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Khosrow Adeli - One of the best experts on this subject based on the ideXlab platform.
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Caliper hematology reference standards ii
American Journal of Clinical Pathology, 2020Co-Authors: Victoria Higgins, Houman Tahmasebi, Mary Kathryn Bohn, Alexandra Hall, Khosrow AdeliAbstract:OBJECTIVES Accurate hematologic test interpretation based on normative reference standards is critical to ensure appropriate clinical decision making. However, healthy pediatric reference data for most hematology parameters are lacking. To address this gap, this study establishes age- and sex-specific hematologic reference standards in the Canadian Laboratory Initiative on Pediatric Reference Intervals (Caliper) cohort of healthy children and adolescents. METHODS Fresh whole blood samples collected from a total of 566 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 47 hematologic parameters on the Beckman Coulter DxH 900. Age- and sex-specific reference standards were calculated based on the Clinical and Laboratory Standards Institute guidelines. RESULTS Reference value distributions for most hematology parameters demonstrated dynamic changes across the pediatric age range with significant age-specific differences observed for 39 of the 47 parameters examined. Sex-specific differences were also observed for eight hematologic parameters, primarily during and after puberty. CONCLUSIONS This study establishes a robust database of pediatric reference standards for 47 hematologic parameters in the Caliper cohort for the first time. These comprehensive reference value data sets report potentially important and physiologically relevant trends in hematologic markers, clearly demonstrating the need for pediatric reference standards for hematologic test interpretation.
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the canadian laboratory initiative on pediatric reference intervals a Caliper white paper
Critical Reviews in Clinical Laboratory Sciences, 2017Co-Authors: Khosrow Adeli, Victoria Higgins, Karin E Trajcevski, Nicole Whiteal HabeebAbstract:Laboratory investigations provide physicians with objective data to aid in disease diagnosis, clinical decision making, and patient follow up. Clinical interpretation of laboratory test results relies heavily on the availability of appropriate population-based reference intervals (i.e. normative values) or decision limits developed through clinical outcome studies. Although reference intervals are fundamental to accurate laboratory test interpretation, and thus critically important to healthcare, the need for sound evidence-based reference intervals has been largely overlooked, particularly in the pediatric population. In the field of pediatric laboratory medicine, accurate age- and sex-specific reference intervals established using samples from healthy children and adolescents have not been readily available, forcing many clinical laboratories to report adult reference intervals with pediatric test results. When pediatric reference intervals are available, they have often been established with a small sample size, inpatient or outpatient samples, outdated methodologies, and/or inappropriate statistical procedures. To address these unacceptable limitations, several national and global initiatives have begun to close the critical evidence gaps in pediatric reference intervals. Notably, the Canadian Laboratory Initiative on Pediatric Reference Intervals (Caliper) has made significant strides towards improving pediatric healthcare in Canada and globally. The present report is a white paper summarizing Caliper, and provides a comprehensive compendium of the data generated through this project over the past decade as a single resource for clinical laboratory specialists, clinicians, and other healthcare workers. Caliper launched an outreach campaign in 2008 to recruit healthy community children and adolescents, and developed a robust statistical algorithm, in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines, to develop accurate age- and sex-specific pediatric reference intervals. The first Caliper direct reference interval study was published in 2012, with age- and sex-specific reference intervals reported for 40 common biochemical markers. To date, Caliper has collected health information and blood samples from over 9700 community children and adolescents, and has established a comprehensive database of age- and sex-specific reference intervals for over 100 biomarkers of pediatric disease. Caliper has also performed a series of transference and verification studies to expand the applicability of the Caliper database to five major analytical platforms, including Abbott, Beckman, Ortho, Roche, and Siemens. Through novel knowledge translation initiatives, the Caliper Reference Interval Database has been made freely available online ( www.Caliperproject.ca ) as well as on a mobile application (Caliper Reference App), and it is used by clinical laboratories across Canada, the United States, and globally. In addition to establishing this comprehensive pediatric reference interval database, Caliper has also performed a series of sub-studies, including examining how reference intervals are affected by pre-analytical factors (i.e. sample stability at specific storage conditions, fasting status and time of sample collection), biological variation (i.e. intraindividual and interindividual biological variation, reference change values), and ethnicity and pubertal development stage. In this white paper, extensive tables of pediatric reference intervals are provided for easy reference for clinical laboratories worldwide. All data reported have been published in over 20 peer reviewed publications and are also available through the Caliper Reference Interval Database as well as the Caliper Reference App for mobile devices.
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Transference of Caliper pediatric reference intervals to biochemical assays on the Roche cobas 6000 and the Roche Modular P
Clinical Biochemistry, 2016Co-Authors: Victoria Higgins, Man Khun Chan, Michelle Nieuwesteeg, Barry R. Hoffman, Irvin L. Bromberg, Doug Gornall, Edward Randell, Khosrow AdeliAbstract:Objectives: The Canadian Laboratory Initiative on Pediatric Reference Intervals (Caliper) has recently established pediatric age- and sex-specific reference intervals for over 85 biochemical markers on the Abbott Architect system. Previously, Caliper reference intervals for several biochemical markers were successfully transferred from Abbott assays to Roche, Beckman, Ortho, and Siemens assays. This study further broadens the Caliper database by performing transference and verification for 52 biochemical assays on the Roche cobas 6000 and the Roche Modular P. Design and methods: Using CLSI C28-A3 and EP9-A2 guidelines, transference of the Caliper reference intervals was attempted for 16 assays on the Roche cobas 6000 and 36 on the Modular P. Calculated reference intervals were further verified using 100 healthy Caliper samples. Results: Most assays showed strong correlation between assay systems and were transferable from Abbott to the Roche cobas 6000 (81%) and the Modular P (86%). Bicarbonate and magnesium were not transferable on either system and calcium and prealbumin were not transferable to the Modular P. Of the transferable analytes, 62% and 61% were verified on the cobas 6000 and the Modular P, respectively. Conclusions: This study extends the utility of the Caliper database to two additional analytical systems, which facilitates the broad application of Caliper reference intervals at pediatric centers utilizing Roche biochemical assays. Transference studies across different analytical platforms can later be collectively analyzed in an attempt to develop common reference intervals across all clinical chemistry instruments to harmonize laboratory test interpretation in diagnosis and monitoring of pediatric disease.
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clsi based transference of Caliper pediatric reference intervals to beckman coulter au biochemical assays
Clinical Biochemistry, 2015Co-Authors: Mohamed Abou El Hassan, Man Khun Chan, Michelle Nieuwesteeg, Edward Randell, Alexandra Stoianov, Petra A T Araujo, Tara Sadeghieh, Yunqi Chen, Khosrow AdeliAbstract:Abstract Objective The Caliper program has established a comprehensive database of pediatric reference intervals using largely the Abbott ARCHITECT biochemical assays. To expand clinical application of Caliper reference standards, the present study is aimed at transferring Caliper reference intervals from the Abbott ARCHITECT to Beckman Coulter AU assays. Design and methods Transference of Caliper reference intervals was performed based on the CLSI guidelines C28-A3 and EP9-A2. The new reference intervals were directly verified using up to 100 reference samples from the healthy Caliper cohort. Results We found a strong correlation between Abbott ARCHITECT and Beckman Coulter AU biochemical assays, allowing the transference of the vast majority (94%; 30 out of 32 assays) of Caliper reference intervals previously established using Abbott assays. Transferred reference intervals were, in general, similar to previously published Caliper reference intervals, with some exceptions. Most of the transferred reference intervals were sex-specific and were verified using healthy reference samples from the Caliper biobank based on CLSI criteria. It is important to note that the comparisons performed between the Abbott and Beckman Coulter assays make no assumptions as to assay accuracy or which system is more correct/accurate. Conclusion The majority of Caliper reference intervals were transferrable to Beckman Coulter AU assays, allowing the establishment of a new database of pediatric reference intervals. This further expands the utility of the Caliper database to clinical laboratories using the AU assays; however, each laboratory should validate these intervals for their analytical platform and local population as recommended by the CLSI.
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clsi based transference of the Caliper database of pediatric reference intervals to beckman coulter dxc biochemical assays
Clinical Biochemistry, 2015Co-Authors: Petra A T Araujo, Man Khun Chan, Edward Randell, Tara Sadeghieh, Yunqi Chen, Dylan Thomas, Victoria Bevilacqua, Khosrow AdeliAbstract:Abstract Background The Caliper program has established a comprehensive database of age- and sex-stratified pediatric reference intervals for over 85 common biochemical markers, largely using the Abbott ARCHITECT assays. To allow a broader application of the Caliper database, we examined transference to 36 Beckman Coulter Synchron Unicel DxC800 assays, based on the CLSI C28-A3/EP9-A3 guidelines. Methods Patient sample comparisons were performed for 36 biochemical assays using 200 serum specimens obtained from pediatric patients on the Abbott ARCHITECT ci8200 and the Beckman Coulter DxC800. For each analyte, R 2 values were calculated to assess the quality of correlation between the platforms. Statistical criteria used to assess transferability included a) regression analysis to create the equation of the line of best fit, b) standardized residual, c) Bland–Altman, and d) quantile–quantile plots. Transferred reference intervals were further verified by analyzing serum samples from 100 healthy children from the Caliper cohort on the Beckman Coulter system. Results The reference intervals for most of the assessed analytes were transferable to Beckman Coulter assays (31 out of 36 studied) and the newly calculated reference intervals were verified through analysis of Caliper reference samples (28 out of 31). Eighteen assays demonstrated excellent correlation (R 2 ≥ 0.95), and 13 assays showed strong correlation (0.77 ≤ R2 ≤ 0.94). Conclusion The current study allowed successful transference of a large number of biochemical markers from the Caliper database to assays on the Beckman Coulter DxC800 platform. Transference should facilitate broader application of Caliper reference intervals at pediatric centers using DxC biochemical assays.
Ronald A Karwoski - One of the best experts on this subject based on the ideXlab platform.
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stratification of long term outcome in stable idiopathic pulmonary fibrosis by combining longitudinal computed tomography and forced vital capacity
European Radiology, 2020Co-Authors: Nicola Sverzellati, Mario Silva, Valeria Seletti, Carlotta Galeone, Stefano Palmucci, Sara Piciucchi, Carlo Vancheri, Venerino Poletti, Sara Tomassetti, Ronald A KarwoskiAbstract:To test HRCT with either visual or quantitative analysis in both short-term and long-term follow-up of stable IPF against long-term (transplant-free) survival, beyond 2 years of disease stability. Fifty-eight IPF patients had FVC measurements and HRCTs at baseline (HRCT0), 10–14 months (HRCT1) and 22–26 months (HRCT2). Visual scoring, Caliper quantitative analysis of HRCT measures, and their deltas were evaluated against combined all-cause mortality and lung transplantation by adjusted Cox proportional hazard models at each time interval. At HRCT1, a ≥ 20% relative increase in Caliper-total lung fibrosis yielded the highest radiological association with outcome (C-statistic 0.62). Moreover, the model combining FVC% drop ≥ 10% and ≥ 20% relative increase of Caliper-total lung fibrosis improved the stratification of outcome (C-statistic 0.69, high-risk category HR 12.1; landmark analysis at HRCT1 C-statistic 0.66, HR 14.9 and at HRCT2 C-statistic 0.61, HR 21.8). Likewise, at HRCT2, the model combining FVC% decrease trend and ≥ 20% relative increase of Caliper-pulmonary vessel–related volume (VRS) improved the stratification of outcome (C-statistic 0.65, HR 11.0; landmark analysis at HRCT1 C-statistic 0.62, HR 13.8 and at HRCT2 C-statistic 0.58, HR 12.6). A less robust stratification of outcome distinction was also demonstrated with the categorical visual scoring of disease change. Annual combined Caliper -FVC changes showed the greatest stratification of long-term outcome in stable IPF patients, beyond 2 years. • Longitudinal high-resolution computed tomography (HRCT) data is more helpful than baseline HRCT alone for stratification of long-term outcome in IPF. • HRCT changes by visual or quantitative analysis can be added with benefit to the current spirometric reference standard to improve stratification of long-term outcome in IPF. • HRCT follow-up at 12–14 months is more helpful than HRCT follow-up at 23–26 months in clinically stable subjects with IPF.
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evaluation of visual and computer based ct analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis
Respirology, 2017Co-Authors: Joseph Jacob, David M Hansell, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Vasileios Kouranos, Athol U WellsAbstract:Background and objective To determine whether computer-based quantification (Caliper software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). Methods A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and Caliper. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. Results Caliper-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (Caliper R = 0.73, visual R = 0.51); DLCO (Caliper R = 0.61, visual R = 0.48); and CPI (Caliper R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was Caliper pulmonary vessel volume (PVV): FVC R = 0.75, DLCO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by Caliper alone demonstrated strong associations with restrictive functional indices: Caliper FVC R = 0.65; DLCO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by Caliper was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (Caliper R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. Conclusion Caliper improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by Caliper demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel Caliper variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new automated index of disease severity in HP.
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chronic hypersensitivity pneumonitis identification of key prognostic determinants using automated ct analysis
BMC Pulmonary Medicine, 2017Co-Authors: Joseph Jacob, David M Hansell, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Athol U WellsAbstract:Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF). Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (Caliper) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185). In CHP, visual/Caliper measures of reticular pattern, honeycombing, visual traction bronchiectasis, and Caliper ILD extent were predictive of mortality (p 6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185). Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.
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automated computer based ct stratification as a predictor of outcome in hypersensitivity pneumonitis
European Radiology, 2017Co-Authors: Joseph Jacob, Brian J Bartholmai, Srinivasan Rajagopalan, Ronald A Karwoski, Simon L F Walsh, S M Mak, W Mok, G Della Casa, K Sugino, Athol U WellsAbstract:Background Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative Caliper-derived CT data can identify distinct disease phenotypes. Mortality prediction using Caliper analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model.
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mortality prediction in idiopathic pulmonary fibrosis evaluation of computer based ct analysis with conventional severity measures
European Respiratory Journal, 2017Co-Authors: Joseph Jacob, Athol U Wells, Brian J Bartholmai, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Arjun Nair, Simon L F Walsh, David M HansellAbstract:Computer-based computed tomography (CT) analysis can provide objective quantitation of disease in idiopathic pulmonary fibrosis (IPF). A computer algorithm, Caliper, was compared with conventional CT and pulmonary function measures of disease severity for mortality prediction. CT and pulmonary function variables (forced expiratory volume in 1 s, forced vital capacity, diffusion capacity of the lung for carbon monoxide, transfer coefficient of the lung for carbon monoxide and composite physiologic index (CPI)) of 283 consecutive patients with a multidisciplinary diagnosis of IPF were evaluated against mortality. Visual and Caliper CT features included total extent of interstitial lung disease, honeycombing, reticular pattern, ground glass opacities and emphysema. In addition, Caliper scored pulmonary vessel volume (PVV) while traction bronchiectasis and consolidation were only scored visually. A combination of mortality predictors was compared with the Gender, Age, Physiology model. On univariate analyses, all visual and Caliper-derived interstitial features and functional indices were predictive of mortality to a 0.01 level of significance. On multivariate analysis, visual CT parameters were discarded. Independent predictors of mortality were CPI (hazard ratio (95% CI) 1.05 (1.02–1.07), p Caliper-derived parameters, in particular PVV, are more accurate prognostically than traditional visual CT scores. Quantitative tools such as Caliper have the potential to improve staging systems in IPF.
Athol U Wells - One of the best experts on this subject based on the ideXlab platform.
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evaluation of visual and computer based ct analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis
Respirology, 2017Co-Authors: Joseph Jacob, David M Hansell, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Vasileios Kouranos, Athol U WellsAbstract:Background and objective To determine whether computer-based quantification (Caliper software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). Methods A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and Caliper. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. Results Caliper-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (Caliper R = 0.73, visual R = 0.51); DLCO (Caliper R = 0.61, visual R = 0.48); and CPI (Caliper R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was Caliper pulmonary vessel volume (PVV): FVC R = 0.75, DLCO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by Caliper alone demonstrated strong associations with restrictive functional indices: Caliper FVC R = 0.65; DLCO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by Caliper was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (Caliper R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. Conclusion Caliper improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by Caliper demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel Caliper variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new automated index of disease severity in HP.
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chronic hypersensitivity pneumonitis identification of key prognostic determinants using automated ct analysis
BMC Pulmonary Medicine, 2017Co-Authors: Joseph Jacob, David M Hansell, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Athol U WellsAbstract:Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF). Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (Caliper) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185). In CHP, visual/Caliper measures of reticular pattern, honeycombing, visual traction bronchiectasis, and Caliper ILD extent were predictive of mortality (p 6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185). Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.
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automated computer based ct stratification as a predictor of outcome in hypersensitivity pneumonitis
European Radiology, 2017Co-Authors: Joseph Jacob, Brian J Bartholmai, Srinivasan Rajagopalan, Ronald A Karwoski, Simon L F Walsh, S M Mak, W Mok, G Della Casa, K Sugino, Athol U WellsAbstract:Background Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative Caliper-derived CT data can identify distinct disease phenotypes. Mortality prediction using Caliper analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model.
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mortality prediction in idiopathic pulmonary fibrosis evaluation of computer based ct analysis with conventional severity measures
European Respiratory Journal, 2017Co-Authors: Joseph Jacob, Athol U Wells, Brian J Bartholmai, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Arjun Nair, Simon L F Walsh, David M HansellAbstract:Computer-based computed tomography (CT) analysis can provide objective quantitation of disease in idiopathic pulmonary fibrosis (IPF). A computer algorithm, Caliper, was compared with conventional CT and pulmonary function measures of disease severity for mortality prediction. CT and pulmonary function variables (forced expiratory volume in 1 s, forced vital capacity, diffusion capacity of the lung for carbon monoxide, transfer coefficient of the lung for carbon monoxide and composite physiologic index (CPI)) of 283 consecutive patients with a multidisciplinary diagnosis of IPF were evaluated against mortality. Visual and Caliper CT features included total extent of interstitial lung disease, honeycombing, reticular pattern, ground glass opacities and emphysema. In addition, Caliper scored pulmonary vessel volume (PVV) while traction bronchiectasis and consolidation were only scored visually. A combination of mortality predictors was compared with the Gender, Age, Physiology model. On univariate analyses, all visual and Caliper-derived interstitial features and functional indices were predictive of mortality to a 0.01 level of significance. On multivariate analysis, visual CT parameters were discarded. Independent predictors of mortality were CPI (hazard ratio (95% CI) 1.05 (1.02–1.07), p Caliper-derived parameters, in particular PVV, are more accurate prognostically than traditional visual CT scores. Quantitative tools such as Caliper have the potential to improve staging systems in IPF.
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evaluation of computer based computer tomography stratification against outcome models in connective tissue disease related interstitial lung disease a patient outcome study
BMC Medicine, 2016Co-Authors: Joseph Jacob, Athol U Wells, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, David M HansellAbstract:To evaluate computer-based computer tomography (CT) analysis (Caliper) against visual CT scoring and pulmonary function tests (PFTs) when predicting mortality in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). To identify outcome differences between distinct CTD-ILD groups derived following automated stratification of Caliper variables. A total of 203 consecutive patients with assorted CTD-ILDs had CT parenchymal patterns evaluated by Caliper and visual CT scoring: honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume, emphysema, and traction bronchiectasis. CT scores were evaluated against pulmonary function tests: forced vital capacity, diffusing capacity for carbon monoxide, carbon monoxide transfer coefficient, and composite physiologic index for mortality analysis. Automated stratification of Caliper-CT variables was evaluated in place of and alongside forced vital capacity and diffusing capacity for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using receiver operating characteristic curve analysis. Cox regression analyses identified four independent predictors of mortality: patient age (P < 0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P = 0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of Caliper variables identified three morphologically distinct groups which were stronger predictors of mortality than all CT and functional indices. The Stratified-CT model substituted automated stratified groups for functional indices in the ILD-GAP model and maintained model strength (area under curve (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86, respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively). Caliper-derived pulmonary vessel volume is an independent predictor of mortality across all CTD-ILD patients. Furthermore, automated stratification of Caliper CT variables represents a novel method of prognostication at least as robust as PFTs in CTD-ILD patients.
Joseph Jacob - One of the best experts on this subject based on the ideXlab platform.
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evaluation of visual and computer based ct analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis
Respirology, 2017Co-Authors: Joseph Jacob, David M Hansell, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Vasileios Kouranos, Athol U WellsAbstract:Background and objective To determine whether computer-based quantification (Caliper software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). Methods A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and Caliper. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. Results Caliper-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (Caliper R = 0.73, visual R = 0.51); DLCO (Caliper R = 0.61, visual R = 0.48); and CPI (Caliper R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was Caliper pulmonary vessel volume (PVV): FVC R = 0.75, DLCO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by Caliper alone demonstrated strong associations with restrictive functional indices: Caliper FVC R = 0.65; DLCO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by Caliper was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (Caliper R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. Conclusion Caliper improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by Caliper demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel Caliper variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new automated index of disease severity in HP.
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chronic hypersensitivity pneumonitis identification of key prognostic determinants using automated ct analysis
BMC Pulmonary Medicine, 2017Co-Authors: Joseph Jacob, David M Hansell, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Athol U WellsAbstract:Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF). Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (Caliper) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185). In CHP, visual/Caliper measures of reticular pattern, honeycombing, visual traction bronchiectasis, and Caliper ILD extent were predictive of mortality (p 6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185). Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.
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automated computer based ct stratification as a predictor of outcome in hypersensitivity pneumonitis
European Radiology, 2017Co-Authors: Joseph Jacob, Brian J Bartholmai, Srinivasan Rajagopalan, Ronald A Karwoski, Simon L F Walsh, S M Mak, W Mok, G Della Casa, K Sugino, Athol U WellsAbstract:Background Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative Caliper-derived CT data can identify distinct disease phenotypes. Mortality prediction using Caliper analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model.
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mortality prediction in idiopathic pulmonary fibrosis evaluation of computer based ct analysis with conventional severity measures
European Respiratory Journal, 2017Co-Authors: Joseph Jacob, Athol U Wells, Brian J Bartholmai, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, Arjun Nair, Simon L F Walsh, David M HansellAbstract:Computer-based computed tomography (CT) analysis can provide objective quantitation of disease in idiopathic pulmonary fibrosis (IPF). A computer algorithm, Caliper, was compared with conventional CT and pulmonary function measures of disease severity for mortality prediction. CT and pulmonary function variables (forced expiratory volume in 1 s, forced vital capacity, diffusion capacity of the lung for carbon monoxide, transfer coefficient of the lung for carbon monoxide and composite physiologic index (CPI)) of 283 consecutive patients with a multidisciplinary diagnosis of IPF were evaluated against mortality. Visual and Caliper CT features included total extent of interstitial lung disease, honeycombing, reticular pattern, ground glass opacities and emphysema. In addition, Caliper scored pulmonary vessel volume (PVV) while traction bronchiectasis and consolidation were only scored visually. A combination of mortality predictors was compared with the Gender, Age, Physiology model. On univariate analyses, all visual and Caliper-derived interstitial features and functional indices were predictive of mortality to a 0.01 level of significance. On multivariate analysis, visual CT parameters were discarded. Independent predictors of mortality were CPI (hazard ratio (95% CI) 1.05 (1.02–1.07), p Caliper-derived parameters, in particular PVV, are more accurate prognostically than traditional visual CT scores. Quantitative tools such as Caliper have the potential to improve staging systems in IPF.
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evaluation of computer based computer tomography stratification against outcome models in connective tissue disease related interstitial lung disease a patient outcome study
BMC Medicine, 2016Co-Authors: Joseph Jacob, Athol U Wells, Brian J Bartholmai, Ryoko Egashira, Anne Laure Brun, Srinivasan Rajagopalan, Ronald A Karwoski, Maria Kokosi, David M HansellAbstract:To evaluate computer-based computer tomography (CT) analysis (Caliper) against visual CT scoring and pulmonary function tests (PFTs) when predicting mortality in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). To identify outcome differences between distinct CTD-ILD groups derived following automated stratification of Caliper variables. A total of 203 consecutive patients with assorted CTD-ILDs had CT parenchymal patterns evaluated by Caliper and visual CT scoring: honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume, emphysema, and traction bronchiectasis. CT scores were evaluated against pulmonary function tests: forced vital capacity, diffusing capacity for carbon monoxide, carbon monoxide transfer coefficient, and composite physiologic index for mortality analysis. Automated stratification of Caliper-CT variables was evaluated in place of and alongside forced vital capacity and diffusing capacity for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using receiver operating characteristic curve analysis. Cox regression analyses identified four independent predictors of mortality: patient age (P < 0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P = 0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of Caliper variables identified three morphologically distinct groups which were stronger predictors of mortality than all CT and functional indices. The Stratified-CT model substituted automated stratified groups for functional indices in the ILD-GAP model and maintained model strength (area under curve (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86, respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively). Caliper-derived pulmonary vessel volume is an independent predictor of mortality across all CTD-ILD patients. Furthermore, automated stratification of Caliper CT variables represents a novel method of prognostication at least as robust as PFTs in CTD-ILD patients.
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Transference of Caliper pediatric reference intervals to biochemical assays on the Roche cobas 6000 and the Roche Modular P
Clinical Biochemistry, 2016Co-Authors: Victoria Higgins, Man Khun Chan, Michelle Nieuwesteeg, Barry R. Hoffman, Irvin L. Bromberg, Doug Gornall, Edward Randell, Khosrow AdeliAbstract:Objectives: The Canadian Laboratory Initiative on Pediatric Reference Intervals (Caliper) has recently established pediatric age- and sex-specific reference intervals for over 85 biochemical markers on the Abbott Architect system. Previously, Caliper reference intervals for several biochemical markers were successfully transferred from Abbott assays to Roche, Beckman, Ortho, and Siemens assays. This study further broadens the Caliper database by performing transference and verification for 52 biochemical assays on the Roche cobas 6000 and the Roche Modular P. Design and methods: Using CLSI C28-A3 and EP9-A2 guidelines, transference of the Caliper reference intervals was attempted for 16 assays on the Roche cobas 6000 and 36 on the Modular P. Calculated reference intervals were further verified using 100 healthy Caliper samples. Results: Most assays showed strong correlation between assay systems and were transferable from Abbott to the Roche cobas 6000 (81%) and the Modular P (86%). Bicarbonate and magnesium were not transferable on either system and calcium and prealbumin were not transferable to the Modular P. Of the transferable analytes, 62% and 61% were verified on the cobas 6000 and the Modular P, respectively. Conclusions: This study extends the utility of the Caliper database to two additional analytical systems, which facilitates the broad application of Caliper reference intervals at pediatric centers utilizing Roche biochemical assays. Transference studies across different analytical platforms can later be collectively analyzed in an attempt to develop common reference intervals across all clinical chemistry instruments to harmonize laboratory test interpretation in diagnosis and monitoring of pediatric disease.
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clsi based transference of Caliper pediatric reference intervals to beckman coulter au biochemical assays
Clinical Biochemistry, 2015Co-Authors: Mohamed Abou El Hassan, Man Khun Chan, Michelle Nieuwesteeg, Edward Randell, Alexandra Stoianov, Petra A T Araujo, Tara Sadeghieh, Yunqi Chen, Khosrow AdeliAbstract:Abstract Objective The Caliper program has established a comprehensive database of pediatric reference intervals using largely the Abbott ARCHITECT biochemical assays. To expand clinical application of Caliper reference standards, the present study is aimed at transferring Caliper reference intervals from the Abbott ARCHITECT to Beckman Coulter AU assays. Design and methods Transference of Caliper reference intervals was performed based on the CLSI guidelines C28-A3 and EP9-A2. The new reference intervals were directly verified using up to 100 reference samples from the healthy Caliper cohort. Results We found a strong correlation between Abbott ARCHITECT and Beckman Coulter AU biochemical assays, allowing the transference of the vast majority (94%; 30 out of 32 assays) of Caliper reference intervals previously established using Abbott assays. Transferred reference intervals were, in general, similar to previously published Caliper reference intervals, with some exceptions. Most of the transferred reference intervals were sex-specific and were verified using healthy reference samples from the Caliper biobank based on CLSI criteria. It is important to note that the comparisons performed between the Abbott and Beckman Coulter assays make no assumptions as to assay accuracy or which system is more correct/accurate. Conclusion The majority of Caliper reference intervals were transferrable to Beckman Coulter AU assays, allowing the establishment of a new database of pediatric reference intervals. This further expands the utility of the Caliper database to clinical laboratories using the AU assays; however, each laboratory should validate these intervals for their analytical platform and local population as recommended by the CLSI.
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clsi based transference of the Caliper database of pediatric reference intervals to beckman coulter dxc biochemical assays
Clinical Biochemistry, 2015Co-Authors: Petra A T Araujo, Man Khun Chan, Edward Randell, Tara Sadeghieh, Yunqi Chen, Dylan Thomas, Victoria Bevilacqua, Khosrow AdeliAbstract:Abstract Background The Caliper program has established a comprehensive database of age- and sex-stratified pediatric reference intervals for over 85 common biochemical markers, largely using the Abbott ARCHITECT assays. To allow a broader application of the Caliper database, we examined transference to 36 Beckman Coulter Synchron Unicel DxC800 assays, based on the CLSI C28-A3/EP9-A3 guidelines. Methods Patient sample comparisons were performed for 36 biochemical assays using 200 serum specimens obtained from pediatric patients on the Abbott ARCHITECT ci8200 and the Beckman Coulter DxC800. For each analyte, R 2 values were calculated to assess the quality of correlation between the platforms. Statistical criteria used to assess transferability included a) regression analysis to create the equation of the line of best fit, b) standardized residual, c) Bland–Altman, and d) quantile–quantile plots. Transferred reference intervals were further verified by analyzing serum samples from 100 healthy children from the Caliper cohort on the Beckman Coulter system. Results The reference intervals for most of the assessed analytes were transferable to Beckman Coulter assays (31 out of 36 studied) and the newly calculated reference intervals were verified through analysis of Caliper reference samples (28 out of 31). Eighteen assays demonstrated excellent correlation (R 2 ≥ 0.95), and 13 assays showed strong correlation (0.77 ≤ R2 ≤ 0.94). Conclusion The current study allowed successful transference of a large number of biochemical markers from the Caliper database to assays on the Beckman Coulter DxC800 platform. Transference should facilitate broader application of Caliper reference intervals at pediatric centers using DxC biochemical assays.
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clsi based transference of the Caliper database of pediatric reference intervals from abbott to beckman ortho roche and siemens clinical chemistry assays direct validation using reference samples from the Caliper cohort
Clinical Biochemistry, 2013Co-Authors: Mathew P Estey, Man Khun Chan, Edward Randell, Ashley H Cohen, David Colantonio, Tina Binesh Marvasti, Edgard Delvin, Jocelyne Cousineau, Vijaylaxmi Grey, Donald GreenwayAbstract:Abstract Objectives The Caliper program recently established a comprehensive database of age- and sex-stratified pediatric reference intervals for 40 biochemical markers. However, this database was only directly applicable for Abbott ARCHITECT assays. We therefore sought to expand the scope of this database to biochemical assays from other major manufacturers, allowing for a much wider application of the Caliper database. Design and methods Based on CLSI C28-A3 and EP9-A2 guidelines, Caliper reference intervals were transferred (using specific statistical criteria) to assays performed on four other commonly used clinical chemistry platforms including Beckman Coulter DxC800, Ortho Vitros 5600, Roche Cobas 6000, and Siemens Vista 1500. The resulting reference intervals were subjected to a thorough validation using 100 reference specimens (healthy community children and adolescents) from the Caliper bio-bank, and all testing centers participated in an external quality assessment (EQA) evaluation. Results In general, the transferred pediatric reference intervals were similar to those established in our previous study. However, assay-specific differences in reference limits were observed for many analytes, and in some instances were considerable. The results of the EQA evaluation generally mimicked the similarities and differences in reference limits among the five manufacturers' assays. In addition, the majority of transferred reference intervals were validated through the analysis of Caliper reference samples. Conclusions This study greatly extends the utility of the Caliper reference interval database which is now directly applicable for assays performed on five major analytical platforms in clinical use, and should permit the worldwide application of Caliper pediatric reference intervals.
