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1.
Front Mol Neurosci ; 14: 739016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776863

RESUMO

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.

2.
Am J Crit Care ; 21(1): 52-8; quiz 59, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22210700

RESUMO

BACKGROUND: The 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.


Assuntos
Cuidados Críticos/métodos , Avaliação em Enfermagem/métodos , Respiração Artificial , Desmame do Respirador/métodos , Centros Médicos Acadêmicos , Adulto , Prática Avançada de Enfermagem , Idoso , Idoso de 80 Anos ou mais , Lista de Checagem , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Cuidados de Enfermagem , Avaliação de Processos e Resultados em Cuidados de Saúde , Valor Preditivo dos Testes , Fatores de Tempo , Adulto Jovem
3.
Am J Crit Care ; 19(5): 431-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20810418

RESUMO

BACKGROUND: The Burns Wean Assessment Program is a 26-factor weaning assessment worksheet and scoring instrument used to reduce practice variability in the clinical management of patients receiving mechanical ventilation. The instrument has been tested in patients in a medical-surgical intensive care unit, but further testing in different populations of adult patients is needed. OBJECTIVES: To determine the relationship between Burns Wean Assessment Program scores and outcomes of weaning trials in patients treated with mechanical ventilation for 3 or more days. METHODS: For 5 years in 5 adult critical care units (surgical, medical, neurological, thoracic-cardiovascular, and coronary care), advanced practice nurses collected scores within 24 hours of a weaning attempt. All patients were managed similarly by using a multidisciplinary pathway, the Burns Wean Assessment Program checklist, protocols for weaning trials, and sedation guidelines. RESULTS: Of 1889 weaning attempts, 1669 (88%) were successful, and 220 (12%) were unsuccessful. Weaning outcomes did not differ according to sex, but significantly more trials were successful in younger patients than in older patients (P = .002) and in patients in different units (P = .01). Regardless of unit, patients with Burns Wean Assessment Program scores greater than 50 were significantly more likely to be weaned successfully (P = .001) than were patients with lower scores. CONCLUSIONS: Systematic tracking of the factors and scores on the Burns Wean Assessment Program may be helpful in care planning and management and in determining weaning potential.


Assuntos
Prática Avançada de Enfermagem , Procedimentos Clínicos , Índice de Gravidade de Doença , Desmame do Respirador/métodos , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Curva ROC , Desmame do Respirador/enfermagem , Desmame do Respirador/normas
4.
Crit Care Nurs Clin North Am ; 16(3): 387-93, ix, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15358387

RESUMO

Many studies have been published on weaning patients from mechanical ventilation, but few have addressed the unique needs of patients with neurologic impairment. Typically, neuroscience patients remain intubated because of concerns over airway protection or neuromuscular weakness. This article discusses special weaning considerations for this patient population. Neurologic-specific weaning trends from a comprehensive ventilator weaning program are also presented.


Assuntos
Cuidados Críticos/métodos , Doenças do Sistema Nervoso/complicações , Insuficiência Respiratória , Desmame do Respirador/métodos , Tosse/etiologia , Cuidados Críticos/normas , Escala de Coma de Glasgow , Síndrome de Guillain-Barré/complicações , Humanos , Miastenia Gravis/complicações , Avaliação das Necessidades , Doenças do Sistema Nervoso/fisiopatologia , Avaliação em Enfermagem/métodos , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Reflexo , Insuficiência Respiratória/complicações , Insuficiência Respiratória/terapia , Traumatismos da Medula Espinal/complicações , Fatores de Tempo , Desmame do Respirador/enfermagem , Desmame do Respirador/normas , Capacidade Vital
5.
Crit Care Nurs Clin North Am ; 16(3): 395-411, ix, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15358388

RESUMO

Care of patients requiring long-term mechanical ventilation (LTMV) is the focus of many hospitals nationwide. Because the care of patients who require LTMV is complex and morbidity and mortality are high, associated costs often exceed reimbursement. This article describes a successful institutional program for the care of the patient population requiring LTMV using advanced practice nurses (APNs) in the role of outcomes managers (OMs). So that others may benefit from the experiences of the clinicians, this article describes the historical background, the selection and qualifications of APNs, the process APNs use to manage and monitor the patients, role challenges, and associated outcomes.


Assuntos
Cuidados Críticos/organização & administração , Procedimentos Clínicos/organização & administração , Profissionais de Enfermagem/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde/organização & administração , Desmame do Respirador/enfermagem , Administração de Caso/organização & administração , Protocolos Clínicos , Medicina Baseada em Evidências , Humanos , Assistência de Longa Duração/organização & administração , Modelos de Enfermagem , Monitorização Fisiológica/enfermagem , Morbidade , Papel do Profissional de Enfermagem , Avaliação em Enfermagem , Pesquisa em Avaliação de Enfermagem , Guias de Prática Clínica como Assunto , Avaliação de Programas e Projetos de Saúde , Desmame do Respirador/métodos , Desmame do Respirador/normas , Virginia/epidemiologia
6.
Crit Care Med ; 31(12): 2752-63, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14668611

RESUMO

OBJECTIVE: To determine the effect of an institutional approach to the care of patients requiring mechanical ventilation for longer than three consecutive days in five adult intensive care units (ICU) on clinical and financial outcomes. DESIGN: A multidisciplinary team was selected from five adult ICUs to design the approach. Planning occurred from August 1999 to September 2000. The process was called outcomes management (OM) and included an evidence-based clinical pathway, protocols for weaning and sedation use, and the selection of four advanced practice nurses (called outcomes managers) to manage and monitor the program. SETTING: The project was completed in a 550-bed mid-Atlantic academic medical center. The ICUs included the following: coronary care, medical ICU, neuroscience ICU, surgical trauma ICU, and thoracic cardiovascular ICU. PATIENTS: The sample included 595 pre-OM patients and 510 post-OM patients mechanically ventilated for greater than three consecutive days. INTERVENTIONS: Full implementation of the OM approach occurred in March 2001. Retrospective baseline (18 months pre-OM) and prospective (12 months OM) clinical and financial data were compared. MEASUREMENTS AND MAIN RESULTS: Statistically significant differences in clinical outcomes were demonstrated in the managed patients compared with those managed before the institutional approach. Outcomes include ventilator duration (median days declined from ten to nine; p =.0001), ICU length of stay (median days declined from 15 to 12; p =.0008), hospital length of stay (median days declined from 22 to 20; p =.0001), and mortality rate (declined from 38% to 31%, p =.02). More than 3,000,000 US dollars cost savings were realized in the OM group. CONCLUSIONS: 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.


Assuntos
Cuidados Críticos/organização & administração , Procedimentos Clínicos/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde/organização & administração , Respiração Artificial/economia , Respiração Artificial/normas , Centros Médicos Acadêmicos , Idoso , Administração de Caso/organização & administração , Redução de Custos , Medicina Baseada em Evidências , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Enfermeiros Clínicos/organização & administração , Papel do Profissional de Enfermagem , Pesquisa em Avaliação de Enfermagem , Equipe de Assistência ao Paciente/organização & administração , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Respiração Artificial/mortalidade , Respiração Artificial/enfermagem , Análise de Sobrevida , Fatores de Tempo , Virginia/epidemiologia
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