BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPi) are a novel option to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib plus abiraterone acetate and prednisone (AAP) is indicated for BRCA1/2 mutation-positive mCRPC. Niraparib plus AAP demonstrated safety and efficacy in the phase 3 MAGNITUDE trial (NCT03748641). In the absence of head-to-head studies comparing PARPi regimens, the feasibility of conducting indirect treatment comparisons (ITC) to inform decisions for patients with first-line BRCA1/2 mutation-positive mCRPC has been explored.
METHODS: A systematic literature review was conducted to identify evidence from randomized controlled trials on relevant comparators to inform the feasibility of conducting ITCs via network meta-analysis (NMA) or population-adjusted indirect comparisons (PAIC). Feasibility was assessed based on network connectivity, data availability in the BRCA1/2 mutation-positive population, and degree of within- and between-study heterogeneity or bias.
RESULTS: NMAs between niraparib plus AAP and other PARPi regimens (olaparib monotherapy, olaparib plus AAP, and talazoparib plus enzalutamide) were inappropriate due to the disconnected network, differences in trial populations related to effect modifiers, or imbalances within BRCA1/2 mutation-positive subgroups. The latter issue, coupled with the lack of a common comparator (except for olaparib plus AAP), also rendered anchored PAICs infeasible. Unanchored PAICs were either inappropriate due to lack of population overlap (vs. olaparib monotherapy) or were restricted by unmeasured confounders and small sample size (vs. olaparib plus AAP). PAIC versus talazoparib plus enzalutamide was not possible due to lack of published arm-level baseline characteristics and sufficient efficacy outcome data in the relevant population.
CONCLUSIONS: The current randomized controlled trial evidence network does not permit robust comparisons between niraparib plus AAP and other PARPi regimens for patients with 1L BRCA-positive mCRPC. Decision-makers should scrutinize any ITC results in light of their limitations. Real-world evidence combined with clinical experience should inform treatment recommendations in this indication.

The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI -  1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI -  1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.

BACKGROUND: It remains unclear whether the use of an orthopaedic traction table (TT) in direct anterior approach (DAA) total hip arthroplasty (THA) results in better outcomes. The aim of this systematic review and network meta-analysis was to compare the THA outcomes through DAA on a standard operating table and the THA outcomes through DAA on a TT.
METHODS: PubMed, Epistemonikos, and Google Scholar were searched for relevant randomized controlled trials (RCTs) up to 01 January 2024. An indirect comparison in network meta-analysis was performed to assess treatment effects between DAA on a TT and DAA on a standard table, using fixed-effects and random-effects models estimated with frequentist approach and consistency assumption. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated for continuous variables and odds ratios (ORs) with 95% CIs were estimated for binary variables.
RESULTS: The systematic review of the literature identified 43 RCTs with a total of 2,258 patients. DAA with TT had a 102.3 mL higher intraoperative blood loss and a 0.6 mmol/L lower Hb 3 days postoperatively compared with DAA without TT (SMD = 102.33, 95% CI 47.62 to 157.04; SMD = - 0.60, 95% CI  - 1.19 to - 0.00). DAA with TT had a 0.15 lower periprosthetic fracture OR compared with DAA without TT (OR 0.15, 95% CI 0.03 to 0.86). There were no further significant differences in surgical, radiological, functional outcomes and in complication rates.
CONCLUSIONS: Based on our findings and taking into account the limitations, we recommend that particular attention be paid to the risk of periprosthetic fracture in DAA on a standard operating table and blood loss in DAA with TT. Since numerous other surgical, radiological, functional outcome parameters and other complication rates studied showed no significant difference between DAA on a standard operating table and DAA with TT, no recommendation for a change in surgical technique seems justified.
METHODS: Level I evidence, because this is a systematic review and meta-analysis of randomized controlled trials.

The use of first-line drugs in clinical practice for attention deficit hyperactivity disorder (ADHD) is limited by their adverse effects. Many novel monoamine reuptake inhibitors (MRIs) with better safety profiles and comparable efficacy are also being tried for ADHD. This network meta-analysis (NMA) has evaluated the efficacy and safety of MRIs in ADHD. The data was extracted from 31 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases, and clinical trial registries. Quality assessment was performed using the risk of bias assessment tool (RoB2) by Cochrane Collaboration, and the random-effects model was used to estimate the effect size. Standardised mean difference (SMD) and 95% credible interval(95%CrI) were reported for the reduction in ADHD rating scale score. Network geometry was visualised, and node splitting was done for the closed triangles. Meta-regression was done for the duration of therapy. PRISMA-NMA guidelines were followed in selecting, analyzing, and reporting findings. The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD. The efficacy of none of the drugs was found to be significantly different as compared to methylphenidate. Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence.

OBJECTIVE: Colonoscopy has a vital role in the diagnosis of inflammatory bowel disease (IBD), as well as in the estimation of disease severity, monitoring response to therapy, and surveillance for neoplasia. We performed a systematic review of randomised trials of various bowel preparations for colonoscopy in IBD.
METHODS: We searched various electronic databases (PubMed, Embase, and CENTRAL) for studies reporting about the use of various strategies to improve colonoscopy preparation in IBD. We included only randomized clinical trials (RCTs). A network meta-analysis was done using a frequentist approach to compare the effectiveness of various bowel preparations. The risk of bias was assessed using Cochrane risk of bias tool 2.0. Other outcome parameters like compliance, tolerance, acceptance, and adverse effects were assessed qualitatively.
RESULTS: Seven RCTs reporting about 960 patients were included. On comparison with 4 liter (L) of poliethylen glycol (PEG), oral sulfate solution (OR=1.1, 95%CI: 0.65-1.86); PEG2L/Ascorbate (OR=0.98, 95%CI: 0.65-1.48); PEG1L (OR=1, 95%CI: 0.55-1.81); PEG2L plus bisacodyl (OR=1.08, 95%CI: 0.71-1.65); PEG4L plus simethicone (OR=1, 95%CI: 0.67-1.50); PEG/ sodium picosulfate and magnesium citrate (SPMC) 1.5L (OR=0.99, 95%CI: 0.55-1.78); SPMC 2L (OR=1.09, 95%CI: 0.61-1.97) had similar effectiveness. Three RCTs reported compliance, five RCTs reported tolerance, two studies reported patient acceptance and five RCTs reported data on the willingness of patients to repeat the procedure in the future. Low-volume preparations had better compliance, tolerance, acceptance, and willingness to repeat. No difference in additional outcomes like change in disease activity after colonoscopy, procedure-related outcomes after colonoscopy like cecal intubation rate, and change in electrolyte levels were found.
CONCLUSIONS: Various bowel preparations had similar effectiveness in respect to colonoscopy preparation in IBD patients. Low-volume preparations have better compliance, tolerance, and acceptance. The systematic review was limited by a small number of included RCTs.

OBJECTIVE: Several monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway diseases, such as chronic sinusitis with nasal polyps (CRSwNP) and asthma. However, the clinical safety of these MoAbs and how to choose them are not clear. Therefore, we aimed to assess the systemic drug- and dose-based safety of MoAbs in chronic airway inflammation using network meta-analysis (NMA).
METHODS: Electronic databases were systematically searched for relevant studies published in English between January 2009 and December 2022. Eligible studies must have clearly reported adverse events (AEs) among the MoAbs\' safety data.
RESULTS: 1). Regarding serious AEs, mepolizumab was significantly safer than placebo; in terms of permanent treatment discontinuation, reslizumab and dupilumab were significantly safer than benralizumab. 2). Regarding asthma worsening, dupilumab was associated with the best safety profile; was safer than dupilumab/300 mg/q2-4w. 3). In terms of injection-site reactions, dupilumab posed a higher risk than placebo; dupilumab/300 mg/qw posed a higher risk than dupilumab/300 mg/q2w and dupilumab/300 mg/q2-4w; lebrikizumab/250 mg/q4w posed a higher risk than lebrikizumab/37.5 mg/q4w; mepolizumab/100 mg/q4w posed a higher risk than mepolizumab/75 mg/q4w; benralizumab/30 mg/q4-8w posed a higher risk than benralizumab/20 mg/q4-8w. 4) In CRSwNP patients combined with asthma, the risks of experiencing AEs were not increased.
CONCLUSIONS: Overall, biologics are safe and well tolerated in chronic inflammatory airway disease. This drug- and dose-based NMA provides further evidence on the different safety profiles of different emerging MoAbs. This information may help guide rational drug use and provide clinical recommendations for choosing MoAbs.
BACKGROUND: SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42023387610).

OBJECTIVE: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general.
METHODS: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met pre-specified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions.
RESULTS: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with three (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation (GRADE) and six (23.1%) used Confidence In Network Meta-analysis (CINeMA). Surface Under the Cumulative Ranking Curve (SUCRA) was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%).
CONCLUSIONS: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms. Those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice.

BACKGROUND: Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs.
OBJECTIVE: We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs.
METHODS: We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework.
RESULTS: Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest.
CONCLUSIONS: PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was \"very low\", and careful interpretation is essential.

BACKGROUND: Type 2 diabetes mellitus (T2DM) represents a significant worldwide health issue, experiencing an increasing incidence rate. Effective dietary strategies are vital for T2DM management, but the optimal dietary patterns remain debated due to inconsistent research outcomes and single-outcome reporting. Network Meta-Analysis (NMA) provides a powerful approach for integrating data from randomized controlled trials (RCTs), enabling a detailed evaluation of the impact of different dietary patterns. This document presents our strategy for a systematic review and network meta-analysis, aimed at assessing the influence of key dietary patterns on glycemic control, lipid profiles, and weight management in individuals with Type 2 Diabetes Mellitus (T2DM).
METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and network meta-analyses guidelines, we conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library, without language or date restrictions. Our objective is to assess the efficacy of various dietary interventions in managing Type 2 Diabetes Mellitus (T2DM). We used standardized mean differences for pairwise comparisons and a Bayesian framework for ranking interventions via Surface Under the Cumulative Ranking Curve (SUCRA). Key analyses include heterogeneity, transitivity, and sensitivity assessments, along with quality and risk evaluations using the Cochrane Collaboration\'s tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
BACKGROUND: This systematic review and network meta-analysis involve aggregate data from previous trials, obviating the need for additional ethical approval. The search strategy will be executed starting October 2023, with all searches completed by December 2023, to encompass the most current studies available. Findings will be shared through academic conferences and peer-reviewed journals focused on diabetes care and nutrition.
BACKGROUND: PROSPERO registration number CRD42023465791.

This review examined the efficacy of surface treatments and adhesive monomers for enhancing zirconia-resin bond strength. A comprehensive literature search in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library yielded relevant in vitro studies. Employing pairwise and Bayesian network meta-analyses, 77 articles meeting inclusion criteria were analyzed. Gas plasma was found to be ineffective, while treatments including air abrasion, silica coating, laser, selective infiltration etching, hot etching showed varied effectiveness. Air abrasion with finer particles (25-53 µm) showed higher immediate bond strength than larger particles (110-150 µm), with no significant difference post-aging. The Rocatec silica coating system outperformed the CoJet system in both immediate and long-term bond strength. Adhesives containing 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) were superior to other acidic monomers. The application of 2-hydroxyethyl methacrylate and silane did not improve bonding performance. Notably, 91.2 % of bonds weakened after aging, but this effect was less pronounced with air abrasion or silica coating. The findings highlight the effectiveness of air abrasion, silica coating, selective infiltration etching, hot etching, and laser treatment in improving bond strength, with 10-MDP in bonding agents enhancing zirconia bonding efficacy.