Updated Network Meta-analysis Research Articles

Comparative efficacy and safety of pharmacological interventions for severe COVID-19 patients: An updated network meta-analysis of 48 randomized controlled trials.

Background:To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19.Methods:We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs).Results:We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients.Conclusion:This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.

Worldwide comparative efficacy of nutraceuticals on lipid profile. an updated systematic review and network meta-analysis

Abstract Introduction In case of patients without indications to statin therapy, those being close to the target and especially with statin intolerance, nutraceuticals might be an additional option of hypercholesterolemia therapy. Despite a large number of nutraceuticals, little is known on their comparative efficacy due to the paucity of head-to-head comparisons. We aimed to assess the lipid-lowering effect of various nutraceuticals by means of network meta-analysis. Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were carefully searched to identify eligible studies to the meta-analysis. We included parallel or crossover randomized clinical trials (RCT), comparing head-to-head or to placebo/no intervention, the following nutraceuticals: a) artichoke, b) berberine, c) bergamot, d) garlic, e) green tea extract, f) plant sterols and stanols, g) policosanols, h) red yeast rice (RYR), i) silymarin, j) spirulina. We did not include soy protein, fiber, and lupin trials, as unlike other nutraceuticals they are in fact dietary interventions. Due to strikingly inconsistent results of policosanols RCTs carried out in Cuba and other countries, we excluded Cuban trials from main analysis. Results From the initially identified 4151 articles we finally included 131 studies. As some studies reported clinically different groups separately, they were split and finally we included 136 records, 134 with data on total cholesterol (TC), 125 with data on low-density cholesterol (LDL-C), 127 that provided information on high-density cholesterol (HDL-c) and 129 that included data regarding triglycerides (TG). Pooled studies covered data for 6755 patients randomized to nutraceutical arms and 6370 randomized to receive placebo/no intervention. For reducing TC bergamot, was identified as the most effective approach (P-score = 1.0) followed by RYR (0.90) and berberine (0.76). For increasing HDL-C, bergamot (0.98), berberine (0.85), and RYR (0.77) were the most effective. While evaluating LDL-C reduction, bergamot (1.00) and RYR (0.90) showed the highest reduction efficacy. Reducing effect of investigated nutraceuticals on TG levels was the highest for bergamot (1.00) and RYR (0.78). Majority of reports regarding Cuban policosanol trials implicated very high effectiveness of those nutraceuticals, which was in contrast to trials conducted in other countries Conclusions Bergamot, berberine, and RYR seemed to be most effective nutraceuticals in terms of lipid-lowering efficacy. Alleged high effectiveness of policosanols was not confirmed in our analysis. This analysis might support the physicians and patients' decisions to use only those nutraceuticals of confirmed efficacy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice

Comparison of mechanistic pathways of metabolic bariatric surgery in diabetic patients

Abstract Background and aims Metabolic bariatric surgeries are potentially efficacious treatment options in patients with type 2 diabetes mellitus (T2DM). However, previous meta-analyses focused on individual operative approaches rather than the mechanistic pathways behind different bariatric procedures. Thus, this updated network meta-analysis aimed to synthesize new evidence and comparatively evaluate the efficacy of bypass against restrictive procedures and standard first-line treatment for patients with T2DM. Methods Embase, Medline and trial registries were searched for randomized controlled trials on bariatric surgeries in patients with T2DM. A Bayesian network meta-analysis was conducted to compare between bypass, restrictive bariatric procedures, medical therapy and lifestyle intervention. Primary outcomes were T2DM remission and improvements in glycated haemoglobin (HbA1c). Secondary outcomes included changes in body mass index (BMI), lipoprotein levels and blood pressure. Results Thirty-two articles comprising 2,071 patients were included. Bypass surgery was statistically superior to restrictive procedures (RR: 2.57, 95% CrI: 1.36 to 5.43), medical therapy (RR: 35.29, 95% Crl: 10.56 to 183.23), and lifestyle intervention (RR: 40.51, 95% Crl: 5.32 to 402.59) in T2DM remission. Both bypass surgery and restrictive procedures were largely comparable in lowering HbA1c (MD: 0.02, 95% Crl: −0.03 to 0.08). In addition, bypass surgery significantly lowered BMI and blood pressure compared to other interventions. While restrictive procedures significantly increased high-density lipoproteins compared to bypass surgery, lifestyle intervention and bypass surgery were statistically superior to restrictive procedures in reducing low-density lipoproteins. Conclusion This study demonstrates that bypass surgery is superior to restrictive bariatric procedures in diabetes remission and glycaemic control. Additionally, significant metabolic advantages support the choice of bypass surgery over restrictive bariatric procedures in T2DM management. Funding Acknowledgement Type of funding sources: None.

Denosumab Versus Bisphosphonates for the Prevention of the Vertebral Fractures in Men with Osteoporosis: An Updated Network Meta-Analysis.

The efficacy of the prevention of vertebral fractures in men with osteoporosis by treatment with denosumab is debated. This study aimed to update the comparative effectiveness of denosumab and bisphosphonates for preventing vertebral fractures in men with osteoporosis. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials that enrolled men with osteoporosis. Fixed-effects network meta-analysis was performed to evaluate the risk of vertebral fractures, and the relative risk (RR) and 95% confident interval (CI) values were calculated. Sixteen studies were included, and the identified bisphosphonates were risedronate, alendronate, zoledronic acid, and ibandronate. Compared with placebo or control, a significant reduction in vertebral fractures was observed for denosumab (RR 0.30, 95%CI 0.13 0.68), risedronate (RR 0.39, 95%CI 0.19 0.77), and zoledronic acid (RR 0.45, 95%CI 0.21 0.98). According to the surface under the cumulative ranking curve (SUCRA), denosumab was the most effective one among the included agents for the risk reduction of vertebral fracture. However, compared with each bisphosphonate, the RR values of denosumab were not significant [RR 0.78 (95%CI 0.25 2.43) vs. risedronate, RR 0.55 (95%CI 0.18 1.75) vs. alendronate, RR 0.66 (95%CI 0.19 2.32) vs. zoledronic acid and RR 1.12 (95%CI 0.08 14.83) vs. ibandronate]. Denosumab effectively reduced the risk of vertebral fractures in men with osteoporosis, and this effect was comparable to that of bisphosphonates.

1077P An updated network meta-analysis of EGFR-TKIs and combination therapy in the first-line treatment of the advanced EGFR mutation positive non-small cell lung cancer

TKIs are standard care option in patients of NSCLC with EGFR mutation. TKIs-based combination treatment modes have shown encouraging outcomes. However, it remains unknown which is the optimal treatment as the first-line regimen for these patients on OS.

CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials

BackgroundUpdated evidence was required to compare the efficacy and safety of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors for patients with hormone receptor-positive and HER2-negative metastatic breast cancer.MethodsA systematic review and network meta-analysis was conducted utilizing data from randomized controlled trials (RCTs) that contained interventions of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were primary outcomes of interest. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% credible intervals (CrIs) were used to assess the survival outcomes and safety profiles, respectively.ResultsA total of 28 RCTs with 12,129 participants were included. Pooled analysis showed that CDK4/6 inhibitors significantly prolonged PFS than PI3K/AKT/mTOR inhibitors (HR, 0.81; 95% CrI, 0.69–0.94), whereas no significant differences were detected regarding OS. After balancing the treatment lines and metastatic sites, the superiority of CDK4/6 inhibitors only appeared in the visceral and non-visceral subgroups. Among CDK4/6 inhibitors, abemaciclib was significantly better than others in ≥3 grade neutropenia (OR, 0.04; 95% CrI, 0.01–0.15). The incidence of stomatitis and digestive disorders was different among diverse kinds of PI3K/AKT/mTOR inhibitors. Discrepancies appeared regarding TRAEs of hepatotoxicity, diarrhea, and hyperglycemia among different interventions.ConclusionsCDK4/6 inhibitors showed better efficacy in PFS, but the benefits disappeared when taking treatment line into consideration. Specific and discrepant safety profiles were found in two categories of agents.Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022321172.

An updated network meta-analysis of EGFR-TKIs and combination therapy in the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer

ObjectivesTyrosine kinase inhibitors (TKIs) are a standard care option in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. TKI-based combination treatment modes show encouraging outcomes. However, it remains unknown which is the optimal treatment as the first-line regimen for these patients on overall survival (OS).Materials and methodsRandomized controlled trials and meeting abstracts that investigated EGFR-TKIs alone or in combination as front-line care for patients with NSCLC were systematically searched in relevant databases and reviewed. Fixed and random effects network meta-analysis models were used to estimate progression-free survival (PFS), OS, overall response rate, and grade three and higher adverse events (AEs). Surface under the cumulative ranking curves (SUCRAs) were used to rank treatment effects.ResultsEighteen studies covering six treatments and involving a total of 4389 patients were included in this network meta-analysis. On OS, the top three treatment were first-generation EGFR-TKIs (1G EGFR-TKIs) plus chemotherapy (SUCRA, 88.1%), osimertinib (SUCRA, 65.8%) and second-generation EGFR-TKIs (2GEGFR-TKIs) (SUCRA, 63.3%). On PFS, the top three treatments were osimertinib (SUCRA, 96.0%), 1G EGFR-TKIs plus chemotherapy (SUCRA, 67.1%), and 1G EGFR-TKIs plus antiangiogenesis (SUCRA, 48.2%). Two types of TKI-based combination therapy have significantly higher risk of grade three and higher AEs than TKI alone.Conclusion1G EGFR-TKIs plus chemotherapy and osimertinib seem to be the two better options as first-line care in advanced NSCLC patients with EGFR-mutation. Osimertinib caused the lowest incidence of AEs. However, TKIs-based combination therapy significantly increased AEs.

The efficacy and tolerability of antibiotics in scrub typhus: an updated network meta-analysis of randomized controlled trials

ObjectivesInadequate treatment of scrub typhus results in severe complications such as septic shock and is also associated with a high median mortality rate of 6%. However, there has been no conclusive evidence about the superiority of different antibiotics in managing scrub typhus in terms of efficacy and tolerability. MethodsWe conducted a network meta-analysis (NMA) using the frequentist method. The included participants were pediatric and adult patients infected with scrub typhus. The primary outcome was the cure rate in the patients included. The subgroup analysis was done according to pediatric or adult patients. ResultsOverall, 14 randomized controlled trials (RCTs) with 1264 participants were included in this study. The NMA revealed that all the investigated antibiotics were associated with cure rates similar to those of doxycycline. The chloramphenicol and minocycline were ranked to be associated with the highest cure rate in the pediatric subgroup and adult subgroup, respectively. Second-generation quinolones, including ofloxacin, ciprofloxacin, and chloramphenicol, were associated with significantly lower adverse event rates than doxycycline. ConclusionThe current updated NMA provides evidence for the efficacy of chloramphenicol and minocycline in scrub typhus management. However, future large-scale RCTs with longer follow-up times are warranted.

Comparison of mechanistic pathways of bariatric surgery in patients with diabetes mellitus: A Bayesian network meta-analysis.

Metabolic bariatric procedures are potentially efficacious treatment options in patients with type 2 diabetes mellitus (T2DM). Previous meta-analyses focused on individual operative approaches rather than the mechanistic pathways behind different bariatric procedures. This updated network meta-analysis aimed to synthesize new evidence and comparatively evaluate the efficacy of metabolic surgery against restrictive procedures and standard first-line treatment for patients with T2DM. Embase, MEDLINE, and trial registries were searched for randomized controlled trials on bariatric surgeries in patients with T2DM on September 3, 2021. A Bayesian network meta-analysis was conducted. The primary outcome was T2DM remission. Secondary outcomes included changes in BMI, lipoprotein levels, and blood pressure. Thirty-two articles were included. Metabolic surgery was statistically superior to restrictive procedures (risk ratio [RR]: 2.57, 95% credibility intervals [CrI]: 1.36-5.43), medical therapy (RR: 35.29, 95% Crl: 10.56-183.23), and lifestyle intervention (RR: 40.51, 95% Crl: 5.32-402.59) in T2DM remission. Metabolic surgery significantly lowered BMI and blood pressure compared with other interventions. Restrictive procedures significantly increased high-density lipoprotein compared with metabolic surgery. Lifestyle intervention and metabolic surgery were statistically superior to restrictive procedures in reducing low-density lipoprotein. The superiority in diabetes remission and favorable metabolic profile support the choice of metabolic surgery over restrictive bariatric procedures.

Comparison of wound closure techniques after thyroid and parathyroid surgery: an updated systematic review and network meta-analysis.

We designed and conducted the present study to evaluate the optimal wound closure technique after thyroid and parathyroid surgery in terms of perioperative safety, efficacy, and cosmetic outcomes. A systematic literature review and network meta-analysis (NMA) was performed according to the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Literature screening was completed at 10/12/2021. A random effects multivariate network meta-analysis under a frequentist framework was implemented. Statistical significance was considered at the level of p < 0.05. Overall, 18 studies and 1314 patients were included. Conventional sutures (CS) received the best ranking (SUCRA: 90.1%) in wound-related morbidity. Metal clips (MC) was the best option for reducing the overall operation (SUCRA: 99%) and wound closure (SUCRA: 72.3%) duration. Moreover, adhesive strips (AS) had the higher probability of minimizing postoperative pain during the 2nd and 3rd postoperative days. Subcuticular suture (SS) was the most probable method for achieving optimal, long-term, patient-assessed, and surgeon-assessed cosmesis. However, MC had the highest mid and long term, independent-assessed, scar ranking (SUCRA 80.5% and 62.9%). Based on the inconclusive results and the several study limitations, further large-scale RCTs are required.

Advantages of short-course rifamycin-based regimens for latent tuberculosis infection: an updated network meta-analysis

We conducted an updated network meta-analysis to elucidate the best regimen for latent tuberculosis infection (LTBI). We searched the PubMed, Embase, and Cochrane Library databases on 16 August 2021 to perform an updated network meta-analysis. Only randomised controlled trials on populations with LTBI that reported the efficacy for preventing incident tuberculosis or the completion rates of treatment regimens were included. The Cochrane Collaboration tool was used to assess the risk of bias. We tested for possible global inconsistency with a χ2 test and local inconsistency by calculating inconsistency factors for each comparison in closed loops. The probability of each regimen being at each possible rank was estimated. Comparison-adjusted funnel plots were obtained to assess publication bias, and sensitivity analysis was performed. The major outcomes were the efficacy for preventing incident tuberculosis and the completion rates of treatment regimens. We identified 27 studies that matched our inclusion criteria; the risk of bias was mostly low. Rifampicin for four months (RFMP-4) was the most likely to be effective (probability: 56.3%) and the second most likely treatment to be completed (probability: 22.4%). By applying a multidimensional scaling approach for ranking based on a scatterplot with the surface under the cumulative ranking values for efficacy and completion rates, RFMP-4 was deemed the best choice for treating LTBI. Similar results were demonstrated after sensitivity analysis. This updated network meta-analysis revealed RFMP-4 to be the best choice for treating LTBI, per simultaneous consideration of efficacy and completion rates.

Combined Immunotherapy with Chemotherapy versus Bevacizumab with Chemotherapy in First-Line Treatment of Driver-Gene-Negative Non-Squamous Non-Small Cell Lung Cancer: An Updated Systematic Review and Network Meta-Analysis.

Background: A network meta-analysis was conducted to summarize randomized control trials and updated results to evaluate the efficacy and safety profiles of existing first-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC) patients without known driver gene mutations. Patients and Methods: Eligible studies were identified following a systematic search of the Cochrane Library, PubMed, Embase, Web of Science, Wanfang Data, and the China Knowledge Resource Integrated Database from January 2000 to December 2021. Results: Nineteen trials involving 8176 patients with driver-gene-negative advanced non-squamous NSCLC were included. For patients with driver-gene-negative advanced NSCLC, immunotherapy + chemotherapy (IC) significantly prolonged overall survival (OS) (hazard ratio (HR), 0.80; 95% confidence intervals (CI): 0.67–0.95) and progression-free survival (PFS) (HR, 0.68; 95% CI: 0.53–0.86) compared with bevacizumab + chemotherapy (BC), with a similar objective response rate and incidence of ≥3 treatment-related adverse events (TRAEs) (risk ratios (RR), 0.98; 95% CI: 0.79–1.21/RR, 0.89; 95% CI: 0.61–1.28; respectively) compared with BC. IC yielded a superior PFS rate (HR, 1.59; 95% CI: 1.05–2.38) compared to BC in the subgroup of patients < 65 years old. Conclusions: Currently, IC is a more efficient first-line therapy for driver-gene-negative advanced non-squamous NSCLC patients, with prolonged PFS and OS, as well as a comparatively lower risk of ≥3 TRAEs compared to BC.

Efficacy of Osteoporosis Medications for Patients With Chronic Kidney Disease: An Updated Systematic Review and Network Meta-Analysis.

Background: Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation. Methods: We systemically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases up to June 2020. Network-meta analysis was used to compare the relative effectiveness of different treatments. A random-effects model was used when heterogeneity was expected. The safety of different treatments was also evaluated in terms of reported major adverse events. Results: A total of 17 studies with data from 10,214 patients who had stage 2–5 CKD, were receiving dialysis, or had a history of kidney transplantation were included in the network meta-analysis. Treatment with teriparatide, denosumab, alendronate, and raloxifene were all associated with a significantly reduced risk of fractures compared to treatment with placebos [teriparatide: odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.10–0.35; denosumab: OR = 0.40, 95% CI: 0.27–0.58; alendronate: OR = 0.61, 95% CI: 0.40–0.92; raloxifene: OR = 0.52, 95% CI: 0.41–0.67]. The rank probability and the surface under the cumulative ranking (SUCRA) values suggested that teriparatide ranked the highest for improvement in vertebral bone mineral density (BMD) (SUCRA = 97.8%), whereas denosumab ranked the highest for improvement in femoral neck BMD (SUCRA = 88.3%). Conclusion: Teriparatide and denosumab seem to be the most effective treatments for preventing bone loss and reducing the risk of fracture in our network comparison. However, because of the limitations and potential biases in the reviewed studies, there is still some uncertainty about the best treatment options for osteoporosis in patients with CKD or a history of kidney transplantation. Systematic Review Registration: [PROSPERO], identifier [CRD42020209830].

Techniques for reconstruction after distal gastrectomy for cancer: updated network meta-analysis of randomized controlled trials.

The choice of the best reconstruction technique after distal gastrectomy (DG) remains controversial and still not defined. The purpose was to perform a comprehensive evaluation within the major type of intestinal reconstruction after DG for gastric cancer. Systematic review and network meta-analyses of randomized controlled trials (RCTs) to compare Billroth I (BI), Billroth II (BII), Billroth II Braun (BII Braun), Roux-en-Y (RY), and Uncut Roux-en-Y (URY). Risk ratio (RR) and weighted mean difference (WMD) were used as pooled effect size measures while 95% credible intervals (CrI) were used to assess relative inference. Ten RCTs (1456 patients) were included. Of these, 448 (33.7%) underwent BI, 220 (15.1%) BII, 114 BII Braun (7.8%), 533 (36.6%) RY, and 141 URY (9.6%). No significant differences were found among treatments for 30-day mortality, anastomotic leak, anastomotic stricture, and overall complications. At 12-month follow-up, RY was associated with a significantly reduced risk of remnant gastritis compared to BI (RR=0.56; 95% Crl 0.35-0.76) and BII reconstruction (RR=0.47; 95% Crl 0.22-0.97). Similarly, despite the lack of statistical significance, RY seems associated with a trend toward reduced endoscopically proven esophagitis compared to BI (RR=0.58; 95% Crl 0.24-1.51) and bile reflux compared to BI (RR=0.48; 95% Crl 0.17-1.41), BII (RR=0.74; 95% Crl 0.20-2.81), and BII Braun (RR=0.65; 95% Crl 0.30-1.43). This network meta-analysis shows that there are five main options for intestinal anastomosis after DG. All techniques seem equally safe with comparable anastomotic leak, anastomotic stricture, overall morbidity, and short-term outcomes. In the short-term follow-up (12 months), RY seems associated with a reduced risk of remnant gastritis and a trend toward a reduced risk of bile reflux and esophagitis.

Comparison of Adjuvant Target Therapy, Immunotherapy, and Chemotherapy for Resected EGFR-Mutant NSCLC – an Updated Network Meta-Analysis of 3300 Patients

Comparison of Adjuvant Target Therapy, Immunotherapy, and Chemotherapy for Resected EGFR-Mutant NSCLC – an Updated Network Meta-Analysis of 3300 Patients

Angiographic Patency of Coronary Artery Bypass Conduits: An Updated Network Meta-Analysis of Randomized Trials

IntroductionThe second best conduit for coronary artery bypass grafting is uncertain. The objective of this study is to determine the second best conduit according to graft patency results from randomized controlled trials using a network meta-analysis.MethodsA systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the no-touch saphenous vein (NT-SV), the radial artery (RA), the right internal thoracic artery (RITA), and the gastroepiploic artery (GEA) in reference to the conventionally harvested saphenous vein (CON-SV). The primary outcome was graft occlusion, and the secondary outcome was all-cause mortality.ResultsA total of 859 studies were retrieved, of which 18 were included. A total of 6,543 patients and 8,272 grafts were analyzed. The weighted mean angiographic follow-up time was 3.5 years. Compared with CON-SV, RA (incidence rate ratio [IRR] 0.56; 95% confidence interval [CI], 0.43-0.74) and NT-SV (IRR 0.56; 95% CI, 0.44-0.70) demonstrated lower graft occlusion. NT-SV and RA were ranked as the best conduits (rank score for NT-SV 0.88 vs. 0.87 for RA, 0.29 for GEA, 0.27 for CON-SV, and 0.20 for RITA). There was no significant difference in late mortality between different conduit types.ConclusionRA and NT-SV are associated with significantly lower graft occlusion rates and are comparably ranked as the best conduit for patency.

Updated network meta-analysis assessing the relative efficacy of 13 GLP-1 RA and SGLT2 inhibitor interventions on cardiorenal and mortality outcomes in type 2 diabetes

Updated network meta-analysis assessing the relative efficacy of 13 GLP-1 RA and SGLT2 inhibitor interventions on cardiorenal and mortality outcomes in type 2 diabetes

An updated systematic review and network meta-analysis comparing open, laparoscopic and robotic-assisted sacrocolpopexy for managing pelvic organ prolapse.

Abdominal sacrocolpopexy is considered as the gold standard treatment for pelvic organ prolapse. Sacrocolpopexy can be performed using open (OSC), laparoscopic (LSC), and robotic-assisted (RSC) approaches. The aim of this study is to compare the outcomes between these three approaches for managing pelvic organ prolapse by conducting a systematic review and network meta-analysis. A systematic search was performed in different databases from their earliest records to April 2021 with no restriction on languages. Only randomized controlled trials that compared the outcomes between OSC, LSC, and RSC were included in this study. A total of 6 studies with 486 participants were included in this study. Operative time was significantly shorter in OSC than in RSC and LSC. The probability rank showed less estimated blood loss in RSC and lowest overall postoperative complications in LSC. Probability scores also showed best anatomical outcomes for postoperative points C and Bp in RSC and for point Ba in LSC. Despite significantly longer operative time, RSC and LSC may provide better anatomical outcomes, less estimated blood loss, and less overall postoperative complications than OSC. However, this study did not find significant differences between RSC and LSC in efficacy and safety.

Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients: an updated network meta-analysis of randomized placebo-controlled trials.

Background: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs).Methods: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates.Results: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96–393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21–30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15–18.30), ivermectin (OR 6.33, 95% CI 1.22–32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12–24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43–17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09–0.19), imatinib (OR 0.49, 95% CI 0.25–0.96), and baricitinib (OR 0.58, 95% CI 0.42–0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08–0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13–0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients.Conclusion: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.

Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis.

BackgroundClopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD.MethodsWe searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses.ResultsWe analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65-0.93) and ticagrelor (HR 0.80; 95% CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95% CrI 0.43-1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed a significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk.ConclusionThis updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.