Clinical impact of pleural fluid Streptococcus pneumoniae PCR testing in children with complicated pneumonia.

BACKGROUND: While Streptococcus pneumoniae (Spn) is the leading cause of pediatric complicated community acquired pneumonia (cCAP), it is infrequently recovered by culture-based methods. We studied the real-world clinical impact of an Spn PCR assay for pleural fluid. METHODS: This pre-post quasi-experimental cohort study compared pathogen detection, antibiotic usage, and outcomes in children hospitalized with cCAP requiring pleural effusion or empyema drainage at Children's Hospital Colorado between 2016 and 2023. Patients were compared across two diagnostic periods: pre-Spn PCR and post-Spn PCR. Cox proportional hazard models compared time from admission to pathogen detection, optimal therapy (narrowest pathogen-directed or guideline-recommended empiric therapy), and MRSA therapy discontinuation between periods. RESULTS: Compared to the pre-Spn PCR cohort (N=149), the post-Spn PCR cohort (N=79) was more likely to have a pathogen detected (73.4% post-PCR vs. 38.9% pre-PCR, p < 0.001), driven by more Spn detections (45.6% vs. 14.1%, p < 0.001). Time to pathogen detection during hospitalization was shorter in the post-Spn PCR period (p < 0.001). The post-PCR cohort was more likely to receive optimal therapy (84.8% vs. 53.0%, p < 0.001), with shorter median times to optimal antibiotics (4.9 vs. 10.0 days, p < 0.001) and MRSA therapy discontinuation (1.5 vs. 2.5 days, p = 0.03). There were no differences in hospital length of stay or readmissions. CONCLUSIONS: Spn molecular testing of pleural fluid in children with cCAP resulted in significantly more microbiologic diagnoses and was associated with the optimization of antibiotics and decreased exposure to MRSA therapy, suggesting its clinical impact for pediatric complicated pneumonia.

Original research: longitudinal evaluation of cognitively demanding daily function using performance-based functional assessment highlights heterogeneous trajectories in cognitive and functional abilities in people with Parkinson's disease.

Background: Longitudinal assessment of functional abilities in Parkinson's disease (PD) is needed to determine the efficacy of cognitive interventions in providing meaningful improvements in daily life. Additionally, subtle changes in instrumental activities of daily living may precede a clinical diagnosis of dementia and could aid earlier detection of and intervention for cognitive decline. Objective: The primary goal was to validate the longitudinal application of the University of California San Diego Performance-Based Skills Assessment (UPSA). An exploratory secondary goal was to determine whether UPSA may identify individuals at higher risk of cognitive decline in PD. Methods: Seventy participants with PD completed the UPSA with at least one follow-up visit. Linear mixed effects modeling was used to identify associations between baseline UPSA score and cognitive composite score (CCS) over time. Descriptive analysis of four heterogeneous cognitive and functional trajectory groups and individual case examples was performed. Results: Baseline UPSA score predicted CCS at each timepoint for functionally impaired and unimpaired groups (p < 0.01) but did not predict the rate change in CCS over time (p = 0.83). Participants displayed heterogenous trajectories in both UPSA and CCS during the follow-up period. Most participants maintained both cognitive and functional performance (n = 54), though some displayed cognitive and functional decline (n = 4), cognitive decline with functional maintenance (n = 4), and functional decline with cognitive maintenance (n = 8). Conclusion: The UPSA is a valid measure of cognitive functional abilities over time in PD. Given the heterogeneity of functional and cognitive trajectories, this performance-based assessment did not predict cognitive decline with this relatively short follow-up. Further work is needed to understand longitudinal functional assessments in PD-associated cognitive impairment.

Astrogliosis and episodic memory in late life: higher GFAP is related to worse memory and white matter microstructure in healthy aging and Alzheimer's disease.

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e., Aß42) and neurodegeneration (i.e., total tau; neurofilament light chain) in 114 older adults (asymptomatic, n = 69; MCI/AD dementia, n = 45). Higher levels of GFAP were associated with lower memory scores (p < 0.0001), such that for 1 SD increase in mean GFAP values, the memory composite score decreased on average by 0.49 (Standard error = 0.071). These results remained significant after controlling for diagnostic status and AD-related blood biomarkers. Higher GFAP was also related to lower WM integrity in regions vulnerable to AD pathology; however, WM integrity did not account for the association between GFAP and memory. Study findings suggest that higher blood levels of a marker of astrogliosis may reflect impoverished memory functions and white matter health, independent of markers of amyloid or neurodegeneration.