VTE identified with screening, major bleeding, and death. We used LMWH as the main comparator for analysis and performed trial sequential analysis (TSA) for each pairwise comparison. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessments, Developments and Evaluations). We analyzed 70 RCTs (55,841 participants). Factor Xa inhibitors decreased postoperative VTE significantly compared with LMWH (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.44-0.68, high certainty). Pentasaccharides probably reduce VTE (OR: 0.61, 95% CI: 0.36-1.02, moderate certainty), while the factor IIa inhibitor dabigatran may reduce VTE (OR: 0.75, 95% CI: 0.40-1.42, low certainty). UFH probably increases VTE compared with LMWH (OR: 1.31, 95% CI: 0.91-1.89, moderate certainty), and other agents like warfarin, aspirin, placebo, and usual care without thromboprophylaxis increase VTE (high certainty). Factor Xa inhibitors may not significantly affect major bleeding compared with LMWH (OR: 1.06, 95% CI: 0.81-1.39, low certainty). No medications had a notable effect on mortality compared with LMWH (very low certainty). TSA suggests sufficient evidence for the benefit of factor Xa inhibitors over LMWH for VTE prevention. Compared with LMWH and aspirin, factor Xa inhibitors are associated with reduced VTE after hip or knee arthroplasty, without an increase in bleeding and likely no impact on mortality.

The comparative efficacy of automated insulin delivery (AID) systems and other treatment options for type 1 diabetes, accounting for the certainty of evidence (CoE), is unknown.

We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov and included outpatient randomised controlled trials (RCTs) published until January 8, 2025, in people with type 1 diabetes with a three-week or longer intervention of AID systems (PROSPERO registration number: CRD42023395492). We performed pairwise and network meta-analyses and used the Risk of Bias tool 2 and the Grading of Recommendations Assessment, Development and Evaluation methods to determine the CoE for each outcome.

A total of 46 studies involving seven insulin treatment options and 4113 participants were included, of which 29 and 17 had low and moderate risks of bias, respectively. The intervention AID systems, including the hybrid closed-loop (HCL), advanced HCL (AHCL) and full closed-loop (FCL) systems, were evaluated in 20, 25 and 1 studies, respectively. The network meta-analysis did not indicate global inconsistencies but did indicate global publication bias for all glycaemic outcomes. The CoE varied between very low and high, depending on the treatment and outcome under consideration. Compared with pump therapy, the percentage of time in the range 70-180 mg/dl was greater with AID use (HCL: 19.7% [95% confidence interval 13.2%; 26.1%], moderate CoE; AHCL: 24.1% [18.2%; 29.9%], moderate CoE; FCL: 25.5% [11.1%; 39.9%], high CoE). Compared with pump therapy, the percentage of time above 180 mg/dl and 250 mg/dl was lower with AHCL, on average, by 19.6% (14.0%; 25.1%), moderate CoE, and 14.8% (8.8%; 20.8%), moderate CoE, respectively. The CoE was very uncertain regarding the overall effect of AID systems on the percentage of time below 70 mg/dl and 54 mg/dl and the HbA1c.

AID systems improve glycaemic outcomes to varying degrees and with varying CoE.

German Federal Ministry of Education and Research (BMBF; grant 01KG2203).