A Prospective Risk Model for Neutropenic Complications in Patients with Malignant Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3328-3328
Author(s):  
Gary H. Lyman ◽  
Jeffrey Crawford ◽  
Debra Wolff ◽  
Eva Culakova ◽  
Marek S. Poniewierski ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Malignant Lymphoma ◽  
Likelihood Ratio ◽  
Cancer Chemotherapy ◽  
Test Performance ◽  
Predictive Value ◽  
Risk Model ◽  
Chemotherapy Regimen ◽  
Performance Characteristics ◽  
Increased Risk

Abstract Background: Myelosuppression including severe and febrile neutropenia continues to represent a major cause of dose-limiting toxicity of cancer chemotherapy. Neutropenic complications in cycle 1 have been shown to frequently lead to reduced dose intensity or addition of a myeloid growth factor. A prospective, nationwide study was undertaken to develop and validate risk models for first cycle neutropenic events associated with cancer chemotherapy. Methods: Patients with malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected practice sites. Data on at least one cycle of chemotherapy were available on 357 patients including 56 with Hodgkin’s disease and 301 with non-Hodgkin’s lymphoma. A logistic regression model for first cycle neutropenic events based on pretreatment characteristics was developed and predictive test performance characteristics examined. Results: Severe or febrile neutropenia occurred in 81 (22.7%) of patients in cycle 1. Two-thirds of patients with one or more neutropenic events experienced their initial event in cycle 1. Significant independent pretreatment predictive factors for first cycle neutropenic complications were: history of renal disease (OR=33.15, P=.011) or recent infection (OR=12.41, P=.035), Caucasian (OR=4.13, P=.053), use of an anthracycline-based chemotherapy regimen (OR=6.9, P<.001), baseline absolute neutrophil count (OR=0.95, P<.001) and lymphocyte count (OR=0.95, P<.001), anemia (OR=2.14, P=.043), elevated lactate dehydrogenase (OR=2.0, P=.040) and elevated bilirubin (OR=2.25, P=.051). Model fit was excellent (P<.001), R2= 0.503 and c-statistic = 0.769 [95% CL: .71–.83, P<.0001]. Individual predicted risk of cycle 1 events based on the model ranged from 0 to 96% with mean and median probabilities of 0.23 and 0.21, respectively. Two-thirds of patients were classified as high risk with mean risk scores in high and low risk subjects of 32.0% and 5.6%, respectively. Model test performance characteristics [±95% CL] included: sensitivity: 92% [84–96]; specificity: 40% [34–46]; likelihood ratio positive: 1.53 [1.36–1.73]; likelihood ratio negative: 0.19 [0.09–0.42]; positive predictive value: 32% [26–38]; negative predictive value: 94% [88–97] and diagnostic odds ratio: 7.92 [3.32–18.91]. Discussion: The risk model identified lymphoma patients at increased risk for first cycle neutropenic complications using common clinical parameters. Validation of the model in a separate population of patients is in progress.

A Risk Model for Chemotherapy-Induced Anemia (CIA) in Cancer Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 754-754
Author(s):  
Gary H. Lyman ◽  
Brandon McMahon ◽  
Nicole M. Kuderer ◽  
Jeffrey Crawford ◽  
Debra Wolff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Likelihood Ratio ◽  
Test Performance ◽  
Predictive Value ◽  
Risk Model ◽  
Performance Status ◽  
Low Risk ◽  
Performance Characteristics ◽  
Hematological Toxicity ◽  
Predictive Test

Abstract Background: Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost (Lyman‚ Value in Health 2005). Current ASH/ASCO guidelines call for intervention at a hemoglobin (Hgb) <10 gm/dl. Treatment options include transfusion or administration of an erythropoietic-stimulating protein (ESP). A recent meta-analysis demonstrated the clinical value of early versus late intervention with an ESP (Lyman‚ Cancer‚ 2005 in press). An accurate and valid risk model for CIA is needed to select patients for ESP treatment early in the course of chemotherapy when it can be most effective. Methods: More than 3‚000 patients with cancer of the breast‚ lung‚ colon and ovary or malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected U.S. practice sites. Data on at least one cycle of chemotherapy were available on 2‚842 patients. A logistic regression model for Hgb <10 gm/dl based on pretreatment characteristics was developed and predictive test performance characteristics examined. Results: Over a median of three cycles of chemotherapy, Hgb <10 gm/dl was reported one or more times in 817 (28.7%) patients. Significant independent predictive factors for Hgb <10 gm/dl include: history of peptic ulcer (OR=1.90; P=.015), myocardial infarction (OR=1.94; P=.009), or congestive heart failure (OR=2.13; P=.017), increasing age (OR=1.02; P=.002), female gender (OR=2.40; P<.001), ECOG performance status (OR=1.24; P=.002), Charlson Comorbidity Index (OR=1.06, P=.002), body surface area (OR=3.75, P<.001), low baseline hemoglobin (OR=1.95, P<.001), pretreatment hematocrit (OR=.85, P<.001), and glomerular filtration rate (OR=0.99, P=.027), and regimens containing anthracyclines (OR=3.21, P<.001), cisplatinum (OR=3.86, P<.001) or carboplatinum (OR=2.71, P<.001). Model fit was excellent (P<.001), R2=0.455 and c-statistic = 0.775 [95% CL: .76–.79, P<.0001]. Individual predicted risk of Hgb <10 gm/dl based on the model ranged from 0 to 98% with mean and median probabilities of 0.28 and 0.22, respectively. Based on a risk cutpoint of 20%, 1,541 patients (55%) were classified as high risk and 1,282 as low risk. The average risks of Hgb <10 gm/dl during chemotherapy in high and low risk subjects were 43% and 12%, respectively. Model test performance characteristics [±95% CL] included: sensitivity: 81% [78–84]; specificity: 56% [54–58]; likelihood ratio positive: 1.85 [1.74–1.96]; likelihood ratio negative: 0.34 [0.29–0.39]; positive predictive value: 43% [40–45]; negative predictive value: 88% [86–90] and diagnostic odds ratio: 5.47 [4.50–6.66]. Conclusions: This risk model identified cancer patients initiating chemotherapy who are at risk for clinically significant anemia using common clinical parameters. Validation of the model in a separate population of patients is in progress.

Final Risk Prediction Model for Neutropenic Complications in Patients Receiving Cancer Chemotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1312-1312 ◽  
Author(s):  
Gary H. Lyman ◽  
Jeffrey Crawford ◽  
Nicole M. Kuderer ◽  
Debra Wolff ◽  
Eva Culakova ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Chemotherapy ◽  
Test Performance ◽  
Risk Model ◽  
Cumulative Risk ◽  
Risk Groups ◽  
Low Risk ◽  
Performance Characteristics ◽  
Risk Patients ◽  
Predicted Risk

Abstract Introduction: Neutropenic complications including severe neutropenia (SN) and febrile neutropenia (FN) represent major dose-limiting toxicities of cancer chemotherapy. A prospective study was undertaken to develop and validate a predictive model for neutropenic events in patients receiving cancer chemotherapy. The final risk model based on mature data is presented. Methods: Between 2002 and 2006, 4458 consenting patients starting a new chemotherapy regimen at 115 randomly selected community oncology practices throughout the United States were enrolled including 3760 with cancers of breast, lung, colorectum, ovary and malignant lymphoma receiving at least one cycle of treatment. Using a 2:1 random split sample methodlogy, a risk model for first-cycle SN or FN was derived and validated based on multivariate logistic regression analysis incorporating pretreatment variable information. The cumulative risk of events over the initial 120 days of treatment was estimated by the method of Kaplan and Meier. High and low risk groups were defined on the basis of the median predicted risk and model test performance characteristics were estimated. Results: Following adjustment for cancer type, important predictive factors included: older age, prior chemotherapy, abnormal hepatic or renal function, low pretreatment white blood count, immunosuppressive medications and planned relative dose intensity >85% as well as use of several specific chemotherapeutic agents including anthracyclines, taxanes, alkylating agents, topoisomerase inhibitors, gemcitabine or vinorelbine. Lower risk of neutropenic complications were associated with primary prophylaxis with a colony-stimulating factor (CSF). Individual risk estimates based on the model ranged from 0–89% with mean and median of 19.2% and 10.1%, respectively. The model was associated with an R2 of 0.34 and demonstrated excellent discrimination with a c-statistic of 0.833 [95% CI: 0.813–0.852, P<.001]. The model predicted risk of cycle 1 SN or FN in high and low risk groups was of 34% and 4%, respectively. The cumulative risk of FN over the initial 120 days was 20% in high risk patients and 5% in low risk patients. Model performance included sensitivity and specificity of 90% and 59%, respectively, with a model diagnostic odds ratio of 12.8 [95% CI: 9.3, 17.7]. Application of the model to the validation data set was associated with similar excellent discrimination and test performance characteristics. CSF prophylaxis applied to high risk patients was associated with significantly lower risk of FN over repeated cycles of chemotherapy [HR = 0.51; 95% CI: 0.35 – 0.75; P <.0001]. Nearly two-thirds of patients classified as high risk but who did not receive primary CSF prophylaxis went on to receive secondary use during subsequent cycles. Discussion: Based on excellent test performance characteristics, the risk model identified patients with a cumulative incidence of FN of at least 20% who are candidates for targeted prophylaxis with a CSF. Further validation of this model in actual clinical practice is currently underway.

Personalizing Cancer Supportive Care: Predicting Neutropenic Complications in Patients Receiving Intermediate Risk Cancer Chemotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1022-1022 ◽  
Author(s):  
Gary H. Lyman ◽  
Eva Culakova ◽  
Marek S. Poniewierski ◽  
Jeffrey Crawford ◽  
David C. Dale ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Cancer Chemotherapy ◽  
Research Funding ◽  
Risk Model ◽  
Chemotherapy Regimen ◽  
Risk Group ◽  
Low Risk ◽  
Severe Neutropenia ◽  
Intermediate Risk

Abstract Abstract 1022 Background: Neutropenic complications represent important dose-limiting toxicities of cancer chemotherapy. We recently developed and validated a risk model for neutropenic complications in patients with solid tumors or lymphoma receiving cancer chemotherapy (Lyman et al. Cancer 2011). While practice guidelines recommend primary colony-stimulating factor (CSF) prophylaxis for patients at >20% risk of febrile neutropenia (FN), many patients receive chemotherapy regimens associated with an intermediate risk (10–20%) of FN. For these patients, the decision to give or withhold primary CSF prophylaxis is based on clinical judgment. We report here the ability of the risk model to identify patients with individual characteristics placing them at high risk for neutropenic complications among patients receiving intermediate risk chemotherapy regimens. Methods: A prospective cohort study was conducted of consenting patients initiating a new chemotherapy regimen at 115 randomly selected US oncology practices between 2002–2006. The risk of cycle 1 severe or febrile neutropenia was estimated [95% CI] utilizing logistic regression analysis adjusting for key clinical factors including: planned chemotherapy, prior chemotherapy, age, abnormal hepatic or renal function, low pretreatment white blood count, and immunosuppressive medications. The cumulative incidence of severe neutropenia and FN across 4 cycles was estimated by the product limit method of Kaplan and Meier. Results: Among 3,760 patients with cancers of breast, lung, ovary, colon, or lymphoma, 2,270 received an intermediate risk chemotherapy regimen based on NCCN guidelines. Overall, in the subpopulation receiving intermediate risk regimens, severe or febrile neutropenia occurred in cycle 1 in 21.4% while FN over 4 cycles was observed in 11%, and primary CSF prophylaxis was utilized in 16.4%. The performance of the risk model was good in this subgroup with a c-statistic of 0.82 [0.80–0.84]. Among the half of patients classified as high risk based on the model despite receiving an intermediate risk chemotherapy regimen, cycle 1 severe or febrile neutropenia occurred in 38% [35%–41%] compared to 5% [4%–6%] of patients classified as low risk based on the model receiving such regimens. Model sensitivity and specificity were 89% and 61%, respectively. The cumulative risk of FN over 4 cycles of chemotherapy was 20% in predicted high risk group versus 5% in the low risk group (Figure). The majority of severe or febrile neutropenia events (67%) and FN events (55%) were observed in cycle 1. One-half of high risk patients who did not receive primary CSF prophylaxis in cycle 1 received CSF during subsequent cycles following a neutropenic event. Conclusions: Our model for predicting neutropenic complications can identify patients at high individual risk for severe neutropenia in cycle 1 or FN in the first 4 cycles of chemotherapy when receiving intermediate risk chemotherapy. This analysis emphasizes the potential value of determining an individual patient's risk of chemotherapy complications based on a validated risk model. Disclosures: Lyman: Amgen: Research Funding. Crawford:Amgen: Consultancy, Honoraria, Research Funding. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kuderer:Amgen: Research Funding.

scholarly journals Quantitative Thresholds Enable Accurate Identification ofClostridium difficileInfection by the Luminex xTAG Gastrointestinal Pathogen Panel

2018 ◽  
Vol 56 (6) ◽  
Author(s):  
Sixto M. Leal ◽  
Elena B. Popowitch ◽  
Kara J. Levinson ◽  
Teny M. John ◽  
Bethany Lehman ◽  
...  
Keyword(s):  
Test Performance ◽  
Predictive Value ◽  
High Specificity ◽  
Clinical Suspicion ◽  
Performance Characteristics ◽  
Accurate Identification ◽  
Data Set ◽  
Content Type ◽  
Molecular Assays ◽  
Stool Samples

ABSTRACTClostridium difficilecolonizes the gastrointestinal (GI) tract, resulting in either asymptomatic carriage or a spectrum of diarrheal illness. If clinical suspicion forC. difficileis low, stool samples are often submitted for analysis by multiplex molecular assays capable of detecting multiple GI pathogens, and some institutions do not report this organism due to concerns for high false-positive rates. Since clinical disease correlates with organism burden and molecular assays yield quantitative data, we hypothesized that numerical cutoffs could be utilized to improve the specificity of the Luminex xTAG GI pathogen panel (GPP) forC. difficileinfection. Analysis of cotested liquid stool samples (n= 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of ≥1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second cotested data set (n= 1,428) yielded 96.5% concordance. To determine test performance characteristics, concordant results were deemed positive or negative, and discordant results were adjudicated via chart review. Test performance characteristics for the MFI cutoff of ≥150 (standard), MFI cutoff of ≥1,200, and 2-SA were as follows (respectively): concordance, 95, 96, and 97%; sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To capture the high sensitivity for organism detection (MFI of ≥150) and high specificity for active infection (MFI of ≥1,200), we developed and applied a reporting algorithm to interpret GPP data from patients (n= 563) with clinician orders only for syndromic panel testing, thus enabling accurate reporting ofC. difficilefor 95% of samples (514 negative and 5 true positives) irrespective of initial clinical suspicion and without the need for additional testing.

Prospective Validation of a Predictive Model for Early Anemia in Patients Receiving Cancer Chemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 460-460
Author(s):  
Gary H. Lyman ◽  
David C. Dale ◽  
Nicole M. Kuderer ◽  
Debra A. Wolff ◽  
Eva Culakova ◽  
...  
Keyword(s):  
Predictive Model ◽  
Odds Ratio ◽  
Risk Model ◽  
Diagnostic Odds Ratio ◽  
Performance Characteristics ◽  
Model Fit ◽  
Lower Sensitivity ◽  
Cancer Type ◽  
C Statistic ◽  
Increased Risk

Abstract Anemia represents the most common hematological toxicity in cancer patients receiving chemotherapy and is associated with considerable morbidity and cost. ASH/ASCO guidelines call for intervention at a hemoglobin (hgb)<10 g/dL. A meta-analysis has demonstrated the clinical value of early (hgb≥10 g/dL) versus late (hgb<10 g/dL) intervention with an erythroid stimulating protein (ESP). An anemia predictive model may help guide intervention sufficiently early in the course of chemotherapy when it can be most effective. A prospective, nationwide study was undertaken to develop and validate risk models for hematologic toxicities of chemotherapy. The analysis presented here is based on 3,640 patients with cancer of the breast, lung, colon and ovary or malignant lymphoma receiving a new regimen prospectively registered at 117 randomly selected U.S. practices. A logistic regression model for hgb<10 g/dL was developed and validated using a 2:1 random selection split sample methodology. Predictive performance characteristics were estimated [±95% CL]. Nadir hgb over 4 cycles of chemotherapy was <8 g/dL in 113 (3%), 8–10 in 959 (26%), 10–12 in 1,847 (51%), and ≥12 in 721 (20%). No significant differences were observed between the two populations. Independent risk factors for nadir hgb<10 g/dL (ORs) were: female gender (1.66); ECOG >1 (1.70); CHF (1.54); history of vascular disease (2.66); ulcer disease (2.58); COPD (1.29); connective tissue disease (1.84); advanced cancer stage (1.19); cancer type and chemotherapy based on anthracyclines (2.15), carboplatin (2.40), gemcitabine (2.48), cyclophosphamide (1.60), etoposide (2.84), topotecan (4.21), or trastuzumab (1.43), planned cycle length >1 week (2.0), while normal baseline hemoglobin, platelet count and GFR were associated with a reduced risk. Model fit was good (P<.001), R2 = 0.35 and c-statistic = 0.81 [.79–.83, P<.0001]. Mean and median predicted risk for hgb<10 g/dL were 0.29 and 0.22, respectively. An increasing risk cutpoint was associated with lower sensitivity and higher specificity. In the highest risk half, quarter and quintile of patients, hgb<10 g/dL was experienced by 47% [45–50], 64% [60–68], and 70% [65–74], respectively. Model performance characteristics at the median risk included: sensitivity: 82% [78–84]; specificity: 64% [62–66]; and diagnostic odds ratio: 7.80 [6.28–9.68]. Most covariates significant in the derivation model remained significant in the validation population. Model fit was good [P<.001] with an R2=.40 and a c-statistic of 0.83 [.81–.86; P<.001]. In the highest risk half, quarter and quintile of patients, hgb<10 g/dL was experienced by 50% [46–54], 67% [62–71], and 70% [65–75], respectively. Test performance of the validation model at the median risk included: sensitivity of 83% [79–86], specificity of 62% [59–66], and a diagnostic odds ratio of 7.90 [5.84–10.69]. Based on good performance characteristics, this validated prediction model identified chemotherapy patients at increased risk for developing clinically significant anemia who may be candidates for early targeted intervention with an ESP. A conditional risk model for subsequent risk of hgb<10 g/dL which includes changes during cycle 1 of chemotherapy has also been developed and will be presented.

A prediction model for chemotherapy-associated thrombocytopenia in cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8616-8616 ◽  
Author(s):  
N. M. Kuderer ◽  
C. W. Francis ◽  
J. Crawford ◽  
D. C. Dale ◽  
D. A. Wolff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prediction Model ◽  
Likelihood Ratio ◽  
Test Performance ◽  
Dose Intensity ◽  
High Specificity ◽  
Performance Characteristics ◽  
Multivariate Logistic Regression Model ◽  
Model Based ◽  
The Impact

8616 Background: Thrombocytopenia (TP) can lead to serious complications, however, little is known about the incidence and risk factors for chemotherapy-associated TP. A prospective, nationwide cohort study was undertaken to better define the impact of TP in cancer treatment. Methods: 2,842 patients with cancer of the breast, lung, colon, ovary or lymphoma initiating a new chemotherapy regimen have been prospectively enrolled at 115 randomly selected US community oncology practices between 2002 and 2005. Risk factors for chemotherapy-associated TP were identified, a multivariate logistic regression model based on pretreatment characteristics was developed, and test performance characteristics were estimated. Results: Over a median of 3 cycles of chemotherapy, minimum recorded platelet counts were: ≥150K in 53% of patients; 100–150K in 26%; 75–100K in 8%; 50–75K in 6% and <50K in 7%. Significant independent predictive factors for platelets <75K include type of cancer (P<.0001), type of chemotherapy including gemcitabine-based (P<.0001), anthracycline-based (P<.0001) and platinum-based (P<.0001) regimens, prior chemotherapy (P<.0001) or surgery (P=.005), age (P=.015), Caucasian ethnicity (P=.022), body surface area (P=.0001), planned relative dose intensity ≥85% (P=.082), diabetes (P=.018), pulmonary disease (P=.011), abnormal baseline platelets (P<.0001), hematocrit (P=0.030), alkaline phosphatase (P=.072) or albumin (P=.017). Model fit was good (Chi-square, P<.0001), R2 = 0.735 and c-statistic = 0.816 [95% CI: 0.792–0.840, P<.0001]. Model test performance characteristics [95% CI] at a ≥20% risk of TP include: sensitivity 56% [51–61]; specificity 88% [87–89]; likelihood ratio positive 4.63 [4.02–5.33]; likelihood ratio negative 0.50 [0.45–0.57]; and diagnostic odds ratio 9.22 [7.23–11.75]. Validation of the model is underway. Conclusions: This prediction model based on pretreatment factors identifies with high specificity patients at risk for clinically important chemotherapy-associated thrombocytopenia early in the treatment course. It may provide a valuable tool for guiding chemotherapy and new supportive care measures. [Table: see text]

Prospective validation of a risk model for first cycle neutropenic complications in patients receiving cancer chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8561-8561 ◽  
Author(s):  
G. H. Lyman ◽  
N. M. Kuderer ◽  
J. Crawford ◽  
D. A. Wolff ◽  
E. Culakova ◽  
...  
Keyword(s):  
High Risk ◽  
Test Performance ◽  
Risk Model ◽  
Selection Process ◽  
Low Risk ◽  
Validation Dataset ◽  
Cancer Type ◽  
General Applicability ◽  
C Statistic ◽  
Increased Risk

8561 Background: A nationwide, prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications (NC) in cancer patients receiving chemotherapy. Methods: 3,596 patients initiating a new chemotherapy regimen with solid tumors or lymphoma were registered at 115 randomly selected sites. Data on at least 1 cycle of chemotherapy were available on 3,468. A logistic regression model for cycle 1 NC was derived and then validated using a split sample random selection process. Results: The risk of cycle 1 NC ranged from 5.5%-30.2%, averaging 18.5% across tumor types. No significant differences in distribution of NC or predictive factors were observed between the derivation dataset (n=2,592) or the validation dataset (n=876). Major independent baseline clinical risk factors for cycle 1 NC in the derivation model include: prior chemotherapy (P=.044), number of myelosuppressive agents (P<.0001), anthracycline-based regimens (P<.0001), planned delivery >85% of standard (P<.0001), cancer type (P<.0001), concurrent antibiotics (P=.023) or phenothiazines (P=.006), abnormal alkaline phosphatase (P=.002), elevated bilirubin (P=.031), low platelets (P=.004), elevated glucose (P=.023) and reduced glomerular filtration rate (P=.013). Reduced risk of cycle 1 NC was associated with primary prophylaxis with a myeloid growth factor (P<.0001). Model R2 was 0.273 and c-statistic 0.80 [95% CI: 0.78–0.82; P<.0001]. At the median predicted risk of cycle 1 NC of 11%, model test performance consisted of: sensitivity 84%; specificity 57% and diagnostic odds ratio (DOR) 7.2 while cycle 1 NC risk was 31% and 6% among high risk and low risk half, respectively. The model performed well in the smaller validation dataset with a model R2 of 0.354 and c-statistic of 0.84 [95% CI: 0.81–0.87, P<.0001]. Test performance of the model in the validation sample included: sensitivity 90%; specificity 62%; DOR 14.1 and risks of 35% and 4% in high risk and low risk patients, respectively. Conclusions: Validation in a randomly selected patient sample suggests that this model has general applicability in identifying patients at increased risk for NC. Further validation in other independent cancer patient populations receiving chemotherapy is planned. [Table: see text]

A Conditional Risk Model for Chemotherapy-Induced Anemia (CIA) in Cancer Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 372-372
Author(s):  
Gary H. Lyman ◽  
Jeffrey Crawford ◽  
Nicole M. Kuderer ◽  
Debra A. Wolff ◽  
Eva Culakova ◽  
...  
Keyword(s):  
Platelet Count ◽  
Cancer Patients ◽  
Predictive Value ◽  
Risk Model ◽  
Low Risk ◽  
Performance Characteristics ◽  
Individual Risk ◽  
Hematological Toxicity ◽  
Cancer Type ◽  
Conditional Risk

Abstract Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost. Current guidelines for chemotherapy-induced anemia call for intervention at a hemoglobin &lt;10 g/dL with treatment options including transfusion or an erythropoietic-stimulating agent (ESA). A meta-analysis of randomized controlled trials has demonstrated the clinical value of early versus late intervention with an ESA (Lyman Cancer, 2006). While anemia risk models based on pretreatment characteristics have recently been validated, recent safety concerns have limited use of the ESAs to patients with moderate or severe anemia. The gradual onset of anemia and response to ESAs over time provides a rationale for selecting patients for ESA support early in the course of chemotherapy. Methods: 3640 patients with solid tumors or malignant lymphoma initiating a new regimen have been prospectively registered at 110 randomly selected U.S. practice sites. A logistic regression risk model for hemoglobin &lt;10 g/dL based on pretreatment characteristics and hematolgic events during cycle 1 was developed and model predictive performance characteristics estimated. Results: Over a median of 3 cycles of chemotherapy, hemoglobin &lt;10 g/dL was reported one or more times in 1072 (29.5%) patients. Significant independent baseline characteristics associated with subsequent hemoglobin &lt;10 g/dL include: female gender, poor ECOG performance status, history of congestive heart failure, vascular disease or chronic pulmonary disease, cancer type, treatment with an anthracycline-, platinum- or etoposide-based regimen and baseline hemoglobin &lt;12 g/dL or platelet count &lt;150000/mm3. In addition, significant independent predictive hematologic changes during cycle 1 include: decrease in hemoglobin &gt;1 g/dL (OR=4.48; P&lt;.0001), decrease in platelet count &gt;100000/mm3 (OR=1.54;P&lt;.0001) or neutrophil count &lt;500/mm3 (OR=1.94; P&lt;.001) as well as hemoglobin &lt;12 g/dL (OR=2.0;P&lt;.001) at the start of cycle 2. Model R2 = 0.581 and c-statistic = 0.901 [95% CI: .89–.91, P&lt;.0001]. The predicted risk of hemoglobin &lt;10 g/dL ranged from 0 to 100% with mean and median probabilities of 0.16 and 0.30, respectively. Based on a risk cutpoint at the mean, 1290 patients (38%) were classified as high risk. The risks of hemoglobin &lt;10 g/dL in high and low risk subjects were 66% and 9%, respectively. Model test performance characteristics [± 95% CLs] included: sensitivity: 82%[80–84]; specificity: 82%[80–83]; positive predictive value: 66%[63–68]; negative predictive value: 91%[90–93] and diagnostic odds ratio: 20.4[16.8–24.6]. Of note, risk of hemoglobin &lt;11 g/dL in high and low risk subjects based on this model were 95% and 34%, respectively. Validation of the model in a separate population of patients is currently under way. Discussion: This conditional risk model based on both pretreatment characteristics and first cycle events identified cancer patients receiving chemotherapy at substantial risk for clinically significant anemia. The use of ESAs early in the course of treatment based on individual risk assessment must consider both the potential benefit and risks and careful monitoring is essential.

Predictive value of 24-hour ambulatory blood pressure monitoring for cardiovascular events

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
V Intan-Goey ◽  
M Scherrenberg ◽  
M Falter ◽  
T Kaihara ◽  
P Dendale
Keyword(s):  
Blood Pressure ◽  
Ambulatory Blood Pressure ◽  
Predictive Value ◽  
Cardiovascular Events ◽  
Risk Model ◽  
Cox Regression ◽  
Blood Pressure Monitoring ◽  
Increased Risk ◽  
Time Periods

Abstract Funding Acknowledgements Type of funding sources: None. Background Hypertension is one of the most important cardiovascular risk factors. Twenty-four-hour ambulatory blood pressure (BP) monitoring remains the gold standard to diagnose hypertension. However, it is still unclear whether different time periods of measurement differ in their predictive value for cardiovascular events. Purpose To investigate whether different time periods of home BP monitoring can be used as a predictor of cardiovascular events and mortality. Methods In this retrospective study, we included patients who had a 24-hour BP measurement between May 2015 and March 2016. Follow-up data were collected up to a maximum of 67 months. BP measurements were taken every 15 minutes from 9 AM until 9 PM and subdivided into 4 time periods, each consisting of 3 hours of measurements. Correlation of BP with major adverse cardiovascular event (MACE) defined as cardiovascular hospitalization and all-cause mortality was examined using a Cox-regression model, which was adjusted for possible confounding factors. Results A total of 301 patients were included for analysis with mean follow-up of 1830,4 days ± 229. The mean age was 64.3 ± 15.2 and 52.8% of patients were female. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) for the 4 time periods were respectively 135,3 ± 16/ 82,6 ± 13,2mmHg, 132,3 ± 15,5/ 79,7 ± 12,7mmHg, 135,3 ± 15,5/ 81,7 ± 12,3mmHg and 136,4 ± 16,4 mmHg/ 81,6 ± 12,1mmHg. MACE occurred in 66 (21.9%) patients. The multivariable Cox proportional hazard risk model revealed that SBP between 12 and 3PM (HR 0.966 95% CI (0.945-0.989)) and the DBP between 6 and 9PM (HR 0.935 95% CI (0.898-0.973)) were associated with a reduced risk for MACE. Furthermore, the SBP between 6 and 9PM (HR 1.044 95% CI (1.021-1.068)) and the DBP between 3 and 6PM (HR 1.05 95% CI (1.013-1.089)) were associated with an increased risk for MACE. Conclusions The risk of cardiovascular events is higher in patients with a high SBP between 6 and 9PM and high DBP between 3 and 6PM. Lower risk is seen when the SBP is high between 12 and 3PM and the DBP is high between 6 and 9PM. These results might be explained by the circadian rhythm of BP. Further study is needed to confirm this time dependent predictive value of BP measurements.

scholarly journals Highly Accurate and Reproducible Diagnosis of Peanut Allergy Using Epitope Mapping

2020 ◽  
Author(s):  
Paul Kearney ◽  
Robert Getts ◽  
Clive Hayward ◽  
David Luta ◽  
Alex Porter ◽  
...  
Keyword(s):  
Likelihood Ratio ◽  
Test Performance ◽  
Predictive Value ◽  
Peanut Allergy ◽  
Skin Prick Testing ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Component Testing ◽  
The Subject ◽  
Sensitivity Specificity

AbstractBackgroundMisdiagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood-based test using a Bead-Based Epitope Assay (“peanut BBEA”) has been developed on the LEAP cohort and then independently validated on the CoFAR2 and POISED cohorts.MethodsDevelopment of the peanut BBEA followed the National Academy of Medicine’s established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 81 subjects from the CoFAR2 study and 84 subjects from the POISED study. All subject samples were analyzed using the BBEA methodology. The peanut BBEA test measures levels of two Ara h 2 epitopes and compares their combination to a pre=specified threshold. If the combination of the two epitope levels is at or below the threshold, then the subject is ruled “Not Allergic”, otherwise the subject is ruled “Allergic”.All allergic diagnoses were OFC confirmed and subjects’ ages were 7-55 years.ResultsIn validation on the CoFAR2 and POISED cohorts, the peanut BBEA test had a combined sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy of 91%, 95%, 95%, 91%, 18.2, 0.09 and 93%, respectively.ConclusionThe peanut BBEA test performance in validation demonstrated overall high accuracy and compared very favorably with existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE and peanut component testing.

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