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BACKGROUND: Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial. METHODS: In a multicenter, randomized trial conducted in seven intensive care units in the United States, we randomly assigned adults undergoing tracheal intubation to receive either ventilation with a bag-mask device or no ventilation between induction and laryngoscopy. The primary outcome was the lowest oxygen saturation observed during the interval between induction and 2 minutes after tracheal intubation. The secondary outcome was the incidence of severe hypoxemia, defined as an oxygen saturation of less than 80%. RESULTS: Among the 401 patients enrolled, the median lowest oxygen saturation was 96% (interquartile range, 87 to 99) in the bag-mask ventilation group and 93% (interquartile range, 81 to 99) in the no-ventilation group (P = 0.01). A total of 21 patients (10.9%) in the bag-mask ventilation group had severe hypoxemia, as compared with 45 patients (22.8%) in the no-ventilation group (relative risk, 0.48; 95% confidence interval [CI], 0.30 to 0.77). Operator-reported aspiration occurred during 2.5% of intubations in the bag-mask ventilation group and during 4.0% in the no-ventilation group (P = 0.41). The incidence of new opacity on chest radiography in the 48 hours after tracheal intubation was 16.4% and 14.8%, respectively (P = 0.73). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, patients receiving bag-mask ventilation had higher oxygen saturations and a lower incidence of severe hypoxemia than those receiving no ventilation. (Funded by Vanderbilt Institute for Clinical and Translational Research and others; PreVent ClinicalTrials.gov number, NCT03026322.).
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Estado Terminal/terapia , Hipóxia/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Oxigênio/sangue , Respiração Artificial/instrumentação , Adulto , Idoso , Feminino , Humanos , Hipóxia/etiologia , Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Máscaras Laríngeas , Masculino , Pessoa de Meia-IdadeRESUMO
Importance: Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain. Objective: To determine the effect of fluid bolus administration on the incidence of severe hypotension, cardiac arrest, and death. Design, Setting, and Participants: This randomized clinical trial enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation at 11 intensive care units in the US between February 1, 2019, and May 24, 2021. The date of final follow-up was June 21, 2021. Interventions: Patients were randomly assigned to receive either a 500-mL intravenous fluid bolus (n = 538) or no fluid bolus (n = 527). Main Outcomes and Measures: The primary outcome was cardiovascular collapse (defined as new or increased receipt of vasopressors or a systolic blood pressure <65 mm Hg between induction of anesthesia and 2 minutes after tracheal intubation, or cardiac arrest or death between induction of anesthesia and 1 hour after tracheal intubation). The secondary outcome was the incidence of death prior to day 28, which was censored at hospital discharge. Results: Among 1067 patients randomized, 1065 (99.8%) completed the trial and were included in the primary analysis (median age, 62 years [IQR, 51-70 years]; 42.1% were women). Cardiovascular collapse occurred in 113 patients (21.0%) in the fluid bolus group and in 96 patients (18.2%) in the no fluid bolus group (absolute difference, 2.8% [95% CI, -2.2% to 7.7%]; P = .25). New or increased receipt of vasopressors occurred in 20.6% of patients in the fluid bolus group compared with 17.6% of patients in the no fluid bolus group, a systolic blood pressure of less than 65 mm Hg occurred in 3.9% vs 4.2%, respectively, cardiac arrest occurred in 1.7% vs 1.5%, and death occurred in 0.7% vs 0.6%. Death prior to day 28 (censored at hospital discharge) occurred in 218 patients (40.5%) in the fluid bolus group compared with 223 patients (42.3%) in the no fluid bolus group (absolute difference, -1.8% [95% CI, -7.9% to 4.3%]; P = .55). Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse. Trial Registration: ClinicalTrials.gov Identifier: NCT03787732.
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Estado Terminal , Hidratação , Parada Cardíaca , Hipotensão , Intubação Intratraqueal , Choque , Adulto , Idoso , Estado Terminal/terapia , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/mortalidade , Parada Cardíaca/terapia , Humanos , Hipnóticos e Sedativos/uso terapêutico , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Hipotensão/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva , Choque/etiologia , Choque/terapia , Vasoconstritores/uso terapêuticoRESUMO
Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.
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Testes Genéticos/métodos , Programas de Rastreamento/métodos , Fibrose Pulmonar/psicologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/genética , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de TempoRESUMO
Rationale: Although relatives of patients with familial pulmonary fibrosis (FPF) are at an increased risk for interstitial lung disease (ILD), the risk among relatives of sporadic idiopathic pulmonary fibrosis (IPF) is not known.Objectives: To identify the prevalence of interstitial lung abnormalities (ILA) and ILD among relatives of patients with FPF and sporadic IPF.Methods: Undiagnosed first-degree relatives of patients with pulmonary fibrosis (PF) consented to participate in a screening study that included the completion of questionnaires, pulmonary function testing, chest computed tomography, a blood sample collection for immunophenotyping, telomere length assessments, and genetic testing.Measurements and Main Results: Of the 105 relatives in the study, 33 (31%) had ILA, whereas 72 (69%) were either indeterminate or had no ILA. Of the 33 relatives with ILA, 19 (58%) had further evidence for ILD (defined by the combination of imaging findings and pulmonary function testing decrements). There was no evidence in multivariable analyses that the prevalence of either ILA or ILD differed between the 46 relatives with FPF and the 59 relatives with sporadic IPF. Relatives with decrements in either total lung or diffusion capacity had a greater than 9-fold increase in their odds of having ILA (odds ratio, 9.6; 95% confidence interval, 3.1-29.8; P < 0.001).Conclusions: An undiagnosed form of ILD may be present in greater than 1 in 6 older first-degree relatives of patients with PF. First-degree relatives of patients with both familial and sporadic IPF appear to be at similar risk. Our findings suggest that screening for PF in relatives might be warranted.
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Família , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais/epidemiologia , Pulmão/diagnóstico por imagem , Idoso , Feminino , Humanos , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Testes de Função Respiratória , Tomografia Computadorizada por Raios XRESUMO
RATIONALE: Cytomegalovirus (CMV)-related morbidities remain one of the most common complications after lung transplantation and have been linked to allograft dysfunction, but the factors that predict high risk for CMV complications and effective immunity are incompletely understood. OBJECTIVES: To determine if short telomeres in idiopathic pulmonary fibrosis (IPF) lung transplant recipients (LTRs) predict the risk for CMV-specific T-cell immunity and viral control. METHODS: We studied IPF-LTRs (n = 42) and age-matched non-IPF-LTRs (n = 42) and assessed CMV outcomes. We measured lymphocyte telomere length and DNA sequencing, and assessed CMV-specific T-cell immunity in LTRs at high risk for CMV events, using flow cytometry and fluorescence in situ hybridization. MEASUREMENTS AND MAIN RESULTS: We identified a high prevalence of relapsing CMV viremia in IPF-LTRs compared with non-IPF-LTRs (69% vs. 31%; odds ratio, 4.98; 95% confidence interval, 1.95-12.50; P < 0.001). Within this subset, IPF-LTRs who had short telomeres had the highest risk of CMV complications (P < 0.01) including relapsing-viremia episodes, end-organ disease, and CMV resistance to therapy, as well as shorter time to viremia versus age-matched non-IPF control subjects (P < 0.001). The short telomere defect in IPF-LTRs was associated with significantly impaired CMV-specific proliferative responses, T-cell effector functions, and induction of the major type-1 transcription factor T-bet (T-box 21;TBX21). CONCLUSIONS: Because the short telomere defect has been linked to the pathogenesis of IPF in some cases, our data indicate that impaired CMV immunity may be a systemic manifestation of telomere-mediated disease in these patients. Identifying this high-risk subset of LTRs has implications for risk assessment, management, and potential strategies for averting post-transplant CMV morbidities.
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Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/imunologia , Fibrose Pulmonar Idiopática/complicações , Transplante de Pulmão , Telômero/imunologia , Transplantados/estatística & dados numéricos , Adulto , Idoso , Citomegalovirus/imunologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/imunologia , Imunidade , Masculino , Pessoa de Meia-IdadeAssuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Fibrose , Progressão da DoençaRESUMO
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory airway disease punctuated by exacerbations (AECOPD). Subjects with frequent AECOPD, defined by having at least two exacerbations per year, experience accelerated loss of lung function, deterioration in quality of life and increase in mortality. Fibroblast growth factor (FGF)23, a hormone associated with systemic inflammation and altered metabolism is elevated in COPD. However, associations between FGF23 and AECOPD are unknown. In this cross-sectional study, individuals with COPD were enrolled between June 2016 and December 2016. Plasma samples were analyzed for intact FGF23 levels. Logistic regression analyses were used to measure associations between clinical variables, FGF23, and the frequent exacerbator phenotype. Our results showed that FGF23 levels were higher in frequent exacerbators as compared to patients without frequent exacerbations. FGF23 was also independently associated with frequent exacerbations (OR 1.02; 95%CI 1.004-1.04; p = 0.017), after adjusting for age, lung function, smoking, and oxygen use. In summary, FGF23 was associated with the frequent exacerbator phenotype and correlated with number of exacerbations recorded retrospectively and prospectively. Further studies are needed to explore the role of FGF 23 as a possible biomarker for AECOPD to better understand the pathobiology of COPD and to help develop therapeutic targets.
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Progressão da Doença , Fatores de Crescimento de Fibroblastos/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Fenótipo , Projetos PilotoRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with elevated mortality. Delay in diagnosis lead to worse outcomes. Guidelines developed at academic medical centers are difficult to replicate in the community. OBJECTIVES: Our primary objective was to ascertain consistency with the 2011 IPF guidelines. Our secondary objective was to conduct an interdisciplinary review to ascertain whether the evidence supported the original diagnosis of IPF or not. METHODS: We asked permission from pulmonologists to review records of patients diagnosed with IPF after 2011. We collected physician demographics and training data; patient demographics, clinical and diagnostic/management data. The clinical data and available images were reviewed by the interdisciplinary review panel. RESULTS: 26 practicing pulmonologists located in the Southeast of the United States consented to participate. Mean age was 48, 70% were male and all had current certification. We reviewed data from 96 patients. The mean age was 71.4 and most were male. Only 23% had the recommended screening for a connective tissue disease and 42.6% were screened for exercise-induced hypoxemia. Among patients with available images for review (n=66), only 50% had a high-resolution CT scan. 22% of patients underwent a surgical biopsy and in only 33% of the cases three lobes were sampled. No patient had documentation that a multidisciplinary discussion occurred. In 20% of the cases with available images, the evidence supported an alternative diagnosis. 56% of eligible candidates were ever started on anti-fibrotics. CONCLUSIONS: Our findings suggest that consistency with the IPF guidelines is low in non-academic settings.
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INTRODUCTION: Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation. METHODS AND ANALYSIS: The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021. ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03928925).
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Estado Terminal , Intubação Intratraqueal , Adulto , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , TraqueiaRESUMO
Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrotic disease characterized by a progressive decline in lung function with a median survival of 3-5 years after diagnosis. The course of disease is highly variable and unpredictable, often punctuated by episodes of acute respiratory failure, known as acute exacerbations. The incidence of IPF is on the rise due to the aging population, as age is the most important risk factor for this disease. Pirfenidone and nintedanib are the two anti-fibrotic drugs approved for IPF which have shown reduction in lung function decline. This review will discuss the efficacy, safety and tolerability profile of pirfenidone from clinical trials and the real-world clinical experience. Pirfenidone reduces the decline in lung function and improves progression-free survival in patients with IPF. It is generally well tolerated with the most common side effects being gastrointestinal and phototoxicity.
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BACKGROUND: Pulmonary artery (PA) enlargement, defined as pulmonary artery to ascending aorta diameter ratio (PA:A)>1 on computed tomography (CT), is a marker of pulmonary vascular disease in chronic lung diseases. PA enlargement is prevalent in cystic fibrosis (CF), but its relationship to hemodynamics and prognostic utility in severe CF are unknown. We hypothesized that the PA:A would have utility in identifying pulmonary hypertension (PH) in severe CF and that PA enlargement would be associated with reduced transplant-free survival. METHODS: We conducted a retrospective study of adults with CF undergoing lung transplant evaluation at a single center between 2000 and 2015. CT, right heart catheterization (RHC), and clinical data were collected. The PA:A was measured from a single CT slice. We measured associations between PA:A and invasive hemodynamic parameters including PH defined as a mPAP ≥25mmHg using adjusted linear and logistic regression models. Kaplan-Meier and adjusted Cox regression models were used to measure associations between PA:A>1, RHC-defined PH, and transplant-free survival in severe CF. RESULTS: We analyzed 78 adults with CF that had CT scans available for review, including 44 that also had RHC. RHC-defined PH defined as a mPAP ≥25mmHg was present in 36% of patients with CF undergoing transplant evaluation. The PA:A correlated with mPAP (r = 0.73; 95% CI 3.87-7.80; p<0.001) and PVR (r = 0.42, p = 0.005) and the PA:A>1 was an independent predictor of PH (aOR 4.50; 95% CI 1.05-19.2; p = 0.042). PA:A>1 was independently associated with increased hazards for death or transplant (aHR 2.69; 95% CI 1.41-5.14; P = 0.003). The presence of mPAP ≥25mmHg was independently associated with decreased survival in this cohort. CONCLUSIONS: PA enlargement is associated with pulmonary hemodynamics and PH in severe CF. PA enlargement is an independent prognostic indicator of PH and decreased survival in this population.
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Fibrose Cística/complicações , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/patologia , Artéria Pulmonar/patologia , Adulto , Estudos de Coortes , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Artéria Pulmonar/fisiopatologiaRESUMO
Idiopathic pulmonary fibrosis (IPF) is one of many clinical syndromes that are associated with aging, and is increasing in both incidence and prevalence with the rapid rise in aging populations world-wide. There is accumulating data on how the biology of aging may influence the susceptibility to lung fibrosis in the elderly. In this review, we explore some of the known "hallmarks of aging," including telomere attrition, genomic instability, epigenetic alterations, loss of proteostasis, cellular senescence and mitochondrial dysfunction in the pathobiology of IPF. Additionally, we discuss age-associated alterations in extracellular matrix that may contribute to the development and/or progression of IPF.
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Envelhecimento/fisiologia , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/fisiopatologia , Humanos , Fibrose Pulmonar Idiopática/genéticaRESUMO
BACKGROUND: Tracheal intubation is common in the care of critically ill adults and is frequently complicated by hypotension, cardiac arrest, or death. We aimed to evaluate administration of an intravenous fluid bolus to prevent cardiovascular collapse during intubation of critically ill adults. METHODS: We did a pragmatic, multicentre, unblinded, randomised trial in nine sites (eight ICUs and one emergency department) around the USA. Critically ill adults (≥18 years) undergoing tracheal intubation were randomly assigned (1:1, block sizes of 2, 4, and 6, stratified by study site) to either an intravenous infusion of 500 mL of crystalloid solution or no fluid bolus. The primary outcome, assessed in the intention-to-treat population, was cardiovascular collapse, defined as a new systolic blood pressure <65 mm Hg; new or increased vasopressor receipt between induction and 2 min after tracheal intubation; or cardiac arrest or death within 1 h of tracheal intubation. Adverse events were assessed in the as-treated population. This trial, which is now complete, is registered with ClinicalTrials.gov, number NCT03026777. FINDINGS: Patients were enrolled from Feb 6, 2017, to Jan 9, 2018, when the data and safety monitoring board stopped the trial on the basis of futility. By trial termination, 337 (63%) of 537 screened adults had been randomly assigned. Cardiovascular collapse occurred in 33 (20%) of 168 patients in the fluid bolus group compared with 31 (18%) of 169 patients in the no fluid bolus group (absolute difference 1·3% [95% CI -7·1% to 9·7%]; p=0·76). The individual components of the cardiovascular collapse composite outcome did not differ between groups (new systolic blood pressure <65 mm Hg 11 [7%] in the bolus group vs ten [6%] in the no-bolus group, new or increased vasopressor 32 [19%] vs 31 [18%], cardiac arrest within 1 h seven [4%] vs two [1%], death within 1 h of intubation two [1%] vs one [1%]). In-hospital mortality was not significantly different in the fluid bolus group (48 [29%]) compared with no fluid bolus (59 [35%]). INTERPRETATION: Administration of an intravenous fluid bolus did not decrease the overall incidence of cardiovascular collapse during tracheal intubation of critically ill adults compared with no fluid bolus in this trial. FUNDING: US National Institutes of Health.
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Soluções Cristaloides/administração & dosagem , Hidratação , Intubação Intratraqueal , Choque/prevenção & controle , Idoso , Estado Terminal , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Choque/epidemiologia , Vasoconstritores/uso terapêuticoRESUMO
Background: Systemic corticosteroids (SC) are an integral part of managing acute exacerbations of COPD (AECOPD). However, the optimal dose and duration vary widely in clinical practice. We hypothesized that the use of a "PowerPlan" order set in the electronic health system (EHS) that includes a 5-day SC order would be associated with a reduced steroid dose and length of stay (LOS) for individuals hospitalized with AECOPD. Patients and methods: We conducted a retrospective cohort study of Medicare recipients discharged with an AECOPD diagnosis from our University Hospital from 2014 to 2016. Our EHS-based "COPD PowerPlan" order set included admission, laboratory, pharmacy, and radiology orders for managing AECOPD. The default SC option included intravenous methyl-prednisolone for 24 hours followed by oral prednisone for 4 days. The primary endpoint was the difference in cumulative steroid dose between the PowerPlan and the usual care group. Secondary endpoints included hospital LOS and readmission rates. Results: The 250 patients included for analysis were 62±11 years old, 58% male, with an FEV1 55.1%±23.6% predicted. The PowerPlan was used in 72 (29%) patients. Cumulative steroid use was decreased by 31% in the PowerPlan group (420±224 vs 611±462 mg, P<0.001) when compared with usual care. PowerPlan use was independently associated with decreased LOS (3 days; IQR 2-4 days vs 4 days; IQR 3-6 days, P=0.022) without affecting 30- and 90-day readmission rates. Conclusion: Use of a standardized EHS-based order set to manage AECOPD was associated with a reduction in steroid dose and hospital LOS.
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Progressão da Doença , Registros Eletrônicos de Saúde/normas , Glucocorticoides/administração & dosagem , Tempo de Internação/estatística & dados numéricos , Metilprednisolona/administração & dosagem , Prednisona/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Esteroides/administração & dosagem , Idoso , Feminino , Hospitalização , Humanos , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados UnidosRESUMO
INTRODUCTION: Hypoxaemia is the most common complication during endotracheal intubation of critically ill adults, and it increases the risk of cardiac arrest and death. Manual ventilation between induction and intubation has been hypothesised to decrease the incidence of hypoxaemia, but efficacy and safety data are lacking. METHODS AND ANALYSIS: The Preventing Hypoxemia with Manual Ventilation during Endotracheal Intubation trial is a prospective, multicentre, non-blinded randomised clinical trial being conducted in seven intensive care units in the USA. A total of 400 critically ill adults undergoing endotracheal intubation will be randomised 1:1 to receive prophylactic manual ventilation between induction and endotracheal intubation using a bag-valve-mask device or no prophylactic ventilation. The primary outcome is the lowest arterial oxygen saturation between induction and 2 min after successful endotracheal intubation, which will be analysed as an unadjusted, intention-to-treat comparison of patients randomised to prophylactic ventilation versus patients randomised to no prophylactic ventilation. The secondary outcome is the incidence of severe hypoxaemia, defined as any arterial oxygen saturation of less than 80% between induction and 2 min after endotracheal intubation. Enrolment began on 2 February 2017 and is expected to be complete in May 2018. ETHICS AND DISSEMINATION: The trial was approved by the institutional review boards or designees of all participating centres. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: NCT03026322; Pre-results.
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Estado Terminal/terapia , Hipóxia/prevenção & controle , Intubação Intratraqueal/métodos , Respiração Artificial/métodos , Adulto , Protocolos Clínicos , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Masculino , Resultado do TratamentoRESUMO
We present the case of a twenty two year old Caucasian male with ulcerative colitis on mesalamine who presented with dry cough, fever, malaise and dyspnea on exertion. He had peripheral eosinophilia and apical ground-glass opacities on computed tomography of the chest. He had no new exposures and his infectious workup was non diagnostic. Bronchoalveolar lavage showed eosinophilia raising the suspicion of mesalamine induced eosinophilic pneumonia. His symptoms improved after discontinuing mesalamine with a tapered dose of steroids.
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Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with an accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A 'frequent exacerbator' is a sub-phenotype of chronic obstructive pulmonary disease (COPD) and is defined as an individual who experiences two or more moderate-to-severe exacerbations per year. This distinct subgroup has higher mortality and accounts for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for using combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: (1) maximizing bronchodilation; (2) reducing inflammation; and (3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies including combination long-acting muscarinic agents plus long-acting beta agonists show promising results compared with monotherapy or a long-acting beta agonist inhaled corticosteroid combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase-4 inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on the identification of various subtypes or 'endotypes' and targeting therapies based on their pathophysiology. This review describes the impact of AECOPD and the challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these individuals.
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Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Doença Pulmonar Obstrutiva Crônica/patologiaRESUMO
Lung cancer accounts for almost one-third of all cancer related deaths. Lung cancer risk persists even after smoking cessation and so many lung cancers now are diagnosed in former smokers. Five-year survival of lung cancer has marginally improved over decades and significantly lags behind that of colon, breast and prostate cancer. Over the past one decade, lung cancer screening trials have shown promising results. Results from National Lung Cancer Screening Trial (NLST), have shown a significant 20% reduction in mortality with annual low dose computed tomography (LDCT) screening. Based on these results, annual LDCT testing has been recommended for lung cancer screening in high risk population. However, development and acceptance of lung cancer screening as a public health policy is still in the nascent stages. Major concerns relate to risk of radiation, overdiagnosis bias, proportion of false positives and cost benefit analysis. This article reviews the literature pertaining to lung cancer screening guidelines and above mentioned concerns.