Network Meta-analysis Research Articles

Efficacy and safety of intranasal medications for allergic rhinitis: Network meta-analysis.

Intranasal antihistamines (INAH), corticosteroids (INCS), and their fixed combinations (INAH+INCS) are one of the cornerstones of the treatment of allergic rhinitis (AR). We performed a systematic review and network-meta-analysis comparing the efficacy and safety of INAH, INCS, and INAH+INCS in patients with AR. We searched four electronic bibliographic databases and three clinical trial databases for randomised controlled trials assessing the use of INAH, INCS, and INAH+INCS in adults with seasonal or perennial AR. We performed a network meta-analysis on the Total Nasal Symptom Score, Total Ocular Symptom Score, Rhinoconjunctivitis Quality-of-Life Questionnaire, development of adverse events, and withdrawals due to adverse events. Certainty of evidence was assessed using GRADE-NMA. We included 167 primary studies, most of which assessed patients with seasonal AR. Among individual medications, azelastine-fluticasone, and fluticasone furoate were the most frequently highest-ranked interventions for efficacy outcomes, being regularly associated with clinically meaningful larger improvements when compared to other active treatments. Considering drug classes, INAH+INCS were the highest-ranked interventions for all outcomes in which they were assessed, followed in most cases by INCS. In 105 out of 184 comparisons in seasonal AR, and 28 out of 97 comparisons in perennial AR, certainty of evidence was considered "high" or "moderate". Intranasal medications for AR display clinically relevant differences in their efficacy, but all show a good safety profile. To our knowledge, this is the first network meta-analysis comparing INAH, INCS, and INAH+INCS in AR, providing relevant evidence for guideline developers and practising physicians on the most efficacious treatments.

Effect of different training modalities on lipid metabolism in patients with type ii diabetes mellitus: a network meta-analysis.

This study to evaluate the effects of different training modalities on blood lipids in type II diabetic patients by Network Meta-analysis, and provide a relevant basis for patients to develop exercise prescriptions to regulate blood lipids. Randomized controlled trials (RCTs) were retrieved from Zhiwang, Wanfang, Wipu, PubMed, EBSCO, Cochrane Library, and Web of Science that were published from the establishment to February 2023. Relevant statistical analyses were performed using Stata 17.0 software and Revman 5.4. A total of 35 randomized controlled trials with 2771 patients with type II diabetes were finally included. The results of Network Meta-analysis showed that, compared with the control group, Chinese traditional fitness exercise (CTF), resistance training (RT), and aerobic training (AT) could reduce total cholesterol (TC) levels; CTF, RT, whole body vibration training (WBV), and AT could reduce triacylglycerol (TG) levels; CTF, WBV and AT could increase High-density lipoprotein cholesterol (HDL) levels; CTF, RT and AT could reduce Low-density lipoprotein cholesterol (LDL) levels. SUCRA probability ranking results showed that CTF was the most effective in reducing TC[SMD= -0.57, 95% CI (-0.83, -0.31), p < 0.001], TG[SMD= -0.24, 95% CI (-0.36, -0.12), p < 0.001], LDL[SMD= -0.52, 95% CI (-0.70, -0.35), p < 0.001]; RT was the most effective in increasing HDL[SMD = 0.14, 95% CI (0.03, 0.26), p < 0.05]. CTF is more effective in improving TC, TG and LDL levels, while RT is most effective in improving HDL levels.

Comparative effectiveness of exercise interventions for primary dysmenorrhea: a systematic review and network meta-analysis.

Exercise is increasingly being promoted as an effective treatment for primary dysmenorrhea (PD). This study aims to conduct a comprehensive network meta-analysis (NMA) of randomized controlled trials to identify the optimal types and dosages of exercise for managing PD in women. Adhering to PRISMA-NMA guidelines, we systematically reviewed RCTs from the Cochrane Library, Web of Science, PubMed, and Embase databases up to May 23, 2024. Data analysis was performed using 'GEMTC' and 'BUGSnet' packages within a Bayesian framework in R and a hierarchy of exercise treatments was also calculated using surface under the cumulative ranking curve (SUCRA) values. Subgroup analyses were conducted to identify the most effective exercise regimens, including duration, frequency, and volume of the exercise interventions. Forty-nine studies representing 3,129 participants (1,640 exercises and 1,489 controls) were included. The results showed that all exercise interventions significantly reduced menstrual pain of the PD patients. Of six exercise intervention modalities based on the study ranked effectiveness, statistically significant reductions in pain intensity were found for resistance exercise and multi-component exercise. Multi-component exercise and stretching exercise were ranked best for menstrual symptoms, while core-strengthening exercise and multi-component exercise had the greatest impact on reducing pain duration. Significant and clinically important reductions or reliefs in pain occurred with 4 to 8 weeks of exercise training from all exercises, with resistance exercise showing the best efficacy when the duration exceeded 8 weeks, followed by multi-component exercise and mind-body exercise. Multi-component exercise and aerobic exercise with 1 to 3 sessions per week induced greater benefit in performance improvements, while resistance exercise with increased frequency showed the enhanced performance. Resistance exercise could elicit better efficacy within` 30-minute training duration, and multi-component exercise was ranked the best if such a training over 30min. This study provided quantitative insight into efficacy and effectiveness of exercise interventions on PD treatments. All six different exercises are associated with positive influence on PD management. Our study indicates that this exercise training induced adaptation may have therapeutic benefits for PD patients; however, such alterations and improvements are affected by exercise regiments.

A Network Meta-Analysis of Vasodilator Therapies in Pulmonary Hypertension Patients Undergoing Mitral Valve Replacement Surgery: Insights for Optimizing Hemodynamics.

Pulmonary hypertension (PH) is a progressive hemodynamic condition associated with significant morbidity and mortality, especially in patients undergoing cardiac surgery. Therefore, the objective of this network meta-analysis (NMA) is to compare the efficacy of various pulmonary vasodilators in perioperative control of PH among patients undergoing mitral valve replacement surgery (MVRS), aiming to address the existing knowledge gap and improve perioperative outcomes. Electronic databases including PubMed, Cochrane Central Registry of Controlled Trials, Scopus, Embase, and Web of Science (WOS) from inception to 17 September 2024. Only randomized controlled trials (RCTs) evaluating vasodilators in PH patients undergoing MVRS were included. We used netmeta package in RStudio to analyze the outcome data with their corresponding mean difference (MD) and confidence intervals (CI). Seventeen RCTs including 862 patients were analyzed. Prostacyclin, nitric oxide (NO), and sodium nitroprusside (SN) significantly reduced mean pulmonary arterial pressure with effect sizes [MD, 95% confidence interval (CI)] of (11.77, -18.78; -4.76; -8.3, -15.9; -0.6; -11.02, -20.1; -3.8, respectively). While no treatment showed significant efficacy on pulmonary capillary wedge pressure, systolic pulmonary arterial pressure, or heart rate, nitroglycerin, NO, and prostacyclin, showed significant increases in cardiac index with effect sizes (MD, 95% CI) of (1, 0.3; 1.7; 1.2 0.8; 1.6; 1.2 0.8; 1.6, respectively). Additionally, NO, prostacyclin, SN, and nitroglycerin demonstrated significant reductions in systemic vascular resistance (SVR), with effect sizes of. (-0.54, -0.82; -0.26, -0.37, -0.65; -0.09; -0.47, -0.77; -0.16; -0.14, -0.24; -0.03, respectively). This NMA highlights prostacyclin, nitroglycerin, NO, and SN as consistently effective in improving hemodynamics for patients with PH undergoing MVRS, and provides valuable insights for surgeons to choose the suitable vasodilator for these surgeries. However, limitations and the need for further RCTs are acknowledged.

A novel way to integrate economic information into clinical practice guidelines.

Clinical guidelines are widely used to support clinical decision making, so they could also provide economic information about medical interventions to promote cost-conscious health care. We developed a new way to integrate economic information into the Finnish Current Care Guidelines. Our development team consisted of clinical guideline specialists and health economists. We first looked at integration of economic information in clinical guidelines of other countries. Our key principle was that economic information should be integrated only to mutually exclusive medical interventions where the extensive choice of one the options will yield a significant cost differences on the national level. For the comparative effectiveness information of the interventions, we primarily looked for network meta-analyses. We then combined the effectiveness information presented as number needed to treat with prices or costs for the interventions and present the result as a cost per responder, which reflects both effectiveness and price or costs. We introduce a process to integrate and present the economic information of the selected interventions in tables in the Current Care Guidelines. Our novel way to integrate economic information into the Current Care Guidelines is an effort to support cost-conscious clinical decision making to promote cost-effective health care in Finland. This process is general and could be used in clinical guidelines in other countries as well.

Efficacy and safety of different noninvasive ventilation strategies for postextubation respiratory support in Neonatal Respiratory Distress Syndrome: a systematic review and network meta-analysis

ObjectiveThe study aimed to compare the efficacy and safety of different noninvasive ventilation (NIV) modalities as primary respiratory support following extubation in Neonatal Respiratory Distress Syndrome (NRDS).MethodsA search was conducted in PubMed, Embase, Cochrane, Web of Science, China National Knowledge Network (CNKI), Wanfang database, VIP, and Chinese Biomedical Literature databases with a search time limit of April 2024 for the year of construction, and included randomized controlled clinical trials of different modes of noninvasive respiratory support after extubation in NRDS. The primary outcome indicators were the need for re-tracheal intubation within 72 h of extubation on noninvasive ventilatory support and carbon dioxide retention (PCO2) 24 h after extubation. Secondary outcome indicators included the incidence of bronchopulmonary dysplasia (BPD), nasal injury, pneumothorax, intraventricular hemorrhage (IVH) or periventricular white matter softening (PVL), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and mortality rate. A systematic review and network meta-analysis of the literature was performed by two investigators who screened, extracted, and evaluated the quality of the data. A systematic review and network meta-analysis were then performed using R software.ResultsA total of 23 studies involving 2,331 neonates were analyzed. These studies examined four noninvasive respiratory modalities: continuous positive airway pressure ventilation (NCPAP), noninvasive intermittent positive pressure ventilation (NIPPV), bi-level positive airway pressure ventilation (N-BiPAP), and noninvasive high-frequency oscillatory ventilation (NHFOV). Results indicated that NHFOV, NIPPV, and N-BiPAP were significantly more effective than NCPAP in reducing the risk of reintubation (all P &amp;lt; 0.05), with NHFOV being the most effective. For carbon dioxide clearance, NHFOV outperformed both NIPPV and NCPAP (P &amp;lt; 0.05). Regarding the reduction of bronchopulmonary dysplasia (BPD) incidence, NHFOV and NIPPV showed a significant advantage over NCPAP.ConclusionsThis network meta-analysis (NMA) suggested that NHFOV is the most effective mode of noninvasive respiratory support post-extubation, while NCPAP is the least effective. However, these findings should be interpreted with caution due to the limited number and quality of the studies included.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier (CRD42024544886).

Monovision versus multifocality for presbyopia during primary phacoemulsification: systematic review and network meta-analysis.

This systematic review and network meta-analysis (NMA) focuses on comparing monovision and bilateral multifocal lenses (bMFIOL) implantation methods in treating presbyopia, a common age-related condition often seen in post-cataract surgery patients. This review focuses on evaluating the efficacy, user satisfaction and limitations of these two approaches through direct or indirect comparison. A comprehensive search was conducted in Medline, Embase, and Cochrane library, considering studies up to 15 July 2022, with direct or indirect comparisons between any monovision and bMFIOL implantation with bilateral cataract surgery. The study protocol has been published in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022340257). Thirty-two studies (3082 patients) were included in the NMA for the primary outcome, complete post-operative spectacle independence. NMA showed monovision to be inferior to bMFIOLs, as bMFIOL was more likely to provide complete spectacle independence (RR = 2.06, 95% CI = 1.34 to 3.15, p = 0.002) compared to monovision. Monovision resulted in less glare compared to bMFIOL (RR = 0.343, 95% CI = 0.181 to 0.651, p = 0.001). There was no statistically significant difference between monovision and bMFIOL for binocular unadjusted distance visual acuity (MD = 70.01, 95% CI = -19.88 to 4.60, p = 0.437) and binocular unadjusted near visual acuity (MD = 5.46, 95% CI = -5.24 to 10.94, p = 0.191). When compared to monovision, bMFIOL provided greater complete spectacle independence at the expense of greater glare. This study was limited by data heterogeneity, and further studies with standardized reporting would be useful.

Effects of different exercise modalities on pediatric and adolescent populations with developmental disorders: a network meta-analysis of randomized controlled trials.

Combat sports, ball sports, neurodevelopmental motor training, and aquatic exercise may be effective exercise modalities for improving symptoms in children and adolescents with developmental disorders. However, the degree of improvement can vary among individuals with specific developmental disorders. Therefore, precise assessment of the individual symptoms of children or adolescents is crucial before selecting specific exercise interventions. PROSPERO (CRD42024545673). • Many studies indicate that exercise as an intervention can have positive effects on individuals with developmental disorders, such as ADHD and autism. However, reported effects vary, and there is no clear consensus on the optimal exercise intervention method yet. • Through a comprehensive network meta-analysis, various exercise interventions for children and adolescents with developmental disorders were compared to determine the optimal approach. The study found that combat sports, ball sports, neurodevelopmental motor training, and aquatic exercise could potentially be effective modalities for improving symptoms in this population.

Spinal Cord Stimulation vs Medical Management for Chronic Back and Leg Pain: A Systematic Review and Network Meta-Analysis.

Chronic back and lower extremity pain is one of the leading causes of disability worldwide. Spinal cord stimulation (SCS) aims to improve symptoms and quality of life. To evaluate the efficacy of SCS therapies compared with conventional medical management (CMM). MEDLINE, Embase, and Cochrane Library were systematically searched from inception to September 2, 2022. Selected studies were randomized clinical trials comparing SCS therapies with sham (placebo) and/or CMM or standard treatments for adults with chronic back or leg pain who had not previously used SCS. Evidence synthesis estimated odds ratios (ORs) and mean differences (MDs) and their associated credible intervals (CrI) through bayesian network meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for network meta-analyses was followed. The primary outcomes were pain-related end points, including pain intensity (measured by visual analog scale) and proportion of patients achieving at least 50% pain relief (responder rate) in the back or leg. Quality of life (measured by EQ-5D index score) and functional disability (measured by the Oswestry Disability Index score) were also considered. A total of 13 studies of 1561 patients were included in the network meta-analysis comparing conventional and novel SCS therapies with CMM across the 6 outcomes of interest at the 6-month follow-up. Both conventional and novel SCS therapies were associated with superior efficacy compared with CMM in responder rates in back (conventional SCS: OR, 3.00; 95% CrI, 1.49 to 6.72; novel SCS: OR, 8.76; 95% CrI, 3.84 to 22.31), pain intensity in back (conventional SCS: MD, -1.17; 95% CrI, -1.64 to -0.70; novel SCS: MD, -2.34; 95% CrI, -2.96 to -1.73), pain intensity in leg (conventional SCS: MD, -2.89; 95% CrI, -4.03 to -1.81; novel SCS: MD, -4.01; 95% CrI, -5.31 to -2.75), and EQ-5D index score (conventional SCS: MD, 0.15; 95% CrI, 0.09 to 0.21; novel SCS: MD, 0.17; 95% CrI, 0.13 to 0.21). For functional disability, conventional SCS was superior to CMM (MD, -7.10; 95% CrI, -10.91 to -3.36). No statistically significant differences were observed for other comparisons. This systematic review and network meta-analysis found that SCS therapies for treatment of chronic pain in back and/or lower extremities were associated with greater improvements in pain compared with CMM. These findings highlight the potential of SCS therapies as an effective and valuable option in chronic pain management.

Reevaluating antibiotic prophylaxis: insights from a network meta-analysis on dry socket and surgical site infections.

Three databases (MEDLINE, Cochrane Library, and Scopus) were searched in December 2021 for 16 Randomised Clinical Trials (RCTs). Three reviewers reviewed the articles on oral antibiotic prophylaxis (ABP) for the prevention of surgical site infection (SSI) and dry socket (DS) after lower third molar (L3M) extraction using the PICO framework. From 1999 to 2021, RCTs involving healthy patients undergoing L3M extraction with ABP, placebo, or no therapy were included. Adverse effects (AEs) associated with antibiotic usage, along with the main outcomes (DS and SSI), were also documented. Three independent investigators selected articles based on pre-established inclusion criteria, with any disagreements resolved by consensus or additional researchers. PRISMA guidelines were followed, involving initial title and abstract screening, followed by full-text evaluation. Exclusion reasons were documented, and the most recent report was included when multiple reports on the same patients were found, with no language restrictions applied. Two investigators evaluated studies quality and quality of evidence respectively using the Cochrane Collaboration tool and GRADEpro GDT. They independently extracted data, focusing on the type of extraction and the number of extracted L3M. They also detailed the use of antibiotics, including dosage, dosage regimen, timing, and duration. Among 16 articles, 15 used a parallel arm design, while one used a crossover design. The antibiotics studied included Amoxicillin+Clavulanic acid (7 articles), Amoxicillin (6), Metronidazole (2), Azithromycin (1), and Clindamycin (2), all compared with no treatment or placebo. A pairwise meta-analysis was used to combine studies with equivalent treatment (direct estimation), and a network meta-analysis compared outcome variables across different treatments (indirect comparison). Two included articles had a low risk of bias and the level of evidence was low according to GRADE. Pooled results supported the use of antibiotics to reduce DS and SSI following L3M extraction with a number needed to treat 25 and 18, respectively. Despite the fact that ABP reduces the risk of DS and SSI, it is recommended to consider systemic conditions and individual patient risk factors before prescribing antibiotics, due to global health threat.

Comparison of the efficacy of updated drugs for the treatment on the improvement of cognitive function in patients with Alzheimer 's disease: A systematic review and network meta- analysis.

The recent emergence of updated drugs for the treatment of Alzheimer's disease (AD) has produced encouraging cognitive and clinical results in clinical trials, but there is still controversy over how to choose effective treatment options among these numerous drugs. The purpose of this network meta-analysis (NMA) is to compare and rank these drugs based on their efficacy. We systematically searched in PubMed, Web of Science databases and Cochrane LIbrary, gov for randomized controlled trials for data from 2020 to 2024, and then performed a random-effect network meta-analysis. Our NMA results showed that in several main indicators ADAS-cog, CDR-SB and ADCS-ADL. GV-971 (MD -2.36, 95 % CI -5.08, 0.35), Lecanemab (MD -2.00, 95 % CI -5.25, 1.26), Donanemab (MD -1.45, 95 % CI -4.70, 1.81), Masupirdine (MD -0.83, 95 % CI -3.49, 1.84) were more effective than placebo in improving ADAS-cog. In terms of CDR-SB, Lecanemab (MD -3.11,95 % CI -5.23, -0.99) was more effective. Compared with placebo, Donanemab was more effective in ADCS-ADL (MD 3.26,95 % CI 1.48,5.05). SUCRA values showed that GV-971 (76.1 % and 68.7 %) could achieve better therapeutic effects in ADAS-cog) and NPI, and Lecanema (98.1 %) was more effective in improving CDR-SB scores than other drugs. Donanemab (99.8 %) may be the most promising way to slow down the decline in ADCS-ADL scores. The effect of Masupirdine (80.7 %) on MMSE was significantly better than that of several other drugs. Donanemab and Lecanemab showed good efficacy in ADCS-ADL and CDR-SB, respectively. GV-971 is the best choice to improve ADAS cogs and NPI.

Comparative effects of different beverages on weight loss in adults: a systematic review and network meta-analysis of randomized trials.

There is a lack of clarity on the comparative effects of different beverages on weight loss in adults. This study aimed at quantifying and ranking the effects of different beverages on weight loss. We searched PubMed, Scopus, and Web of Science up to January 2023. We included randomized trials evaluating the comparative effects of two or more beverages, or compared a beverage against a control group (water, no intervention), for weight loss in adults. We conducted a random-effects network meta-analysis (NMA) with a Bayesian framework to estimate mean difference [MD] and 95% credible interval [CrI]. In total, 78 randomized trials with 4168 participants were eligible. Low/no-calorie sweetened beverages (LNCSB) was effective for weight loss compared with water (MD: -0.79 kg, 95% CrI: -1.35, -0.18), milk (MD: -0.80 kg, 95% CrI: -1.59, -0.01), fruit juice (MD: -0.83 kg, 95% CrI: -1.47, -0.13), sugar-sweetened beverages (SSB) (MD: -1.08 kg, 95% CrI: -1.65, -0.50), and no intervention (MD: -1.19 kg, 95% CrI: -1.93, -0.41). However, in sensitivity analyses, no significant effect was seen in trials with a low risk of bias and those that implemented calorie restriction. LNCSB drinking was effective for waist circumference reduction compared with water (MD: -1.85 cm, 95% CrI: -3.47, -0.22). The certainty of evidence from most comparisons was rated low. This study suggested evidence of low certainty that intake of LNCSBs can result in a small weight loss when used as a substitute for other beverages. Considering the low certainty of evidence, more research is needed to compare the effects of different beverages on body weight. Not applicable, but the protocol of this systematic review was registered at PROSPERO (registration number: CRD42023407937).

The Effectiveness of Steroids and Antioxidants in the Management of Cisplatin-induced Ototoxicity: A Comprehensive Systematic Review of the Literature and Network Meta-Analysis

Abstract Background: Cisplatin efficacy in cancer therapy is hindered by dose-dependent toxicities, including ototoxicity. Its mechanisms involve cochlear damage and oxidative stress. Gender and age affect susceptibility, with limited treatment options for adults. Objective: To assess the effectiveness of steroids compared to antioxidants (AOs) in preventing and managing cisplatin-induced ototoxicity. Materials and Methods: Data were collected from multiple sources including Medline, CENTRAL, PubMed, and Springer Nature Journals. Adults and pediatrics with the clinical diagnosis of cisplatin-induced ototoxicity, interventional studies (including single-arm studies) were included. Studies with a focus on chemotherapy agents other than cisplatin were excluded. Results: The study encompassed 10 randomized controlled trials spanning 2004–2023 across Canada, Israel, The Netherland, Spain, Turkey, Greece, Italy, and Iran. It aimed to evaluate interventions for preventing cisplatin-induced ototoxicity, including intratympanic injections and oral dietary supplements. Based on the results of this systematic review, thiosulfate-hyaluronate gel showed a 1.3 dB reduction in hearing loss; dexamethasone injections had minimal efficacy; L-N-acetylcysteine (L-NAC) offered significant otoprotection with daily infusion; and transtympanic L-NAC showed no significant benefit. Salicylate usage yielded no decrease in hearing loss. AO dietary supplements showed no difference in results between groups. However, based on the network meta-analysis results, it appears that steroids perform best in reducing cisplatin-induced ototoxicity at higher frequencies (8000 Hz), followed by placebo and then AO. Conclusion: A further molecular and targeted therapy is needed to target the cyto/ototoxic activity and further prevent such deterioration in hearing and promote chemotherapy regime without ototoxic effects.

Wound closure techniques after wide excision for hidradenitis suppurativa: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin areas, clinically characterized by recurrent inflamed nodules, abscesses, sinus tracts, and severe scars. Systemic treatments may provide temporary relief, while wide surgical excision offers prolonged disease-free periods. We evaluated the most efficient wound closure methods following wide excision of HS lesions in terms of recurrence, functionality, and quality of life. A systematic literature search was conducted in PubMed, Embase, Cochrane, and ClinicalTrials.gov, adhering to the PRISMA 2020 criteria. We included original studies published until February 2024, focusing on wound closure methods post-wide excision for HS. Data from 121 papers were analyzed using network and direct meta-analysis methods to compare recurrence and postoperative complication rates. From 1181 articles, 121 were included in the meta-analysis after removing duplicates and excluding publications that did not meet the inclusion criteria. Recurrence rates were associated with the type of reconstruction technique as follows: primary closure, 25% (95% confidence interval [CI], 20-30%); skin grafts, 18% (95% CI, 14-22%), and flaps, 12% (95% CI, 9-15%). Secondary intention healing showed a recurrence rate of 28% (95% CI, 23-33%). Flaps were associated with the lowest recurrence rates compared to other surgery techniques.

Comparative Safety of Ultrasound Enhancing Agents: A Systematic Review and Bayesian Network Meta-Analysis: Comparative Safety Evaluation of Optison.

Ultrasound enhancing agents (UEAs), including Optison, Definity, and Lumason, enhance the diagnostic performance of echocardiography, particularly in patients with suboptimal acoustic windows. However, there remains a paucity of comparative safety assessments among the Food and Drug Administration (FDA)-approved UEAs. A PRISMA-guided systematic literature review performed in August 2023 searched Medline, Embase, Cochrane Library, and grey literature. Randomized and non-randomized comparative evidence on safety of contrast enhanced procedures were included. A feasibility assessment ensured homogeneity across studies by comparing patient characteristics and outcomes. Bayesian hierarchical network meta-regression was employed to indirectly compare published safety outcomes across different UEAs. In addition, adverse events (AEs) between 2019-2023 for each UEA were retrieved from the FDA Adverse Events Reporting System (FAERS), and comparative safety outcomes were derived using annual UEA administration in the US. Screening of 4146 records rendered 19 studies for inclusion in the indirect comparison analysis after feasibility assessment. Optison demonstrated favorable safety in direct comparisons with Definity and Lumason across the majority of investigated AEs. Network meta-regression results on serious adverse events (SAEs) within 30 minutes revealed odds ratios (ORs) of 0.59 (95% confidence interval: 0.27-1.23) and 0.63 (0.29-1.33) for Optison vs. Lumason and Definity, respectively, indicating a decreased risk of SAEs for Optison vs. Lumason and Definity, further supported by statistically significant ORs within FAERS: 0.01 (0-0.02), P<0.001 and 0.15 (0.05-0.48), P=0.001, for Optison vs. Lumason and Definity, respectively. In conclusion, our results restate the favorable comparative safety profile of Optison, providing new evidence to inform clinical decision-making.

Effects of different types of intermittent fasting on metabolic outcomes: an umbrella review and network meta-analysis.

Intermittent fasting (IF) holds promise for enhancing metabolic health. However, the optimum IF forms and their superiority over continuous energy restriction (CER) remain unclear due to disconnected findings. We systematically searched PubMed, Embase, and the Cochrane databases for meta-analyses of randomized controlled trials (RCTs) investigating the association between IF and metabolic health outcomes. Subsequently, we performed an umbrella review and network meta-analysis (NMA) to evaluate the efficacy of different forms of IF (time-restricted eating (TRE), alternate-day fasting (ADF), and 5:2 diet (regular eating for 5days and energy restriction for 2days per week)) compared to CER and usual diets on metabolic health outcomes. To assess the certainty of both direct and indirect estimates, we employed the Confidence in Network Meta-Analysis (CINeMA) approach. Additionally, we calculated the surface under the cumulative ranking curve (SUCRA) for each dietary strategy to determine their ranking in terms of metabolic health benefits. Ten of the best and non-redundant meta-analysis studies, involving 153 original studies and 9846 participants, were included. When considering direct evidence only, all IF forms significantly reduced body weight compared to usual diets. In NMAincorporating indirect evidence, all IF regimens alsosignificantly reduced body weight compared to usual diets. In the SUCRA of NMA, IF ranked higher than usual diets or CER in 85.4% and 56.1% of the outcomes, respectively. ADF had the highest overall ranking for improving metabolic health (ranked first: 64.3%, ranked second: 14.3%). Overall, all IF forms demonstrate potentials to improve metabolic health, with ADF appearing to produce better outcomes across investigated outcomes. Further high-quality trials are warranted to confirm the (relative) efficacy of IF on metabolic health. PROSPERO (record no: CRD42022302690).

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

Vancomycin combined with piperacillin/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: a systematic review and network meta-analysis.

To explore whether vancomycin plus piperacillin/tazobactam actually increases nephrotoxicity compared with other anti-pseudomonal beta-lactams (BLs). PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP were searched from inception to October 2023. The primary outcomes were acute kidney injury (AKI) as defined as acute increase in serum creatinine of 0.3 mg/dL or 50% and severe Stage 2-3 AKI. We included 70 studies (76 638 patients). Network meta-analysis indicated that vancomycin plus piperacillin/tazobactam was associated with significantly higher AKI risk than vancomycin plus cefepime (OR 2.55, 95% CI 2-3.28), vancomycin plus meropenem (OR 2.26, 95% CI 1.71-3.02) and vancomycin plus other uncommonly used BLs (OR 2.47, 95% CI 1.87-3.29). Also, vancomycin + piperacillin/tazobactam was associated with significantly higher Stage 2-3 AKI risk than vancomycin + cefepime (OR 2.22, 95% CI 1.34-3.62), vancomycin + meropenem (OR1.96, 95% CI 1.22-3.25) and vancomycin + uncommonly used BLs (OR 2.81, 95% CI 1.66-4.91). Vancomycin plus piperacillin/tazobactam did not result in a significant difference in the incidence of receiving dialysis treatment, mortality, length of stay and time to AKI. Subgroup analyses of studies conducting propensity score matching demonstrated vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates than vancomycin + cefepime (OR 2.19, 95% CI 1.38-3.47) and vancomycin + meropenem (OR 1.38, 95% CI. 1.18-1.60). Subgroup analysis of critically ill patients and children indicated that vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates. Vancomycin + piperacillin/tazobactam significantly increased the risk of AKI and severe Stage 2-3 AKI compared with vancomycin plus other BLs. More prospective studies are needed.

The importance of incorporation of real-world evidence into the guidelines on the pharmacological treatment of schizophrenia.

The quantity and quality of real-world data and real-world evidence in schizophrenia research are at a high level. However, these results are not included in the grading systems used to develop treatment guidelines for schizophrenia. A meta-analysis and a network meta-analysis have independently provided evidence that the results of randomized clinical trials in schizophrenia adequately translate to real-world settings. The authors propose the incorporation of a synthesis of evidence derived from analyses of randomized controlled trials and real-world data as a novel and highest level of evidence in grading instruments used to develop treatment guidelines for schizophrenia.

Comparing the effectiveness of five traditional Chinese exercises in improving balance function in older adults: a systematic review and Bayesian network meta-analysis

Background Despite numerous studies affirming the potential of traditional Chinese exercises (TCEs) in enhancing balance in older adults, systematic integration is lacking. This study evaluated the effectiveness of five TCEs—Baduanjin, Liuzijue, Tai Chi, Wuqinxi, and Yijinjing—in improving balance among older adults using network meta-analysis. Methods This meta-analysis was registered in PROSPERO with the registration number CRD42023481450. Related articles indexed by Web of Science, Cochrane, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases before October 2023 were searched. Randomized controlled trials (RCTs) involving TCEs interventions to improve balance function conducted in older adults who aged ≥60 years were included. Two researchers used Review Manager to assess the quality of the studies, and analyzed the data using Stata and R. Results In total, 46 RCTs and 3,333 older adults were included. The aforementioned TCEs had positive effects on improving balance in older adults. Tai Chi revealed significant intervention effects in performing the Single-Leg Stand with eyes Closed (SLSC), 6-Min Walk Test (6MWT), and Short Form 36-Item Physical Component Summary (SF-36PCS). Liuzijue significantly improved performance in the Timed Up and Go Test (TUGT), 6MWT, SF-36PCS, and Berg Balance Scale (BBS). Baduanjin, Wuqinxi, and Yijinjing showed noteworthy intervention effects on the BBS. Tai Chi ranked highest in the SLSC, 6MWT, and SF-36PCS in the surface under the cumulative ranking, while Liuzijue and Yijinjing ranked highest in the TUGT and BBS, respectively. Conclusion Tai Chi, Liuzijue, and Yijinjing improved the static, dynamic, and overall balance outcomes, respectively. Older adults can make a reasonable choice among these TCEs based on their needs.