Frequentist Network Meta-analysis Research Articles

Effectiveness of eHealth Interventions in Improving Medication Adherence Among Patients With Cardiovascular Disease: Systematic Review and Meta-Analysis.

Nonadherence to medication among patients with cardiovascular diseases undermines the desired therapeutic outcomes. eHealth interventions emerge as promising strategies to effectively tackle this issue. The aim of this study was to conduct a network meta-analysis (NMA) to compare and rank the efficacy of various eHealth interventions in improving medication adherence among patients with cardiovascular diseases (CVDs). A systematic search strategy was conducted in PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure Library (CNKI), China Science and Technology Journal Database (Weipu), and WanFang databases to search for randomized controlled trials (RCTs) published from their inception on January 15, 2024. We carried out a frequentist NMA to compare the efficacy of various eHealth interventions. The quality of the literature was assessed using the risk of bias tool from the Cochrane Handbook (version 2.0), and extracted data were analyzed using Stata16.0 (StataCorp LLC) and RevMan5.4 software (Cochrane Collaboration). The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. A total of 21 RCTs involving 3904 patients were enrolled. The NMA revealed that combined interventions (standardized mean difference [SMD] 0.89, 95% CI 0.22-1.57), telephone support (SMD 0.68, 95% CI 0.02-1.33), telemonitoring interventions (SMD 0.70, 95% CI 0.02-1.39), and mobile phone app interventions (SMD 0.65, 95% CI 0.01-1.30) were statistically superior to usual care. However, SMS compared to usual care showed no statistical difference. Notably, the combined intervention, with a surface under the cumulative ranking curve of 79.3%, appeared to be the most effective option for patients with CVDs. Regarding systolic blood pressure and diastolic blood pressure outcomes, the combined intervention also had the highest probability of being the best intervention. The research indicates that the combined intervention (SMS text messaging and telephone support) has the greatest likelihood of being the most effective eHealth intervention to improve medication adherence in patients with CVDs, followed by telemonitoring, telephone support, and app interventions. The results of these network meta-analyses can provide crucial evidence-based support for health care providers to enhance patients' medication adherence. Given the differences in the design and implementation of eHealth interventions, further large-scale, well-designed multicenter trials are needed. INPLASY 2023120063; https://inplasy.com/inplasy-2023-12-0063/.

Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis

ObjectivesTo assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs).Design and settingSystematic review and frequentist network meta-analysis...

Comparative Efficacy of Various Exercise Therapies and Combined Treatments on Inflammatory Biomarkers and Morphological Measures of Skeletal Muscle among Older Adults with Knee Osteoarthritis: A Network Meta-Analysis

Osteoarthritis is associated with high risks of sarcopenia in older populations. Exercise interventions are promising treatments for musculoskeletal impairments in knee osteoarthritis (KOA). The purpose of this study was to identify the comparative effects of exercise monotherapy and its adjunct treatments on muscle volume and serum inflammation for older individuals with KOA. A literature search in the electronic databases was comprehensively performed from this study’s inception until April 2024 to identify relevant randomized controlled trials (RCTs) that reported muscle morphology and inflammation outcomes after exercise. The included RCTs were analyzed through a frequentist network meta-analysis (NMA). The standard mean difference (SMD) with a 95% confidence interval was estimated for treatment effects on muscle morphology and inflammation biomarkers. The relative effects on each main outcome among all treatment arms were compared using surface under the cumulative ranking (SUCRA) scores. The certainty of evidence (CoE) was assessed by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) ranking system. Probable moderators of the treatment efficacy were investigated by network meta-regression analysis. This study included 52 RCTs (4255 patients) for NMA. Among the 27 identified treatment arms, isokinetic training plus physical modality as well as low-load resistance training plus blood-flow restriction yielded the most optimal treatment for inflammation reduction (−1.89; SUCRA = 0.97; CoE = high) and muscle hypertrophy (SMD = 1.28; SUCRA = 0.94; CoE = high). The patient’s age (β = −0.73), the intervention time (β = −0.45), and the follow-up duration (β = −0.47) were identified as significant determinants of treatment efficacy on muscle hypertrophy. Exercise therapy in combination with noninvasive agents exert additional effects on inflammation reduction and muscle hypertrophy compared to its corresponding monotherapies for the KOA population. However, such treatment efficacy is likely moderated by the patient’s age, the intervention time, and the follow-up duration.

Effects of exercise on depression and anxiety in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials.

Exercise has been identified as a promising non-pharmacological therapy for the management of depression, but there is still controversy over which type is most effective. We aimed to compare and rank the types of exercise that improve depression in postmenopausal women by quantifying information from randomized controlled trials (RCTs). The PubMed, Web of Science, SPORTDiscus, CNKI, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases were searched to identify articles published from inception to 1 March 2024 reporting RCTs that examined the effectiveness of exercise on depression in postmenopausal women. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for RCTs. The quality of the evidence for each comparison was graded using the online confidence in network meta-analysis tool (CINeMA). Standardized mean differences (SMDs) were calculated using the mean and standard deviation of pre-to-post intervention changes and then pooled using a random effects model in a pairwise meta-analysis using Review Manager 5.4. Then, a frequentist network meta-analysis was conducted using a random effects model was conducted to evaluate the efficacy of different exercise types using the network package of Stata 15. This study included 26 studies involving 2,170 participants. The pairwise meta-analysis revealed that exercise had a significant positive effect on depression in postmenopausal women (SMD = -0.71, 95% confidence interval [CI] = -0.94 to -0.48; I2 = 78%). The network meta-analysis revealed that mind-body exercise (SMD = -0.97, 95% CI = -1.28 to -0.67), aerobic exercise (SMD = -0.58, 95% CI = -0.88 to -0.27) and multicomponent exercise (SMD = -0.57, 95% CI = -1.15 to -0.002) significantly reduced depression compared to the control intervention. Mind-body exercise had the highest probability of being the most effective intervention. Exercise interventions also showed positive effects on anxiety. Most studies were judged to have some concerns regarding their risk of bias, and the confidence in evidence was often very low according to CINeMA. For postmenopausal women, there is very low to moderate quality evidence that exercise interventions are an effective antidepressant therapy, with mind-body exercise most likely being the optimal type. This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42024505425).

O-313 Increased risk of preterm deliveries in long term survivors of children, adolescent, and young adult exposure to chemotherapy or chemo-radiotherapy: a systematic review and meta-analysis

Abstract Study question What is the long-term impact on pregnancy outcomes of a childhood adolescent, and young adult (AYA) exposure to chemotherapy or chemo-radiotherapy? Summary answer Whereas preterm delivery and pregnancy loss were significantly increased in chemotherapy and chemo-radiotherapy groups compared to control group, live birth rate was not affected. What is known already The impact of radiotherapy on the uterus has been widely described. Lately, studies have underlined the potential negative effect of chemotherapy on the womb. Indeed, three recent publications have reported that adult females treated with hematopoietic stem cell transplantation (HSCT) in childhood had a reduced uterus volume, both after conditioning by total body irradiation (TBI) and after alkylating agents-based regimen. The pregnancy outcome will depend in part on the uterine volume and its vascularization. Therefore, a history of chemotherapy or chemo-radiotherapy may be associated to an increased risk of obstetrical complications. Study design, size, duration A systematic review and meta-analysis were performed on comparative studies. Searches were conducted on Medline, Embase and the Cochrane Library from 1990 to April 2023, using the main following search terms: cancer survivors, bone marrow transplantation, chemotherapy, radiotherapy, pregnancy outcome, pregnancy complications, preterm delivery, and pregnancy loss. All studies reporting live birth rate (LBR) in adult females who have received chemotherapy and/or chemo-radiotherapy during childhood and AYA < 25 years were included. Participants/materials, setting, methods Two independent reviewers carried out the study selection, the bias assessment using the ROBINS-I tool and data extraction. The primary outcome was the LBR. The main secondary outcomes were preterm delivery and pregnancy loss rates. For each outcome, a random-effect frequentist network meta-analysis (NMA) was carried out to estimate risk ratios with their 95% confidence intervals. Sensitivity analyses were conducted by excluding studies at high risk of bias and leave-one out method. Main results and the role of chance After reviewing 2,328 abstracts, 25 studies were retained for review. Eight studies were included in the meta-analysis on LBR: 3,997 females became pregnant leading to 2,878 live births. The NMA shows a moderate heterogeneity/inconsistency (τ²= 0.012, I²=58% [11%; 80%]) and did not show any significant impact of treatments on LBR. Sensitivity analyses lead to the same conclusions. Six studies reported a total of 125 preterm deliveries out of 1,976 started pregnancies and were included in the NMA (τ²= 0.07, I²=19% [0%; 62%]). Chemo-radiotherapy was significantly associated with higher risk of preterm delivery compared to the control group (3.44 [1.94; 6.09]) and chemotherapy group (1.93 [1.19; 3.15]). The chemotherapy group was associated with a statistically higher risk of preterm delivery than the control group (1.78 [1.01; 3.13]). Eight studies including 606 pregnancy loss out of 3,653 started pregnancies were entered in the NMA (τ²= 0, I²=0% [0%; 65%]). Chemo-radiotherapy was associated with significantly higher risk of pregnancy loss compared to the control group (1.80 [1.34; 2.43]) and chemotherapy group (1.68 [1.26; 2.25]). No statistical difference was shown in the risk of pregnancy loss between the chemotherapy and the control groups (1.07 [0.87; 1.32]). Limitations, reasons for caution Study selection was focused on live birth rate; therefore, the research was probably not exhaustive for the secondary outcomes. Adjustment on parity or history of hormonal replacement therapy (HRT) was not performed because of a lack of data. Subgroup analysis on the type of chemotherapy was not possible. Wider implications of the findings This meta-analysis reports a negative impact of chemotherapy or chemo-radiotherapy on obstetric outcomes. Further studies including clear information on parity and use of HRT are needed. Moreover, a description on the type of chemotherapy could help to refine these conclusions. Trial registration number Not applicable

Efficacy of pharmacologic interventions on magnetic resonance imaging biomarkers in patients with nonalcoholic fatty liver disease: systematic review and network meta-analysis.

Several agents are under investigation for nonalcoholic fatty liver disease (NAFLD). We assessed the comparative efficacy of pharmacologic interventions for patients with NAFLD focusing on magnetic resonance imaging (MRI) biomarkers. We searched Medline, Embase, and CENTRAL. We included randomized controlled trials of more than 12weeks of intervention that recruited patients with biopsy-confirmed or MRI-confirmed NAFLD and assessed the efficacy of interventions on liver fat content (LFC) and fibrosis by means of MRI. We performed random-effects frequentist network meta-analyses and assessed confidence in our estimates using the CINeMA (Confidence in Network Meta-Analysis) approach. We included 47 trials (8583 patients). Versus placebo, thiazolidinediones were the most efficacious for the absolute change in LFC, followed by vitamin E, fibroblast growth factor (FGF) analogs, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with mean differences ranging from -7.46% (95% confidence interval [-11.0, -3.9]) to -4.36% (-7.2, -1.5). No differences between drug classes were evident. Patients receiving GLP-1 RAs or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs were more likely to achieve ≥30% relative reduction in LFC. Among agents, efruxifermin produced the largest reduction in LFC compared to placebo [-13.5% (-18.5, -8.5)], followed by pioglitazone, while being superior to most interventions. The effect of interventions on magnetic resonance elastography assessed fibrosis was small and insignificant. The confidence in our estimates was low to very low. Several drug classes may reduce LFC in patients with NAFLD without a significant effect on fibrosis; nevertheless, trial duration was small, and confidence in the effect estimates was low.

Oncological outcomes in minimally invasive vs. open distal pancreatectomy: a systematic review and network meta-analysis.

Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and laparoscopic approaches for distal pancreatectomies (DP) in patients with pancreatic adenocarcinoma (PDAC). This systematic review and network meta-analysis aims to explore the oncological outcomes of laparoscopic distal pancreatectomy (LDP), robotic distal pancreatectomy (RDP) and open distal pancreatectomy (ODP). A systematic search was conducted for studies reporting laparoscopic, robotic or open surgery for DP. Frequentist network meta-analysis of oncological outcomes (overall survival, resection margins, tumor recurrence, examined lymph nodes, administration of adjuvant therapy) were performed. Fifteen studies totalling 9,301 patients were included in the network meta-analysis. 1,946, 605 and 6,750 patients underwent LDP, RDP and ODP respectively. LDP (HR: 0.761, 95% CI: 0.642-0.901, p = 0.002) and RDP (HR: 0.757, 95% CI: 0.617-0.928, p = 0.008) were associated with overall survival (OS) benefit when compared to ODP. LDP (HR: 1.00, 95% CI: 0.793-1.27, p = 0.968) was not associated with OS benefit when compared to RDP. There were no significant differences between LDP, RDP and ODP for resection margins, tumor recurrence, examined lymph nodes and administration of adjuvant therapy. This study highlights the longer OS in both LDP and RDP when compared to ODP for patients with PDAC. https://www.crd.york.ac.uk/, PROSPERO (CRD42022336417).

Comparison of venovenous extracorporeal membrane oxygenation, prone position and supine mechanical ventilation for severely hypoxemic acute respiratory distress syndrome: a network meta-analysis.

Severe acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS. We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence. Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59-0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57-0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66-0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63-1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72-1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals. In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain.

Comparison of checkpoint inhibitor–based regimens as first-line therapy in advanced hepatocellular carcinoma: A Frequentist Network meta-analysis of randomized clinical trials.

e16136 Background: Multiple immune checkpoint inhibitor (ICI) based regimens have shown better responses and survival rates than previously used sorafenib/lenvatinib in advanced hepatocellular carcinoma (HCC). However, there was no direct comparison done among different ICI-based regimens. This network meta-analysis focuses on the efficacy of different ICI-based regimens in advanced HCC as first-line therapy. Methods: A comprehensive literature search was performed on PubMed, and Embase from the inception of data till 12/30/2023 with keywords for “Hepatocellular carcinoma” AND “Immune Checkpoint Inhibitors”. We screened 5120 articles and included 8 randomized clinical trials (RCTs, N = 5834). “R” software and netmeta package was used to conduct this network meta-analysis. Atezolizumab + cabozantinib was randomly chosen as the comparator group. Results: 2208 patients were treated with ICI-based two-drug regimens, 1102 patients were treated with ICI monotherapy, 1937 patients were treated with sorafenib, and 399 patients were treated with lenvatinib. Overall survival (OS) was 0.63 (0.43-0.93), 0.64 (0.43-0.98), and 0.69 (0.48-0.99) in favor of sintilimab + bevacizumab, atezolizumab + bevacizumab, and camrelizumab + rivoceranib, respectively, as compared to atezolizumab + cabozantinib. Progression free survival (PFS) was 0.83 (0.54-1.27), 0.89 (0.58-1.35), and 0.94 (0.61-1.45) in favor of camrelizumab + rivoceranib, sintilimab + bevacizumab, and atezolizumab + bevacizumab, respectively, as compared to atezolizumab + cabozentinib. Odds ratio of overall response rate (ORR) 2.03 (0.67-6.13), 1.7 (0.65-4.43), and 1.46 (0.58-3.67) in favor of sintilimab + bevacizumab, camrelizumab + rivoceranib, and tremlimumab + durvalumab, respectively, as compared to atezolizumab + cabozantinib. P-scores for each regimen are in Table. Conclusions: Among ICI combinations, better survival and response rates were reported with sintilimab + bevacizumab, atezolizumab + bevacizumab, and camrelizumab + rivoceranib. Therefore, these regimens should be preferred for treatment of advanced HCC as first line therapy in patients who can tolerate these regimens. [Table: see text]

Risk of adjacent level fracture after percutaneous vertebroplasty and kyphoplasty vs natural historyfor the management of osteoporotic vertebral compression fractures: a network meta-analysis of randomized controlled trials.

Percutaneous vertebroplasty and kyphoplasty are common interventions for osteoporotic vertebral compression fractures. However, there is concern about an increased risk of adjacent-level fractures after treatment. This study aimed to compare the risk of adjacent-level fractures after vertebroplasty and kyphoplasty with the natural history after osteoporotic vertebral compression fractures. A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to the natural history after osteoporotic vertebral compression fractures. Frequentist network meta-analysis was conducted using the "netmeta" package, and heterogeneity was assessed using Q statistics. The pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using random effects. Twenty-three RCTs with a total of 2838 patients were included in the analysis. The network meta-analysis showed comparable risks of adjacent-level fractures between vertebroplasty, kyphoplasty, and natural history after osteoporotic vertebral compression fractures with a mean follow-up of 21.2 (range: 3-49.4 months). The pooled RR for adjacent-level fractures after kyphoplasty compared to natural history was 1.35 (95% CI, 0.78-2.34, p = 0.23) and for vertebroplasty compared to natural history was 1.16 (95% CI, 0.62-2.14) p = 0.51. The risk of bias assessment showed a low to moderate risk of bias among included RCTs. There was no difference in the risk of adjacent-level fractures after vertebroplasty and kyphoplasty compared to natural history after osteoporotic vertebral compression fractures. The inclusion of a large patient number and network meta-analysis of RCTs serve evidence-based clinical practice. The risk of adjacent-level fracture following percutaneous vertebroplasty or kyphoplasty is similar to that observed in the natural history after osteoporotic vertebral compression fractures. RCTs have examined the risk of adjacent-level fracture after intervention for osteoporotic vertebral compression fractures. There was no difference between vertebroplasty and kyphoplasty patients compared to the natural disease history for adjacent compression fractures. This is strong evidence that interventional treatments for these fractures do not increase the risk of adjacent fractures.

P.067 Pharmacological prophylaxis for chronic migraine: A systematic review and network meta-analysis of randomized controlled trials

Background: We performed a network meta-analysis of randomized controlled trials to assess the comparative effectiveness of available pharmacological prophylaxis for migraines. Methods: We searched MEDLINE, EMBASE, Web of Science, Scopus, PsycINFO and Cochrane CENTRAL up to October 2023 for trials that: (1) enrolled adults diagnosed with chronic migraine, and (2) randomized them to any prophylactic medication vs. another medication or placebo. We performed a random-effects frequentist network meta-analysis for patient-important outcomes. Results: We included 193 randomized trials. Compared to placebo, CGRP monoclonal antibodies (mean difference [MD] -1.7, 95%CI: -1.1 to -2.2), injection of botulinum toxin (MD -1.8, 95%CI: -0.7 to -2.9), calcium channel blockers (MD -1.8, 95%CI: -0.5 to -3.0), beta-blockers (MD -1.4, 95%CI: -0.2 to -2.6), and anticonvulsants (MD -1.1, 95%CI: -0.4 to -1.8) were among the most effective treatments in reducing average number of headache days per months. Anticonvulsants (Risk Ratio [RR] 2.3, 95%CI: 1.8 to 3.0), calcium channel blockers (RR 1.8, 95% CI: 1.1 to 3.1), and tricyclic antidepressants (RR 2.3, 95% CI: 1.3 to 3.8) showed the highest risk of discontinuation due to adverse events. Conclusions: Our findings suggest that CGRP inhibitors, botulinum toxin, and beta-blockers may provide the greatest benefit, and tolerability, for reducing the frequency of migraine headaches.

Stroke Risk After Mitral Valve Interventions: A Systematic Review and Network Meta-Analysis

Previous research indicates varying stroke rates after mitral valve (MV) interventions. This study aimed to compare post-procedural stroke risks following transcatheter and surgical MV interventions. Electronic databases were searched from inception to February 2024 for studies comparing stroke rates after mitral transcatheter edge-to-edge repair (mTEER), surgical MV repair/replacement, or guideline-directed medical therapy (GDMT). Primary endpoints were all-time and early (<30 days) stroke. Secondary outcomes included new-onset atrial fibrillation and 1-year all-cause mortality. A frequentist network meta-analysis was employed to compare outcomes. The network meta-analysis included 18 studies (3 randomized clinical trials and 15 observational), with 51,703 patients. mTEER was associated with a decreased risk of all-time (odds ratio [OR] 0.61, 95% CI 0.41-0.89) and early stroke (OR 0.41, 95% CI 0.33-0.51) compared with surgery, and a similar risk of all-time (OR 1.54, 95% CI 0.76-3.12) and early stroke (OR 2.12, 95% CI 0.53-8.47) compared with GDMT. Conversely, surgery was associated with an increased risk of all-time (OR 2.55, 95% CI 1.17-5.57) and early stroke (OR 5.15, 95% CI 1.27-20.84) compared with GDMT. There were no statistically significant differences in the risk of new-onset atrial fibrillation (OR 0.38, 95% CI 0.11-1.31) and 1-year all-cause mortality (OR 1.43, 95% CI 0.91-2.24) between mTEER vs. surgery. In conclusion, mTEER was associated with a lower risk of stroke and similar risks of new-onset atrial fibrillation and 1-year mortality compared with surgical MV interventions. Further studies are needed to understand the mechanisms of stroke and to determine strategies to reduce stroke risk following MV interventions.

Comparative effects of different antiplatelet strategies in carriers of CYP2C19 loss-of-function alleles: a network meta-analysis.

Carriers of cytochrome 2C19 (CYP2C19) loss of function (LoF) alleles treated with clopidogrel have impaired drug metabolism resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored. Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI) were included. A frequentist network meta-analysis was conducted to estimate mean difference (MD) or odds ratios (OR) and 95% confidence intervals (CI). The primary outcome was platelet reactivity assessed by VerifyNow and reported as P2Y12 reaction unit (PRU). The secondary outcome was the rate of HPR. Standard-dose of clopidogrel (75 mg daily) was used as reference treatment. A total of 12 RCTs testing 6 alternative strategies (i.e., clopidogrel 150 mg, prasugrel 3.75 mg, 5 mg, and 10 mg, ticagrelor 90 mg bid, and adjunctive cilostazol 100 mg bid) were included in the network. Compared with standard-dose clopidogrel, the greatest reduction in PRU was observed with prasugrel 10 mg (MD -127.91; 95% CI -141.04; -114.78) and ticagrelor 90 mg bid (MD -124.91; 95% CI -161.78; -88.04), followed by prasugrel 5 mg (MD -76.33; 95% CI -98.01; -54.65) and prasugrel 3.75 mg (MD -73.00; 95% CI -100.28; -45.72). Among other strategies, adjunctive cilostazol (MD-42.64; 95% CI -64.72; -20.57) and high-dose clopidogrel (MD -32.11; 95% CI -51.33; -12.90) were associated with a modest reduction in PRU compared with standard-dose clopidogrel. Among carriers of CYP2C19 LoF alleles undergoing PCI, standard-dose prasugrel or ticagrelor are most effective in reducing platelet reactivity, while double-dose clopidogrel and additional cilostazol showed modest effects. Reduced-dose of prasugrel may represent a balanced strategy to overcome HPR without a significant increase in bleeding. The clinical implications of these pharmacodynamic findings warrant further investigation.

Efficacy and Safety of Direct Oral Anticoagulants for Acute Treatment of Venous Thromboembolism in Older Adults: A Network Meta-Analysis of Randomised Controlled Trials.

This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in adults aged 75 and over undergoing acute venous thromboembolism (VTE) treatment. PubMed, Embase and the CENTRAL were searched up to 25 December 2023. The incidence of VTE recurrence and bleeding events was assessed. Employing a frequentist network meta-analysis approach, interventions not directly compared could be indirectly assessed through the 95% confidence interval (CI), enhancing the interpretability of the search results. The surface under the cumulative ranking curves (SUCRA) was utilized to generate the relative ranking probabilities for each group. Our study, analysing 6 randomised controlled trials with 3665 patients, compares direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in adults aged 75 and over with acute venous thromboembolism. Edoxaban reduces VTE recurrence risk compared with VKAs (risk ratio [RR] .50, 95% CI 0.27 - .95), while apixaban significantly decreases bleeding risk compared with VKAs (RR .23, 95% CI 0.08 - .69), edoxaban (RR .28, 95% CI 0.09 - .86) and rivaroxaban (RR .28, 95% CI 0.09 - .86). Despite low overall evidence quality, apixaban consistently ranks highest for both efficacy and safety. Findings underscore the nuanced efficacy-safety balance in this population, emphasizing cautious interpretation due to evidence limitations. Apixaban emerges as a favourable choice for acute VTE treatment in the elderly, displaying reduced bleeding risk compared to other treatments while maintaining comparable efficacy. Future studies should explore diverse anticoagulants efficacy and safety in older populations. Additionally, clinical prediction models tailored to geriatric cohorts are crucial for guiding treatment duration decisions.

Individual dipeptidyl peptidase-4 inhibitors and acute kidney injury in patients with type 2 diabetes: A systematic review and network meta-analysis.

This network meta-analysis of randomized controlled trials aimed to determine whether any individual dipeptidyl peptidase-4 (DPP-4) inhibitors increase the risk of acute kidney injury (AKI). The Medical Literature Analysis and Retrieval System Online via PubMed, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were systematically searched to identify relevant studies. The primary outcome was AKI. A frequentist network meta-analysis was performed using a random-effects model to account for heterogeneity. Twenty-nine studies involving 56 117 participants were included. There were 918 cases of AKI (1.63%). The risk of bias was generally considered to be low. The only DPP-4 inhibitor that significantly increased the frequency of AKI when compared with placebo was sitagliptin (risk ratio 1.65, 95% confidence interval 1.22-2.23). However, because one study showed significant outliers in the funnel plot, in a highly heterogeneous population composed solely of patients undergoing surgery for coronary artery bypass graft, we conducted a post-hoc sensitivity analysis to exclude this study. The results showed no statistically significant difference in the risk of AKI between sitagliptin and placebo. Individual DPP-4 inhibitors do not appear to increase the risk of AKI. However, sitagliptin may be associated with AKI in patients with underlying severe cardiovascular disease.

Comparative efficacy of antioxidant therapies for sepsis and septic shock in the intensive care unit: A frequentist network meta-analysis

BackgroundAntioxidant therapy is gaining traction in managing sepsis and septic shock, owing to its perceived positive impact on patient outcomes. This study sought to compare the efficacy of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium, and N-acetylcysteine, both individually and in combination with other compounds such as vitamin B1, hydrocortisone, propolis, and glutamine) in treating sepsis or septic shock in the intensive care unit (ICU). MethodsThe study involved randomized and multi-arm trials with sepsis or septic shock patients using melatonin, vitamin C, vitamin E, selenium, or N-acetylcysteine. Studies were sourced from PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO - Clinical Trials Registry Platform for the frequentist network meta-analysis on 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores. The risk of bias was assessed using the Physiotherapy Evidence Database scale. Therapies were compared directly and indirectly using R software. ResultsThe study of 56 trials involving 9,366 patients was included. Bias assessment revealed that 89.3 % of trials achieved excellent or good quality. Based on treatment ranking and pairwise comparisons, melatonin with propolis (SUCRA = 93.29 %) is effective in improving SOFA scores, statistically significant, with no publication bias (p= 0.73). High-dose vitamin C (SUCRA = 83.97 %), vitamin C with vitamin B1 (SUCRA = 78.72 %), and melatonin (SUCRA = 67.03 %) are potential therapies for organ dysfunction. Melatonin (SUCRA = 88.22 %) and high-dose vitamin C (SUCRA = 80.75 %) were the most effective in reducing 28-day mortality rates. However, analysis indicated that the results for 28-day mortality rates were not statistically significant. Also, these results contained publication bias (p= 0.02). ConclusionThe study offers fresh perspectives on antioxidant therapy treatments for sepsis or septic shock in ICU, emphasizing the combination of melatonin and propolis notably reduces SOFA scores for those patients.

Incisional Wound Irrigation for the Prevention of Surgical Site Infection

Surgical site infections (SSIs) are common postoperative complications and associated with significant morbidity, mortality, and costs. Prophylactic intraoperative incisional wound irrigation is used to reduce the risk of SSIs, and there is great variation in the type of irrigation solutions and their use. To compare the outcomes of different types of incisional prophylactic intraoperative incisional wound irrigation for the prevention of SSIs in all types of surgery. PubMed, Embase, CENTRAL, and CINAHL databases were searched up to June 12, 2023. Included in this study were randomized clinical trials (RCTs) comparing incisional prophylactic intraoperative incisional wound irrigation with no irrigation or comparing irrigation using different types of solutions, with SSI as a reported outcome. Studies investigating intracavity lavage were excluded. This systematic review and network meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two reviewers independently extracted the data and assessed the risk of bias within individual RCTs using the Cochrane Risk of Bias 2 tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A frequentist network meta-analysis was conducted, and relative risks (RRs) with corresponding 95% CIs were reported. The primary study outcome was SSI. A total of 1587 articles were identified, of which 41 RCTs were included in the systematic review, with 17 188 patients reporting 1328 SSIs, resulting in an overall incidence of 7.7%. Compared with no irrigation, antiseptic solutions (RR, 0.60; 95% CI, 0.44-0.81; high level of certainty) and antibiotic solutions (RR, 0.46; 95% CI, 0.29-0.73; low level of certainty) were associated with a beneficial reduction in SSIs. Saline irrigation showed no statistically significant difference compared with no irrigation (RR, 0.83; 95% CI, 0.63-1.09; moderate level of certainty). This systematic review and network meta-analysis found high-certainty evidence that prophylactic intraoperative incisional wound irrigation with antiseptic solutions was associated with a reduction in SSIs. It is suggested that the use of antibiotic wound irrigation be avoided due to the inferior certainty of evidence for its outcome and global antimicrobial resistance concerns.

Efficacy of different routes of acetaminophen administration for postoperative pain in children: a systematic review and network meta-analysis.

Acetaminophen is the most common drug used to treat acute pain in the pediatric population, given its wide safety margin, low cost, and multiple routes for administration. We sought to determine the most efficacious route of acetaminophen administration for postoperative acute pain relief in the pediatric surgical population. We conducted a systematic review of randomized controlled trials (RCTs) that included children aged between 30days and 17yr who underwent any type of surgical procedure and that evaluated the analgesic efficacy of different routes of administration of acetaminophen for the treatment of postoperative pain. We searched MEDLINE, CENTRAL, Embase, CINAHL, LILACs, and Google Scholar databases for trials published from inception to 16 April 2023. We assessed the risk of bias in the included studies using the Cochrane Risk of Bias 1.0 tool. We performed a frequentist network meta-analysis using a random-effects model. Our primary outcome was postoperative pain using validated pain scales. We screened 2,344 studies and included 14 trials with 829 participants in the analysis. We conducted a network meta-analysis for the period from zero to two hours, including six trials with 496 participants. There was no evidence of differences between intravenous vs rectal routes of administration of acetaminophen (difference in means, -0.28; 95% confidence interval [CI], -0.62 to 0.06; very low certainty of the evidence) and intravenous vs oral acetaminophen (difference in means, -0.60; 95% CI, -1.20 to 0.01; low certainty of the evidence). For the comparison of oral vs rectal routes, we found evidence favouring the oral route (difference in means, -0.88; 95% CI, -1.44 to -0.31; low certainty of the evidence). Few trials reported secondary outcomes of interest; when comparing the oral and rectal routes in the incidence of nausea and vomiting, there was no evidence of differences (relative risk, 1.20; 95% CI, 0.81 to 1.78). The available evidence on the effect of the administration route of acetaminophen on postoperative pain in children is very uncertain. The outcomes of postoperative pain control and postoperative vomiting may differ very little between the oral and rectal route. Better designed and executed RCTs are required to address this important clinical question. PROSPERO (CRD42021286495); first submitted 19 November 2021.

A systematic review and network meta-analysis on the effectiveness of exercise-based interventions for reducing the injury incidence in youth team-sport players. Part 2: an analysis by movement patterns

The objectives of this network meta-analysis were: (a) to estimate and compare the pooled effects of some injury prevention programs (IPPs) whose exercise-based components were categorized using a movement pattern-specific taxonomy on reducing overall and some specific body regions (lower extremity, thigh, knee, and ankle) injury incidences in youth team sport athletes and (b) to explore the individual effects of these components on the injury incidence rates (IIRs) previously mentioned. Searches were performed in PubMed, Web of Science, SPORTDiscus, and Cochrane Library. Eligible criteria were: exercise-based interventions comprised of exercises involving athletic motor skill competencies and evaluated against a control group, overall IIRs were reported, and youth (≤19 years old) team sport players. For the current analysis, a taxonomy based on movement patterns was employed for exercise component identification (upper body pushing and pulling; lower body concentric and eccentric; core; mechanics; acceleration; and lower body stability). Pooled effects were calculated by frequentist random effects pairwise and network meta-analyses. Nineteen studies were included. Most of the IPPs exhibit risk reduction when compared to their control groups on overall, lower extremity, and ankle injuries. Interventions comprised of lower body concentric and eccentric, core, mechanics, and lower body stability exercises were the most effective measures for reducing these injuries. None of the IPPs demonstrated to be effective for reducing thigh injuries, and contradictory results were found for knee injuries. Individual analysis at component level revealed that the lower body (bilateral and unilateral, concentric, and eccentric) component was the only one associated with a significant reduction on overall injuries. Indirect evidence suggests that interventions incorporating lower body concentric and eccentric, core, mechanics, and lower body stability exercises might be the most effective for reducing overall, lower extremity, and ankle injuries in youth team sports.

Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.