This institutional approach to the care of patients ventilated >3 days improved all clinical and financial outcomes of interest. To date, few similar initiatives have demonstrated similar results. The approach and lessons learned in this process improvement project may be helpful to other institutions attempting to improve outcomes in this vulnerable population.

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Amyotrophic lateral sclerosis (ALS) is a terminalneurodegenerative disease. Clinical and molecular observations suggest that ALS pathology originates at a single site and spreads in an organized and prion-like manner, possibly driven by extracellular vesicles. Extracellular vesicles (EVs) transfer cargo molecules associated with ALS pathogenesis, such as misfolded and aggregated proteins and dysregulated microRNAs (miRNAs). However, it is poorly understood whether altered levels of circulating extracellular vesicles or their cargo components reflect pathological signatures of the disease. In this study, we used immuno-affinity-based microfluidic technology, electron microscopy, and NanoString miRNA profiling to isolate and characterize extracellular vesicles and their miRNA cargo from frontal cortex, spinal cord, and serum of sporadic ALS (n = 15) and healthy control (n = 16) participants. We found larger extracellular vesicles in ALS spinal cord versus controls and smaller sized vesicles in ALS serum. However, there were no changes in the number of extracellular vesicles between cases and controls across any tissues. Characterization of extracellular vesicle-derived miRNA cargo in ALS compared to controls identified significantly altered miRNA levels in all tissues; miRNAs were reduced in ALS frontal cortex and spinal cord and increased in serum. Two miRNAs were dysregulated in all three tissues: miR-342-3p was increased in ALS, and miR-1254 was reduced in ALS. Additional miRNAs overlapping across two tissues included miR-587, miR-298, miR-4443, and miR-450a-2-3p. Predicted targets and pathways associated with the dysregulated miRNAs across the ALS tissues were associated with common biological pathways altered in neurodegeneration, including axon guidance and long-term potentiation. A predicted target of one identified miRNA (N-deacetylase and N-sulfotransferase 4; NDST4) was likewise dysregulated in an in vitro model of ALS, verifying potential biological relevance. Together, these findings demonstrate that circulating extracellular vesicle miRNA cargo mirror those of the central nervous system disease state in ALS, and thereby offer insight into possible pathogenic factors and diagnostic opportunities.

BackgroundThe Burns Wean Assessment Program (BWAP) assessment checklist is designed to assist clinicians in the systematic evaluation of 26 clinical factors important to weaning. The authors recently described the relationship of the BWAP score (derived from the checklist) to weaning trial outcomes (weaning success or failure) in patients receiving mechanical ventilation for 3 days or longer in 5 adult critical care units. A BWAP score of 50 or higher was significantly associated with weaning success regardless of the specific category of patient (surgical, medical, cardiovascular, etc). This secondary analysis extends the evaluation of the BWAP checklist as it focuses on the importance of each individual BWAP factor to weaning outcomes in 5 different populations of patients. Objectives To identify the relative importance of the 26 BWAP factors to weaning success in patients undergoing mechanical ventilation for 3 days or longer in 5 adult critical care units. Methods BWAP checklists were completed within 24 hours of a weaning attempt in surgical-trauma, medical, neurological, thoracic-cardiovascular, and coronary care units in a 5-year period. Advanced practice nurses using a multidisciplinary pathway, the BWAP checklist, protocols for weaning trials, and sedation guidelines managed the patients similarly. Results A total of 20 BWAP factors were significantly associated with successful weaning in all units combined (P ≤ .02). However, some differences in the importance of the BWAP factors to weaning outcome exist between units, with the neuroscience intensive care unit deviating the most from the other units. Conclusions Although not all BWAP factors are significantly associated with weaning success, most are predictive. Restructuring the BWAP as a unit-specific weaning checklist and potential predictor may assist clinicians to address factors that may impede weaning more efficiently and effectively. (Am J Crit Care. 2012;21:52-59) by AACN on May 12, 2018 http://ajcc.aacnjournals.org/ Downloaded from Why greater gains in outcomes are not forthcoming despite the adoption of processes from randomized controlled trials is puzzling. Some explanations include increased complexity of care, sophistication and dominance of technological additions to the care environment, higher acuity, decreased staffing, and in academic centers, limitations on hours of service of house staff resulting in a decrease in continuity of care. [16][17][18][19][20][21] Regardless, determining how best to wean, the essential clinical and psychological elements required, and processes of care to make it all work in busy critical care units remain worthy goals. To these ends, clinical testing and evolution of the Burns Wean Assessment Program (BWAP), designed to assist clinicians in managing patients who require LTMV, has been a focus of the authors' work in the area of weaning. 5,6,[22][23][24][25][26][27] The BWAPThe BWAP consists of a 26-factor bedside checklist (see Figure), a BWAP score, and applications for storing and tracking BWAP a...