11 research outputs found
Advancing the science of patient safety and quality improvement to the next level
This paper describes our journey to advance the science and practice of patient safety and quality improvement. The journey began with efforts to identify hazards through an incident reporting system called the Intensive Care Unit Safety Reporting System. We quickly found that identifying hazards was merely a first step. We also needed to investigate and learn from these hazards to prevent patient harm. Therefore, we developed the Comprehensive Unit-based Safety Program (CUSP) to identify and learn from local defects and improve teamwork and safety culture. Teams across many units faced common problems, such as healthcare-acquired infections, for which there is empiric evidence on prevention practices, but the evidence is unreliably applied. This discovery led us to develop a model to translate research into practice (TRIP). We combined TRIP with CUSP for the Keystone ICU Project design, with the goal of improving care for adult patients in Michigan intensive care units (ICUs). The resulting dramatic and sustained reductions in central line-associated bloodstream infections (CLABSIs) in Michigan led to a national initiative to reduce CLABSIs across the United States. Applying the perspectives from different academic disciplines helped us learn how this national effort succeeded, an approach we also used to study cardiac surgery-related errors. Still, the CLABSI effort addressed one type of harm, while patients are at risk for over a dozen and care systems relying more on the heroism of clinicians than on safe design. Current efforts include building a quality management infrastructure to support improvement work and defining the skills, resources, and accountability needed at every level of a health system. We are also partnering with patients, their loved ones, and others to eliminate all harms, optimize patient experience and outcomes, and reduce waste. In this trans-disciplinary systems approach, we hope to reduce all harms, improve productivity, and enhance joy for clinicians
Local GM-CSF–Dependent Differentiation and Activation of Pulmonary Dendritic Cells and Macrophages Protect against Progressive Cryptococcal Lung Infection in Mice
Reducing Elementary School Children's Risks for Chronic Diseases through School Lunch Modifications, Nutrition Education, and Physical Activity Interventions
Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.
BackgroundForced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD.ObjectiveTo determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD.Study design and methodsThe SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease.ResultsLower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC).InterpretationThe %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD
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Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease.
Rationale: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives: Examine the impact of depressive symptoms compared with FEV1% on COPD morbidity. Methods: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV1% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. Results: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV1% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV1% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV1%, explaining 30-67% of heterogeneity. FEV1% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16-32% of heterogeneity. Depressive symptoms accounted for 3-17% variance in change over time in PROs. In contrast, FEV1% accounted for 1-4% variance over time in PROs. Conclusions: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes
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The Effects of Rare SERPINA1 Variants on Lung Function and Emphysema in SPIROMICS
Rationale: The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, SERPINA1 (serpin peptidase inhibitor, clade A, member 1), in determining chronic obstructive pulmonary disease risk and severity is controversial.Objectives: To comprehensively evaluate the effects of rare SERPINA1 variants on lung function and emphysema phenotypes in subjects with significant tobacco smoke exposure using deep gene resequencing and alpha-1 antitrypsin concentrations.Methods: DNA samples from 1,693 non-Hispanic white individuals, 385 African Americans, and 90 Hispanics with ≥20 pack-years smoking were resequenced for the identification of rare variants (allele frequency < 0.05) in 16.9 kB of SERPINA1.Measurements and Main Results: White PI Z heterozygotes confirmed by sequencing (MZ; n = 74) had lower post-bronchodilator FEV1 (P = 0.007), FEV1/FVC (P = 0.003), and greater computed tomography-based emphysema (P = 0.02) compared with 1,411 white individuals without PI Z, S, or additional rare variants denoted as VR. PI Z-containing compound heterozygotes (ZS/ZVR; n = 7) had lower FEV1/FVC (P = 0.02) and forced expiratory flow, midexpiratory phase (P = 0.009). Nineteen white heterozygotes for five non-S/Z coding variants associated with lower alpha-1 antitrypsin had greater computed tomography-based emphysema compared with those without rare variants. In African Americans, a 5' untranslated region insertion (rs568223361) was associated with lower alpha-1 antitrypsin and functional small airway disease (P = 0.007).Conclusions: In this integrative deep sequencing study of SERPINA1 with alpha-1 antitrypsin concentrations in a heavy smoker and chronic obstructive pulmonary disease cohort, we confirmed the effects of PI Z heterozygote and compound heterozygote genotypes. We demonstrate the cumulative effects of multiple SERPINA1 variants on alpha-1 antitrypsin deficiency, lung function, and emphysema, thus significantly increasing the frequency of SERPINA1 variation associated with respiratory disease in at-risk smokers
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Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD
BackgroundBronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Research questionIs consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?Study design and methodsWe retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEV1 (FEV1-BDR), change in FVC (FVC-BDR), and change in in FEV1, FVC or both (ATS-BDR). Using generalized linear models adjusted for demographics, smoking history, FEV1 % predicted after bronchodilator administration, and number of visits that the participant completed, we assessed the association of BDR group: (1) consistent BDR, (2) inconsistent BDR, and (3) never BDR with asthma, CT scan features, blood eosinophil levels, and FEV1 decline in participants without COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) and the entire cohort (participants with or without COPD).ResultsBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEV1-BDR and FVC-BDR definitions. Eosinophils did not vary consistently among BDR groups. Consistent BDR was associated with FEV1 decline over time relative to never BDR in the entire cohort. In participants with GOLD stage 0 disease, both the inconsistent ATS-BDR group (OR, 3.20; 95% CI, 2.21-4.66; P < .001) and consistent ATS-BDR group (OR, 9.48; 95% CI, 3.77-29.12; P < .001) were associated with progression to COPD relative to the never ATS-BDR group.InterpretationDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease
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Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in COPD
BackgroundImproved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets.Research questionWhich physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations?Study design and methodsWe applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations.ResultsSputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations.InterpretationBiomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations.Trial registryClinicalTrials.gov; No.: NCT01969344; URL: www.Clinicaltrialsgov