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Gary H Lyman - One of the best experts on this subject based on the ideXlab platform.
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integrative omics to detect bacteremia in patients with Febrile Neutropenia
PLOS ONE, 2018Co-Authors: Rachel S Kelly, Gary H Lyman, Jessica Laskysu, Sai Ching J Yeung, Richard Stone, Jeffrey M Caterino, Sean C Hagan, Lindsey R Baden, Brett Glotzbecker, Christopher J CoyneAbstract:BACKGROUND Cancer chemotherapy-associated Febrile Neutropenia (FN) is a common condition that is deadly when bacteremia is present. Detection of bacteremia depends on culture, which takes days, and no accurate predictive tools applicable to the initial evaluation are available. We utilized metabolomics and transcriptomics to develop multivariable predictors of bacteremia among FN patients. METHODS We classified emergency department patients with FN and no apparent infection at presentation as bacteremic (cases) or not (controls), according to blood culture results. We assessed relative metabolite abundance in plasma, and relative expression of 2,560 immunology and cancer-related genes in whole blood. We used logistic regression to identify multivariable predictors of bacteremia, and report test characteristics of the derived predictors. RESULTS For metabolomics, 14 bacteremic cases and 25 non-bacteremic controls were available for analysis; for transcriptomics we had 7 and 22 respectively. A 5-predictor metabolomic model had an area under the receiver operating characteristic curve of 0.991 (95%CI: 0.972,1.000), 100% sensitivity, and 96% specificity for identifying bacteremia. Pregnenolone steroids were more abundant in cases and carnitine metabolites were more abundant in controls. A 3-predictor gene expression model had corresponding results of 0.961 (95%CI: 0.896,1.000), 100%, and 86%. Genes involved in innate immunity were differentially expressed. CONCLUSIONS Classifiers derived from metabolomic and gene expression data hold promise as objective and accurate predictors of bacteremia among FN patients without apparent infection at presentation, and can provide insights into the underlying biology. Our findings should be considered illustrative, but may lay the groundwork for future biomarker development.
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burden of chemotherapy induced Febrile Neutropenia hospitalizations in us clinical practice by use and patterns of prophylaxis with colony stimulating factor
Supportive Care in Cancer, 2017Co-Authors: Derek Weycker, Spiros Tzivelekis, Mark Atwood, Jacob Garcia, Maureen Reiner, Gary H LymanAbstract:Introduction Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of Febrile Neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice.
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granulocyte colony stimulating factors in the prevention of Febrile Neutropenia review of cost effectiveness models
Expert Review of Pharmacoeconomics & Outcomes Research, 2017Co-Authors: Kelly Fust, Spiros Tzivelekis, Gary H Lyman, Anju Parthan, Michael Maschio, Guillermo Villa, Milton C WeinsteinAbstract:ABSTRACTIntroduction: We reviewed the evolution of the methods used in cost-effectiveness analyses of granulocyte colony-stimulating factors (G-CSFs) in the primary and secondary prevention of Febrile Neutropenia (FN) in patients receiving myelosuppressive cancer chemotherapy.Areas covered: FN is a side effect of myelosuppressive chemotherapy associated with significant morbidity, mortality, and costs. The risk of FN may depend on the drugs used within a chemotherapy regimen, and an FN event may cause chemotherapy dose reductions or delays in subsequent cycles.Expert commentary: More recent pharmacoeconomic models have reflected these clinical observations by modeling sequential chemotherapy regimens to account for FN risk on a per-cycle basis, and by accounting for chemotherapy dose reductions and consequent survival losses.
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the impact of chemotherapy dose intensity and supportive care on the risk of Febrile Neutropenia in patients with early stage breast cancer a prospective cohort study
SpringerPlus, 2015Co-Authors: Eva Culakova, Gary H Lyman, David C Dale, Jeffrey Crawford, Marek S Poniewierski, Debra A WolffAbstract:Background Febrile Neutropenia (FN) is a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. This study evaluated the time course of neutropenic events and patterns of supportive care interventions in patients receiving chemotherapy for early-stage breast cancer treated in oncology community practices.
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risk and consequences of chemotherapy induced Febrile Neutropenia in patients with metastatic solid tumors
Journal of Oncology Practice, 2015Co-Authors: Derek Weycker, Rich Barron, Alex Kartashov, John Edelsberg, Gary H LymanAbstract:Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, Febrile Neutropenia is a frequent complication associated with morbidity, mortality, and economic costs.
R Anderson - One of the best experts on this subject based on the ideXlab platform.
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Febrile Neutropenia a prospective study to validate the multinational association of supportive care of cancer mascc risk index score
Supportive Care in Cancer, 2004Co-Authors: Almarie Uys, B L Rapoport, R AndersonAbstract:The objective of this study was to prospectively validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score in an attempt to accurately predict on presentation with Febrile Neutropenia those cancer patients who are at low- or high-risk for development of serious medical complications during the episode. Patients who presented with Febrile Neutropenia during November 2000 and July 2002 were prospectively enrolled in the protocol. All patients were hospitalized until recovery or outcome of the event and were treated with broad-spectrum, empiric, intravenous antibiotic therapy. The MASCC risk-index score (based on seven independent factors present at onset of Febrile Neutropenia) was calculated in 64 patients with 80 Febrile neutropenic episodes. Patients with a score of ≥21 were regarded as low risk; patients with a score of <21 were regarded as high risk. Of the 80 Febrile neutropenic episodes, 58 were classified as low-risk and 22 as high-risk patients. Fifty-seven (98.3%) of the 58 low-risk patients recovered without complications, and three (13.6%) of the 22 high-risk patients did not develop medical complications. One low-risk patient developed a fungal infection but recovered completely in comparison to 11 high-risk patients (50%) who developed serious medical complications (p<0.001). None of the low-risk patients died. However, eight (36.4%) of the 22 high-risk patients died during the Febrile neutropenic episode (p<0.001), six as a consequence of sepsis and two due to rapidly uncontrolled cancer. We correctly predicted 98.3% of low-risk patients and 86.3% of high-risk patients. This study had a positive predictive value of 98.3% and a negative predictive value of 86.4% with both a sensitivity and specificity of 95%. The MASCC risk-index score correctly identifies low- and high-risk patients at presentation with Febrile Neutropenia.
Derek Weycker - One of the best experts on this subject based on the ideXlab platform.
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burden of chemotherapy induced Febrile Neutropenia hospitalizations in us clinical practice by use and patterns of prophylaxis with colony stimulating factor
Supportive Care in Cancer, 2017Co-Authors: Derek Weycker, Spiros Tzivelekis, Mark Atwood, Jacob Garcia, Maureen Reiner, Gary H LymanAbstract:Introduction Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of Febrile Neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice.
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risk of chemotherapy induced Febrile Neutropenia in cancer patients receiving pegfilgrastim prophylaxis does timing of administration matter
Supportive Care in Cancer, 2016Co-Authors: Derek Weycker, Spiros Tzivelekis, Rich Barron, Jacqueline Figueredo, May HagiwaraAbstract:Purpose Contrary to the approved indication for pegfilgrastim prophylaxis, some patients receive it on the same day as the last administration of chemotherapy in clinical practice, which could adversely impact risk of Febrile Neutropenia (FN). An evaluation of the timing of pegfilgrastim prophylaxis and FN risk was undertaken.
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risk and consequences of chemotherapy induced Febrile Neutropenia in patients with metastatic solid tumors
Journal of Oncology Practice, 2015Co-Authors: Derek Weycker, Rich Barron, Alex Kartashov, John Edelsberg, Gary H LymanAbstract:Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, Febrile Neutropenia is a frequent complication associated with morbidity, mortality, and economic costs.
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incidence treatment and consequences of chemotherapy induced Febrile Neutropenia in the inpatient and outpatient settings
Journal of Oncology Pharmacy Practice, 2014Co-Authors: Derek Weycker, Richard Barron, Alex Kartashov, Jason C Legg, Gary H LymanAbstract:ObjectiveTo examine the incidence, treatment, and consequences of Febrile Neutropenia across inpatient and outpatient care settings.MethodsData were obtained from Humedica's National Electronic Health Record-Derived Longitudinal Patient-Level Database (2007–2010). The study population included adult patients who received myelosuppressive chemotherapy for a solid tumor or non-Hodgkin’s lymphoma. For each patient, each chemotherapy regimen course and each cycle within each regimen course was characterized. Febrile Neutropenia episodes were identified on a cycle-specific basis based on any of the following: (1) absolute neutrophil count <1.0 × 109/L and evidence of infection or fever; (2) inpatient diagnosis of Neutropenia, fever, or infection; (3) outpatient diagnosis of Neutropenia and non-prophylactic antimicrobial use; or (4) mention of Febrile Neutropenia in physician notes. Febrile Neutropenia episodes were categorized as inpatient or outpatient based on the initial setting of care (i.e. acute-care inp...
Sophia Koo - One of the best experts on this subject based on the ideXlab platform.
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meta analysis and cost comparison of empirical versus pre emptive antifungal strategies in hematologic malignancy patients with high risk Febrile Neutropenia
PLOS ONE, 2015Co-Authors: Monica Fung, Jane J Kim, Francisco M Marty, Michael Schwarzinger, Sophia KooAbstract:Background Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk Febrile Neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.
Benjamin Djulbegovic - One of the best experts on this subject based on the ideXlab platform.
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colony stimulating factors for chemotherapy induced Febrile Neutropenia
Cochrane Database of Systematic Reviews, 2014Co-Authors: Rahul Mhaskar, Gary H Lyman, O Clark, Tobias Engel Ayer Botrel, L Paladini, Benjamin DjulbegovicAbstract:Background Febrile Neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with Febrile Neutropenia. However, the results of these trials are conflicting. Objectives To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced Febrile Neutropenia in individuals diagnosed with cancer. Search methods We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. In addition, we also searched for economic evaluations via MEDLINE(R) In-Process & Other Non-Indexed Citations, Embase, CENTRAL and NHS Economic Evaluation Database in May 2015 to support a Brief Economic Commentary (BEC). Selection criteria We searched for randomized controlled trials (RCTs) and economic evaluations that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced Febrile Neutropenia in adults and children. Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Main results Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in Febrile Neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of Neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results. No full economic evaluations were identified. Several of the included RCTs identified economic benefits regarding a reduction in overall length of stay attributable to the use of CSF plus antibiotics, however they fell short of undertaking a full economic evaluation. Authors' conclusions The use of a CSF plus antibiotics in individuals with chemotherapy-induced Febrile Neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of Neutropenia, faster recovery from fever and shorter duration of antibiotics use. The current scarcity of relevant economic evaluations highlights an evidence gap and the need for further research fully explore the cost-effectiveness of these treatment alternatives.
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colony stimulating factors for chemotherapy induced Febrile Neutropenia a meta analysis of randomized controlled trials
Journal of Clinical Oncology, 2005Co-Authors: O Clark, Gary H Lyman, Aldemar Araujo Castro, L G Clark, Benjamin DjulbegovicAbstract:Purpose Current treatment for Febrile Neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN. Methods An exhaustive literature search was undertaken including major electronic databases (CANCERLIT, EMBASE, LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All randomized controlled trials that compare CSFs plus antibiotics versus antibiotics alone for the treatment of established FN in adults and children were sought. A meta-analysis of the selected studies was performed. Results More than 8,000 references were screened, with 13 studies meeting eligibility criteria for inclusion. The overall mortality was not influenced significantly by the use of CSF (od...
