Methodological and reporting quality assessment of network meta-analyses in anesthesiology: a systematic review and meta-epidemiological study.

PURPOSE: The scientific rigour of the conduct and reporting of anesthesiology network meta-analyses (NMAs) is unknown. This systematic review and meta-epidemiological study assessed the methodological and reporting quality of NMAs in anesthesiology. METHODS: We searched four databases, including MEDLINE, PubMed, Embase, and the Cochrane Systematic Reviews Database, for anesthesiology NMAs published from inception to October 2020. We assessed the compliance of NMAs against A Measurement Tool to Assess Systematic Reviews (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement for Network Meta-Analyses (PRISMA-NMA), and PRISMA checklists. We measured the compliance across various items in AMSTAR-2 and PRISMA checklists and provided recommendations to improve quality. RESULTS: Using the AMSTAR-2 rating method, 84% (52/62) of NMAs were rated "critically low." Quantitatively, the median [interquartile range] AMSTAR-2 score was 55 [44-69]%, while the PRISMA score was 70 [61-81]%. Methodological and reporting scores showed a strong correlation (R = 0.78). Anesthesiology NMAs had a higher AMSTAR-2 score and PRISMA score if they were published in higher impact factor journals (P = 0.006 and P = 0.01, respectively) or followed PRISMA-NMA reporting guidelines (P = 0.001 and P = 0.002, respectively). Network meta-analyses from China had lower scores (P < 0.001 and P < 0.001, respectively). Neither score improved over time (P = 0.69 and P = 0.67, respectively). CONCLUSION: The current study highlights numerous methodological and reporting deficiencies in anesthesiology NMAs. Although the AMSTAR tool has been used to assess the methodological quality of NMAs, dedicated tools for conducting and assessing the methodological quality of NMAs are urgently required. STUDY REGISTRATION: PROSPERO (CRD42021227997); first submitted 23 January 2021.

RéSUMé: OBJECTIF: La rigueur scientifique de la conduite et de la communication des méta-analyses en réseau (MAR) en anesthésiologie est inconnue. Cette revue systématique et étude méta-épidémiologique a évalué la qualité méthodologique et de communication des MAR en anesthésiologie. MéTHODE: Nous avons mené des recherches dans quatre bases de données, soit MEDLINE, PubMed, Embase et la base de données des revues systématiques Cochrane, pour trouver des MAR en anesthésiologie publiées depuis la création de ces bases de données jusqu'en octobre 2020. Nous avons évalué la conformité des MAR par rapport à trois outils, soit : AMSTAR-2 (outil de mesure pour évaluer les revues systématiques), PRISMA-NMA et les listes de contrôle PRISMA. Nous avons mesuré la conformité de divers éléments des listes de contrôle AMSTAR-2 et PRISMA et formulé des recommandations pour améliorer la qualité. RéSULTATS: En utilisant la méthode de notation AMSTAR-2, 84 % (52/62) des MAR ont reçu la cote « extrêmement faible ¼. Quantitativement, le score médian [écart interquartile] sur l'AMSTAR-2 était de 55 [44-69] %, tandis que le score PRISMA était de 70 [61-81] %. Les scores méthodologiques et de communication ont montré une forte corrélation (R = 0,78). Les MAR en anesthésiologie avaient un score AMSTAR-2 et un score PRISMA plus élevés si elles étaient publiées dans des revues à facteur d'impact plus élevé (P = 0,006 et P = 0,01, respectivement) ou avaient suivi les lignes directrices de PRISMA-NMA en matière de communication des résultats (P = 0,001 et P = 0,002, respectivement). Les méta-analyses en réseau provenant de Chine avaient des scores plus faibles (P < 0,001 et P < 0,001, respectivement). Aucun des deux scores ne s'est amélioré au fil du temps (P = 0,69 et P = 0,67, respectivement). CONCLUSION: La présente étude met en évidence de nombreuses lacunes méthodologiques et de communication dans les MAR en anesthésiologie. Bien que l'outil AMSTAR ait été utilisé pour évaluer la qualité méthodologique des MAR, il est urgent de disposer d'outils spécialisés pour mener des MAR et en évaluer la qualité méthodologique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021227997); soumis pour la première fois le 23 janvier 2021.

Epidemiological, methodological, and statistical characteristics of network meta-analysis in anaesthesia: a systematic review.

BACKGROUND: Network meta-analyses (NMAs) combine direct and indirect estimates to provide mixed (or network) estimates of effect sizes. The scientific rigour of the conduct and reporting of anaesthesia NMAs is unknown. This review assessed the epidemiological, methodological, and statistical characteristics of anaesthesia NMAs. METHODS: We searched four databases for anaesthesia NMAs and developed a 64-item checklist to evaluate NMAs. For 29 binary items, we defined compliance as 'the ratio of NMAs that was awarded a 'yes' for that item, divided by the total number of NMAs. The compliance of such binary items was reclassified as very low (≤25%), low (26-50%), fair (51-75%), and high (>75%). We amalgamated findings from 29 key items to provide specific recommendations (post hoc). We compared the compliance of NMAs in anaesthesia across 26 items, with that of cancer NMAs and Cochrane NMAs, and analysed improvement over time (post hoc). RESULTS: Among 62 included NMAs, compliance was low (26-50%) for protocol registration, use of PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for NMA), publication bias assessment, evidence appraisal, reporting of Bayesian methodology and consistency evaluation. Compliance was very low (≤25%) for bias assessment, biostatistician involvement, search specialist, and use of predefined important differences. CONCLUSIONS: Anaesthesia NMAs need improvement in their conduct and reporting. Anaesthesia journals should mandate the registration of protocols and reporting of NMAs using PRISMA-NMA. Authors should carefully assess publication bias, and use updated bias assessment tools, and evidence appraisal methods designed for NMAs. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021227608.

Analgesic Efficacy of Adjuvant Medications in the Pediatric Caudal Block for Infraumbilical Surgery: A Network Meta-Analysis of Randomized Controlled Trials.

Various adjuvants are added to local anesthetics in caudal block to improve analgesia. The comparative analgesic effectiveness and relative rankings of these adjuvants are unknown. This network meta-analysis (NMA) sought to evaluate the comparative analgesic efficacy and relative ranking of caudal adjuvants added to local anesthetics (versus local anesthetics alone) in pediatric infra-umbilical surgery. We searched the United States National Library of Medicine database (MEDLINE), PubMed, and Excerpta Medica database (Embase) for randomized controlled trials (RCTs) comparing caudal adjuvants (clonidine, dexmedetomidine, ketamine, magnesium, morphine, fentanyl, tramadol, dexamethasone, and neostigmine) among themselves, or to no adjuvant (control). We performed a frequentist NMA and employed Cochrane's 'Risk of Bias' tool to evaluate study quality. We chose the duration of analgesia (defined as 'the time from caudal injection to the time of rescue analgesia') as our primary outcome. We also assessed the number of analgesic dose administrations and total dose of acetaminophen within 24 h. The duration of analgesia [87 randomized control trials (RCTs), 5285 patients] was most prolonged by neostigmine [mean difference: 513 min, (95% confidence interval, CI: 402, 625)]. Dexmedetomidine reduced the frequency of analgesic dose administrations within 24 h [29 RCTs, 1765 patients; -1.2 dose (95% CI: -1.6, -0.9)] and the total dose of acetaminophen within 24 h [18 RCTs, 1156 patients; -350 mg (95% CI: -467, -232)] the most.  Among caudal adjuvants, neostigmine (moderate certainty), tramadol (low certainty), and dexmedetomidine (low certainty) prolonged the duration of analgesia the most. Dexmedetomidine also reduced the analgesic frequency and consumption more than other caudal adjuvants (moderate certainty).

Differential methylation of the type 2 diabetes susceptibility locus KCNQ1 is associated with insulin sensitivity and is predicted by CpG site specific genetic variation.

AIMS: Epigenetic mechanisms regulate gene expression and may influence the pathogenesis of type 2 diabetes through the loss of insulin sensitivity. The aims of this study were to measure variation in DNA methylation at the type 2 diabetes locus KCNQ1 and assess its relationship with metabolic measures and with genotype. METHODS: DNA methylation from whole blood DNA was quantified using pyrosequencing at 5 CpG sites at the KCNQ1 locus in 510 individuals without diabetes from the 'Relationship between Insulin Sensitivity and Cardiovascular disease' (RISC) cohort. Genotype data was analysed at the same locus in 1119 individuals in the same cohort. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp. RESULTS: DNA methylation at the KCNQ1 locus was inversely associated with insulin sensitivity and serum adiponectin. This association was driven by a methylation-altering Single Nucleotide Polymorphism (SNP) (rs231840) which ablated a methylation site and reduced methylation levels. A second SNP (rs231357), in weak Linkage Disequilibrium (LD) with rs231840, was also associated with insulin sensitivity and DNA methylation. These SNPs have not been previously reported to be associated with type 2 diabetes risk or insulin sensitivity. CONCLUSION: Evidence indicates that genetic and epigenetic determinants at the KCNQ1 locus influence insulin sensitivity.