Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS)

Critical Care Medicine, Journal Year: 2024, Volume and Issue: 53(1), P. e15 - e28

Published: Nov. 22, 2024

To summarize the delirium treatment trial literature, identify unique challenges in trials, and formulate recommendations to address each older adults. A 39-member interprofessional international expert working group of clinicians (physicians, nurses, pharmacists) nonclinicians (biostatisticians, epidemiologists, methodologists) was convened. Four panels were assembled explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, novel research designs). provide background context, a review randomized controlled trials (RCTs) published between 2003 2023 conducted evidence gaps identified. The four addressed identified subtopics. For subtopic, proposed through virtual discussion before live, full-day, in-person conference. General agreement reached for recommendation across entire via moderated conference discussion. Recommendations synthesized iteratively discussed rounds meetings draft reviews. We systematic literature review, yielding 43 RCTs treatments. From this eight identified, made based on panel input. start with design interventions that consider multifactorial nature delirium, include both pharmacological nonpharmacologic approaches, target pathophysiologic pathways where possible. Selecting appropriate at-risk patients moderate vulnerability may maximize effectiveness. Targeting at least severity duration will those most likely experience adverse outcomes. Delirium should be primary outcome choice; measurement short- long-term clinical outcomes relevance. Finally, plans handling informative censoring missing data are key. By addressing gaps, our serve as roadmap advancing

Language: Английский

Chemokine associations with blood cerebrospinal fluid barrier permeability and delirium

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 43, P. 100920 - 100920

Published: Dec. 5, 2024

Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines chemokines cross the brain barrier during delirium, directly impairing function. It not known whether these molecules reach higher levels when cerebrospinal fluid (BCSFB) impaired. Here, human hip-fracture patients, we tested influence of BCSFB integrity on CSF assessed their association with delirium. IP-10, eotaxin, eotaxin 3 TARC showed weak to moderate correlations permeability, as measured Qalbumin ratio, while MCP1, IL-8, MIP1α MIP1β no significant correlation. Chemokines were associated univariate analysis or stratified dementia status, exploratory analyses elevated Eotaxin (CCL11) (CCL3) Modelling systemic inflammation, used bacterial LPS (250 μg/kg) sterile laparotomy surgery mice demonstrate de novo synthesis at choroid plexus (CP) microvasculature. Gene expression data CP-enriched Il1b, Tnfa, Cxcl1 Ccl3 both models immunohistochemistry cytokine chemokine CP stromal (IL-1β, CCL2/MCP1) epithelial cells (CXCL10/IP-10) Larger studies required confirm findings associations permeability Preclinical warranted determine might play role pathophysiology

Language: Английский