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Third‐generation (third‐gen) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the management of advanced EGFR‐mutated non‐small cell lung cancer (NSCLC). However, a head‐to‐head comparison of efficacy and safety among third‐gen EGFR TKIs is lacking. Seven randomized controlled trials with 3012 patients were included. All third‐gen TKIs significantly prolonged progression‐free survival (PFS) compared to first‐generation (first‐gen) TKIs, with no significant differences in PFS or objective response rate among the third‐gen TKIs. Furmonertinib ranked highest for PFS (HR, 0.82; 95% credible intervals [CrI], 0.72–0.94). Aumolertinib demonstrated the best intracranial control (HR, 0.74; 95% CrI, 0.63–0.89). Osimertinib (HR, 0.90; 95% CrI, 0.83–0.99) and lazertinib (HR, 0.89; 95% CrI, 0.79–1.00) showed overall survival benefits over first‐gen TKIs. Furmonertinib, aumolertinib, and osimertinib had lower rates of severe treatment‐related adverse events (TRAEs), while befotertinib exhibited the highest risk of grade ≥3 TRAEs (RR, 3.96; 95% CrI, 2.35–7.17). This study is the first head‐to‐head comparison of third‐gen EGFR‐TKIs using a Bayesian network meta‐analysis, offering critical insights into efficacy and safety. Our results support personalized selection of third‐gen EGFR TKIs for patients with advanced EGFR‐mutated NSCLC, particularly for subpopulations with CNS metastases or different mutation subtypes. Third‐generation EGFR‐TKIs are the current first‐line standard for advanced EGFR‐mutated NSCLC. While all improve PFS versus first‐generation TKIs, no significant PFS or ORR differences exist among them. Furmonertinib, aumolertinib, and osimertinib show better tolerability, with distinct toxicity profiles. These findings may guide decision‐making between clinicians and patients in selecting the most appropriate therapeutic option.

Background Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients undergoing noncardiac surgery remains controversial. Methods The final search took place on June 10, 2023. Randomized controlled trials including ketamine, ulinastatin, dexmedetomidine, parecoxib, and midazolam on the prevention and treatment of POCD in elderly undergoing noncardiac surgery were collected. A Bayesian network meta‐analysis was performed to quantitatively combine the evidence. Results A total of 35 randomized trials were finally included in this systematic review, and the overall risk of bias is Allocation concealment. These anesthetic adjuvant drugs did not show significant differences in preventing POCD on postoperative days 1 and 7 compared with each other, but ulinastatin may be more effective in preventing POCD than dexmedetomidine [odds ratio (OR) = 0.28, 95% confidence interval (CI) = (0.10, 0.71)] and parecoxib [OR = 0.3, 95% CI = (0.10, 0.82 on postoperative day 3. The efficiency ranking results also find that ulinastatin and ketamine might provide better effects regarding POCD prevention. Conclusions Ketamine and ulinastatin might have better effects in preventing POCD in elderly patients undergoing noncardiac surgery. Our meta‐analysis provided evidence for the use of ulinastatin and ketamine in the prevention of POCD in elderly patients undergoing noncardiac surgery.

Background The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)‐positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first‐line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta‐analysis was to evaluate the efficacy and safety of first‐line regimens for advanced HER2‐positive breast cancer by indirect comparisons. Methods A systematic review and Bayesian network meta‐analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression‐free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety. Results Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22–0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43–0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%. Conclusions Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first‐line therapy for patients with HER2‐positive breast cancer. We conducted a network meta‐analysis to compare all treatment regimens from randomized controlled trials for advanced HER2‐positive breast cancer in first‐line setting.

Endocrine therapy has become the fundamental treatment option for hormone receptor-positive (HR+) and receptor tyrosine-protein kinase erbB-2-negative (HER2−) metastatic breast cancer (mBC). While treatments incorporating cyclin-dependent kinase (CDK)4 and 6 inhibitors are more prevalent than ever, comparisons among those regimens are scarce. The aim of the present study was to identify the most effective maintenance treatment for patients with HR+ and HER2− mBC. To this end, databases including PubMed, Embase, Cochrane Library, Scopus and Google Scholar were searched from inception to August, 2023. The endpoints comprised overall survival (OS) and progression free survival (PFS). For dichotomous variants, hazard ratios (HRs) and odds ratios (ORs) were generated, while standard mean difference (SMD) was used for consecutive variants by Bayesian network meta-analysis to make pairwise comparisons among regimens, to determine the optimal therapy. These processes were conducted using Rstudio 4.2.2 orchestrated with STATA 17.0 MP. A total of 16 randomized controlled trials including 7,174 patients with 11 interventions were analyzed. Compared with aromatase inhibitor (AI), palbociclib plus AI (PalboAI) exhibited a significantly longer PFS up to the 36th month of follow-up [HR=1.7; 95% credible interval, 1.36-2.16], including on the 3rd [OR=2.22; 95% confidence interval (CI), 1.10-4.47], 6th (OR=2.39; 95% CI, 1.21-4.69), 12th (OR=1.94; 95% CI, 1.34-2.79), 18th (OR=2.38; 95% CI, 1.65-3.44), 24th (OR=2.39; 95% CI, 1.67-3.43), 30th (OR=2.10; 95% CI, 1.62-2.74) and 36th (OR=2.66; 95% CI, 1.37-5.18) month of follow-up. Additionally, abemaciclib plus fulvestrant exhibited significant effects compared with AI alone between 12 and 36 months. Ribociclib plus fulvestrant, ribociclib plus AI and dalpiciclib plus AI exerted significant effects compared with AI alone between 12 and 30 months. Considering the effect on OS and PFS together with adverse reactions, safety, medical compliance and route of administration, PalboAI was found to be the optimal treatment for HR+/HER2−mBC. However, additional head-to-head clinical trials are warranted to confirm these findings.

Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers (donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment. Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health (CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment. Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events (TAEs), serious adverse events (SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents (CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine (mean difference (e) = -0.77, 95% confidence interval (CI): 0.25-1.32; MD = 1.05, 95% CI: 0.18-1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine (MD = -1.30, 95% CI: -2.27 to -0.42; MD = -1.67, 95% CI: -3.36 to -0.06; MD = -2.27, 95% CI: -3.91 to -0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale-cognitive scores compared with placebo. Memantine (MD = 2.71, 95% CI: 1.05-7.29) improved global status (Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg (odds ratio (OR) = 3.04, 95% CI: 1.86-5.41) contributed to higer risk of adverse events than placebo. Galantamine (OR = 5.64, 95% CI: 1.31-26.71) increased the risk of nausea. Rivastigmine (OR = 16.80, 95% CI: 1.78-319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea. Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.

To compare the efficacy and safety of different surgical procedures for patients with single‐segment lumbar spinal stenosis (LSS), Bayesian network meta‐analysis (NMA) was conducted in this study. Randomized controlled trials (RCTs) which reported 2 years' results after surgery were searched from PubMed, Embase, and Cochrane Register of Controlled Trials up to February 2021. Eligible RCTs that contained at least two of the following surgical procedures, bilateral decompression via the unilateral approach (BDUL), decompression with conventional laminectomy (CL), decompression with fusion (DF), endoscopic decompression (ED), interspinous process devices only (IPDs), decompression with interlaminar stabilization (DILS), decompression with lumbar spinal process‐splitting laminectomy (LSPSL), and minimally invasive tubular decompression (MTD), would be included after screening based on the inclusion and exclusion criteria. The primary outcome was Oswestry Disability Index (ODI). Twenty eligible RCTs were included, with a total of 2201 patients enrolled. The NMA showed that the following surgical procedures ranked first (surface under the cumulative ranking) when compared with CL and DF: DILS for ODI (SUCRA 87.8%); LSPSL for back pain (95%); and MTD for leg pain (95.6%). MTD ranked among the top three surgical procedures for most outcomes. The quality of the synthesized evidence was low according to the Grading of Recommendations Assessment, Development, and Evaluation criteria. DILS, LSPSL, MTD, IPDs, and ED are the most effective procedures for patients with single‐segment LSS. Because of combining efficacy and safety, MTD may be the most promising routine surgical option for treating single‐segment LSS. To compare the safety and efficacy of different surgical procedures for the treatment of single‐segment lumbar spinal stenosis, Bayesian network meta‐analysis was conducted and the overall ranking orders of surgical procedures were also calculated.

Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first‐line chemotherapy. Additionally, particular first‐line targeted therapies have shown survival improvements in selected populations. Optimal first‐line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first‐line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first‐line and maintenance regimens in advanced NSCLC patients. Bayesian network meta‐analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first‐line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first‐line with maintenance treatments, (1) first‐line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first‐line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first‐line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild‐type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH‐positive patients with squamous histology, and (6) first‐line chemotherapy+bevacizumab, maintenance bevacizumab or first‐line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first‐line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed to achieve effective therapy for patients with EGFR mutation L858R or nonsquamous histology. First‐line with maintenance therapies have shown benefits in selected advanced NSCLC populations. Here, first‐line with maintenance treatments are compared within patient groups and clinically meaningful benefits are shown for particular first‐line with maintenance therapies in selected patients.

ObjectiveCommercial Chinese polyherbal preparations (CCPPs) are increasingly used for infantile anorexia (IA), but comparative effectiveness and safety differences among them remain unclear. This Bayesian network meta-analysis compares various CCPPs for IA to inform clinical practice.MethodsWe systematically searched CNKI, Wanfang, VIP, China Biology Medicine, PubMed, Web of Science, Embase, and Cochrane Library for RCTs on CCPPs for IA up to 9 April 2024. Study quality was assessed using the Cochrane RoB tool. Primary outcomes were overall effective rate, weight change, hemoglobin (Hb) levels, and adverse reactions. This research implemented Bayesian network meta-regression to ascertain the impact of different CCPPs and durations of treatment on the effectiveness and safety to treat IA.Results141 RCTs (n = 16,963 patients; 49 CCPPs) were included. For overall effective rate, Huaji Oral Solution (HJKFY), Jianpi Pills + Reference Drug (JPW + RD), and Erkangning (EKN) showed significant superiority vs. control (all RR > 1.54, P < 0.05). Regarding weight change, Erpixing Granules (EPXKL) and Xiaoer Fufang Jineijin Chewable Tablets + RD (XEFFJNJJJP + RD) demonstrated significant benefits (MD = 2.26 and 2.10, P < 0.05 for XEFFJNJJJP + RD). For Hb levels, Jianbaoling Granules (JBLKL), Erbao Granules + RD (EBKL + RD), and Shenqu Xiaoshi Oral Solution + RD (SQXSKFY + RD) showed significant advantages (all MD > 10.72, P < 0.05). CCPPs exhibited a favorable safety profile, with mostly mild adverse reactions.ConclusionCCPPs are significantly more effective and safer than control treatments for IA. Different CCPPs excelled on specific outcomes: HJKFY for overall efficacy, EPXKL for weight gain, and JBLKL for Hb improvement. These findings require confirmation via larger, high-quality, multi-center RCTs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024535550.

This study aims to evaluate and compare the gastrointestinal adverse effects associated with different GLP-1 receptor agonists (GLP-1RAs) and multi-target analogs in patients with type 2 diabetes mellitus (T2DM) using a Bayesian network meta-analysis. A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted to identify randomized controlled trials (RCTs) assessing the gastrointestinal adverse events of GLP-1RAs in T2DM patients. Inclusion criteria included adult patients with confirmed T2DM receiving any GLP-1RA, with the outcomes focused on gastrointestinal adverse events such as nausea, vomiting, diarrhea, constipation, dyspepsia, and reduced appetite. Bayesian network meta-analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the comparison of gastrointestinal side effects among different GLP-1RAs. A total of 48 RCTs involving 27,729 participants were included in the analysis. The overall incidence of gastrointestinal adverse events was 11.66%, with nausea being the most frequent (21.49%) and reduced appetite the least frequent (5.49%). Tirzepatide had the highest risk of inducing nausea and diarrhea, while dulaglutide and lixisenatide had the lowest risks. Exenatide exhibited the highest incidence of vomiting, while dulaglutide showed a lower risk. Semaglutide demonstrated a significantly higher risk of diarrhea compared to other GLP-1RAs. This study highlights significant differences in the gastrointestinal adverse event profiles of various GLP-1RAs. Tirzepatide exhibited the highest risk of gastrointestinal side effects, whereas dulaglutide and exenatide showed relatively better tolerability. These findings provide valuable insights for clinicians to make informed treatment decisions, emphasizing the importance of individualized therapy based on patient tolerance. CRD42024592308.

Computer-based scaffolding provides temporary support that enables students to participate in and become more proficient at complex skills like problem solving, argumentation, and evaluation. While meta-analyses have addressed between-subject differences on cognitive outcomes resulting from scaffolding, none has addressed within-subject gains. This leaves much quantitative scaffolding literature not covered by existing meta-analyses. To address this gap, this study used Bayesian network meta-analysis to synthesize within-subjects (pre-post) differences resulting from scaffolding in 56 studies. We generated the posterior distribution using 20,000 Markov Chain Monte Carlo samples. Scaffolding has a consistently strong effect across student populations, STEM (science, technology, engineering, and mathematics) disciplines, and assessment levels, and a strong effect when used with most problem-centered instructional models (exception: inquiry-based learning and modeling visualization) and educational levels (exception: secondary education). Results also indicate some promising areas for future scaffolding research, including scaffolding among students with learning disabilities, for whom the effect size was particularly large (ḡ = 3.13).