Frequentist Network Meta-analysis Research Articles

Loco-regional therapies competing with radiofrequency ablation in potential indications for hepatocellular carcinoma: a network meta-analysis.

There is no clear consensus on the relative ranking of interventional and radiation techniques with indications similar to those of radiofrequency ablation (RFA) for the treatment of early hepatocellular carcinoma (HCC). We used a network meta-analysis to compare the efficacy of non-surgical treatments for early HCC. We searched databases for randomized trials assessing the efficacy of loco-regional treatments for HCCs ≤5 cm with no extrahepatic spread or portal invasion. The primary outcome was the pooled hazard ratio (HR) for overall survival (OS), and secondary outcomes included overall and local progression-free survival (PFS). A frequentist network meta-analysis was performed, and the relative ranking of therapies was assessed with P-scores. Nineteen studies comparing 11 different strategies in 2,793 patients were included. Chemoembolization plus RFA improved OS better than RFA alone (HR 0.52, 95% confidence interval [CI] 0.33-0.82; P-score=0.951). Cryoablation, microwave ablation, laser ablation, and proton beam therapy had similar effects on OS compared with RFA. For overall PFS, but not local PFS, only chemoembolization plus RFA performed significantly better than RFA (HR 0.61, 95% CI 0.42-0.88; P-score=0.964). Injection of percutaneous ethanol or acetic acid was significantly less effective than RFA for all measured outcomes, while no differences in progression outcomes were identified for other therapies included in the network. Our results suggest that chemoembolization combined with RFA is the best option for local treatment of early HCC. Cases with potential contraindications for RFA may benefit from a tailored approach using thermal or radiation modalities.

Exploring the comparative cardiovascular death benefits of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a frequentist and Bayesian network meta-analysis-based scoring.

Cardiovascular death (CV death) is the most objective component of the primary or secondary endpoint in cardiovascular outcome trials (CVOTs) conducted with sodium-glucose cotransporter 2 inhibitors (SGLT-2is). CV death is often incorporated into primary composite outcomes. It is combined with major adverse cardiovascular events (MACEs) in trials with atherosclerotic cardiovascular disease (ASCVD) at baseline and with hospitalization due to heart failure (hHF) in trials with heart failure at baseline. Unlike the primary composites, CV death reduction by itself demonstrated significant variations among the CVOTs with SGLT-2is. Moreover, the impact of the individual agents within the SGLT-2i group on the reduction in CV death has not been explored objectively. This network meta-analysis was undertaken to construct a hierarchy based on indirect pairwise comparisons and rankings among the individual agents within SGLT-2is. A Cochrane library-based web search yielded 13 randomized controlled trials for analysis. Stata/BE 17.0 and RStudio 2022.07.1 Build 554 software were used to conduct a frequentist and Bayesian network meta-analysis. The effect size was assessed based on the risk ratio (RR). Ranking of the individual agents was performed with a frequentist approach (P-score and a multidimensional scaling [MDS] rank system) and a Bayesian ranking (surface under the cumulative ranking [SUCRA]). Regarding the overall data, SGLT-2is reduced the CV death risk by 12% (RR: 0.88, 95% CI 0.80-0.96). All three scoring methods resulted in empagliflozin scoring the highest. There was a 15% RR reduction in CV death (95% CI 0.71-1.02) in the ASCVD and multiple cardiovascular risk factor (MRF) groups and an 11% RR reduction in the HF group, with empagliflozin ranking the highest in the former group and dapagliflozin in the latter. Empagliflozin ranked the highest compared to the other SGLT-2is in the overall population and the trials including type 2 diabetes (T2D) patients with ASCVD or MRF at baseline, while dapagliflozin ranked the highest in the trials of patients with HF at baseline. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022381556, identifier CRD42022381556.

Pharmacologic interventions for the therapy of postanesthetic shivering in adults: a systematic review and network meta-analysis.

Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering. Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery. Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks. Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.

Management of Adult Unruptured Brain Arteriovenous Malformations: An Updated Network Meta-Analysis.

The management of unruptured brain arteriovenous malformations (ubAVMs) is a complex challenge to neurovascular practitioners. This meta-analysis aimed to identify the optimal management of ubAVMs comparing conservative management, embolization, radiosurgery, microsurgical resection, and multimodality. The search strategy was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the Ovid Medline, Embase, Web of Science, and Cochrane Library databases to identify relevant papers. Using R version 4.1.1., a frequentist network meta-analysis was conducted to compare different management modalities for the ubAVMs. Overall, the conservative group had the lowest risk of rupture (P-score=0.77), and the lowest rate of complications was found in the conservative group (P-score=1). Among different interventions, the multimodality group had the highest rupture risk (P-score=0.34), the lowest overall complications (P-score=0.75), the best functional improvement (P-score=0.65), and the lowest overall mortality (P-score=0.8). However, multimodality treatment showed a significantly higher risk of rupture (odds ratio [OR]=2.13; 95% confidence interval [95% CI]=1.18-3.86) and overall complication rate (OR=5.56; 95% CI=3.37-9.15) compared to conservative management; nevertheless, there were no significant differences in overall mortality or functional independence when considered independently. Conservative management is associated with the lowest rupture risk and complication rate overall. A multimodal approach is the best option when considering mortality rates and functional improvement in the context of existing morbidity/symptoms. Microsurgery, embolization, and radiosurgery alone are similar to the natural history in terms of functional improvement and mortality, but have higher complication rates.

The effect of adjuvants added to local anaesthetics for single-injection upper extremity peripheral regional anaesthesia: A systematic review with network meta-analysis of randomised trials.

Peripheral regional anaesthesia is frequently used for upper extremity surgery. To prolong the duration of analgesia, adjuvants can be added to single-injection local anaesthetics. Despite attempts to compare several adjuvants in pairwise meta-analyses, a comprehensive comparison is still missing. The objective of this network meta-analysis was to determine the effectiveness of adjuvants in upper extremity peripheral nerve blocks. A systematic review of randomised controlled trials with network meta-analyses. A literature search in Embase, CENTRAL, MEDLINE and Web of Science was performed up to March 2023. Randomised trials comparing different adjuvants injected perineurally in peripheral upper extremity nerve blocks were eligible. Frequentist network meta-analysis was conducted using a random effects model with physiological saline as the comparator. The primary endpoint was the ratio of means (ROM) of the duration of analgesia. The review included 242 randomised controlled trials with a total of 17 391 patients. Twenty-eight adjuvants were compared in the largest networks. Most network estimations consisted of a high proportion of direct evidence. Fourteen adjuvants increased the duration of analgesia significantly by the following factors, ROM [95% confidence interval (CI)]: dexamethasone 1.95 (1.79 to 2.13), buprenorphine 1.83 (1.51 to 2.24), butorphanol 1.84 (1.41 to 2.39), potassium chloride 1.89 (1.15 to 3.11), dexmedetomidine 1.70 (1.59 to 1.81), sufentanil 1.70 (1.27 to 2.29), ketorolac 1.68 (1.24 to 2.27), midazolam 1.55 (1.24 to 1.94), tramadol 1.52 (1.32 to 1.75), nalbuphine 1.50 (1.30 to 1.72), morphine 1.43 (1.09 to 1.88), magnesium sulfate 1.42 (1.20 to 1.67), clonidine 1.36 (1.24 to 1.50) and fentanyl 1.23 (1.08 to 1.40).Inconsistency in network meta-analysis was substantial. Overall side effect rates were low with all adjuvants. The best interventions to prolong the duration of analgesia were dexamethasone, followed by dexmedetomidine, opioids, electrolytes, ketorolac and midazolam. There are general concerns about the quality of underlying studies and the risk of publication bias. PROSPERO 2018 CRD42018115722.

Periprocedural antithrombotic strategies in acute coronary syndromes undergoing percutaneous coronary intervention: Have we discarded bivalirudin too soon?

BackgroundPublication of the BRIGHT-4 trial results has restimulated discussion about the optimal periprocedural antithrombotic strategy for patients undergoing percutaneous coronary intervention (PCI) with acute coronary syndromes (ACS). It is possible that variation in the infusion duration, may contribute to observed differences in safety-efficacy profiles of bivalirudin in this clinical setting. MethodsUp to December 2022, randomized controlled trials (RCTs) comparing bivalirudin (either administered peri-procedurally or accompanied by postprocedural infusion) and heparin, both with or without GPI, were searched and entered in a frequentist network meta-analysis. Co-primary endpoints were trial-defined major adverse composite events (MACE) and major bleeding. Incident rate ratios (IRR) and 95 % confidence intervals (CI) were estimated. Results10 RCTs (N = 57,137 patients/month) were included. As compared to heparin, prolonged bivalirudin infusion resulted in lower rates of major bleeding (IRR 0.58, 95 % CI 0.36–0.91), but there was no differences in MACE rates between these strategies. With regard to NACE, prolonged bivalirudin infusion yielded lower risk (IRR 0.86, 95 % CI 0.77–0.96), whereas both bivalirudin and heparin increased risk when coupled with GPI (IRR 1.24, 95 % CI 1.01–1.51 and IRR 1.24, 95 % CI 1.06–1.44, respectively). Both these combination strategies also increased minor bleeding rates (IRR 1.49, 95 % CI 1.16–1.93 and IRR 1.58, 95 % CI 1.29–1.95, respectively, for bivalirudin and heparin). Results were consistent across several sensitivity analyses. ConclusionIn patients with ACS undergoing PCI, procedural bivalirudin administration followed by prolonged infusion results in lower major bleeding rates, but there does not appear to be a difference in observed MACE.

Systematic review and network meta-analysis of the accuracy of the orthodontic mini-implants placed in the inter-radicular space by image-guided-based techniques

ObjectiveThe aim of the present systematic review and network meta-analysis (NMA) is to analyze the accuracy of image-guided-based orthodontic mini-implants placement techniques in the inter-radicular space.MethodsThe study was conducted under the PRISMA recommendations. Three databases were searched up to July 2022. In vitro randomized experimental trials (RETs) including static computer-aided implant surgery (s-CAIS), mixed reality (MR), soft tissue static computer-aided implant surgery (ST s-CAIS) and conventional free-hand technique (FHT) for the orthodontic mini-implants placement in the inter-radicular space were selected. The risk of bias was assessed using the Current Research Information System scale. A random effects model was used in the NMA. Direct comparisons were combined with a random effects model in a frequentist NMA to estimate indirect comparisons, and the estimated effect size of the comparisons between techniques were analyzed by difference of means. Inconsistency was assessed with the Q test, with a significance level of p < 0.05, and a net heat plot.ResultsA total of 92 articles was identified, and 8 RETs (8 direct comparisons of 4 techniques) were included in the NMA, which examined 4 orthodontic mini-implants placement techniques: s-CAIS, MR, ST s-CAIS, and FHT. Taking FHT as reference, s-CAIS and ST s-CAIS showed statistically significant coronal and apical deviation. In addition, s-CAIS showed statistically significant angular deviation. However, MR did not show statistically significant differences with respect to FHT, which presented the highest p-score. At the coronal deviation, ST s-CAIS presented the highest P-score (0.862), followed by s-CAIS (0.721). At the apical deviation, s-CAIS presented the highest P-score (0.844), followed by ST s-CAIS (0.791). Finally, at the angular deviation s-CAIS presented again the highest P-score (0.851).ConclusionsWithin the limitations of this study, it was found that the image-guided-based orthodontic mini-implants placement techniques showed more accuracy than the free-hand conventional placement technique; specially the computer-aided static navigation techniques for the orthodontic mini-implants placed in the inter-radicular space.

Comparative efficacy and safety of anti-PD-1/L1 antibody plus anti-VEGF antibody and anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A systematic review and network meta-analysis.

e16148 Background: Anti-PD-1/L1 antibody combined with anti-VEGF antibody and anti-PD-1/L1 antibody combined with VEGFR-targeted tyrosine kinase inhibitor are both effective first-line therapies for uHCC in clinical practice widely. However, direct comparisons across the two regimens are not available. We conducted a network meta-analysis of them in terms of overall survival (OS), progression free survival (PFS), objective response rate (ORR) and incidence of treatment-related adverse events (TRAEs). Methods: After a literature research performed in PubMed, MEDLINE, Embase, the Cochrane library and several major scientific societies from January 1 2007 to November 6 2022, 3,279 records were obtained. 6 phase III trials has been identified for the final analysis: REFLECT, IMbrave150, ORIENT-32, COSMIC-312, Qin 2022 and LEAP-002. The experiments were broadly classified into three groups: anti-PD-1/L1 antibody + anti-VEGF antibody (IMbrave150 and ORIENT-32), anti-PD-1/L1 antibody + VEGFR-targeted tyrosine kinase inhibitor (COSMIC-312, Qin 2022 and LEAP-002) and intermediate reference group (lenvatinib vs sorafenib, REFLECT). We derived hazard ratios (HR) with 95% confidence intervals (95%CI) for OS and PFS, odds ratio (OR) for ORR and relative risks (RR) for all grade and grade ≥3 TRAEs. With fixed effect models to estimate the indirect pooled HRs, ORs, RRs and 95%CI, a frequentist network meta-analysis was conducted using sorafenib as intermediate reference. Results: 4,012 patients were included in the analysis overall, among them, 1815 patients were treated with anti-PD-1/L1 antibody+VEGF-antibody (A+A), 1,099 patients were treated with anti-PD-1/L1 antibody+VEGFR-TKI (A+T), 877 patients were treated with lenvatinib (LEN) and 1,320 patients were treated with sorafenib (SOR). With a p-score of 98%, the combination of A+A provided the greatest reduction in the risk of death, was not significantly different from A+T (HR=0.84, 95%CI: 0.66-1.06). Besides, A+T were associated with the greatest effect in prolonging PFS and improving ORR with 91% for p-score, but there are no statistical differences with A+A (HR=1.06, 95%CI: 0.87-1.30, OR=0.82, 95%CI: 0.47-1.46). Considering the risk of TRAEs, A+A were significantly safer than A+T (RR=0.91, 95%CI: 0.84-0.98) in all grade of TRAEs and ≥3 grade (RR=0.91, 95%CI: 0.84-0.98). Conclusions: The combination of anti-PD-1/L1 antibody and anti-VEGF antibodies has the greatest probability of delivering the longest OS, while anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor is correlated with larger PFS benefit at the cost of a lower safety rate.

Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis.

The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis. For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524. The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2-13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59-0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69-0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75-1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%). The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma. Institut National du Cancer and Ligue Nationale Contre le Cancer.

Comparing bronchial thermoplasty with biologicals for severe asthma: Systematic review and network meta-analysis

BackgroundBronchial thermoplasty (BT) has shown favorable safety and efficacy in several randomized controlled trials (RCTs), but has not been directly compared to biological therapies. MethodsElectronic literature searches were performed on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, to retrieve RCTs of BT or FDA-approved biologicals against controls in patients with severe asthma. Six outcomes were analyzed: Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), the number of patients experiencing ≥1 asthma exacerbation, annualized exacerbation rate ratio (AERR), oral corticosteroid dose reduction (OCDR), and morning peak expiratory flow rate (amPEF). Random-effects, Frequentist network meta-analysis (NMA) were performed, and therapies were ranked using P-scores. ResultsTwenty-nine RCTs (15,547 patients) were included. Fewer patients treated with BT experienced ≥1 asthma exacerbation (risk ratio [RR] = 0.66, 95%CI = 0.45–0.98) compared to control. AERR of BT versus control was non-significant, but significant improvements in ACQ score (mean difference [MD] −0.41, 95%CI -0.63 to −0.20), AQLQ score (MD = 0.54, 95%CI = 0.30–0.77), amPEF and OCDR were found. No significant differences between BT and biologics were seen across indirect comparisons of all studies. ConclusionsDespite the lack of head-to-head comparative trials, this NMA suggests that BT is non-inferior to biologicals in terms of quality-of-life scores, and represents a promising alternative for patients with severe asthma.

Efficacy of Laser in Hair Removal: A Network Meta-analysis

ABSTRACT Background Laser hair removal is an increasingly prevalent trend of cosmetic procedures. The purpose of this study was to assess the effectiveness of hair reduction among several types of laser interventions. Methods The selected studies searched in PubMed and EMBASE were assessed for quality of evidence, and extracted data on absolute hair count and hair reduction rate. Qualitative data were synthesized using standardized mean difference (SMD) in frequentist network meta-analysis because various measurement units were used among selected studies. Inconsistency and small study effects were examined by design-by-treatment interaction model and comparison-adjusted funnel plot. Results A total of 13 randomized controlled trials (RCTs) (n = 652) were contributed to network meta-analysis. Pooled results revealed that diode laser showed significantly lower absolute hair count within three-month (SMD = −13.21, 95% confidence interval [CI]: −22.25 to −4.17) and around six months follow-up (SMD = −11.01, 95% CI: −18.24 to −3.77) as compared with those in control group, but no significant difference among laser interventions. All side effects observed were transient without leaving any permanent scars. Conclusion Eliminating unwanted hair with lasers or intense pulsed light is safe and effective; however, which type of intervention is more beneficial in the long-term process should be studied with a longer follow-up time.

Success rate of external, endonasal, and transcanalicular laser DCR with or without silicone stent intubation for NLD obstruction: a network meta-analysis of randomized controlled trials.

To define and compare the effectiveness of external dacryocystorhinostomy (EX-DCR), endonasal (EN-DCR), and transcanalicular laser-assisted (TL-DCR) with or without silicone stent (S) intubation. Studies were retrieved from PubMed, Scopus, and WoS. Frequentist and Bayesian network meta-analyses were performed and pooled estimations were expressed as risk ratio (RR). We included all original investigations of prospective, randomized controlled trials comparing success rate for any two of the following six surgical procedures: standard EX-DCR with or without S, cold EN-DCR with or without S, and TL-DCR with or without S. The primary outcome measure was the objective success rate. Thirty-two studies with 3277 cases were included in the final quantitative analysis. TL-DCR with S was inferior to EN-DCR with S (RR: 1.20; 95% CI: 1.05-1.37), EX-DCR with S (RR: 1.17 95% CI: 1.05-1.29), EN-DCR without S (RR: 1.18; 95% CI: 1.03-1.35), and EX-DCR without S (RR: 1.15; 95%CI: 1.05-1.26) in frequentist statistics. No other statistical difference was found between other surgeries. When we excluded studies with additional interventions (nasal and revision surgery) for sensitivity analysis, 23 studies with 2468 cases were included to analysis. The success rates of TL-DCR with S and EN-DCR without S became similar (RR: 1.14 95% CI: 0.99-1.30) but there was no change in other outcomes. Similar results were found in Bayesian statistics. The surface under the cumulative ranking curve was higher for EN-DCR with S (0.75), whereas it was higher for EX-DCR with S (0.56) after sensitivity analysis. Between endoscopic and external and transcanalicular laser without S procedures, there is no statistical difference. The rank probability showed that EN-DCR with S was a more appropriate surgical option when patients with nasal disease were included, whereas EX-DCR with S was a more appropriate surgical option when patients with nasal disease were excluded from the analysis.

O133 Network meta-analysis of neoadjuvant therapy in rectal cancer

Abstract Introduction Locally advanced rectal cancer can be treated with neoadjuvant chemoradiotherapy prior to surgical resection. This treatment can significantly downstage rectal tumours and consequently lead to improved long term survival and reduced risk of local reoccurrence. Controversy exists regarding the optimal regime for neoadjuvant therapy. A network meta-analysis allows the integration of multiple treatments to be compared simultaneously in a single analysis. This network meta-analysis aims to assess which neoadjuvant regime gives the highest rate of pathological complete response (pCR). Methods An extensive literature search for randomised controlled trials of neoadjuvant therapy in rectal cancer was performed. The primary outcome was pCR at surgical resection. Direct and indirect comparisons were performed with a frequentist Network Meta-Analysis and results tested for consistency. Results Following critical appraisal of 3720 studies, 16 randomised control trials were included in the study. Regimes of neoadjuvant therapy included short course radiotherapy with concurrent chemotherapy or without, long course chemoradiotherapy, long course chemoradiotherapy with either induction of consolidation chemotherapy, and radiotherapy alone (45gy). Short course radiotherapy combined with chemotherapy was shown to produce significantly higher pCR in patients with rectal cancer. Short course radiotherapy without chemotherapy was shown to have the lowest rate of pCR. Conclusion There is strong evidence to suggest that short course chemoradiotherapy is the best regime to produce the highest pCR in patients with rectal cancer.

Effects of Pharmacological Intervention on Recovery After Sevoflurane Anesthesia in Children: a Network Meta-analysis of Randomized Controlled Trials.

Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions.

Relative Efficacy of Cervical Total Disc Arthroplasty Devices and Anterior Cervical Discectomy and Fusion for Cervical Pathology: A Network Meta-Analysis.

Systematic Review and Meta Analysis. This study sought to compare patient-reported outcomes, success, complications, and radiographic outcomes directly and indirectly between different cervical total disc arthroplasty (TDA) devices and anterior cervical discectomy and fusion (ACDF). Patients of prospective randomized controlled trials of 1-level cervical TDA with a minimum of 2years follow up were identified in the literature. A frequentist network meta-analysis model was used to compare each outcome across the different TDA devices included and ACDF using the mixed effect sizes. 15 studies were included for quantitative analysis, reporting the outcomes of 2643 patients with an average follow-up was 67.3months (range: 24-120months), 1417 of whom underwent TDA and 1226 of whom underwent ACDF. Nine TDA devices were compared to ACDF, including the Bryan, Discover, Kineflex, M6, Mobi-C, PCM, Prestige ST, ProDisc-C, and Secure-C cervical prostheses. Several devices outperformed ACDF for certain outcomes, including Visual Analog Scale (VAS) Arm, Physical Component Score of the Short-Form Health Survey (SF PCS), neurological success, satisfaction, index-level secondary surgical interventions (SSI), and adjacent level surgeries. Cumulative ranking of each intervention assessed demonstrated the highest performance with the M6 prosthesis (P = .70), followed by Secure-C (P = .67), PCM (P = .57), Prestige ST (P = .57), ProDisc-C (P = .54), Mobi-C (P = .53), Bryan (P = .49), Kineflex (P = .49), Discover (P = .39), and ACDF (P = .14). Cervical TDA was found to be superior on most outcomes assessed in the literature of high-quality clinical trials. While most devices demonstrated similar outcomes, certain prostheses such as the M6 were found to outperform others across several outcomes assessed. These findings suggest that the restoration of near-normal cervical kinematics may lead to improved outcomes.

Efficacy and safety of proton pump inhibitors and H2 receptor antagonists in the initial non‑eradication treatment of duodenal ulcer: A network meta‑analysis.

The present network meta-analysis aimed to enhance the corresponding evidence with respect to the efficacy and safety of pharmaceuticals treatments. Frequentist network meta-analysis was used. Medical literature up to November 2022 was searched for randomized clinical trials assessing the efficacy and safety of these pharmaceuticals, either compared with each other or compared with placebo. With the exception of ranitidine (300 mg four times daily) and vonoprazan (20 mg once daily) having lower safety than placebo, the efficacy and safety of the remaining treatments were superior to placebo. Cimetidine (400 mg four times daily) and pantoprazole (40 mg once daily) were ranked first in terms of efficacy. The frequentist network meta-analysis shows that for cimetidine (except 400 mg once daily), famotidine, rabeprazole, ilaprazole, lansoprazole (except 7.5 mg once daily) and omeprazole (except 10 mg once daily or 30 mg once daily), the efficacy comparison between the different doses of each of the aforementioned pharmaceuticals did not indicate statistically significant differences. In conclusion, pantoprazole (40 mg once daily) was the best choice for the initial non-eradication treatment of patients with duodenal ulcer, and cimetidine (400 mg twice daily), omeprazole (20 mg once daily), lansoprazole (15 mg once daily), ilaprazole (5 mg once daily) and rabeprazole (10 mg once daily) could be used as the first choice. If the aforementioned pharmaceuticals cannot be prescribed, famotidine (40 mg twice daily) is recommended.

Noninvasive Oxygenation Strategies in Adult Patients With Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-Analysis

Several recently published randomized controlled trials have evaluated various noninvasive oxygenation strategies for the treatment of acute hypoxemic respiratory failure. Which available noninvasive oxygen strategies are effective for acute hypoxic respiratory failure? A systematic review of Medline, Embase, Cochrane CENTRAL, CINAHL, Web of Science, MedRxiv, and Research Square was conducted from inception to October 1, 2022. A random effects frequentist network meta-analysis was performed, and the results are presented using absolute risk difference per 1,000 patients. The Grading of Recommendations, Assessment, Development and Evaluation framework was used to rate the certainty of the evidence. Mortality, invasive mechanical ventilation, duration of hospitalization and ICU stay, ventilator-free days, and level of comfort are reported. Thirty-six trials (7,046 patients) were included. It was found that helmet CPAP probably reduces mortality compared with standard oxygen therapy (SOT) (231 fewer deaths per 1,000; 95%CI, 126-273 fewer) (moderate certainty). A high-flow nasal cannula (HFNC) probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000; 95%CI, 40.5-157.5 fewer) (moderate certainty). All noninvasive oxygenation strategies may reduce the duration of hospitalization as compared with SOT (low certainty). Helmet bilevel ventilation (4.84days fewer; 95%CI, 2.33-7.36days fewer) and helmet CPAP (1.74days fewer; 95%CI, 4.49 fewer-1.01 more) may reduce the duration of ICU stay as compared with SOT (both low certainty). SOT may be more comfortable than face mask noninvasive ventilation and no different in comfort compared with an HFNC (both low certainty). A helmet interface for noninvasive ventilation probably reduces mortality and the risk of mechanical ventilation, as well as the duration of hospital and ICU stay. An HFNC probably reduces the risk of invasive mechanical ventilation and may be as comfortable as SOT. Further research is necessary to understand the role of these interfaces in acute hypoxemic respiratory failure.

A network meta-analysis of the antithrombotic strategies in patients with atrial fibrillation and percutaneous coronary interventions: Focus on bleeding

BackgroundWe performed a network meta-analysis of randomized controlled trials comparing non-vitamin K antagonist oral anticoagulant (NOAC)-based versus vitamin K antagonists (VKA)-based regimens in patients with atrial fibrillation (AF) and acute coronary syndromes or PCI, aiming to examine the precise impact of recently established antithrombotic strategies on major bleeding as primary end-point and other safety and efficacy as secondary end-points. MethodsA literature search was conducted for randomized controlled trials. Our search took place in three major databases. The primary endpoint of our study was bleeding. To combine direct and indirect evidence across trials, a frequentist network meta-analysis with a random-effects model was used. ResultsFive studies were found eligible for the meta-analysis enrolling a total of 11,542 patients. Five studies (N = 4903 patients) contributed to the network. Compared to the triple antithrombotic therapy (TAT)-based VKA, only the dual antithrombotic therapy (DAT) based NOAC reduced the bleeding (RR 0.57, 95%CI 0.40–0.82). There was no statistically significant difference between DAT-based VKA (RR = 0.66, 95%CI = 0.40–1.09) or TAT-based NOAC (RR = 0.80, 95%CI = 0.43–1.49). DAT-based NOAC ranked best (P-score = 0.91), followed by DAT-based VKA (P-score = 0.67), TAT-based NOAC (P-score = 0.40), and TAT-based VKA (P-score = 0.03). ConclusionThe network meta-analysis of four antithrombotic strategies, demonstrated that in patients with AF undergoing PCI the combination of DAT-based NOAC is associated with a significantly lower risk of major bleeding events. This strategy does not seem to be less effective in terms of prevention of ischemic events compared to the other regimens.

Clinical outcomes of renin angiotensin system inhibitor-based dual antihypertensive regimens in chronic kidney disease: a network meta-analysis

This study comprehensively investigated clinical outcomes associated with renin angiotensin system inhibitor-based dual antihypertensive regimens in non-dialysis chronic kidney disease (CKD) patients. Keyword searches of databases were performed per PRISMA-NMA guidelines. Frequentist network meta-analysis were conducted with 16 head-to-head randomized controlled trials. The effect sizes of dichotomous and continuous variables were estimated with odds ratio (OR) and standard mean differences (SMD), respectively. The protocol is registered in PROSPERO (CRD42022365927). Dual antihypertensive regimens with combination of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) demonstrated substantially reduced odd of major cardiovascular disease (CVD) events over other regimens including angiotensin converting enzyme inhibitor (ACEI) monotherapy (OR 3.19) and ARB monotherapy (OR 2.64). Most significant reductions in systolic (SBP) and diastolic blood pressure (DBP) were observed with ARB-based CCB dual regimen over ACEI monotherapy (SMD 17.60 SBP and 9.40 for DBP), ACEI-based CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP). However, insignificant differences were noticed for the odds of hyperkalemia, end stage renal disease progression, and all-cause mortality. ARB-based CCB regimen has the greatest benefits on BP reduction as well as major CVD risks in non-dialysis CKD patients.

Comparative Effectiveness of Combined and Single Neurostimulation and Traditional Dysphagia Therapies for Post-Stroke Dysphagia: A Network Meta-Analysis

Background Comparative therapeutic benefits of combined and single neurostimulation therapies including neuromuscular electrical stimulation (NMES), pharyngeal electrical stimulation (PES), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and traditional dysphagia therapy (TDT) remain unknown in post-stroke dysphagia (PSD) rehabilitation. Therefore, we performed the first network meta-analysis (NMA) to determine comparative effectiveness of combined and single neurostimulation and traditional dysphagia therapies for PSD. Methods A frequentist NMA model was performed with therapy effect sizes presented as standardized mean differences (SMD) and corresponding 95% confidence interval (95% CI) for therapy comparisons while netrank function ranked the therapies in R-Software. Meta-regression models for study characteristics were analyzed using Bayesian NMA Model. Results Overall, 50 randomized controlled studies with 2250 participants were included. NMES + TDT 3.82 (95% CI, 1.62-6.01), tDCS + TDT 3.34 (95% CI, 1.09-5.59), rTMS + TDT 3.32 (95% CI, 1.18-5.47), NMES 2.69 (95% CI, 0.44-4.93), and TDT 2.27 (95% CI, 0.12-4.41) demonstrated very large effect in improving swallowing function. NMES + TDT −0.50 (95% CI, −0.68 to −0.32, rTMS + TDT −0.44 (95% CI, −0.67 to −0.21), TDT −0.28 (95% CI, −0.46 to −0.10), and NMES −0.19 (95% CI, −0.34 to −0.04) demonstrated medium to small effect in reducing pharyngeal transit time (PTT). rTMS −0.51 (95% CI, −0.93 to −0.08) demonstrated medium effect in reducing oral transit time (OTT). No significant therapy comparison differences were found for reducing aspiration/penetration. The highest ranked therapy was NMES + TDT for better swallowing function and reduction of PTT, rTMS for reduction of OTT, and tDCS + TDT for reduction of aspiration/penetration. Therapeutic effects of the therapies were moderated by frequency, sessions, and duration. Conclusion Combined therapies including NMES + TDT, tDCS + TDT, and rTMS + TDT demonstrate better therapeutic effect for improved swallowing function and reduction of PTT, OTT, and aspiration/penetration for PSD.