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.

Abstract Background Community-acquired pneumonia (CAP) is a significant public health concern associated with increased rates of hospital admissions and mortality. The purpose of the current study was to compare beta-lactam plus azithromycin or doxycycline vs fluoroquinolones in adults hospitalized with CAP. Methods We searched several databases from inception to 10 June 2024. Two reviewers independently screened, selected, and extracted data. Disagreements were resolved by consensus or a third reviewer. Study quality was assessed in duplicate with the Cochrane Risk of Bias 2 for randomized studies and the Newcastle-Ottawa Scale for nonrandomized studies. Meta-analysis was conducted by a random effect model when feasible. Network meta-analysis was performed to compare direct and indirect evidence. The GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation) was followed to rate the certainty of evidence. Results Twenty studies were included (20 beta-lactam + azithromycin, 7 beta-lactam + doxycycline, 12 levofloxacin, and 4 moxifloxacin): 6 were randomized, enrolling 861 participants (mean age, 61.8 years; 43.2% women), and 14 were nonrandomized, enrolling 185 928 participants (mean age, 65.2 years; 42.9% women). Direct comparison and network meta-analysis results showed no statistically significant differences and likely equal effectiveness between beta-lactam + azithromycin and beta-lactam + doxycycline in terms of in-hospital mortality, need for intensive care unit admission or invasive mechanical ventilation, or safety outcomes including Clostridioides difficile infection and QT prolongation. Conclusions The current evidence demonstrated no likely difference in outcomes between azithromycin and doxycycline in adults hospitalized with CAP receiving beta-lactam. Head-to-head randomized clinical trials are needed to validate these results.

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.

Abstract Background The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. Methods We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. Results Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46–.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36–1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. Conclusions Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.

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 .

Objective: The objective of this investigation was to evaluate the agreement rate on judgments made using the Murad tool by different systematic review teams. Introduction: Evaluating the methodological quality of case reports and case series is challenging but some tools do exist for this purpose. We leveraged the presence of studies that have been evaluated by different systematic review teams to assess the inter-consensus agreement among different teams on Murad tool domains. Methods: Using a back-citation method, we identified systematic reviews that used the Murad tool and retrieved all the included primary studies. We selected studies that were assessed by more than 1 systematic review team. We calculated observed agreement and Gwet’s agreement coefficient on judgments made about each signaling question. Results: We identified 982 systematic reviews that cited the Murad tool and collectively cited 59,080 references. The final data comprised of 81 duplicated case reports and series assessed by more than 1 systematic review team. Overall, the signaling questions had very high observed agreement with 5 of the 8 questions having agreement over 75%. The signaling questions with the highest agreement addressed the adequacy of the ascertainment of the exposure (coefficient 0.959), ascertainment of the outcome (coefficient 0.829), presence of a dose-response gradient (perfect agreement), and clarity of reporting (coefficient 0.755). Conclusion: The current study demonstrates overall high agreement among different systematic review teams that used the Murad tool for appraisal of the same case series and case reports. Leveraging duplicated studies across systematic reviews is a feasible way to retrospectively assess the reliability of the tool.