The University of Colorado School of Medicine is the medical school of the University of Colorado system. It is located at the Anschutz Medical Campus in Aurora, Colorado, one of the four University of Colorado campuses, six miles east of downtown Denver at the junction of Interstate 225 and Colfax Avenue.
OBJECTIVES:To update evidence-based management recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with sepsis or septic shock. DESIGN:A panel of 68 international experts, representing 13 international organizations, as well as six methodologists, was convened. A formal conflict-of-interest policy was developed at the onset of the process and applied throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and subgroup leads as well as within subgroups, served as an integral part of the guideline development process. METHODS:New priority topics and recommendations from the prior guideline iteration were used to identify Population, Intervention, Control, and Outcomes (PICO) questions likely to have new or updated evidence. We conducted a systematic review to identify the best available evidence, summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or conditional, or as a good practice statement. "In our practice," statements were included when evidence was inconclusive to issue a recommendation but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 61 statements on the management of children with sepsis or septic shock. Overall, five were strong recommendations, 24 were conditional recommendations, and ten were good practice statements. For 22 PICO questions, no recommendations could be made, but, for seven of these, "in our practice" statements were provided. Compared with the 2020 guidelines, 20 recommendations were new, 13 were updated for clarity and/or new evidence, six were reviewed but not changed, and 22 were carried forward based on consensus of the panel that new evidence was not available. Only three recommendations were based on high or moderate certainty of evidence. CONCLUSIONS:Updated management guidelines were issued by a panel of international experts for the best care of children with sepsis or septic shock, acknowledging that most aspects of care continue to have relatively low quality of evidence.
Importance:As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies. Objective:To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion. Design, Setting, and Participants:This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, at 26 hospitals in 20 US states. Case patients presented with COVID-19-like illness and positive SARS-CoV-2 nucleic acid or antigen test results; control patients had COVID-19-like illness but tested negative for SARS-CoV-2. Exposure:Receipt of a 2024-2025 COVID-19 vaccine at least 7 days before illness onset. Main Outcomes and Measures:Main outcomes were COVID-19-associated hospitalization and severe in-hospital outcomes (supplemental oxygen therapy, acute respiratory failure, intensive care unit admission, and invasive mechanical ventilation or death). Logistic regression was used to estimate the odds of vaccination in case and control patients, adjusting for demographics, clinical characteristics, and enrollment region. The VE was estimated as (1 - adjusted odds ratio) × 100%. Results:A total of 8493 patients (median [IQR] age, 66 [54-76] years; 4338 female [51.1%]), including 1888 case patients with COVID-19 (among whom 951 [50.4%] had successful whole-genome sequencing, including 348 [36.6%] with KP.3.1.1, 218 [22.9%] with XEC, and 134 [14.1%] with LP.8.1 infections) and 6605 control patients were enrolled. Vaccine effectiveness against COVID-19-associated hospitalization was 40% (95% CI, 27%-51%), and protection was sustained through 90 to 179 days after vaccination. Vaccine effectiveness was higher against the most severe outcome of invasive mechanical ventilation or death at 79% (95% CI, 55%-92%). It was 49% (95% CI, 25%-67%) against hospitalization with KP.3.1.1, 34% (95% CI, 4%-56%) against XEC, and 24% (95% CI, -19% to 53%) against LP.8.1, with increasing median time since dose receipt among vaccinated case patients due to sequential circulation patterns (60, 89, and 141 days, respectively). The VE was similar against lineages with spike protein S31 deletion (41% [95% CI, 22%-56%]) and T22N and F59S substitutions (37% [95% CI, 9%-57%]). Conclusions and Relevance:In this multicenter, case-control analysis of VE, 2024-2025 COVID-19 vaccines may have provided protection against hospitalizations and severe in-hospital outcomes as multiple JN.1 descendant lineages circulated. Monitoring COVID-19 VE, including stratifying by SARS-CoV-2 lineage and spike protein mutations, remains important to guide COVID-19 vaccine composition and recommendations.
PURPOSE:The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. METHODS:We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS:PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION:PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.
This article presents a Delphi consensus developed by a panel of editors-in-chief of anaesthesiology and pain medicine journals to guide the responsible use of large language models (LLMs) in academic publishing. LLMs offer potential benefits for scientific writing, including language editing, summarisation, translation, information organisation, and support for non-native English speakers, but their misuse raises concerns about accuracy, transparency, confidentiality, and research integrity. Through a three-round modified Delphi process involving 53 editors-in-chief or their delegates, 59 statements were generated and categorised into guidance for authors, editors, reviewers, and publishers with a particular attention to LLM disclosure practices and perceived risks. The consensus recognises that LLMs are useful tools in academic publishing for authors, reviewers, and editors. However, their use must be guided by ethics, legality, and principles of transparency and accountability. LLMs may assist with limited editorial and authorial tasks provided that their use is fully disclosed and all outputs are verified by humans. The consensus also emphasises the inappropriateness of using LLMs to generate original or ideative content, which should remain a strictly human responsibility. Moreover, LLMs must not generate data, references, conclusions, or entire manuscripts, nor be used for editorial decisions or peer-review reports. Editors expressed concerns about 'hallucinations', erosion of critical skills, confidentiality breaches, and the proliferation of low-quality LLM-generated manuscripts. The resulting guidance highlights transparency, human accountability, and careful verification as essential principles for integrating LLMs into scholarly workflows while preserving the integrity of scientific publishing.
Although the broad outlines of a healthy diet are clear, controversy has arisen surrounding certain foods and nutrients. This review updates contemporary nutrition controversies and the extent to which they may promote or protect against cardiovascular disease (CVD). In this review, beef tallow, ultraprocessed foods, full-fat dairy, seed oils, medium chain triglyceride oils, seafood, and alternative sweeteners are considered. Three groupings included: 1) evidence of harm with a recommendation to limit or avoid; 2) lacking in evidence for harm or benefit; and 3) evidence of benefit. The evidence of harm category included beef tallow, due to association with increased low-density lipoprotein cholesterol, ultraprocessed foods associated with worsened cardiometabolic health, and artificial sweeteners owing to correlations with increased CVD. Within the category lacking in evidence were full-fat dairy, medium chain triglyceride, monk fruit, and stevia. Finally, evidence of benefit included seed oils and seafood based on improved CVD outcomes.
