The Experts below are selected from a list of 24036 Experts worldwide ranked by ideXlab platform
Jogarao V S Gobburu - One of the best experts on this subject based on the ideXlab platform.
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the role of sn 38 exposure ugt1a1 28 polymorphism and baseline bilirubin level in predicting severe irinotecan toxicity
The Journal of Clinical Pharmacology, 2007Co-Authors: Roshni P Ramchandani, Yaning Wang, Brian Booth, Amna Ibrahim, John R Johnson, Atiqur Rahman, Mehul Mehta, Federico Innocenti, Mark J Ratain, Jogarao V S GobburuAbstract:Irinotecan, an anticancer drug, is associated with severe and potentially fatal diarrhea and neutropenia. The objective of this analysis was to evaluate the role of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and baseline bilirubin on the maximum decrease (nadir) in Absolute Neutrophil Counts following irinotecan. This analysis extended the work of a previous study that examined the effect of UGT1A1 genotypes on the incidence of severe neutropenia in 86 advanced cancer patients following irinotecan treatment. Regression analysis showed that the Absolute Neutrophil Count nadir depended on SN-38 exposure (AUC) and UGT1A1*28 homozygous 7/7 genotype. An increased SN-38 AUC and the 7/7 genotype were significantly associated with a lower Absolute Neutrophil Count nadir (R2 = .49). An alternate model suggested that higher baseline bilirubin and the 7/7 genotype were also significantly associated with a lower Absolute Neutrophil Count nadir, although with a lower coefficient of determination (R2 = .31). Based on these findings and other reports, the irinotecan label was modified to indicate the role of UGT1A1*28 polymorphism in the metabolism of irinotecan and the associated increased risk of severe neutropenia. The label modifications also included recommendations for lower starting doses of irinotecan in patients homozygous for the UGT1A1*28 (7/7) polymorphism.
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The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity.
Journal of clinical pharmacology, 2007Co-Authors: Roshni P Ramchandani, Yaning Wang, Brian Booth, Amna Ibrahim, John R Johnson, Atiqur Rahman, Mehul Mehta, Federico Innocenti, Mark J Ratain, Jogarao V S GobburuAbstract:Irinotecan, an anticancer drug, is associated with severe and potentially fatal diarrhea and neutropenia. The objective of this analysis was to evaluate the role of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and baseline bilirubin on the maximum decrease (nadir) in Absolute Neutrophil Counts following irinotecan. This analysis extended the work of a previous study that examined the effect of UGT1A1 genotypes on the incidence of severe neutropenia in 86 advanced cancer patients following irinotecan treatment. Regression analysis showed that the Absolute Neutrophil Count nadir depended on SN-38 exposure (AUC) and UGT1A1*28 homozygous 7/7 genotype. An increased SN-38 AUC and the 7/7 genotype were significantly associated with a lower Absolute Neutrophil Count nadir (R2 = .49). An alternate model suggested that higher baseline bilirubin and the 7/7 genotype were also significantly associated with a lower Absolute Neutrophil Count nadir, although with a lower coefficient of determination (R2 = .31). Based on these findings and other reports, the irinotecan label was modified to indicate the role of UGT1A1*28 polymorphism in the metabolism of irinotecan and the associated increased risk of severe neutropenia. The label modifications also included recommendations for lower starting doses of irinotecan in patients homozygous for the UGT1A1*28 (7/7) polymorphism.
Richard G Bachur - One of the best experts on this subject based on the ideXlab platform.
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The Influence of Age on the Diagnostic Performance of White Blood Cell Count and Absolute Neutrophil Count in Suspected Pediatric Appendicitis.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2016Co-Authors: Richard G Bachur, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Jonathan E Bennett, Kelly A Sinclair, Peter S. Dayan, Michael C. MonuteauxAbstract:OBJECTIVE White blood cell (WBC) Count and Absolute Neutrophil Count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC Count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC Count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC Count and ANC across three age groups:
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the influence of age on the diagnostic performance of white blood cell Count and Absolute Neutrophil Count in suspected pediatric appendicitis
Academic Emergency Medicine, 2016Co-Authors: Richard G Bachur, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Jonathan E Bennett, Kelly A Sinclair, Peter S. Dayan, Michael C. MonuteauxAbstract:OBJECTIVE White blood cell (WBC) Count and Absolute Neutrophil Count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC Count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC Count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC Count and ANC across three age groups: <5, 5-11, and 12-18 years of age. Diagnostic performance of WBC Count and ANC was then assessed at specific cut-points. RESULTS A total of 2,133 patients with a median age of 10.9 years (interquartile range = 8.0-13.9 years) were studied. Forty-one percent had appendicitis. The area under the curve (AUC) for WBC Count was 0.69 (95% confidence interval [CI] = 0.61 to 0.77) for patients < 5 years of age, 0.76 (95% CI = 0.73 to 0.79) for 5-11 years of age, and 0.83 (95% CI = 0.81 to 0.86) for 12-18 years of age. The AUCs for ANC across age groups mirrored WBC performance. At a commonly utilized WBC cut-point of 10,000/mm3 , the sensitivity decreased with increasing age: 95% (<5 years), 91% (5-11 years), and 89% (12-18 years) whereas specificity increased by age: 36% (<5 years), 49% (5-12 years), and 64% (12-18 years). CONCLUSION WBC Count and ANC had better diagnostic performance with increasing age. Age-adjusted values of WBC Count or ANC should be considered in diagnostic strategies for suspected pediatric appendicitis.
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validation and refinement of a prediction rule to identify children at low risk for acute appendicitis
JAMA Pediatrics, 2012Co-Authors: Anupam B Kharbanda, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Richard G Bachur, Jonathan E Bennett, Kelly A SinclairAbstract:atlowrisk,misclassifying42patients(4.5%[95%CI,3.4%6.1%]) with appendicitis. We refined the prediction rule, resultinginamodelthatidentifiedpatientsatlowriskwith (1) an Absolute Neutrophil Count of 6.7510 3 /µL or less and no maximal tenderness in the right lower quadrant or (2) an Absolute Neutrophil Count of 6.7510 3 /µL or less with maximal tenderness in the right lower quadrant but no abdominal pain with walking/jumping or coughing. This refined rule had a sensitivity of 98.1% (95% CI, 97.0%-98.9%), specificity of 23.7% (21.7%-25.9%), and negative predictive value of 95.3% (92.3%-97.0%).
Michael C. Monuteaux - One of the best experts on this subject based on the ideXlab platform.
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The Influence of Age on the Diagnostic Performance of White Blood Cell Count and Absolute Neutrophil Count in Suspected Pediatric Appendicitis.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2016Co-Authors: Richard G Bachur, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Jonathan E Bennett, Kelly A Sinclair, Peter S. Dayan, Michael C. MonuteauxAbstract:OBJECTIVE White blood cell (WBC) Count and Absolute Neutrophil Count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC Count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC Count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC Count and ANC across three age groups:
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the influence of age on the diagnostic performance of white blood cell Count and Absolute Neutrophil Count in suspected pediatric appendicitis
Academic Emergency Medicine, 2016Co-Authors: Richard G Bachur, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Jonathan E Bennett, Kelly A Sinclair, Peter S. Dayan, Michael C. MonuteauxAbstract:OBJECTIVE White blood cell (WBC) Count and Absolute Neutrophil Count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC Count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC Count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC Count and ANC across three age groups: <5, 5-11, and 12-18 years of age. Diagnostic performance of WBC Count and ANC was then assessed at specific cut-points. RESULTS A total of 2,133 patients with a median age of 10.9 years (interquartile range = 8.0-13.9 years) were studied. Forty-one percent had appendicitis. The area under the curve (AUC) for WBC Count was 0.69 (95% confidence interval [CI] = 0.61 to 0.77) for patients < 5 years of age, 0.76 (95% CI = 0.73 to 0.79) for 5-11 years of age, and 0.83 (95% CI = 0.81 to 0.86) for 12-18 years of age. The AUCs for ANC across age groups mirrored WBC performance. At a commonly utilized WBC cut-point of 10,000/mm3 , the sensitivity decreased with increasing age: 95% (<5 years), 91% (5-11 years), and 89% (12-18 years) whereas specificity increased by age: 36% (<5 years), 49% (5-12 years), and 64% (12-18 years). CONCLUSION WBC Count and ANC had better diagnostic performance with increasing age. Age-adjusted values of WBC Count or ANC should be considered in diagnostic strategies for suspected pediatric appendicitis.
Rebecca D. Jackson - One of the best experts on this subject based on the ideXlab platform.
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Association Between Absolute Neutrophil Count and Variation at TCIRG1: The NHLBI Exome Sequencing Project
Genetic epidemiology, 2016Co-Authors: Elisabeth A. Rosenthal, Vahagn Makaryan, Amber A. Burt, David R. Crosslin, Daniel Seung Kim, Joshua D. Smith, Deborah A. Nickerson, Alexander P. Reiner, Stephen S. Rich, Rebecca D. JacksonAbstract:Neutrophils are a key component of innate immunity. Individuals with low Neutrophil Count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family. Here, we report on nine rare missense variants at evolutionarily conserved sites in TCIRG1 that are associated with lower Absolute Neutrophil Count (ANC; p = 0.005) in 1,058 participants from three cohorts: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and Jackson Heart Study (JHS) of the NHLBI Grand Opportunity Exome Sequencing Project (GO ESP). These results validate the effects of TCIRG1 coding variation on ANC and suggest that this gene may be associated with a spectrum of mild to severe effects on ANC.
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Association Between Absolute Neutrophil Count and Variation atTCIRG1: The NHLBI Exome Sequencing Project: Association Between Absolute Neutrophil Count and Variation atTCIRG1
Genetic epidemiology, 2016Co-Authors: Elisabeth A. Rosenthal, Vahagn Makaryan, Amber A. Burt, David R. Crosslin, Daniel Seung Kim, Joshua D. Smith, Deborah A. Nickerson, Alexander P. Reiner, Stephen S. Rich, Rebecca D. JacksonAbstract:Neutrophils are a key component of innate immunity. Individuals with low Neutrophil Count are susceptible to frequent infections. Linkage and association between congenital neutropenia and a single rare missense variant in TCIRG1 have been reported in a single family. Here, we report on nine rare missense variants at evolutionarily conserved sites in TCIRG1 that are associated with lower Absolute Neutrophil Count (ANC; p = 0.005) in 1,058 participants from three cohorts: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and Jackson Heart Study (JHS) of the NHLBI Grand Opportunity Exome Sequencing Project (GO ESP). These results validate the effects of TCIRG1 coding variation on ANC and suggest that this gene may be associated with a spectrum of mild to severe effects on ANC.
Kelly A Sinclair - One of the best experts on this subject based on the ideXlab platform.
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The Influence of Age on the Diagnostic Performance of White Blood Cell Count and Absolute Neutrophil Count in Suspected Pediatric Appendicitis.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2016Co-Authors: Richard G Bachur, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Jonathan E Bennett, Kelly A Sinclair, Peter S. Dayan, Michael C. MonuteauxAbstract:OBJECTIVE White blood cell (WBC) Count and Absolute Neutrophil Count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC Count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC Count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC Count and ANC across three age groups:
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the influence of age on the diagnostic performance of white blood cell Count and Absolute Neutrophil Count in suspected pediatric appendicitis
Academic Emergency Medicine, 2016Co-Authors: Richard G Bachur, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Jonathan E Bennett, Kelly A Sinclair, Peter S. Dayan, Michael C. MonuteauxAbstract:OBJECTIVE White blood cell (WBC) Count and Absolute Neutrophil Count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC Count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC Count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC Count and ANC across three age groups: <5, 5-11, and 12-18 years of age. Diagnostic performance of WBC Count and ANC was then assessed at specific cut-points. RESULTS A total of 2,133 patients with a median age of 10.9 years (interquartile range = 8.0-13.9 years) were studied. Forty-one percent had appendicitis. The area under the curve (AUC) for WBC Count was 0.69 (95% confidence interval [CI] = 0.61 to 0.77) for patients < 5 years of age, 0.76 (95% CI = 0.73 to 0.79) for 5-11 years of age, and 0.83 (95% CI = 0.81 to 0.86) for 12-18 years of age. The AUCs for ANC across age groups mirrored WBC performance. At a commonly utilized WBC cut-point of 10,000/mm3 , the sensitivity decreased with increasing age: 95% (<5 years), 91% (5-11 years), and 89% (12-18 years) whereas specificity increased by age: 36% (<5 years), 49% (5-12 years), and 64% (12-18 years). CONCLUSION WBC Count and ANC had better diagnostic performance with increasing age. Age-adjusted values of WBC Count or ANC should be considered in diagnostic strategies for suspected pediatric appendicitis.
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validation and refinement of a prediction rule to identify children at low risk for acute appendicitis
JAMA Pediatrics, 2012Co-Authors: Anupam B Kharbanda, Nanette C Dudley, Lalit Bajaj, Michelle D Stevenson, Charles G Macias, Manoj K Mittal, Richard G Bachur, Jonathan E Bennett, Kelly A SinclairAbstract:atlowrisk,misclassifying42patients(4.5%[95%CI,3.4%6.1%]) with appendicitis. We refined the prediction rule, resultinginamodelthatidentifiedpatientsatlowriskwith (1) an Absolute Neutrophil Count of 6.7510 3 /µL or less and no maximal tenderness in the right lower quadrant or (2) an Absolute Neutrophil Count of 6.7510 3 /µL or less with maximal tenderness in the right lower quadrant but no abdominal pain with walking/jumping or coughing. This refined rule had a sensitivity of 98.1% (95% CI, 97.0%-98.9%), specificity of 23.7% (21.7%-25.9%), and negative predictive value of 95.3% (92.3%-97.0%).
