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.

Despite limited breakthroughs in COPD pharmacotherapy, recent trials have shown promising results for biologics in COPD patients. However, robust evidence synthesis in this area is currently lacking.

We conducted a systematic review of MEDLINE, EMBASE, and Cochrane CENTRAL from inception to July 17, 2024, to identify randomized trials of biologic medications in patients with COPD. We performed a random effects frequentist network meta-analysis and present the results using relative risk (RR) and 95% confidence intervals (CI). We used the GRADE framework to rate the certainty of the evidence. Outcomes of interest included exacerbations, change in FEV1, change in quality of life, and serious adverse events.

Dupilumab reduced exacerbations as compared to placebo (RR 0.68 [95% CI 0.59 to 0.79]) (high certainty). Benralizumab (RR 0.89 [95% CI 0.78 to 1]), itepekimab (RR 0.81 [95% CI 0.61 to 1.07]) and tezepelumab (RR 0.83 [95% CI 0.61 to 1.12]) may reduce exacerbations as compared to placebo (all low certainty). Dupilumab probably reduced exacerbations more than mepolizumab (RR 0.74 [95% CI 0.62 to 0.89]) (moderate certainty). Dupilumab may reduce exacerbations more than tezepelumab (RR 0.82 [95% CI 1.14]) (low certainty). For all patients, no treatment improved FEV1 above the pre-specified minimal clinically important difference (MCID) of 0.1 L. Dupilumab probably has no meaningful effect on FEV1 compared to placebo (MD 0.07 [95% CI 0.02 to 0.13]) (moderate certainty). However, in the subgroup of patients with blood eosinophils ≥300/mcL, both tezepelumab (MD 0.15 [95% CI 0.05 to 0.26]) and dupilumab (MD 0.13 [95% CI 0.06 to 0.19]) probably improved FEV1 above the MCID.

Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. Other biological therapies, including tezepelumab, have no important effect on patient-relevant outcomes.

Comparative effectiveness data of COVID-19 vaccines remain limited. We conducted a systematic review and network meta-analysis (NMA) feasibility assessment of effectiveness studies of Omicron-adapted COVID-19 vaccines.

Searches in MEDLINE and Embase up to February 2025 identified studies comparing the effectiveness of Omicron-adapted COVID-19 vaccines, either directly or against no recent vaccine. Two investigators independently selected articles reporting adjusted vaccine effectiveness (VE). A feasibility assessment determined the appropriateness of a common comparator and evaluated effect modifiers (EMs). Data extraction and risk-of-bias assessment were performed by one investigator and validated by a second investigator. Bayesian NMAs using random-effects models were performed for base-case analyses, data permitting.

The review identified 25 studies for Omicron-adapted COVID-19 vaccines: 16 for XBB formulations, eight of which were included in NMAs, all for mRNA formulations, representing 29.9 million participants. BNT162b2 had the largest evidence base. Comparisons between XBB.1.5-adapted BNT162b2 (Comirnaty) and mRNA-1273 (Spikevax) found that both vaccines are effective and comparable against XBB-related hospitalizations, infections, and medically attended visits in adults Among elderly, the estimated effectiveness against XBB-related hospitalizations favored BNT162b2.

Findings of this NMA of observational studies support the effectiveness of XBB.1.5-adapted mRNA vaccines. Limitations included assumptions on EMs and sparse evidence networks.

To comprehensively compare and rank hormone therapy for patients with perimenopausal syndrome.

A comprehensive search was conducted on PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang databases from inception to August 20, 2024. The quality of the included randomized controlled trials (RCTs) were measured by the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was applied to grade the quality of evidence in this network meta-analysis. Network plots were depicted to show direct and indirect comparisons of hormone therapy for each outcome. The influences of different hormone therapy on the outcomes were illustrated via forest plots and league tables. Rank probabilities showed the ranking of different administration routes.

Seven studies involving 704 perimenopausal syndrome patients were included. The rank probabilities suggested that oral estradiol (E2) combined with medroxyprogesterone and general health guidance had the highest likelihood to be the optimal therapy for the severity of menopausal syndrome. General health guidance combined with oral E2 was less likely to have a nausea and vomiting, and breast pain.

Oral E2 and medroxyprogesterone or general health guidance combined with oral E2 may be the effective and safe option for the management of perimenopausal syndrome.

This study evaluates and compares the effectiveness and safety of febuxostat and allopurinol in chronic kidney disease (CKD) stages 3-5 patients with asymptomatic hyperuricemia using a network meta-analysis.

A systematic review and network meta-analysis were conducted, adhering to PRISMA-NMA guidelines. Searches included PubMed, Embase, Cochrane Library, and Chinese databases up to June 2024. Randomized controlled trials (RCTs) and cohort studies were assessed for methodological rigor using GRADE.

A total of 12 RCTs and 4 cohort studies (n = 2,423 participants) were included. Febuxostat was associated with greater improvements in estimated glomerular filtration rate compared to allopurinol (MD, 4.99 mL/min/1.73 m2; 95%CI -0.65 to 10.78; certainty: low) and placebo (MD, 4.72 mL/min/1.73 m2; 95%CI 0.67 to 8.82; low). Serum uric acid reduction was also more pronounced with febuxostat (MD, -0.61 mg/dL; 95%CI -1.15 to -0.05; moderate). Safety outcomes, including major cardiovascular events and adverse events, showed no significant differences between febuxostat and allopurinol. Subgroup analyses revealed enhanced effectiveness of febuxostat at six months of treatment.

This analysis provides robust evidence that febuxostat might offers greater improvements in kidney function and uric acid levels compared to allopurinol or placebo in asymptomatic hyperuricemia with CKD stage 3-5 patients, without compromising safety. These findings can guide clinical decision-making and treatment optimization.

Aerobic exercise improves cognitive functions in older adults with mild cognitive impairment (MCI), while dance, combining music and synchronized movement, offers additional cognitive benefits. Despite music's potential role in enhancing cognitive outcomes, most research on aerobic exercise has not considered the impact of accompanying music. This review compared the effectiveness of aerobic exercise with music, aerobic exercise without music, and dance on cognitive function in adults with MCI. A total of 38 papers from 25 randomized controlled trials (N = 2048) were synthesized. The multilevel meta-analyses showed that compared to the control group, global cognition was improved by aerobic exercise with music (g = 1.2 [0.47, 1.94]), aerobic exercise without music (g = 0.48 [0.18, 0.79]), and dance (g = 0.55 [0.13, 0.96]). Dance also enhanced short-term memory (g = 0.41 [0.24, 0.59]), learning efficiency (g = 0.39 [0.14, 0.65]), and retrieval fluency (g = 0.7 [0.19, 1.22]). Bayesian network meta-analyses indicated that aerobic exercise with music had the highest probability of being the most effective for improving global cognition, executive function, and processing speed. Dance was likely to be the most beneficial for enhancing short-term memory, learning efficiency, and retrieval fluency. This study supports that incorporating music in exercise amplifies the cognitive benefits beyond exercise alone for individuals with MCI. The "Music Exercise Synergy Model" is proposed to explain the cognitive benefits of combining music with exercise. Dance strategically uses music for coordination, offering psychological, social, cognitive, and neurobiological benefits and contributing to the observed enhancements in memory functions.

Several studies have demonstrated the positive impact of non-pharmacological Traditional Chinese Medicine (TCM) therapies on pain, fatigue, sleep quality, and quality of life in cancer survivors. However, no research has compared the effectiveness of these therapies. This study aims to compare various interventions and identify the most effective non-pharmacological TCM therapies to provide evidence-based recommendations for cancer survivors.

A systematic search was conducted in PubMed, Embase, Web of Science, CNKI, and Wanfang Data. RCTs investigating the effects of Taichi, Qigong, acupuncture, acupressure, TCM emotional therapy, and mixed therapies as interventions for cancer survivors were screened was conducted. Data from the creation of the database to February 2025 were included. Two independent reviewers evaluated the study quality. A Bayesian Network Meta-analysis was conducted to carry out a random effects model.

Seventy-one RCTs involving 6473 patients were included in the analysis. Network meta-analysis showed significance for all five intervention therapies in pain control in cancer patients. The best efficacy was observed for acupressure (SMD=-1.1 [-1.55, -0.66]) and Taichi/Qigong (SMD=-1.08[-1.64, -0.53]), followed by TCM emotional therapy (SMD=-0.93 [-1.42, -0.44]) and acupuncture (SMD=-0.54 [-0.93, -0.15]), with the latter showing comparatively lower efficacy. None of the interventions demonstrated superior efficacy in improving fatigue compared to the control group. Mixed therapies (SMD=-1.36[-2.56, -0.28]) demonstrated the greatest effect in improving sleep quality. Taichi/Qigong (SMD=1.87 [0.96, 2.83]) demonstrated certain advantages in improving quality of life. However, acupuncture and TCM emotional therapy had no significant effect on sleep quality or overall quality of life.

The evidence from this study suggests that acupressure and Taichi/Qigong are recommended as the most effective therapies for pain relief and quality of life improvement, respectively. The efficacy of these therapies for fatigue remains inconclusive. However, due to the limited number of included studies and the high risk of bias, these results should be interpreted with caution. Future studies should include more rigorously designed high-quality randomized controlled trials to confirm their long-term efficacy and safety.

PROSPERO CRD42024601976.

In the Phase 3 DREAMM-7 study of patients with relapsed/refractory multiple myeloma (RRMM) who received ≥ 1 prior therapy, belantamab mafodotin plus bortezomib and dexamethasone (BVd) demonstrated a progression-free survival (PFS) benefit versus daratumumab plus bortezomib and dexamethasone (DVd). This study aimed to indirectly compare the efficacy of BVd against alternative regimens in this patient population. A systematic literature review (SLR; December 2021-February 4, 2024) was performed to identify relevant efficacy data. Studies were selected based on the Population-Intervention-Comparators-Outcomes-Study design framework criteria and independently reviewed for inclusion in the network meta-analysis (NMA) if they had a connection to DREAMM-7 (approved in the US or EU, or likely to be a future DREAMM-7 comparator). Each trial had a common comparator arm, allowing for a connected network between the trials and linkage by shared treatments. The primary analysis was PFS in the intent-to-treat population from each study, and secondary analyses examined other endpoints. All endpoints were also evaluated in subgroups by lenalidomide-exposure, -refractoriness, and other patient characteristics. The SLR identified 12 comparator studies comprising 12 comparator regimens (each contained a proteasome inhibitor [bortezomib or carfilzomib] plus dexamethasone), all of which were included in the NMA with the DREAMM-7 study. BVd improved PFS versus all comparators, including daratumumab plus carfilzomib and dexamethasone, isatuximab plus carfilzomib and dexamethasone, and DVd. Overall survival was also improved by belantamab mafodotin plus bortezomib and dexamethasone over the other regimens. This study provides compelling evidence for belantamab mafodotin, plus bortezomib and dexamethasone, in early lines of treatment for RRMM.

The evidence for the effect of cupping therapy on chronic nonspecific low back pain (CLBP) remains controversial, and existing researches didn't consider outcomes influenced by factor of selection of interventions in control group. This review and network meta-analysis is to compare the effects of diverse interventions in cupping therapy control groups for CLBP, with the objective of identifying the suitable control intervention against cupping therapy for CLBP.

Studies were identified by a comprehensive search of databases, such as PubMed, Embase, Cochrane Library, Web of Science and China National Knowledge Infrastructure (CNKI), up to June, 2024. A total of 10 randomized control trials (RCT) were included in this network meta-analysis (NMA).

The results showed that compared with cupping therapy, minimum negative pressure cupping therapy (MNPCT) (SMD = - 0.01; 95 %CI: - 0.92 to 0.89), air circulating cupping therapy (ACCT) (SMD = - 0.05; 95 %CI: - 0.63 to 0.54) and diclofenac (SMD = - 0.13; 95 %CI: - 1.13 to - 0.87) was no significantly different from improvement of pain intensity. But there was significant difference between cupping therapy and D-ibuprofen (SMD = - 1.11; 95 %CI: - 2.08 to - 0.13), paracetamol (SMD = - 1.12; 95 %CI: - 1.80 to - 0.43) or usual care (SMD = - 1.18; 95 %CI: - 2.56 to - 1.06). The order of intervention effect by SUCRA diagram was as follows: cupping therapy (77.7 %) > MNPCT (75.2 %) > ACCT (73.8 %) > diclofenac (68.8 %) > D-ibuprofen (26.3 %) > paracetamol (24.5 %) > usual care (3.8 %). The quality of evidence for network estimates was moderate to very low due to the risk of bias and imprecision.

The results of this study suggest that usual care was the least effective in alleviating the pain intensity of CLBP, which might serve as the most appropriate intervention in the control group in cupping-related RCTs. MNPCT and ACCT have similar effects with cupping therapy for CLBP. Future research may be based on some objective clinical outcomes and control interventions with physiological inertia to isolate the true effect of cupping therapy or SCT from psychological biases.

The protocol was registered on the international prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42024527513.

This systematic review with network meta-analysis (NMA) analysed the current evidence on in vitro studies comparing trueness of fit, surface roughness, colour stability, surface wettability, water sorption, water solubility, and microbial adhesion between conventional and digital denture bases.

From inception until December 2023, a systematic search of published in-vitro studies from Scopus, PubMed, and the Cochrane Central Register of Controlled Studies was conducted. The protocol was registered in PROSPERO (CRD42024531416). NMA compared properties related to dimensional accuracy and surface properties between conventional and digital dentures. The ranking was performed using the surface area under the cumulative ranking guidelines.

A total of 6004 articles were initially identified, of which 342 duplicates were removed, and 5566 were excluded by screening the titles and abstracts. A total of 96 articles were assessed by full-text reading, and 43 were included in the quantitative synthesis. As per the NMA results, MIL demonstrated significantly higher trueness of fit when compared with conventional compression moulding (standardized mean differences [SMD] = -2.25 [95% CI: -4.09, -0.40]), P = .017 (<.05) and TDP (SMD = -1.57 [95%CI: -3.14, -0.01]) P < .05. MIL demonstrated significantly lower surface roughness when compared with conventional compression moulding (SMD = -0.99 [95% CI: -1.72, -0.26]), P = .008 (<.05), and TDP (SMD = -1.08 [95%CI: -1.95, -0.22]) P < .05.

There is conclusive evidence that milled digital denture bases demonstrate higher trueness of fit and lower surface roughness than 3D-printed denture bases and conventional denture bases, as demonstrated by the concurrent network and pairwise results.

In vitro studies show that milled digital dentures exhibit higher accuracy and lower surface roughness. The clinical performance of milled dentures in relation to these properties needs to be evaluated by high-quality randomized controlled clinical trials.

Since the 1990s, there has been a rise in the number of publications assessing the effects of applying non-invasive brain stimulation (NIBS) to treat patients with drug-resistant depression. This involves applying magnetic fields or electrical currents to the surface of the skull to influence the superficial neurons in the cerebral cortex. Due to the evidence regarding symptom reduction in these types of patients, such as irritability or hostility, there was a rise in the use of this technique to reduce negative mood, including anger state. This decrease in anger state could also help reduce other problems such as violence proneness. In this sense, the anger state of individuals who are prone to violence might be affected by interfering with the excitability of the prefrontal cortex (PFC), a key brain region responsible for behavioral regulation. Thus, we conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. After initially identifying 2426 sources, we eventually included a total of 69 publications for the systematic review, from which 45 were employed for the meta-analysis. Only a few of them highlighted a significant contribution of using NIBS techniques on different regions of the PFC to reduce anger state or violence when compared to participants receiving sham stimulation in normative and clinical samples. Furthermore, the comparison of effect sizes between groups that received real stimulation on several regions of the PFC and those that received sham stimulation did not reveal a significant difference in reducing anger state or violence. In addition, despite most of the conclusions being consistent, considerable heterogeneity existed across studies regarding certain PFC regions, which could be explained by the type of NIBS employed. Therefore, using superficial stimulation over the PFC as a general tool for reducing violence proneness should be approached with caution, except in specific cases.

The application of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in patients with early stroke has recently received considerable attention, but the optimal protocol remains inconclusive. This study intends to evaluate and compare the effects of different protocols of tDCS and rTMS on improving motor function, activities of daily living (ADL), and neurological function in patients with early stroke, and to comprehensively assess their efficacy and safety.

MEDLINE, Embase, Cochrane Library, and Web of Science were searched. Risk of bias (RoB) was assessed using the Cochrane Risk of Bias 2.0 tool, and Bayesian NMA was conducted using R4.3.1 and Stata16.

The results of NMA showed that after early intervention, bilateral application of high- and low-frequency rTMS (BL-rTMS) performed best in improving the upper extremity motor function at the end of intervention (SUCRA: 92.8%) and 3 months (SUCRA: 95.4%). Besides, low-frequency rTMS (LF-rTMS) performed best in improving the lower extremity motor function (SUCRA: 67.7%). BL-rTMS was the most effective in ameliorating the ADL at the end of intervention (SUCRA: 100%) and 3 months (SUCRA: 85.6%). In terms of the NIHSS scores, BL-rTMS had the highest probability of being the most effective measure at the end of intervention (SUCRA: 99.7%) and 3 months (SUCRA: 97.05%). Besides, LF-rTMS (0%), 5 Hz-rTMS (0%), and intermittent theta-burst stimulation (iTBS) (0%) all exhibited a good safety profile.

BL-rTMS is the optimal stimulation protocol for improving upper extremity motor function, ADL, and neurological function in early stroke, with long-term efficacy.

Chronic lower back pain (CLBP) severely affects an individual's quality of life and increases reliance on healthcare services. Previous meta-analyses have primarily examined the effects of essential oils and herbal remedies separately, without considering their combined therapeutic potential. The present meta-analysis integrated both treatment modalities to evaluate the efficacy of botanical extract-based therapies for CLBP management. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with data extracted from randomized controlled trials (RCTs) conducted up to July 2024. A comprehensive search of several databases identified 13 RCTs that met the inclusion criteria, focusing on interventions using plant extracts, including various herbal formulations and essential oils. The meta-analysis demonstrated that botanical extract-based treatments, whether applied topically, combined with massage or administered orally, were more effective compared with a placebo in reducing pain, enhancing lumbar flexibility and extending walking duration in patients with CLBP. These findings support the role of botanical extracts as viable therapeutic options for CLBP management, emphasizing their potential integration into comprehensive pain management strategies. However, further research is necessary to explore their long-term efficacy and underlying mechanisms. The present study is registered in PROSPERO (registration no. CRD42024554015).

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).

Residual sleepiness can occur in adult patients with obstructive sleep apnea (OSA) despite adequate treatment with continuous positive airway pressure (CPAP). Various wake-promoting agents (WPAs) have been shown to reduce residual sleepiness in CPAP-treated patients with OSA. This systematic review and network meta-analysis aimed to compare the efficacy and safety of WPAs in this setting.

We searched MEDLINE, Scopus, and ClinicalTrials.gov up to 9 January 2025 for randomized controlled trials (RCTs) examining WPAs for treating sleepiness in patients with OSA. Included were all RCTs that explored the efficacy and/or safety of any approved WPAs (i.e., modafinil, armodafinil, solriamfetol, or pitolisant) in patients with OSA (aged ≥ 18 years) treated with CPAP but who are still sleepy [Epworth sleepiness scale (ESS) score ≥10]. Studies that were conducted in patients whose comorbidities cause daytime somnolence [i.e., psychiatric conditions (other than depression), other sleep disorders, medical or surgical conditions], open label extension studies, and studies published in a language other than English were excluded. The primary outcomes included ESS, maintenance of wakefulness test (MWT), and adverse events. Two authors independently assessed the risk of bias using the revised Cochrane risk-of-bias tool for randomized trials 2.0.

In total, 14 RCTs studying four WPAs (total N = 2969) including modafinil (six RCTs; 200-400 mg/day), armodafinil (four RCTs; 150-250mg/day), solriamfetol (two RCTs; 37.5-300 mg/day), and pitolisant (two RCTs; 5-40 mg/day) were included. Solriamfetol, modafinil, and armodafinil were efficacious in reducing subjective sleepiness as measured by ESS [mean difference (95% confidence interval) at ≤ 4 weeks: -3.84 (-5.60, -2.07), -2.44 (-3.38, -1.49), and -2.41 (-3.60, -1.21) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: -4.11 (-6.14, -2.08), -2.88 (-3.85, -1.91), -2.46 (-3.68, -1.24) for solriamfetol, armodafinil, and modafinil, respectively] and clinical global impression of change, as well as the objective MWT [at ≤ 4 weeks: 11.66 min (9.70, 13.61), 3.61 min (2.48, 4.73), and 2.52 min (1.27, 3.76) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: 10.34 min (4.16, 16.52) for solriamfetol]. Pitolisant showed later improvements in ESS [at > 4 weeks: -2.70 (-3.66, -1.73)], with limited data on MWT. Sensitivity analyses restricted to U.S. Food and Drug Administration-approved solriamfetol dosages (37.5-150 mg/day) still showed higher efficacy, but lower anxiety risk.

Among all WPAs, solriamfetol demonstrated the highest efficacy on ESS and MWT, with the latter being significant. Modafinil demonstrated the best clinician impression, albeit not statistically significant. All four WPAs were associated with a low risk of serious or adverse events.

PROSPERO registration number, CRD42022359237.

Metabolic dysfunction associated steatotic liver disease (MASLD) is a universal hepatic disease, and many recent randomized clinical trials (RCTs) have explored whether hypoglycemic agents may be beneficial for its treatment. This study aimed to assess the relative effectiveness of each hypoglycemic agent for MASLD.

China National Knowledge Infrastructure（CNKI）, WanFang, Weipu, PubMed, Embase, The Cochrane Library, and Web of Science Core Collection were searched for RCTs on the efficacy of hypoglycemic agents in MASLD published up to December 31, 2024. All statistical analyses were performed using R version 4.3.3. The network meta-analysis was conducted using Bayesian statistical methods.

A total of 26 hypoglycemic agents for treating MASLD in 37 studies with 2406 participants were included. Empagliflozin was most effective in improving liver stiffness measurement (LSM), whereas liraglutide showed significant benefits in body weight, body mass index (BMI), and waist circumference. Both sodium-glucose co-transporter 2 (SGLT-2) inhibitors (e.g., empagliflozin) and glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide) improved liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT]), glucose metabolism (fasting plasma glucose [FPG], and homeostasis model assessment of insulin resistance [HOMA-IR]), and lipid profiles. Pioglitazone had limited benefits in these outcomes. Secondary outcomes such as inflammatory markers and fibrosis showed minimal changes.

Several hypoglycemic agents can improve laboratory and imaging indicators in adult patients with MASLD. Liraglutide is more effective than other agents, whereas empagliflozin emerged as the most effective for reducing LSM. However, different agents have different effects on the indicators; therefore, the relevant agents must be selected according to the specific patient condition.

The relative efficacy and safety of tirzepatide was compared with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM) treated with basal insulin using a network meta-analysis (NMA).

A systematic literature review was performed to identify randomized controlled trials of GLP-1 RAs in patients with T2DM treated with insulin and an antihyperglycaemic drug. For the NMA, studies included trials with 100% of patients treated with basal insulin background therapy with a titration scheme comparable to the SURPASS-5 trial. The following data were extracted for efficacy and safety assessment at the primary endpoint of each study: changes from baseline in glycated haemoglobin (HbA1c) and body weight and the incidence of nausea, vomiting or diarrhoea, hypoglycaemia, and patients discontinuing treatment because of adverse events. In this study, a comparative analysis of tirzepatide was performed with the GLP-1 RAs dulaglutide, exenatide, and lixisenatide in addition to placebo.

A total of six studies were included across the analyses. Tirzepatide 5, 10, and 15 mg showed statistically significant, greater reductions in HbA1c and body weight at the primary endpoint versus all GLP-1 RA comparators and placebo. Tirzepatide 5, 10, and 15 mg showed a statistically significant, higher likelihood of experiencing nausea compared with those who received placebo or exenatide 2 mg; no statistically significant differences were observed when compared with all other GLP-1 RA comparators. No statistically significant differences were observed in the proportions of patients who discontinued treatment because of adverse events when tirzepatide 5, 10, and 15 mg were compared with GLP-1 RA comparators, apart from tirzepatide 10 and 15 mg versus placebo.

Tirzepatide demonstrated statistically significantly greater reductions in HbA1c and body weight when compared with selected GLP-1 RAs and placebo in patients with T2DM treated with basal insulin. Overall, the safety profile of tirzepatide was similar to that of GLP-1RAs.

Cerebellum has been a emerging target for non-invasive brain stimulation (NIBS) on post-stroke patients in recent years. While research is emerging on the impact of cerebellar repetitive transcranial magnetic stimulation (rTMS) on post-stroke patients, and its integrated effect remain unclear.

The objective of this review is to evaluate the efficacy of cerebellar rTMS on stroke rehabilitation.

We searched PubMed, EMBASE, and Web of Science databases from inception to 31 March 2024 for randomized controlled trials (RCTs) and case studies reporting effects of cerebellar rTMS on patients with stroke.

This review included 18 studies (n = 638 participants), consisting of 14 RCTs and 4 case reports. A total of 6 studies focused on post-stroke dysphagia, while 12 studies investigated post-stroke motor dysfunction. Comparative analysis between treatment and control groups revealed statistically significant improvements in swallowing function, as measured by the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) (P = 0.02), the Penetration Aspiration Scale (PAS) (P < 0.001), and the Standardised Swallowing Assessment (SSA) (P < 0.001). Moreover, cerebellar rTMS treatment showed significant enhancements in balance abilities and activity of daily living among stroke patients, as indicated by significant increases in the Berg Balance Scale (BBS) (P = 0.003) and the Barthel Index (BI) (P = 0.04) compared to the control group.

Existing evidence suggests that cerebellar rTMS holds promise in mitigating post-stroke swallowing dysfunction and motor dysfunction. Stimulation by cerebellar rTMS appears to be an efficacious technique for enhancing stroke rehabilitation.

Assessment measures for suicidal behavior range from depression scales to longer suicide-specific instruments. In this review, we systematically summarize and discuss the currently used instruments for assessing suicidal behavior in the context of ketamine and its enantiomers. We searched Medline/PubMed, Embase, and PsycINFO databases for ketamine (and its enantiomers) human studies exploring this drug's antisuicidal effects on major depressive disorder patients, published from February 2000 to June 2023. Forty-six studies were included, identifying 16 assessment tools, mostly explicit and clinician-rated measures. Prominent tools included the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAM-D), and both the clinician and patient-rated Beck Scales for Suicide Ideation (SSI and BSS). With the exception of the Suicide Ideation and Behavior Assessment Tool (SIBAT), to the best of our knowledge, no other instrument that assesses suicidality seems to be specifically developed for measuring treatment response in rapid-acting antidepressants trials. Most scales have been validated in conventional antidepressant or psychotherapy contexts, though, for MADRS, as well as for SSI, BDI, and HAM-D, efforts have been made towards investigating their psychometric properties in the field of rapid-acting antidepressants. The heterogeneity of suicidal behavior assessment in ketamine studies may hinder adequate comparisons between them. Although there does not seem to be a universally preferable instrument for measuring suicidal behavior to date, the MADRS potentially emerges as an adequately recommended choice.

Non-invasive brain stimulation (NIBS) has the potential to treat generalized anxiety disorder (GAD). To assess the efficacy (response/remission/post-treatment continuous anxiety severity scores) and acceptability (failure to complete treatment for any reason) of NIBS, we searched PubMed, Web of Science, and the Cochrane Library (as of April 2024) for articles on NIBS for GAD and conducted a network meta-analysis of eight randomized trials (20 treatment arms, 405 participants). Data were pooled using standardized mean difference (SMD) and odds ratio (OR) with 95 % confidence interval (CI). Repetitive transcranial magnetic stimulation (rTMS) was the most widely studied treatment for GAD. The right dorsolateral prefrontal cortex (DLPFC) was the most common treatment target for GAD. High-frequency rTMS showed higher response rates (OR 291.40, 95 % CI 13.08 to 6490.21) and remission rates (OR 182.14, 95 % CI 8.72 to 3805.76) compared with other active therapies. Continuous theta burst stimulation (cTBS) greatly improved continuous post-treatment anxiety severity scores (SMD -2.56, 95 % CI -3.16 to -1.96). No significant differences in acceptability were found between the treatment strategies and the sham stimulation group. These findings provide evidence to consider NIBS techniques as alternative or adjunctive treatments for GAD.

As the population ages rapidly, cognitive impairment, especially in conditions like Alzheimer's disease (AD) and mild cognitive impairment (MCI), has become a crucial public health issue. Nutritional interventions have garnered attention as a promising non-pharmacological strategy for maintaining cognitive function and decelerating its decline.

This study aimed to evaluate the effectiveness of various nutritional interventions in preventing cognitive impairment and elucidate intricate biological pathways linking nutritional interventions to cognitive function through a comprehensive approach involving systematic review, network meta-analysis (NMA), and Mendelian randomization (MR) analysis.

We utilized pair-wise comparisons and NMA to evaluate the efficacy of different nutritional interventions on cognitive function in patients with decreased cognitive abilities. A systematic search in three biomedical databases was performed for double-blinded, randomized controlled trials (RCTs) or head-to-head comparisons up to December 31, 2024. The NMA has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022331173). Moreover, to clarify the biological mechanisms linking nutritional interventions to cognitive impairment, we conducted two-sample MR analyses to assess the potential causal relationships between 9 genetically predicted nutrient levels derived from extensive genome-wide association studies (GWASs) and 12 biomarkers linked to brain aging.

This study encompassed 52 trials with 8452 participants, 9 GWASs examining genetically predicted nutrient levels with a total of 603,996 participants, and 12 GWASs investigating brain aging biomarkers with a total of 2,405,530 participants. The NMA demonstrated that the multi-ingredient intervention outperformed other interventions significantly (standardized mean difference [SMD] = 2.03; 95 % credible interval [95 % CrI] = 0.97-3.09, P = 0.0002). In the MR analysis, the findings indicated that the multi-ingredient intervention was linked to reduced C-reactive protein (CRP) levels (odds ratios [OR] = 0.96, 95 % confidence interval [95 % CI] = 0.93-0.99, P = 0.014), suggesting that the multi-ingredient intervention may mitigate cognitive impairment by reducing inflammation.

Our NMA amalgamated evidence underscoring multi-ingredient interventions as the most efficacious strategy for attenuating cognitive decline in individuals with MCI and AD. Furthermore, the MR analysis unveiled the mechanisms underpinning the protective effects of multi-ingredient interventions, potentially offering benefits even in the early stages of neurodegeneration by mitigating oxidative stress and inflammation.

This study evaluated how different exercise interventions affect maximal oxygen uptake (VO2max) in adults with overweight or obesity. We systematically searched five databases from inception to February 2025 to identify relevant randomized controlled trials (RCTs). We used the Cochrane risk of bias tool. A Bayesian network meta-analysis with a random-effects model was conducted. A total of 93 RCTs involving 4,446 participants were included. The network meta-analysis showed high-intensity interval training (HIIT) ranked highest (Surface Under the Cumulative Ranking Curve [SUCRA]: 82.5%; Standardized Mean Difference [SMD]: 4.85; 95%Credible Interval [CrI]: 3.90, 5.80), followed by high-intensity aerobic training (HAT) (SUCRA: 76.7%; SMD: 4.72; 95%CrI: 3.78, 5.68), and combined aerobic and resistance training (CT) (SUCRA: 69.1%; SMD: 4.52; 95%CrI: 3.48, 5.60), with resistance training (RT) least effective (SUCRA: 18.3%; SMD: 2.57; 95%CrI: 1.32, 3.86). All six interventions effectively improved VO2max in overweight or obese adults. Among them, HIIT was most beneficial. Coaches and fitness professionals should consider these findings to help adults with overweight or obesity achieve optimal outcomes.

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.

Thrombopoietin receptor agonists-romiplostim, eltrombopag and avatrombopag-are commonly used as second-line treatments for immune thrombocytopenia (ITP).

A Markov model was developed to estimate the cost effectiveness of the three TPO-RAs in adults with insufficient response to previous treatment from the perspective of the UK National Health Service (NHS). The model considered the effects of bleeding events, concomitant ITP medications, rescue therapies and treatment related adverse events over a lifetime horizon. Model inputs for effectiveness were based on a network meta-analysis and other published literature on ITP management. Other model inputs included costs (e.g., drug acquisition and administration) and healthcare resource utilisation.

Avatrombopag was associated with higher quality-adjusted life-years (QALYs) (10.979) than romiplostim (10.628) and eltrombopag (10.085), producing incremental QALYs of -0.351 and -0.894, respectively. Avatrombopag was associated with lower total costs (GBP £319,334) compared with romiplostim (GBP 406,361 [cost saving of GBP 87,027]) and higher total costs compared with eltrombopag (GBP 313,987 [incremental cost of GBP 5347]). Avatrombopag therefore dominated romiplostim (more effective and less expensive) and was cost-effective versus eltrombopag (incremental cost-effectiveness ratio of GBP 5982 per QALY).

Avatrombopag is a cost-effective treatment compared with romiplostim and eltrombopag for the second-line treatment of adults with ITP from the perspective of the UK NHS.

This systematic review and network meta-analysis (NMA) was to investigate the effects of different exercise modalities on inflammatory markers in cancer patients. Using the standardized mean difference (SMD) as the effect size, a Bayesian random-effects network meta-analysis and regression analysis were conducted. Searches were performed across five databases for randomized controlled trials (RCTs) involving cancer patients, with exercise as the intervention, reported outcomes related to inflammatory markers, and interventions lasting more than four weeks, up to June 2024. A total of 57 RCTs (3106 patients) were included. The Cochrane risk of Bias Tool was utilized to assess the RCTs, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was employed to evaluate the quality of evidence. NMA results indicate that regular exercise is effective in reducing inflammation in cancer patients, with combined high-intensity aerobic and resistance exercises proving to be the most beneficial. The type, intensity, and total volume of exercise are critical factors in achieving positive outcomes. It is recommended to design exercise programs for cancer patients that combine aerobic and resistance training, with a gradual increase in intensity to ensure safety.

This study aimed to rank dry off interventions for the prevention of new intramammary infections (IMI) and the cure of existing IMI in quarters of dry cows using two network meta-analyses. Randomized controlled trials reported in 137 papers were assessed for inclusion eligibility. Network meta-analyses were performed separately for the incidence risk of IMI and cure risk of IMI. For cure of IMI, 29 trials with 10 dry off interventions were included. Both selective and blanket dry cow therapy, either in combination with an internal teat sealant or as a singular intervention, resulted in a better cure risk compared with the non-antimicrobial interventions. No differences were observed between the antimicrobial based interventions. For the incidence risk of IMI, 54 trials were included, representing 18 dry off interventions. The incidence risk of IMI was similar for the various selective dry cow treatments when antimicrobials were administered together with an internal teat sealant, either at quarter or cow level. Also, they did not differ from the evaluated blanket dry cow treatment interventions or when an internal teat sealant was applied alone. Selective dry cow therapy with internal teat sealant is therefore likely a suitable intervention option to simultaneously maintain a low incidence risk of IMI and a high cure risk of IMI, all the while lowering the antimicrobial use in dairy herds. Circumstances in the herd, including the distribution and prevalence of mastitis pathogens, should be evaluated before results are utilized in dairy practice given the heterogeneity of included studies.

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.

The aim of this systematic review and network meta-analysis (NMA) is to compare and rank the effects of different genetic polymorphisms on the susceptibility of temporomandibular disorders (TMDs) occurrence.

The central question formulated was: "Are genetic polymorphisms involved in the etiology of TMDs?" Following PROSPERO registration (CRD42024507886), electronic searches were conducted in five databases for publications up to November 2024.

Sixty-three studies were included in the systematic review and 7 composed the NMA. The qualitative analysis summarized the association between 120 genes (and 206 polymorphisms) and TMDs. Thirty-two polymorphisms (in 24 genes) were linked to overall TMDs, while 22 polymorphisms (in 22 genes) with degenerative bone changes in the temporomandibular joint (TMJ). Additionally, 17 polymorphisms were identified in cases of painful chronic TMD, while 12 polymorphisms in intra-articular disorders. These polymorphisms were in genes related to neurotransmission (COMT, ADRB2, DRD2, ANKK1, SLC6A4 and HTR2A), inflammatory mediators (TNFα, IL10 and MMP1), sex hormones (ESR1and ESRRB), oxidative stress (GSTM1) and bone metabolism (VDR). A protective effect for myalgia occurrence with the COMT_rs165774 polymorphism compared to the wild-type genotype was found in the pairwise meta-analysis (AG genotype: OR: 0.33; 95 %CI: 0.14, 0.76; p < 0.01 and GG genotype: OR: 0.32; 95 %CI: 0.14, 0.74; p < 0.01) and this polymorphism showed the highest probability of being associated with the myalgia (97 %) and arthralgia (93 %) conditions.

Genetic polymorphisms in genes related to neurotransmission, inflammatory response, and sex hormones seem to be risk factors related to the TMDs pathogenesis.

To conduct a systematic review and network meta-analysis to evaluate the safety and efficacy of intrapolyp steroid injection compared with oral steroids, nasal steroid wash, nasal steroid spray, and a control group in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

PubMed, Scopus, Web of Science, Embase, and CENTRAL.

Both randomized and non-randomized clinical trials were included. For risk of bias assessment, we used the RoB-2 and ROBINS-I tools. Our outcomes focused on safety and efficacy, including rates of visual disturbance and bleeding, as well as improvements in nasal polyps evaluated through three domains: endoscopic, radiologic, and patient-reported assessments. Safety data were pooled as events (%), while efficacy data were pooled as mean difference (MD) or standardized mean difference (SMD).

Eight clinical trials involving 579 patients were analyzed. The pooled analyses showed low event rates for visual disturbances (event rate = 0.64%, 95% CI [0.00%, 2.23%]) and bleeding (event rate = 0.61%, 95% CI [0.00%, 2.25%]). Additionally, intrapolyp steroid injections were found to be comparable with oral steroids, with no statistically significant differences. Moreover, intrapolyp steroid injections demonstrated some superiority over nasal sprays, nasal washes, and the control group.

This network meta-analysis confirms that intrapolyp steroid injections have a favorable safety and efficacy profile as a viable management option for CRSwNP. The injections showed comparable efficacy with oral steroids and demonstrated certain advantages over other treatments, such as nasal sprays and washes. Further research with larger sample sizes and standardized protocols are needed. Laryngoscope, 135:1872-1883, 2025.

The U.S. Food and Drug Administration approved three disease-modifying treatments for mild cognitive impairment and early Alzheimer's disease: aducanumab, lecanemab, and donanemab, which showed little efficacy, serious side effects, and are costly. Repetitive transcranial magnetic stimulation (rTMS) may overcome these difficulties by its safe, cheap, and potentially disease-modifying properties that extend beyond Aβ removal.

We aim to compare the efficacy on cognitive function, tolerability, and acceptability of rTMS with aducanumab, lecanemab, and donanemab in people with mild cognitive impairment and Alzheimer's disease.

We systematically reviewed relevant randomized placebo-controlled trials in PubMed, the CENTRAL, the CINHAL, and the ClinicalTrials.gov and performed a random-effect network meta-analysis.

Nineteen randomized placebo-controlled trials with 6918 participants were included. rTMS was significantly more effective than placebo/sham stimulation. In addition, rTMS was significantly more effective than aducanumab, lecanemab, and donanemab. Furthermore, rTMS was not significantly inferior to placebo/sham stimulation in tolerability and acceptability, whereas aducanumab, lecanemab, and donanemab were significantly inferior to placebo/sham stimulation in tolerability and acceptability. rTMS was significantly superior to lecanemab and donanemab in acceptability. No significant differences were observed in the remaining comparisons.

rTMS may be more effective, tolerable, and acceptable than aducanumab, lecanemab, and donanemab. Long-term direct comparison studies are needed.

Graves orbitopathy is a specialized immunoinflammatory disorder related to abnormal thyroid function. Due to the complexity of the disease and its propensity to reoccur, targeted treatment is essential to improve the symptoms.

This study aims to assess the efficacy and safety of various treatments for active thyroid eye disease.

We conducted a comprehensive search for randomized controlled trials (RCTs), and ongoing RCTs registered on Controlled Trials, targeting treatments for thyroid eye disease until November 20, 2024. Employing a Bayesian framework, this network meta-analysis calculated risk ratios (RRs) or mean differences (MDs) with 95% CIs to size the effects for the predetermined outcomes. The study is registered with PROSPERO (CRD42024548030).

The primary outcomes evaluated were overall response rate, clinical activity score (CAS), proptosis, diplopia, and adverse events.

For the overall response rate, teprotumumab (RR 5.5, 95% CI 2.3 to 16), mycophenolate combined intravenous glucocorticosteroids (IVGCs) demonstrated effectiveness over no treatment, ranked from most to least effective. Notably, teprotumumab showed the highest efficacy in reducing CAS (MD -1.57, 95% CI -3.81 to 0.68) and proptosis (MD -2.29, 95% CI -2.73 to -1.86). For diplopia improvement, teprotumumab and IVGCs were effective compared with no treatment.

Teprotumumab emerges as potentially the most effective treatment for reducing inflammation and increasing overall response rates when compared with no treatment; oral mycophenolate combined with IVGCs appears to be the best for improving proptosis. While some treatments raise safety concerns due to reported adverse events, oral methotrexate combined with IVGCs appear to offer a favorable balance between efficacy and safety among the evaluated treatments.

Both surgical and non-surgical treatments for acute Achilles tendon ruptures (aATRs) exist, but the optimal management strategy, especially regarding weight-bearing timing, remains unclear. This study investigates combinations of primary treatment (open surgical repair, percutaneous/minimally invasive repair and non-surgical treatment) and rehabilitation strategies (Early Weight Bearing [EWB] vs. Late Weight Bearing [LWB]) for aATRs, analysing re-rupture risk, complication rates and recovery outcomes.

Systematic review and network meta-analysis registered in PROSPERO (CRD42023389413). Medline, Scopus, Web of Science, CINAHL, ClinicalTrials.gov, and Cochrane Library were searched for studies assessing primary treatments and rehabilitation strategies for aATR in adults (>18 years old) with at least six months of follow-up.

Forty-one studies (23 randomised-controlled-trials, 17 non-randomised-studies-of-intervention) comprising 5566 patients and 82 treatment arms were included. Network meta-analysis was performed for re-rupture risk and other outcomes, reporting odds ratios and treatment rankings. Open surgical repair combined with LWB has the lowest re-rupture risk (2%, 95%CI 1%-3%). EWB facilitates faster recovery but marginally increases complication risks, though not statistically significant. Non-surgical treatment shows a higher re-rupture rate than surgical options (12% vs. 2%/4%, p < 0.001). Major wound complications are rare (2.8%), with percutaneous repair having a higher risk of sural nerve injury (4% vs. 1%, p = 0.02). Deep vein thrombosis/pulmonary embolism risk is higher with non-surgical treatment (2% vs. 1%, p = 0.04). EWB leads to faster return-to-sport and higher Achilles Tendon Rupture Scores.

Open surgical repair with LWB reduces re-rupture risk, while EWB offers faster recovery and higher patient satisfaction. Non-surgical treatment has the highest re-rupture and DVT/PE risk. Percutaneous repair increases sural nerve injury risk compared to open surgery, with no significant difference in wound complications. In patients with no contraindications, open surgical repair should be considered the gold standard, with no statistical difference in major and minor wound complications when compared to percutaneous treatment.

Level I.

Acute Mountain Sickness (AMS), the most prevalent high-altitude illness, necessitates effective preventive measures due to rising sudden high-altitude exposure from tourism and occupational activities. Current Pharmacological prophylaxis lack robust comparisons, dose optimization, and confounder-adjusted analysis.

This network meta-analysis (NMA) included 28 randomized controlled trials (RCTs), evaluated healthy individuals with a rapid ascent to >2500 m, compared 13 drugs for AMS incidence, severe AMS (SAMS) incidence, Lake Louise Score (LLS), peripheral oxygen saturation (SpO2), and pulmonary artery pressure (PAP). Quality was evaluated using Cochrane Risk of Bias tools and CINeMA (Confidence in Network Meta-Analysis) for evidence grading. Network meta-regression adjusted for ascent altitude and exposure duration to identify "time" windows or "height" windows.

250 mg BID acetazolamide (OR=0.31, 95%CI: 0.20-0.47) demonstrated a 5-day preventive efficacy window, while 375 mg BID acetazolamide (OR=0.31, 95%CI: 0.18-0.54) showed a shorter 3-day window. 4 mg BID dexamethasone (OR=0.29, 95%CI: 0.16-0.54) and 600 mg TID ibuprofen (OR=0.44, 95%CI: 0.3-0.64) also significantly reduced AMS incidence. No pharmacological interventions reduced SAMS incidence. After altitude adjustment, sildenafil (40 mg TID; MD=-1.11, 95%CI: -2.01--0.25) attenuated altitude-induced PAP elevation.

Moderate-dose acetazolamide (125-250 mg BID) effectively prevents AMS with a longer prophylactic window compared to high-dose regimens (375 mg BID). There is no pharmacological intervention to prevent SAMS and no high-quality evidence to prevent high-altitude-induced PAP elevation. Our findings delineate the efficacy duration of acetazolamide across doses, while underscoring the imperative for robust clinical trials to advance the evidence base.

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.

Most initial experience with Left bundle branch are pacing (LBBAP) has involved lumenless leads (LLLs). Recently, stylet-driven leads (SDLs) have also been introduced for LBBAP. This study examined the clinical success rates, outcomes, and complication rates between SDLs and LLLs.

A systematic review of randomized clinical trials and observational studies comparing LLL and SDL up to November 30, 2024, was conducted. Random- and fixed-effects meta-analyses assessed the impact of implant technology on outcomes, including pacing metrics, lead complications, and procedural parameters. In total, 11 studies with 12,916 patients (SDLs: 3920; LLLs: 8996) were included. Implant success rates were comparable between SDL and LLL (RR 1.00, 95% CI 0.96-1.04, P = 0.96). SDL was associated with shorter procedure time (MD - 11.94 min, 95% CI - 19.48 to - 4.40, P = 0.002) and shorter fluoroscopy times, though this differences was not statistically significant (MD - 1.27 min, 95% CI - 2.92 to 0.39, P = 0.13). Pacing metrics, including impedance, pacing threshold, and R-wave amplitude, also showed no significant differences during follow-up (up to 28 months). However, SDLs were associated with a significantly higher risk of lead-related complications compared to LLLs (RR 1.89, 95% CI 1.47-2.41, P < 0001).

LBBAP using SDL is feasible and demonstrates comparable success rates with a shorter procedure duration. A higher incidence of lead-related complications was observed in the SDL group; however, due to potential confounding factors and the absence of randomized head-to-head comparisons, no definitive conclusions can be drawn regarding causality. Further prospective studies are warranted to clarify this association.

Although the high-protein diets (HPDs) on weight control and body composition management are well investigated, mix results have been reported across studies and this variability may be attributed to differences in the composition of other macronutrients within HPDs. The aim of this study was to evaluate the impacts of HPDs with varied macronutrient compositions on body composition and cardiometabolic health outcomes through a systematic review, pairwise, and network meta-analysis.

A comprehensive search of four databases (PubMed, Embase, CINAHL, and Web of Science) was conducted to identify relevant randomized controlled trials. A total of 83 articles were selected for systematic review and both meta-analyses.

Significant reduction in body mass (BM) (standardized mean difference [SMD] = -0.25; 95% CI: -0.40, -0.11), body mass index (BMI) (SMD = -0.26; 95% CI: -0.38, -0.15), waist circumference (WC) (SMD = -0.19; 95% CI: -0.33, -0.04), fat mass (FM) (mean difference [MD] = -0.64 kg; 95% CI: -0.98, -0.29), along with increase in lean body mass (LBM) (MD = 0.34 kg; 95% CI: 0.11, 0.57) were observed with HPDs regiments compared to normal-protein diets. Specifically, the high-protein, moderate-carbohydrate and high-fat diet ranked the best in reducing BM, BMI, WC, FM, systolic blood pressure, diastolic blood pressure and increasing LBM; while the high-protein, low-carbohydrate and high-fat diet obtained the highest score in reducing triglyceride and increasing high-density lipoprotein cholesterol.

HPDs effectively reduce FM and increase LBM, and offers potential cardiometabolic benefits. Additionally, the manipulation of carbohydrate content in HPDs may further influence these outcomes.

PROSPERO (CRD42023483907).

This study aims to comprehensively evaluate the hematologic toxicity profiles, toxicity spectrum, and safety rankings of immune checkpoint inhibitors (ICIs) used for digestive system tumors. The PubMed, Cochrane Library, Web of Science, and Embase databases were systematically searched from inception to August 2024 to identify randomized controlled trials (RCTs). The primary outcome was anemia, while secondary outcomes included neutropenia, neutrophil count decreased, thrombocytopenia, platelet count decreased, leukopenia, white blood cell (WBC) count decreased, lymphocyte count decreased, and febrile neutropenia (FN). Subgroup analyses were performed based on tumor type, country category, study phase, ICI regimen, control group, chemotherapy regimen, ICI plus different chemotherapy regimens. Two reviewers independently selected the studies, extracted data according to pre-specified criteria, and assessed the risk of bias using the Cochrane Collaboration risk of bias tool. RevMan 5.4 software was utilized to visualize the risk of bias assessments. Stata 16.0 was used to conduct network meta-analysis, sensitivity analysis and meta-regression. 25 phase II and III RCTs (n = 15216) were included. The general safety of ICIs ranked from high to low for grade 1-5 anemia were as follows: avelumab, nivolumab, pembrolizumab, sintilimab, camrelizumab, and tislelizumab. For grade 3-5 anemia, the general safety profile of the ICIs were as follows, from highest to lowest: avelumab, nivolumab, pembrolizumab, sintilimab, and camrelizumab. Compared to chemotherapy, treatment-related hematologic toxicities with ICIs occurred primarily in grade 1-5 anemia, neutropenia, thrombocytopenia, leukopenia, and WBC count decreased. Taking ICI monotherapy, nivolumab plus ipilimumab were generally safer than taking chemotherapy, one ICI drug with chemotherapy, or two ICI drugs with chemotherapy. In terms of grade 1-5 hematologic toxicities, tislelizumab had the highest risk of neutropenia and leukopenia; the primary treatment-adverse events (AEs) for sintilimab was neutrophil count decreased and WBC count decreased; the primary treatment-related AE associated with nivolumab was platelet count decreased; camrelizumab posed the highest risk for lymphocyte count decreased. In terms of grade 3-5 hematologic toxicities, pembrolizumab was predominantly linked to neutropenia; sintilimab showed the greatest risk for neutrophil count decreased, platelet count decreased, and lymphocyte count decreased; avelumab was most associated with WBC count decreased. FN primarily manifested as grade 3-5, with camrelizumab having the highest risk. Among agents used in gastric or gastroesophageal junction cancer, avelumab demonstrated the most favorable safety profile for anemia. Each treatment regimen has its unique safety profile. Early identification and management of ICI-related hematologic toxicities are essential in clinical practice.Systematic Review Registration: PROSPERO CRD42024571508.

The objective of the study was to investigate the comparative effectiveness of non-surgical interventions for adults with chronic sciatica. EMBASE, MEDLINE, Cochrane Library, and CINAHL were searched until 7th June 2024 for randomized controlled trials (RCTs) of non-surgical interventions in adults (aged 18 or older) with chronic sciatica (3 months or longer). Primary outcomes were leg pain intensity and physical function at short-, medium-, and long-term follow-up. Two reviewers independently conducted the screening process, data extraction, and risk of bias assessment (with the Cochrane risk of bias 2.0 tool). Frequentist random effects network meta-analysis was conducted, and evidence confidence was evaluated with the CINEMA method. Fifty RCTs (4,920 participants) were included. At short-term, spinal manipulative therapy (mean difference [MD] -61.01, 95% CI -94.64 to -27.39), exercise + neural mobilization (MD -60.01, -93.08 to -26.95), and soft tissue anesthetic injections (MD -60.01, -99.08 to -20.95) showed the largest reductions in leg pain intensity versus placebo (all based on very low confidence evidence). Epidural magnesium injections improved physical function at short-term (MD -40.45, -54.00 to -26.89; very low confidence). Long-term reductions in leg pain occurred with epidural steroid + ketamine injections (MD -15.51, -21.50 to -9.52) and epidural injections + physical therapy (MD -12.01, -17.27 to -6.75; very low confidence). In summary, the evidence is very uncertain regarding the effectiveness of non-surgical interventions in patients with chronic sciatica. Future RCTs should minimize bias and include larger sample sizes to improve the confidence on the evidence base for chronic sciatica. Protocol registration PROSPERO (CRD42022361572) Perspective: Currently, no high-quality evidence confirms the superior effectiveness of any non-surgical intervention for patients with chronic sciatica. While some treatments may provide short-term leg pain relief, the very low confidence of the evidence highlights the need for rigorous and large-scale trials to better guide clinical decision-making.

Neuromodulation therapies (including non-invasive and invasive neuromodulation) are being used to treat painful diabetic neuropathy (PDN).

A systematic search of the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted, from their inception until 1 October 2024, to identify randomized controlled trials (RCTs) on neuromodulation therapies for PDN. Data were collected on pain intensity of various adjunctive therapies for PDN, including transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation, repetitive transcranial magnetic stimulation, pulsed electromagnetic field therapy, spinal cord stimulation (SCS), transcranial direct current stimulation, frequency rhythmic electrical modulation system, mesodiencephalic modulation, and sham.

The data from an aggregate of 12 separate studies, comprising a total sample size of 922 participants, was subject to analysis. All seven neuromodulation therapies exhibited better outcomes in pain intensity compared to the Sham intervention, with TENS achieving the highest ranking, followed by SCS. At the final follow-up time point, statistically significant reductions in pain intensity (vs. Sham) was only observed for SCS.

The results of this network meta-analysis should facilitate the development of clinical guidance and enhance the decision-making process for both patients and healthcare professionals, thereby identifying the most appropriate PDN treatment options.

PROSPERO: CRD42024597208.

We systematically review and compare the available evidence on the various types of regional anesthesia and topical anesthesia (TA) in vitreoretinal surgery and evaluate their respective outcomes. The principles outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) extension for network meta-analysis were adhered to throughout this systematic review. The primary outcome measures were intraoperative pain score, the number of patients requiring additional anesthesia, and the number of adverse events. A preestablished protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), ID Number: (CRD42023449755). Fifty-three studies were screened in full text, resulting in 11 with nearly 1076 patients who met our criteria. Most patients had a retrobulbar block, and the average surgical time was 48 minutes. Regarding the pain score, sub-Tenon (ST) injection had the best results, and TA was significantly less effective when compared to ST and peribulbar (PB) injection (SMD=1.28 and 0.88, 95% confidence interval (CI) to 2.46 and 0.18 to 1.58). ST had significantly less risk of requiring additional anesthesia when compared to all other techniques. Six studies reported adverse events, and PB had the least risk of an adverse event. Future research should continue to explore direct comparisons between each type.

Seagrass forest restoration programs have become a global priority to reverse their decline and regain their ecosystem services. However, defining the restoration effectiveness has remained controversial, probably due to the wide selection of procedures experienced mainly on short-term periods and local scales. Here, scientific literature from 40 years of experience on experimental works and active restoration interventions of the Mediterranean foundation seagrass Posidonia oceanica has been systematically summarized through a meta-analysis. Twenty-five variables concerning the characteristics of the site selection, procedural context, and plant performance evidenced the best practices for the seagrass restoration. Results have evidenced the importance of the correct selection of the donor and receiving site, the use of plagiotropic cuttings bearing at least three shoots, and the need of monitoring the total extent of restored area for long term periods, considering more than one plant trait to define the plant performance. Higher biological levels should be also considered to estimate the recovery of the habitat structure and ecosystem functioning.

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.