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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.

IntroductionRosacea is a chronic skin condition characterised by papules, pustules, transient erythema (flushing), persistent erythema, telangiectasia and phymatous changes. Rosacea can be associated with substantial effects on quality of life. Rosacea is most commonly treated with topical therapy, but little is known about the relative efficacy of these treatment options.Since most randomised controlled trials of topical rosacea therapies do not include active comparators (ie, head-to-head comparisons), indirect comparisons must be made to understand the relative efficacy, safety and tolerability of these treatment options. The aim of this study is to conduct a living network meta-analysis evaluating topical therapies for moderate to severe rosacea. The results of this study can guide clinical decision-making and improve patient outcomes.Methods and analysisData search will be conducted in the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Web of Science and Embase. Screening of titles, abstracts and full papers, as well as data extraction, will be conducted by two independent researchers in duplicate. Primary outcomes will include mean change in absolute lesion count, Investigator Global Assessment (IGA) and treatment discontinuation for adverse events or side effects. Secondary outcomes will include percentage change in lesion count, changes in quality of life, Patient Global Assessment, Clinician Erythema Assessment (CEA) and change in rosacea facial redness. For each outcome with enough qualified data, a network meta-analysis using a random-effects model will be carried out. We plan for a living review with continuous updating of the analysis as new treatments become available.Ethics and disseminationDissemination in a peer-reviewed scientific journal is planned.PROSPERO registration numberCRD420251103231.

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.

IntroductionIgA nephropathy (IgAN) is the most common primary glomerular disease in adults. In recent years, there have been many significant advances in treating IgAN, with multiple successful clinical trials. We aim to determine the comparative effectiveness of available pharmaceutical interventions for treating IgAN.Methods and analysisA systematic review and network meta-analysis (NMA) will be conducted to assess the comparative effectiveness and safety of various pharmacological interventions available for adults with IgAN. All randomised controlled trials (RCTs) or quasi-RCTs which have evaluated pharmacological interventions in IgAN will be included. Both published studies and those available only as conference abstracts will be considered. A systematic literature search will be conducted using Ovid MEDLINE(R) ALL, Embase, Cochrane Kidney and Transplant Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry and ClinicalTrials.gov from inception to the present. Data extraction and risk of bias assessments using Cochrane Risk of Bias 2.0 will be performed by two reviewers independently, and differences resolved through consensus. Primary outcomes assessed will be kidney function and death, and secondary outcomes will be cardiovascular disease, other adverse events and patient-reported outcomes. The NMA will be conducted using a Bayesian NMA with Markov Chain Monte Carlo simulation methods in a random-effects model framework. The certainty of the evidence will be assessed using the Confidence In Network Meta-Analysis(CINeMA) tool to manage the Grading of Recommendations, Assessment, Development and Evaluations(GRADE) assessment.After initial publication, the NMA will be maintained as a ‘living model’ in an open-source web application. A living ‘auto-search’ will be created and updated monthly to identify new evidence as it becomes available for synthesis. If new relevant studies are identified, after risk of bias assessment, data will be extracted and incorporated into the model, and findings will be updated accordingly. This will potentially provide a continuous overview of the rapidly changing therapeutic landscape of IgAN in the coming years and in future may help us to design ‘living guidelines’ for the management of IgAN.Ethics and disseminationThe findings will be published in international peer-reviewed journals. No results are being presented in this protocol.PROSPERO registration numberCRD420251050367.