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BACKGROUND: Antimicrobial stewardship is a systematic effort to change prescribing attitudes that can provide benefit in the provision of care to persons with cystic fibrosis (CF). Our objective was to decrease the unwarranted use of broad-spectrum antibiotics and assess the impact of an empiric antibiotic algorithm using quality improvement methodology. METHODS: We assembled a multidisciplinary team with expertise in CF. We assessed baseline antibiotic use for treatment of pulmonary exacerbation (PEx) and developed an algorithm to guide empiric antibiotic therapy. We included persons with CF admitted to Children's National Hospital for treatment of PEx between January 2017 and March 2020. Our primary outcome measure was reducing unnecessary broad-spectrum antibiotic use, measured by use consistent with the empiric antibiotic algorithm. The primary intervention was the initiation of the algorithm. Secondary outcomes included documentation of justification for broad-spectrum antibiotic use and use of infectious disease (ID) consult. RESULTS: Data were collected from 56 persons with CF who had a total of 226 PEx events. The mean age at first PEx was 12 (SD 6.7) years; 55% were female, 80% were white, and 29% were Hispanic. After initiation of the algorithm, the proportion of PEx with antibiotic use consistent with the algorithm increased from 46.2% to 79.5%. Documentation of justification for broad-spectrum antibiotics increased from 56% to 85%. Use of ID consults increased from 17% to 54%. CONCLUSION: Antimicrobial stewardship initiatives are beneficial in standardizing care and fostering positive working relationships between CF pulmonologists, ID physicians, and pharmacists.
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Fibrose Cística , Algoritmos , Antibacterianos/uso terapêutico , Criança , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Feminino , Hospitalização , Humanos , Pulmão , Masculino , Adulto JovemRESUMO
BACKGROUND: Pulmonary complications of sickle cell disease (SCD) contribute to excess morbidity and mortality. The burden of pulmonary dysfunction among Nigerians with SCD has not been well elucidated. OBJECTIVES: The objectives of this study are to describe the frequency and pattern of spirometry abnormalities in SCD and to explore the association between pulmonary dysfunction and selected parameters. METHODS: A cross-sectional study among adolescents and adults with SCD attending a University Teaching Hospital and healthy age- and gender-matched controls. Respiratory symptoms, oxygen saturation, spirometry, complete blood counts, and fetal hemoglobin (Hb) were measured. RESULTS: A total of 245 participants with SCD and 216 controls were included in the study. Frequency of respiratory symptoms was similar between the two groups. The median forced expiratory volume 1 (FEV1), forced vital capacity (FVC), and the FEV1/FVC were significantly lower in SCD as compared to controls (P = 0.000 in all instances). The frequency of abnormal pulmonary patterns was higher in SCD as compared to controls with abnormal spirometry pattern in 174 (71%) and 68 (31.5%) of participants with SCD and controls, respectively (P = 0.000). The suggestive of restrictive pattern was predominant (48% vs. 23%), but obstructive (11.8% vs. 7.4%) and mixed patterns (11% vs. 0.9%) were also found among SCD versus controls. Hb concentration was positively associated with FEV1 and FVC, whereas white cell count and age were negatively associated with FVC and FEV1, respectively. CONCLUSION: There is a high burden of pulmonary dysfunction in SCD among Nigerians which may be related to the severity of disease. There is a need for further research to explore the effectiveness of potential interventions so as to harness the benefits from monitoring and early detection.
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Background: Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality.Methods: We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions. Participants were divided into four subcommittees on the basis of expertise: 1) acute chest syndrome, 2) lower airways disease and pulmonary function, 3) sleep-disordered breathing and hypoxia, and 4) pulmonary vascular complications of SCD. Before the workshop, a comprehensive literature review of each subtopic was conducted. Clinically important questions were developed after literature review and were finalized by group discussion and consensus.Results: Current knowledge is based on small, predominantly observational studies, few multicenter longitudinal studies, and even fewer high-quality interventional trials specifically targeting the pulmonary complications of SCD. Each subcommittee identified the three or four most important unanswered questions in their topic area for researchers to direct the next steps of clinical investigation.Conclusions: Important and clinically relevant questions regarding sickle cell lung disease remain unanswered. High-quality, multicenter, longitudinal studies and randomized clinical trials designed and implemented by teams of multidisciplinary clinician-investigators are needed to improve the care of individuals with SCD.
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Anemia Falciforme/complicações , Pneumopatias/epidemiologia , Guias de Prática Clínica como Assunto/normas , Pesquisa , Síndrome Torácica Aguda/etiologia , Adulto , Asma/etiologia , Criança , Gerenciamento Clínico , Medicina Baseada em Evidências/normas , Humanos , Hipertensão Pulmonar/etiologia , Pneumopatias/fisiopatologia , Capacidade de Difusão Pulmonar , Síndromes da Apneia do Sono/etiologia , Sociedades Médicas , Volume de Ventilação Pulmonar , Estados UnidosRESUMO
Acute chest syndrome(ACS) is the most common pulmonary complication of sickle cell disease (SCD), the second most common cause of hospitalization and the primary cause of death in patients with sickle cell disease. Its highest prevalence is in early childhood. The pathogenesis of ACS is unknown but many predisposing conditions and mechanisms have been implicated including infections, pulmonary fat embolism, asthma and ischemic reperfusion injury. These conditions are associated with inflammation and therefore, the use of corticosteroids has been advocated because of their anti-inflammatory properties. Although, significant benefits from their use have been shown, there is great reluctance in using them because of reports of serious adverse effects, such as readmission to the hospital due rebound pain crisis, stroke, renal infarction, coma and even death. The current article reviews the evidence in favor and against the use of corticosteroids in ACS. Emphasis is given on the potential benefits vs. risks among the different types of corticosteroids, the importance of the dosing regimen and the role of underlying co-morbidities.
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Síndrome Torácica Aguda/tratamento farmacológico , Anemia Falciforme/complicações , Glucocorticoides/uso terapêutico , Síndrome Torácica Aguda/etiologia , Anemia Falciforme/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
The use of high oxygen concentrations is frequently necessary in the treatment of acute respiratory distress syndrome (ARDS) and bronchopulmonary dysplasia (BPD). High oxygen concentrations, however, are detrimental to cell growth and cell survival. Glutamine (Gln) may be protective to cells during periods of stress and recently has been shown to increase survival in A549 cells exposed to lethal concentrations of oxygen (95% O2). We found that supplemental Gln enhances cell growth in A549 cells exposed to moderate concentrations of oxygen (60% O2). We therefore evaluated the effect of moderate hyperoxia on the cell cycle distribution of A549 cells. At 48 h there was no significant difference in the cell cycle distribution between 2 mM Gln cells in 60% O2 and 2 mM cells in room air. Furthermore, 2 mM Gln cells in 60% O2 had stable protein levels of cyclin B1 consistent with ongoing cell proliferation. In contrast, at 48 h, cells not supplemented with glutamine (Gln-) in 60% O2 had evidence of growth arrest by both flow cytometry (increased percentage of G1 cells) and by decreased protein levels of cyclin B1. G1 growth arrest in the Gln- cells exposed to 60% O2 was not, however, associated with induction of p21 protein. At 72 and 96 h, Gln- cells in 60% O2, began to demonstrate a partial loss of G1 checkpoint regulation and an increase in apoptosis, indicating an increased sensitivity to oxygen toxicity. Glutathione (GSH) concentrations were then measured. 2 mM Gln cells in 60% O2 were found to have higher concentrations of GSH compared to Gln- cells in 60% O2, suggesting that Gln confers protection to the cell during exposure to hyperoxia through up-regulation of GSH. When cells in 60% O2 were given higher concentrations of Gln (5 and 10 mM), cell growth at 96 h was increased compared to cells grown in 2 mM Gln (P<0.04). Clonal survival was also increased in cells exposed 60% O2 and supplemented with higher concentrations of Gln compared to Gln- cells in 60% O2. These studies suggest that supplemental glutamine may improve cell growth and cell viability and therefore may be beneficial to the lung during exposure to moderate concentrations of supplemental oxygen.
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Linhagem Celular/efeitos dos fármacos , Glutamina/farmacologia , Oxigênio/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular/citologia , Linhagem Celular/metabolismo , Sobrevivência Celular , Ensaio de Unidades Formadoras de Colônias , Ciclina B/análise , Ciclina B/metabolismo , Ciclina B1 , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/análise , Ciclinas/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Glutationa/análise , Glutationa/metabolismo , Humanos , Interfase/efeitos dos fármacos , Oxigênio/toxicidade , Fatores de TempoRESUMO
Although a common complication of mechanical ventilation in acute respiratory failure, spontaneous pneumothorax has been rarely reported among patients on chronic, intermittent, noninvasive positive pressure support. We report the first case of recurrent pneumothoraces associated with nocturnal bilevel positive airway pressure ventilation via a nasal mask.A 26-year old man with chronic respiratory failure secondary to an unclassified neuromuscular condition suffered four separate episodes of spontaneous pneumothorax over a 12-month period. Two episodes occurred while he was asleep on bilevel positive airway pressure support. He was found to have numerous subpleural blebs, and we propose a mechanism for their development. Following open pleurodesis and blebectomy, the patient has not had another pneumothorax. Given the increasing utilization of chronic nocturnal bilevel positive airway pressure ventilation, we suggest that healthcare providers and patients be made aware of this potentially life-threatening complication.