Background: Sepsis affects 25 million children and neonates annually, causing significant mortality and morbidity. Early identification and treatment are crucial for improving outcomes. Identifying children at risk is challenging due to clinical heterogeneity and overlap with other conditions. Current evaluations of sepsis criteria adopt a variable-centred approach, evaluating each criterion independently. The objective of this study was to explore associations between patterns of sepsis screening criteria and sepsis risk in children screened in the emergency department (ED) to identify distinct profiles that describe the clinical heterogeneity of suspected sepsis.
Methods: This secondary analysis involved 3473 children screened for sepsis across 12 EDs in Queensland, Australia. Bayesian profile regression was used to construct data-driven clinical profiles derived from sepsis screening criteria and their association with suspected sepsis, defined as senior medical officer diagnosis and antibiotic administration in the ED. Posterior risk probabilities (Prs) with 95% credible intervals (CIs) were calculated for each profile. Profiles were internally validated by assessing their association with sepsis, septic shock, organ dysfunction and infection sources, in both adjusted and unadjusted models.
Results: Seven distinct clinical profiles were identified. Two profiles were labelled as high risk of suspected sepsis (profile 1, n=22: Pr 0.73, 95% CI 0.55, 0.89; profile 2, n=150: Pr 0.69, 95% CI 0.59, 0.80), four as moderate risk and one as low risk. High-risk profiles were characterised by severe illness indicators and elevated lactate levels. Moderate-risk profiles included criteria such as altered behaviour, young age (<3 months) and respiratory distress. High-risk profiles had strong associations with all clinical outcomes.
Conclusions: Seven clinical profiles were identified that varied in their risk of suspected sepsis and associated outcomes. Validation of these profiles in diverse populations and identification of which profiles are likely to benefit from certain interventions is needed.
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http://dx.doi.org/10.1136/bmjpo-2024-003100 | DOI Listing |
Eur Urol
March 2025
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Electronic address:
Owing to the "cold" tumor immune microenvironment of prostate cancer, immune-targeting agents have shown limited efficacy in patients with advanced prostate cancer, highlighting the need for new therapies with novel mechanisms of action. In this context, T-cell engagers (TCEs), which induce T-cell-mediated killing of cancer cells by binding the CD3 receptor on T cells and a specific tumor antigen expressed on malignant cells, represent a promising therapeutic option. Multiple studies have explored the use of TCEs in previously treated patients with metastatic castration-resistant prostate cancer, and several ongoing trials are currently assessing novel TCEs either as single agents or in combinatorial regimens with molecules with a distinct mechanism of action (eg, androgen receptor pathway inhibitors and other immune-targeting agents).
View Article and Find Full Text PDFJ Appl Microbiol
March 2025
Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Science, Addis Ababa University, P.O.Box 9086, Addis Ababa, Ethiopia.
Aims: Mycobacterium tuberculosis (Mtb) remains a major global health challenge, particularly due to increasing drug resistance. Beyond the well-characterized mutations, the mechanisms involved in driving resistance appear to be more complex. This study investigated the differential gene expression of Ethiopian drug-resistant Mtb sub-lineage 4.
View Article and Find Full Text PDFJ Med Chem
March 2025
EaStCHEM School of Chemistry, University of Edinburgh, David Brewster Road, Edinburgh, Scotland EH9 3FJ, U.K.
Cyclophilins have been implicated in the pathophysiology of metabolic dysfunction-associated steatohepatitis (MASH). Pharmacological inhibition of the cyclophilin B isoform has the potential to attenuate liver fibrosis in MASH, but current cyclophilin inhibitors in clinical trials lack isoform selectivity. We previously reported the novel tri-vector small-molecule inhibitor that exhibited improved subtype selectivity by simultaneously engaging three pockets on the surface of cyclophilins.
View Article and Find Full Text PDFBMJ Open
March 2025
Centre for Work and Mental Health, Nordlandssykehuset HF, Bodo, Norway.
Purpose: The Norwegian Neck and Back Registry (Norsk Nakke og Rygg Register, NNRR) was established to improve the quality of diagnosis and treatment in patients with neck and back complaints at Departments of Physical Medicine and Rehabilitation (PMR) in Norwegian hospitals. The purpose of this cohort profile is to describe the data from registered patients from 2016 to 2022 and linkage opportunities.
Participants: The registry includes adult patients with neck and back complaints referred to PMR multidisciplinary neck and back outpatient clinics in Norwegian hospitals.
BMJ Open
March 2025
Zhejiang Province First People's Hospital of Wuyi County, Wuyi, Zhejiang, China.
Objective: To identify different work engagement profiles among new nurses in China and explore demographic and personal factors that predict different work engagement profiles.
Design: A cross-sectional study.
Methods: From 1 April to 30 June 2022, a cross-sectional survey was conducted in 11 tertiary hospitals across five provinces in China.
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