Barnes-Jewish Hospital is the largest hospital in the U.S. state of Missouri. Located in the Central West End neighborhood of St. Louis, it is the adult teaching hospital for the Washington University School of Medicine and a major component of the Washington University Medical Center. In 2018, Barnes-Jewish was named one of the top twenty hospitals in the United States by U.S. News & World Report in its annual ranking.S.
This systematic review and meta-analysis compared bacterial semi-quantification of respiratory samples from the BIOFIRE FILMARRAY Pneumonia (PN) Panels with quantitative and semi-quantitative culture methods (qCMs). Fourteen studies comprising 1,654 samples were included. Across both bronchoalveolar lavage-like and endotracheal aspirate-like specimens, the BIOFIRE PN Panel reported consistently higher bacterial loads than qCMs, with pooled mean differences of 1.17 and 0.95 log, respectively. Discrepancies decreased as culture-reported bacterial burden increased. The concordance rate in identifying the predominant pathogen was 94%, supporting the panel's clinical relevance. However, differential reporting at lower bacterial loads suggests that existing culture-based thresholds may not translate directly to molecular diagnostics. These findings highlight the need for pathogen- and method-specific interpretive thresholds to optimize the diagnostic utility of semi-quantitative molecular results and inform antimicrobial stewardship decisions.
Recent studies have highlighted the pivotal role of the kynurenine pathway (KP) in systemic inflammatory disorders. Although KP modulation has been explored in diseases such as dementia and schizophrenia, its therapeutic potential in rheumatologic diseases remains largely unexplored. The objective of this article is to explore the potential role of the galantamine-memantine combination, with or without N-acetylcysteine (NAC), in regulating KP metabolism and its possible relevance to the pathophysiology of rheumatologic diseases. This article proposes a novel therapeutic strategy involving a combination of galantamine, a modulator of nicotinic receptor, and memantine, a N-methyl-D-aspartate receptor antagonist, with or without NAC, to target KP dysfunction in rheumatologic diseases. Galantamine and memantine may exert synergistic neuroimmune effects by reducing the production of neurotoxic KP metabolites, such as quinolinic acid, while promoting protective branches of the pathway. NAC, through its antioxidant properties, may further support this approach by mitigating oxidative stress and restoring immune balance. This combined therapy seeks to address key mechanisms of inflammatory rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, osteoarthritis, and psoriatic arthritis. This multifaceted approach may represent a potential direction for the treatment of rheumatologic diseases by integrating metabolic, neuroimmune, and antioxidant pathways. If future studies support the proposed mechanistic interactions, galantamine-memantine combination could potentially be explored as an adjunctive strategy alongside existing therapies. However, its clinical impact on treatment requirements or health care costs remains unknown and requires investigation in well designed randomized controlled trials. SIGNIFICANCE STATEMENT: A growing body of evidence in rheumatologic diseases implicates the kynurenine pathway (KP) metabolism. The galantamine-memantine combination, with or without N-acetylcysteine, through its regulatory action in KP could potentially be explored as an adjunctive strategy alongside existing therapies. Future randomized controlled trials are essential to establish efficacy, safety, and optimal patient selection.
PURPOSE:Mechanically ventilated emergency department (ED) patients require appropriate postintubation sedation and analgesia. Many investigators have published reports of their interventions to improve ED postintubation sedation and analgesia, but this work has not been systematically or critically evaluated. METHODS:We performed a systematic review of studies reporting original clinical research on interventions to improve ED postintubation sedation and analgesia. We identified studies for inclusion via a secondary analysis of a recent scoping review on ED postintubation sedation and analgesia. Two investigators independently abstracted data and graded study quality; a third investigator adjudicated any disagreements. RESULTS:We identified 22 studies meeting our inclusion criteria, of which 11 were conference abstracts. Meta-analysis was not pursued due to substantial heterogeneity, primarily in outcome definitions. Methods described included educational interventions (n = 18) and protocols, guidelines, order sets, and checklists (n = 16). Ten studies reported improvement in a prespecified primary outcome directly related to ED postintubation sedation. Outcome definitions were heterogeneous. Most interventions were not described in adequate detail to permit replication, and implementation science techniques and frameworks were identified in only 3 studies. CONCLUSION:There is a small- to moderate-sized body of evidence to guide interventions to improve ED postintubation sedation and analgesia that is limited by heterogeneous outcome definitions and poor reporting of methods. Future work should include consistent, patient-centered outcome selection and rigorous reporting in adherence to guidelines on education and implementation research.
We evaluated whether an antibiotic stewardship bundle, which included audit-and-feedback, could reduce antibiotic overuse at hospital discharge. We performed a stepped-wedge cluster randomized trial across participating units at 10 hospitals to evaluate the effect of a discharge-focused stewardship bundle. The trial ran from 12/5/22-11/17/23. After a 24-week baseline period, one hospital crossed into the intervention arm every 2 weeks. The intervention consisted of a) disseminating institutional guidelines for oral antibiotic step-down therapy; and b) prospective audit-and-feedback on inpatients receiving antibiotics who had an anticipated discharge in the next 48 hours. The primary outcome was post-discharge antibiotic use. Secondary outcomes included inpatient antibiotic use, length-of-stay, and readmissions. After the intervention ended, providers and stewardship personnel from each hospital were surveyed and interviewed, respectively, to assess acceptability and feasibility. There were 21,782 patient-admissions included (14,228 baseline period; 7,554 intervention period). Median age was 66 years, with 61% male (Table 1). At the hospital-level, the average number of patients audited per week was 20; one-quarter of audits led to feedback. There were 3,133 (21.9%) patients prescribed post-discharge antibiotics at baseline compared to 1,645 (21.8%) during the intervention (OR 1.02; 95% CI 0.95-1.09). The mean post-discharge duration was 7.1 days (SD 5.2) at baseline compared to 7.6 days (SD 5.6) during the intervention (RR 1.02; 95% CI 0.98-1.07). Inpatient antibiotic duration was shorter during the intervention (RR 0.91; 95% CI 0.86-0.97), but there was no difference in length-of-stay and readmissions (Table 2). One hundred twelve inpatient providers were sent a post-intervention survey; 40 (35.7%) responded; 94% felt that the initiative improved antibiotic-prescribing at discharge (Table 3). However, many stewardship teams reported difficulty in accurately identifying when patients would be discharged (Table 4). An antibiotic stewardship bundle, which included audit-and-feedback, did not reduce antibiotic use at discharge. The bundle was acceptable to providers but difficult for stewardship teams to implement. Yvonne Burnett, PharmD, BCIDP, InflaRx: Honoraria|Melinta Therapeutics: Honoraria
