A Novel Method for Assessing the Effect of Case-Mix and Model Calibration on the Receiver Operating Characteristic (ROC) Plot, With a Case Study in Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 52 ◽  
pp. 114
Author(s):  
M. Sadatsafavi ◽  
P. Saha-Chaudhuri ◽  
J. Petkau
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Receiver Operating Characteristic ◽  
Pulmonary Disease ◽  
Model Calibration ◽  
Operating Characteristic ◽  
Case Mix ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Novel Method

scholarly journals Identification of lipid biomarker from serum in patients with chronic obstructive pulmonary disease

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ding Liu ◽  
Maureen Meister ◽  
Shiying Zhang ◽  
Chi-In Vong ◽  
Shuaishuai Wang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Receiver Operating Characteristic ◽  
Pulmonary Disease ◽  
Operating Characteristic ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Lipid Ratios ◽  
Lipid Species ◽  
Potential Biomarkers ◽  
Receiver Operating

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment. The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status. Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD. Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD. Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems. It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism. Methods In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group). After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species. Later, the comparisons of individual lipids were performed between controls and patients with COPD. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers. Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated. Results Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD. Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change. In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers. Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity. Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years. Conclusion Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD. Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD.

scholarly journals Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 502
Author(s):  
Sara Carpi ◽  
Beatrice Polini ◽  
Dario Nieri ◽  
Nevio Dubbini ◽  
Alessandro Celi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Receiver Operating Characteristic ◽  
Pulmonary Disease ◽  
Extracellular Vesicles ◽  
Operating Characteristic ◽  
Expression Profiles ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Group B

MicroRNAs (miRNAs) are a class of short non-coding RNAs involved in the regulation of gene expression and the control of several cellular processes at physiological and pathological levels. Furthermore, extracellular vesicles (EV), which are small membrane-bound vesicles secreted by cells in the extracellular environment, contain functional miRNAs. The remarkable deregulation of many miRNAs has been demonstrated in respiratory diseases. Among them, miR-206, miR-133a-5p, and miR-133a-3p are striated muscle-specific miRNAs (myo-miRNA), related to skeletal muscle dysfunction, one of the commonest systemic manifestations in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, their circulating expression in COPD patients is not demonstrated. For these reasons, we performed a pilot study to analyze the expression profiles of myo-miRNAs in plasma-derived EV from patients with COPD. We analyzed the expression profiles of selected myo-miRNAs in plasma-derived EV from COPD. Receiver operating characteristic analyses were carried out to evaluate whether selected plasma miRNAs were able to discriminate between different groups of COPD patients. We found EV-embedded myo-miRNAs in the bloodstream of COPD patients. Specifically, miR-206, miR-133a-5p and miR-133a-3p were significantly upregulated in group B patients. Receiver operating characteristic analyses of the combination of these selected miRNAs showed their high capacity to discriminate group B from other COPD patients. Our data provide evidence that myo-miRNA are present in EV in the plasma of COPD patients and their expression (miR-206, miR-133a-5p, and miR-133a-3p) can discriminate group B from group C patients. The future analysis of a larger number of patients should allow us to obtain more refined correlations.

PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease

2018 ◽  
Vol 71 (11) ◽  
pp. 963-970
Author(s):  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
Dunja Rogić ◽  
Ivana Rako ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Operating Characteristic ◽  
Fragment Length Polymorphism ◽  
Characteristic Curve ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Pon1 Gene

AimsChronic obstructive pulmonary disease (COPD) is characterised with oxidative stress. Paraoxonase 1 (PON1) is an enzyme, coded by PON1 gene, with distinctive antiatherogenic and antioxidative roles. We aimed to investigate the frequencies of Q192R, L55M and −108C>T polymorphisms and association of those polymorphisms with paraoxonase and arylesterase activities in patients with COPD.MethodsPON1 genotype was determined by PCR–restriction fragment length polymorphism method. PON1 activity was measured by paraoxon and phenylacetate.ResultsOnly −108C>T polymorphism resulted in significantly different distribution of genotypes and alleles, with higher frequency of TT genotype and T allele in patients compared with control subjects. Moreover, T allele (OR 2.29 (95% CI 1.54 to 3.41); p<0.001) as well as TT genotype (OR 5.00 (95% CI 2.19 to 11.43); p<0.001) showed an association with the disease. −108C>T polymorphism was suggested as a significant diagnostic predictor for the disease (OR (95% CI) 2.65 (1.53 to 4.59), p=0.001), with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84 to 0.93) and with 83.90% of correctly classified cases.ConclusionsHigher frequency of TT genotype and T allele could contribute to the observed reduction of PON1 activity in patients with COPD. T allele and TT genotype are associated with COPD, and the PON1−108C>T polymorphism could be a potential predictor of the disease.

scholarly journals How to Address Uncertainty in Health Economic Discrete-Event Simulation Models: An Illustration for Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 40 (5) ◽  
pp. 619-632
Author(s):  
Isaac Corro Ramos ◽  
Martine Hoogendoorn ◽  
Maureen P. M. H. Rutten-van Mölken
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Economic ◽  
Pulmonary Disease ◽  
Discrete Event Simulation ◽  
Discrete Event ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Modeling Uncertainty ◽  
Event Simulation

Background. Evaluation of personalized treatment options requires health economic models that include multiple patient characteristics. Patient-level discrete-event simulation (DES) models are deemed appropriate because of their ability to simulate a variety of characteristics and treatment pathways. However, DES models are scarce in the literature, and details about their methods are often missing. Methods. We describe 4 challenges associated with modeling heterogeneity and structural, stochastic, and parameter uncertainty that can be encountered during the development of DES models. We explain why these are important and how to correctly implement them. To illustrate the impact of the modeling choices discussed, we use (results of) a model for chronic obstructive pulmonary disease (COPD) as a case study. Results. The results from the case study showed that, under a correct implementation of the uncertainty in the model, a hypothetical intervention can be deemed as cost-effective. The consequences of incorrect modeling uncertainty included an increase in the incremental cost-effectiveness ratio ranging from 50% to almost a factor of 14, an extended life expectancy of approximately 1.4 years, and an enormously increased uncertainty around the model outcomes. Thus, modeling uncertainty incorrectly can have substantial implications for decision making. Conclusions. This article provides guidance on the implementation of uncertainty in DES models and improves the transparency of reporting uncertainty methods. The COPD case study illustrates the issues described in the article and helps understanding them better. The model R code shows how the uncertainty was implemented. For readers not familiar with R, the model’s pseudo-code can be used to understand how the model works. By doing this, we can help other developers, who are likely to face similar challenges to those described here.

scholarly journals Diaphragm Ultrasound Distinguishes Exacerbation From Stable Status in Chronic Obstructive Pulmonary Disease

2021 ◽  
Author(s):  
Tai Joon An ◽  
Yeun Jie Yoo ◽  
Jeong Uk Lim ◽  
Wan Seo ◽  
Chan Kwon Park ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Operating Characteristic ◽  
Forced Expiratory Volume ◽  
Diaphragm Muscle ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
The Status

Abstract Background: The importance of evaluating the diaphragm muscle in chronic obstructive pulmonary disease (COPD) is widely accepted. However, the role of diaphragm ultrasound (DUS) in COPD is not fully understood. We set this study to evaluate the role of DUS for distinguishing the status of COPD. Methods: COPD patients who underwent DUS were enrolled between March 2020 and November 2020. The diaphragm thickening fraction (TFmax) and diaphragm excursion (DEmax) during maximal deep breathing were measured. Patients were divided into exacerbation and stable groups. Demographics, lung function, and DUS findings were compared between the two groups. Receiver operating characteristic (ROC) curve and univariate/multivariate logistic regression analyses were performed.Results: Fifty-five patients were enrolled. The exacerbation group had a lower body mass index (BMI) (20.9 vs. 24.2, p = 0.003), lower TFmax (94.8 ± 8.2% vs. 158.4 ± 83.5%, p = 0.010), and lower DEmax (30.8 ± 11.1 mm vs. 40.5 ± 12.5 mm, p = 0.007) compared to stable group. The areas under the TFmax (0.745) and DEmax (0.721) curves indicated fair results for distinguishing exacerbation. The patients were divided into low and high TFmax and DEmax groups based on calculated cut-off values. Low TFmax (odds ratio [OR] 8.40; 95% confidence interval [CI] 1.55–45.56) and low DEmax (OR 11.51; 95% CI 1.15–115.56) were associated with exacerbation after adjusting for age, sex, BMI, forced vital capacity and forced expiratory volume in 1 sec.Conclusion: TFmax and DEmax distinguished exacerbation from stable status. We describe the DUS cut-off values for determining an exacerbation status in this study.

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