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Helicobacter pylori infections are responsible for tremendous morbidity and mortality worldwide, leading to efforts to eradicate the organism. However, the effectiveness of antimicrobial therapy has been undermined by the progressive development of antimicrobial resistance. Treatments and treatment guidelines have been based on traditional pairwise meta-analyses of randomised controlled trials. More recently, network meta-analyses have also been used in an attempt to provide useful information to the clinician regarding which therapies appear best and which to avoid as the least efficacious. However, both forms of meta-analysis have been undermined by the same problems including the poor quality of the clinical trials using unoptimised regimens and incomparable comparisons related to marked geographic and ethnic genotypic and phenotypic heterogeneity. In addition, the comparator regimens often consist of invalid strawman comparisons. New approaches concerning H. pylori treatment and analysis of therapies are needed. H. pylori therapies should be based on antimicrobial stewardship, as in other infectious diseases. This approach requires the use of only optimised therapies proven to be reliably highly effective in the local population (eg, a cure rate of >90%) for both the study and the comparator regimens. Meta-analyses should be restricted to regimens that meet these criteria and must take into account the presence of marked geographical and host genetic and phenotypic heterogeneity. In addition, to provide clinically relevant results, treatment outcomes should focus on, and present, actual cure rates in addition to odd ratios.

BackgroundCompromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population.AimTo provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES.MethodsAn independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size.Results56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as ‘high quality’ according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=−1.60, 95% CI −1.82 to −1.38, I2=67%) and all seven cognitive domains, with the SMD ranging from −0.87 to −1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=−1.90), Trail Making Test (TMT) (SMD=−1.36), Continuous Performance Test-Identical Pairs (SMD=−1.33), Hopkins Verbal Learning Test (SMD=−1.24), Brief Visuospatial Memory Test (SMD=−1.18), Mazes (SMD=−1.16), Category Fluency (SMD=−1.01), Spatial Span (SMD=−0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=−0.38).ConclusionsOur meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.

BackgroundThe prevalence of prolonged grief disorder (PGD) and its symptoms among the bereaved population in China vary considerably.AimsThis meta-analysis aims to estimate the prevalence of PGD and its symptoms among bereaved individuals in China.MethodsWe conducted a literature search in major Chinese and English databases from their inception to 4 October 2023, for cross-sectional studies on the prevalence of PGD or its symptoms in bereaved Chinese individuals. The risk of bias of the included studies and certainty of the evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data (‘JBI checklist’) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE), respectively. The ‘metaprop’ package in R V.4.1.2 was used to synthesise the prevalence.ResultsA total of 28 studies involving 10 994 bereaved individuals were included in the analysis, with JBI checklist scores between 3 and 7. The combined prevalence (95% confidence interval) of PGD and its symptoms was 8.9% (4.2% to 17.6%) and 32.4% (18.2% to 50.8%), respectively. PGD and its symptoms were most prevalent among those who had lost their only child (22.7%) and those bereaved by earthquakes (80.4%), respectively. The GRADE system assigned a very low certainty level to the evidence for the pooled prevalence of PGD and its symptoms.ConclusionsThe pooled prevalence of PGD and its symptoms indicate a potential high need for grief counselling services among bereaved individuals in China. This need is particularly pronounced in those who have lost their only child and those bereaved due to earthquakes. Further methodologically rigorous studies are needed to provide more accurate prevalence estimates.PROSPERO registration numberCRD42023432553.

IntroductionMigraine, a major headache disorder of high prevalence, affects approximately one billion individuals globally and imposes a substantial socioeconomic burden. Acupuncture, as a modality of complementary and alternative medicine, is increasingly used by patients for migraine management. Nevertheless, the effectiveness of acupuncture in randomised controlled trials (RCTs) for this condition remains a subject of debate. The varying non-specific effects of different sham acupuncture (SA) techniques complicate the accurate assessment of true therapeutic effectiveness of acupuncture. This protocol details a systematic review and network meta-analysis (NMA) aimed at comprehensively evaluating both the effectiveness of acupuncture compared with various sham controls and the differential non-specific effects of different SA methods in migraine. Our aims involve: (1) evaluating the effectiveness of acupuncture relative to SA controls in migraine treatment; (2) comparing the effect sizes across different SA methods and (3) identifying potential factors that influence the outcomes associated with various sham interventions.Methods and analysisWe will undertake a thorough investigation using multiple databases, including Wanfang Data, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov, PubMed, Chongqing VIP Database, SinoMed, Cochrane Central Register of Controlled Trials, Chinese Clinical Trial Register, International Traditional Medicine Clinical Trial Registry and China National Knowledge Infrastructure, spanning from their initial records up to 12 November 2024. The inclusion criteria are RCTs that compare acupuncture with SA controls for migraine treatment. Studies with waiting-list or no-treatment controls will be included only if they also contain an SA arm. Studies focusing exclusively on chronic migraine patients (≥15 headache days per month) will be excluded. Two independent reviewers will perform study selection, data extraction using a standardised prepiloted form and risk of bias assessment. The primary outcome will be the standardised mean difference (SMD) in migraine frequency measures, allowing for the inclusion of various frequency metrics (eg, migraine attacks, migraine days, headache days). Secondary outcomes will include response rate (≥50% reduction in frequency), days with acute medication use, the number of migraine days per month, pain intensity (measured using tools such as the Visual Analogue Scale or Numeric Rating Scale), and scores from migraine-specific questionnaires, among others. The Cochrane Risk of Bias tool 2 (RoB 2) will be employed for bias assessment, along with the Confidence in Network Meta-Analysis online tool and the Grading of Recommendations Assessment, Development and Evaluation system. A frequentist NMA will be executed using Stata (V.18.0). The network structure will comprise: acupuncture as a single node (or multiple nodes if heterogeneity warrants), different SA methods as separate nodes, and waiting-list/no-treatment as a single node. In terms of continuous outcomes, the synthesis will be conducted using the SMD with a 95% CI for estimating effects. Heterogeneity, network inconsistency and potential publication bias will be scrutinised. As needed, meta-regression, subgroup analyses and sensitivity analyses will be executed.Ethics and disseminationSince this research is based on data from published sources, it does not necessitate formal ethical clearance. The results will be shared via articles in scholarly journals and during presentations at academic symposiums.PROSPERO registration numberCRD42024620550.

With the increase in the number of novel drugs for inflammatory bowel disease (IBD), comparing therapeutic options or strategies has become a key challenge in IBD trials. Head-to-head trials designed and powered to enable formal comparisons are the gold standard in comparative research. Indeed, these trials are requested by some health authorities for evaluating the positioning of new treatments in IBD, as well as helping prescribing physicians to select the most appropriate treatment options for their patients. Despite head-to-head trials including aminosalicylate therapy in IBD having been performed decades ago, the first results of a randomized controlled trial directly comparing biologic agents with different modes of action have only now been published, mainly owing to important methodological issues. This Perspective provides an overview of the past, current and future concepts in IBD trial design, with a detailed focus on the role of comparative research and the challenges and pitfalls in undertaking and interpreting the results from such studies.As the number of novel drugs for inflammatory bowel disease (IBD) increases, comparison of therapeutic options has become a key challenge in IBD trials. Here, the authors provide an overview of IBD trial design with a focus on comparative research and the head-to-head trials format.

IntroductionHigh blood pressure (BP) in obese populations poses significant cardiovascular risks, yet the comparative effectiveness of various weight loss interventions on BP remains unclear. This systematic review and network meta-analysis (NMA) aims to assess the comparative effectiveness of weight loss interventions in overweight/obese adults with prehypertension/hypertension on BP change and adverse events (AEs).Methods and analysisA systematic review and Bayesian NMA of randomised controlled trials of weight loss interventions in overweight/obese patients with prehypertension/hypertension will be conducted. PubMed, EMBASE and the Cochrane library (CENTRAL) and relevant references will be searched up to June 2025. Primary outcomes are changes in systolic and diastolic BP; secondary outcomes include AEs, body weight reduction (kg) and quality of life. Study selection, data extraction and methodological quality assessment using Cochrane risk of bias (RoB) 2.0 will be performed by independent two authors. A Bayesian NMA will be conducted using BUGSnet, with surface under the cumulative ranking curve to rank interventions. Subgroup analyses will explore heterogeneity by baseline BP severity, intervention duration and comorbidities, and sensitivity analyses will be performed for robustness of the results by RoB and sample size.Ethics and disseminationEthical approval is not required for this systematic review as it will involve analysis of data only from previously published studies. The results will be disseminated through presentations at international conferences and publication in peer-reviewed journals.PROSPERO registration numberCRD42022376688.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge–purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 ( P =3.01 × 10 −7 ) in SOX2OT and rs17030795 ( P =5.84 × 10 −6 ) in PPP3CA . Two additional signals were specific to Europeans: rs1523921 ( P =5.76 × 10 − 6 ) between CUL3 and FAM124B and rs1886797 ( P =8.05 × 10 − 6 ) near SPATA13 . Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance ( P =4 × 10 −6 ), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of morbidity and mortality due to chronic liver disease. There is an extensive body of evidence focusing on pharmacotherapy for MASLD. Reviews on the topic have been largely limited to the efficacy of select agents, subgroups or outcomes. The current is a protocol for a comprehensive systematic review and network meta-analysis (NMA) evaluating the efficacy of examined pharmaceutical interventions in improving hepatic outcomes of MASLD.Methods and analysisMEDLINE, Scopus, Web of Science, the Cochrane Library database and multiple trial registries will be searched for clinical trials on MASLD pharmacotherapy. Histological, radiological and paraclinical outcomes will be considered along with safety and tolerability. Screening and data extraction will be conducted by pairs of independent reviewers. Risk of bias (RoB) will be assessed using the Cochrane RoB 2 tool. Pairwise random-effects meta-analyses will be conducted followed by random-effects frequentist NMAs—according to the length of intervention—for each outcome in clinically distinct MASLD subgroups. Other effect moderators will be examined in subgroup analyses and meta-regression. Certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation and Confidence in Network Meta-Analysis approaches.Ethics and disseminationEthics approval was waived (Alborz University of Medical Sciences; approval ID: IR.ABZUMS.REC.1404.121) as no new data will be generated. Information from published records will be used in compliance with their Copyright agreements. Results will be submitted for peer review and publication in a scientific journal.PROSPERO registration numberCRD420251125615.

IntroductionInduction of labour (IOL) is a commonly performed obstetric intervention, particularly when delivery is deemed more beneficial than continuing the pregnancy due to maternal or fetal indications. When the cervix is unfavourable for delivery, cervical ripening is performed prior to IOL. A wide variety of mechanical, pharmacological and combination methods are used, but the optimal approach balancing efficacy, safety and patient experience remains uncertain. Conventional aggregate data (AD) meta-analyses lack individual-level data, limiting exploration of patient-level factors for personalised medicine and do not address concerns about the trustworthiness of data presented in peer-reviewed randomised controlled trials (RCTs). This protocol describes an individual participant data (IPD) network meta-analysis (NMA) designed to evaluate and rank cervical ripening methods for IOL using only high quality, trustworthy data.Methods and analysisWe will identify eligible parallel-group RCTs enrolling pregnant women with a singleton, cephalic fetus at ≥34 weeks’ gestation requiring cervical ripening, through comprehensive searches of Ovid MEDLINE, Embase, Emcare, Scopus, Cochrane Pregnancy and Childbirth Register, WHO International Clinical Trials Registry Platform, clinicaltrials.gov and reference lists of prior reviews. The interventions we consider will be selected via Delphi consensus with international clinical experts. Eligible trial investigators will be invited to contribute de-identified IPD; AD will be used if IPD is unavailable. Trials will be assessed for trustworthiness using the Trustworthiness in RAndomised Clinical Trials checklist and the IPD Integrity Tool, with only eligible studies included in the primary analysis. All statistical analyses will follow a pre-specified statistical analysis plan (SAP) finalised before any analyses are conducted. A two-stage, contrast-based, frequentist IPD-NMA will compare cervical ripening methods for three co-primary outcomes: vaginal birth, composite adverse perinatal outcomes and composite adverse maternal outcomes. Subgroup analyses will assess effect modifiers (eg, parity, age and previous caesarean), with treatment rankings presented using the surface under the cumulative ranking curve and rank-heat plots. Sensitivity analyses will examine the impact of bias, missing data and population criteria.Ethics and disseminationThis study has been approved by the Monash University Human Research Ethics Committee (No. 48189). IPD will be de-identified and securely transferred for storage on a Monash University-hosted shared network drive. Findings will be disseminated via peer-reviewed publications, conference abstracts and the Cervical Ripening for Induction of Labour Collaborative Evidence Network Meta-Analysis (CIRCLE-NMA) website (https://circlenma.com). Patient and public involvement will guide the communication and interpretation of results.PROSPERO registration numberCRD420251077464.