Murad, M Hassan

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix I and Appendix II). Updates are published regularly and can be found on the ASCO Publications website .

Abstract Background Prosthetic joint infection (PJI) represents an important complication of total joint arthroplasty, affecting approximately 2% of patients. However, considerable heterogeneity in outcome definitions renders cross-study and clinical comparisons challenging. Methods We performed a meta-epidemiological study and systematic review of cohort studies and randomized controlled trial (RCTs) reporting clear definitions of PJI outcomes. Relevant data regarding outcome definitions of treatment success or failure were extracted and categorized into 7 outcome domains: clinical signs and symptoms, imaging, microbiology, mortality, antibiotics-related, surgical-related, and histology. A network plot was generated to visualize domains combinations. Data on patient-reported outcome measures (PROMs) were also collected. Based on these results, we finally proposed a working definition of PJI core outcome set. Results The literature search identified 7585 references, leading to 461 studies. The majority were retrospective (416/461, 90.2%), with limited representation of prospective studies (37/461, 8.0%) and RCTs (8/461, 1.7%). Outcome reporting was highly heterogeneous, with the clinical criterion being the most frequently used domain, combined with microbiological, surgical, and mortality-related outcomes. In contrast, histopathological, imaging, and antibiotic-related criteria were rarely reported. Thirty-six PROMs were included in only 111 (24.1%) studies, most commonly the Knee Society Score (26%) and Harris Hip Score (23%). Conclusions We showed substantial heterogeneity in PJI outcome definitions, with inconsistent reporting across key domains, limiting comparability and evidence synthesis. Standardized, consensus-based outcomes incorporating patient-reported and antibiotic-related measures are needed, and the proposed core outcome set may support harmonized research and clinical practice aligned with the new PJI definition.

Objective To examine the potential errors of a general large language model (LLM) (ie, Claude 3.5 Sonnet) on data extraction from randomised controlled trials (RCTs). Design and setting An empirical study comparing Claude 3.5 Sonnet extractions against a human-performed verification dataset. The extraction tasks for Claude 3.5 Sonnet were based solely on original RCT portable document format (PDF) files. For PDFs that could not be directly extracted by Claude 3.5 Sonnet, optical character recognition was employed to convert them into text format before extraction. Participants A random sample of 664 trials was selected from a well-established trial bank and a final data pool was established based on rigorous manual cross-checking as a reference standard. Data sources PubMed, EMBASE, Scopus, Web of Science (all databases) and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2023. Eligibility criteria for selecting studies RCTs on children involving medication and adverse events. Main outcome measures Claude 3.5 Sonnet was applied to extract the basic information (eg, trial design, population information and source of funding) and adverse outcomes (ie, name of adverse events, number of events). Claude 3.5 Sonnet outputs were compared against the final data pool and all errors were recorded. Results are presented as error rates and with 95% CI, estimated using a generalised linear mixed model. Results For the 664 trials, a total of 23 069 data cells were extracted via Claude 3.5 Sonnet, with 10 624 for basic information and 12 445 for adverse outcomes. The overall error rate for data extraction was 6.6% (95% CI 5.4% to 8.2%), with 5.7% (95% CI 5.2% to 6.1%) in basic information and 7.6% (95% CI 4.9% to 11.8%) in adverse outcomes. When stratified the 1542 total errors by error types, misallocation (assigning data to incorrect fields; 57.1%, 881/1542) and missed or omitted data (incomplete extraction of available data; 23.2%, 357/1542) accounted for the two most frequent errors, with misallocation occurring more in basic information (53.3%, 470/881), while missed or omitted data occurred more in adverse outcomes (96.1%, 343/357). Post hoc analysis examining the association between trial reporting quality (assessed using Consolidated Standards of Reporting Trials (CONSORT) 2025 and LLM data extraction error rates indicated that higher CONSORT adherence was associated with lower extraction error rates. Conclusions The data extraction error of Claude was relatively low, but it alerts LLM applications in evidence synthesis. Detailed checking for LLM outputs should be the primary consideration for evidence synthesisers.

Objectives This study aims to compare the reliability and accuracy of three large language models (LLMs) (Claude, Gemini and GPT) in assessing the risk of bias of nonrandomised studies using the ROBINS-I tool. Methods and analysis We conducted a secondary analysis of 171 nonrandomised studies previously assessed with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool by two independent human review teams. Only studies with concordant human domain-level ratings were included. Each study was independently assessed twice by Claude, Gemini and Generative Pre-trained Transformer (GPT) using agent-based structured implementations of the ROBINS-I tool. Reliability (agreement between two runs of the same LLM) was evaluated using percent agreement and Gwet’s AC1. Accuracy (agreement with human reviewers) was assessed only for studies with consistent LLM ratings, using the same metrics. Results Claude demonstrated high reliability across all domains (79.5–98.0% agreement, AC1=0.729–0.975). Gemini showed moderate-to-high reliability (agreement 76.7–100%, AC1=0.680–1.0). GPT exhibited lower reliability overall, though domain-level agreement ranged from 70.9–95.6% (AC1=0.596–0.944). In terms of accuracy, Claude showed overall poor agreement with human reviewers (14.4–68.5% agreement; low AC1 values). Gemini demonstrated moderate-to-high accuracy in several domains, including deviations from intended interventions (79.6%, AC1=0.848) and measurement of outcomes (73.9%, AC1=0.702), with the highest overall agreement (40.0%, AC1=0.672). GPT showed variable accuracy, with the highest in measurement of outcomes (62.8%, AC1=0.571) and classification of interventions (57.8%, AC1=0.498), but poor performance in selection (14.3%, AC1 = −0.041) and overall agreement (23.0%, AC1=0.267). Conclusions Claude was internally consistent but poorly aligned with human reviewers. Gemini achieved both high reliability and moderate-to-high accuracy, whereas GPT had lower reliability and mixed accuracy. Current off-the-shelf LLMs cannot reliably perform ROBINS-I risk of bias assessments.

Abstract Context Central precocious puberty (CPP). Objective To summarize the available supporting evidence for the Endocrine Society guidelines about the management of CPP. Methods Multiple databases (MEDLINE, EMBASE, Scopus) were searched to identify studies that addressed the Endocrine Society Guideline Development Panel's 10 clinical questions. Identified studies were selected and appraised, and data were extracted by pairs of independent trained reviewers. Results The systematic review yielded 3796 citations, of which 32 citations were included. The systematic review and meta-analysis demonstrate that in children with CPP, with no central nervous system symptoms, the rate of magnetic resonance imaging identification of pathogenic lesions (ie, hamartomas and brain tumors) was 6% (35 noncomparative studies with 5541 children with CPP). For girls with idiopathic CPP, gonadotropin-releasing hormone agonist (GnRHa) treatment was associated with +2.7 cm adult height gain compared to those who did not receive treatment (21 comparative observational studies with 1835 girls [mean age 8.20 ± 1.08 years]). The review did not identify any studies that assessed the clinical questions on: benefits of additional evaluation in cases of early thelarche, differentiation of slowly vs rapidly progressing CPP, order of biochemical testing to establish and monitor the diagnosis of CPP, genetic testing for individuals diagnosed with CPP, and chronological age and/or bone age for discontinuation of GnRHa treatment. Conclusion This systematic review addresses various aspects of CPP evaluation and treatment of CPP and will support the development of the Endocrine Society guidelines.

Introduction Increasing publication of fraudulent clinical trials poses a serious threat to evidence-based medicine. In the VITALITY Study I, we demonstrated that contamination by retracted trials significantly distorts evidence synthesis. The upcoming VITALITY Study II will take a step further and investigate how such problematic evidence undermines the credibility of guideline recommendations. Methods and analyses The VITALITY Study II will adopt a retrospective cohort design and will be structured as three work packages (WPs). To start with, a cohort of clinical practice guidelines (CPGs) that were contaminated by retracted trials and/or meta-analyses that included retracted trials will be established based on forward citation searching (WP1). Then, recommendations from these CPGs that used evidence from retracted trials and/or meta-analyses that synthesised these retracted trials will be re-evaluated after removing such problematic evidence, in terms of both the direction and strength of effect sizes (WP2). Finally, the subsequent impact on patient outcomes attributable to distorted recommendations will be estimated on a hypothetical population, measured by the number of expected benefit loss and the number of expected harm increment per 100 000 patients (WP3). Ethics and dissemination Formal ethical approval is not necessary for this study as it does not involve human or animal participants, nor does it involve the collection of primary data. We will disseminate the findings through publication in peer-reviewed journals and, whenever possible, presentations at academic conferences.

ABSTRACT Objectives Systematic evidence reviews (SERs) produced by the U.S. Agency for Healthcare Research and Quality (AHRQ) Evidence‐based Practice Center (EPC) Program use contextual questions to provide context and background information on the topic. There is currently no standardized approach to address contextual questions in systematic reviews. This study explored the use of publicly available large language models (LLMs) in addressing contextual questions. Study Design Using a set of 20 published and 5 yet to be published SERs, we selected one contextual question per report and used it as a prompt to elicit answers from an LLM (ChatGPT, Bard, Claude, or Perplexity). Two independent reviewers rated the results using a priori established evaluation criteria ( https://osf.io/4k3cu/ ), comparing the response in the SER to LLM‐generated responses. The study was guided by six research questions addressing feasibility, validity of content, validity of structure, mistakes, congruence between responses, and incremental validity of using LLMs to address contextual questions. Results Using minimal prompt engineering produced relevant responses and documented the feasibility of LLM‐generated answers to contextual questions. Responses differed in content and format and are not reproducible (e.g., LLMs update regularly), but LLMs were able to produce articulate, clinically plausible, and well‐structured responses. We detected few factual errors, contradictions, and no instance of suspected bias, but citations supporting LLM‐generated responses could often not be produced or could not be verified (‘confabulations’). Congruence with human generated responses varied, with LLM‐generated responses providing more background on the topic and SERs providing more nuanced answers in response to the contextual question. Results regarding incremental validity were mixed and may depend on the tool. Conclusion LLMs are potentially helpful in addressing contextual questions in systematic reviews but human expertise remains essential for using the generated information in a meaningful way.

Objectives To describe the incidence, presentation and long-term health outcomes of suicidal thoughts and behaviours (STBs) in children aged 12 years or under. Methods This population-based study included children identified through the Rochester Epidemiology Project who presented between 2005 and 2023 with STBs across primary, secondary and tertiary care centres in Olmsted County, Minnesota, USA. Information related to the patient and family characteristics, presentation, prior history and outcomes was manually extracted by two independent researchers. Patients were excluded if the index visit note could not be located, the patient had no suicidal ideation, attempts, intent or plan, was older than 12 years 11 months at the index date, less than 2 years old or was a duplicate entry. Results The average annual population was 28,035 children, of which 637 presented with STBs (mean (SD) age, 10.6 (1.7) years; 51.2% girls, 76.3% White, average follow-up 7 years). The majority of the cases presented to the emergency department (ED) 491 (77.1%). The annual incidence per 100,000 person-years tripled from 68.8 in 2005 to 208.6 in 2023. Overall, 105 patients (16.5%) presented with a suicidal attempt. There were no cases of death by suicide. A prior psychiatric diagnosis was present in 454 (71.3%). STB events were preceded by a precipitating event in 471 (73.9%), the most common of which was an argument with a parent, followed by a bullying event and family distress. A specific suicide plan was reported by 328 (51.5%) with laceration reported most frequently, followed by hanging and overdose. Significant predictors of a suicide attempt were previous use of mood stabilisers (OR 3.21; 95% CI 1.24 to 7.97) and having a specific plan (OR 2.73; 95% CI 1.72 to 4.41). Children who had suicidal attempts had more subsequent ED visits (3.50 vs 2.58; p=0.009) and hospitalisations for psychiatric reasons (1.90 vs 1.30; p=0.003) and psychiatric hospitalisation days (12.70 vs 9.04; p=0.048). Subsequent suicide attempts occurred in 31% of the cohort during follow-up. Conclusion STBs in preadolescent children are rare but are increasing in incidence. Such children have significant psychological diagnoses, use of mental health services, and subsequent suicide attempts. Novel age-appropriate interventions are needed.

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 ). Updates are published regularly and can be found at www.asco.org/genitourinary-cancer-guidelines .