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  • 1
    Language: English
    In: Leukemia, 2018-11, Vol.32 (11), p.2316-2325
    Description: The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Leukemia, 2020-09, Vol.34 (9), p.2473-2478
    Subject(s): Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Antibodies, Bispecific - therapeutic use ; Recurrence ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Humans ; Adolescent ; Child, Preschool ; Female ; Male ; Antineoplastic Agents - therapeutic use ; Child ; Philadelphia Chromosome ; Pediatrics ; Health aspects ; Children ; Index Medicus ; Letter ; Acute lymphocytic leukaemia ; Cancer
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Pediatric blood & cancer, 2019-09, Vol.66 (9), p.e27876-n/a
    Description: Background Widespread implementation of electronic health records (EHR) has created new opportunities for pediatric oncology observational research. Little attention has been given to using EHR data to identify patients with pediatric hematologic malignancies. Methods This study used EHR‐derived data in a pediatric clinical data research network, PEDSnet, to develop and evaluate a computable phenotype algorithm to identify pediatric patients with leukemia and lymphoma who received treatment with chemotherapy. To guide early development, multiple computable phenotype‐defined cohorts were compared to one institution's tumor registry. The most promising algorithm was chosen for formal evaluation and consisted of at least two leukemia/lymphoma diagnoses (Systematized Nomenclature of Medicine codes) within a 90‐day period, two chemotherapy exposures, and three hematology‐oncology provider encounters. During evaluation, the computable phenotype was executed against EHR data from 2011 to 2016 at three large institutions. Classification accuracy was assessed by masked medical record review with phenotype‐identified patients compared to a control group with at least three hematology‐oncology encounters. Results The computable phenotype had sensitivity of 100% (confidence interval [CI] 99%, 100%), specificity of 99% (CI 99%, 100%), positive predictive value (PPV) and negative predictive value (NPV) of 100%, and C‐statistic of 1 at the development institution. The computable phenotype performance was similar at the two test institutions with sensitivity of 100% (CI 99%, 100%), specificity of 99% (CI 99%, 100%), PPV of 96%, NPV of 100%, and C‐statistic of 0.99. Conclusion The EHR‐based computable phenotype is an accurate cohort identification tool for pediatric patients with leukemia and lymphoma who have been treated with chemotherapy and is ready for use in clinical studies.
    Subject(s): epidemiology ; pediatric oncology ; leukemias (acute) ; lymphoma ; computable phenotype ; Lymphoma - drug therapy ; Algorithms ; Humans ; Adolescent ; Child, Preschool ; Leukemia - drug therapy ; Female ; Male ; Registries ; Electronic Health Records ; Pediatrics ; Medical research ; Care and treatment ; Leukemia ; Medical records ; Antineoplastic agents ; Epidemiology ; Antimitotic agents ; Chemotherapy ; Electronic records ; Medicine, Experimental ; Lymphomas ; Genetic aspects ; Children ; Research institutes ; Health aspects ; Cancer ; Index Medicus
    ISSN: 1545-5009
    E-ISSN: 1545-5017
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Cancer, 2017-10-01, Vol.123 (19), p.3781-3790
    Description: BACKGROUND: Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. METHODS: A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. RESULTS: From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. CONCLUSIONS: The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781–3790.
    Subject(s): health services research ; pediatric oncology ; risk prediction ; supportive care ; Oncology ; Cancer Research ; febrile neutropenia ; Predictive Value of Tests ; Uncertainty ; Datasets as Topic ; Humans ; Child, Preschool ; Risk ; Bacteremia - diagnosis ; Models, Statistical ; Neoplasms ; Staphylococcal Infections - diagnosis ; Gram-Negative Bacterial Infections - diagnosis ; Retrospective Studies ; Immunocompromised Host ; Febrile Neutropenia - microbiology ; Child ; Staphylococcus aureus ; Decision-making ; Care and treatment ; Bacterial infections ; Analysis ; Research ; Risk factors ; Neutropenia ; Index Medicus ; Abridged Index Medicus
    ISSN: 0008-543X
    E-ISSN: 1097-0142
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: American journal of hematology, 2017-02, Vol.92 (2), p.141-148
    Description: Black patients with acute myeloid leukemia (AML) experience higher mortality than White patients. We compared induction mortality, acuity of illness prior to chemotherapy, and insurance type between Black and White patients to assess whether acuity of presentation mediates the disparity. Within a retrospective cohort of 1,122 children with AML treated with two courses of standard induction chemotherapy between 2004 and 2014 in the Pediatric Health Information System (PHIS) database, the association between race (Black versus White) and inpatient mortality during induction was examined. Intensive Care Unit (ICU)‐level resource utilization during the first 72 hours following admission for initial AML chemotherapy was evaluated as a potential mediator. The total effect of race on mortality during Induction I revealed a strong association (unadjusted HR 2.75, CI: 1.18, 6.41). Black patients had a significantly higher unadjusted risk of requiring ICU‐level resources within the first 72 hours after initial presentation (17% versus 11%; RR 1.52, CI: 1.04, 2.24). Mediation analyses revealed the indirect effect of race through acuity accounted for 61% of the relative excess mortality during Induction I. Publicly insured patients experienced greater induction mortality than privately insured patients regardless of race. Black patients with AML have significantly greater risk of induction mortality and are at increased risk for requiring ICU‐level resources soon after presentation. Higher acuity amongst Black patients accounts for a substantial portion of the relative excess mortality during Induction I. Targeting factors affecting acuity of illness at presentation may lessen racial disparities in AML induction mortality.
    Subject(s): Severity of Illness Index ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Hospitals, Pediatric - statistics & numerical data ; Humans ; Induction Chemotherapy - methods ; Child, Preschool ; Infant ; Male ; Treatment Outcome ; Socioeconomic Factors ; Insurance, Health - statistics & numerical data ; Intensive Care Units, Pediatric - statistics & numerical data ; Leukemia, Myeloid, Acute - mortality ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Leukemia, Myeloid, Acute - drug therapy ; Female ; Retrospective Studies ; African Continental Ancestry Group ; Child ; Leukemia, Myeloid, Acute - ethnology ; Induction Chemotherapy - mortality ; Cohort Studies ; Chemotherapy ; Analysis ; Children's hospitals ; Children ; Mediation ; Health aspects ; Epidemiology ; Medical informatics ; Cancer ; African Americans ; Whites ; Racial differences ; Leukemia ; Mortality ; Index Medicus
    ISSN: 0361-8609
    E-ISSN: 1096-8652
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Pediatric blood & cancer, 2016-11, Vol.63 (11), p.1943-1948
    Description: Background The UK ALLR3 (R3) regimen has been adopted to treat pediatric relapsed acute lymphoblastic leukemia (ALL) by many centers in the United States and has become a preferred therapeutic backbone for testing novel agents in clinical trials. A detailed toxicity profile of this platform has not previously been reported. The toxicity and response rates for its use beyond first relapse are unknown. Procedures We performed a multi‐institutional, retrospective study including children with relapsed ALL treated with the R3 reinduction chemotherapy backbone block 1 across five pediatric centers. Data were extracted from medical records and analyzed. Results Fifty‐nine patients were included in the study, including 16 patients with ≥2nd relapse. Ninety‐seven percent of patients experienced at least one Grade ≥3 nonhematologic adverse event (AE). Grade 3 or higher infection was reported in 90% of patients. Other nonhematologic Grade ≥3 AEs included electrolyte abnormalities, elevation in hepatic enzymes, and pain. Eighty‐five percent of patients achieved a complete remission (CR). There were no significant differences in the incidence of AEs, CR rate, and rate of minimal residual disease negativity between patients with 1st or ≥2nd relapse. Conclusion Our study confirmed that R3 block 1 is a highly active reinduction regimen in childhood relapsed ALL. However, it was associated with a high incidence of severe toxicities, particularly infection. The toxicity profiled in our report should be used to inform optimal supportive care and future clinical trial design with the R3 backbone, particularly when new agents are combined with this regimen.
    Subject(s): relapsed ALL ; reinduction ; adverse events ; Humans ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Child, Preschool ; Induction Chemotherapy ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Adult ; Female ; Retrospective Studies ; Child ; Complications and side effects ; Enzymes ; Chemotherapy ; Acute lymphocytic leukemia ; Cancer
    ISSN: 1545-5009
    E-ISSN: 1545-5017
    Source: Alma/SFX Local Collection
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  • 7
    Language: English
    In: The Journal of pediatrics, 2009, Vol.154 (3), p.447-449
    Description: Many children with influenza are treated with antibiotics. In this report, we describe the rate and indications for antibacterial use in children hospitalized with influenza. A total of 333 of 729 (46%) patients received 〉2 days of treatment with antibacterial medications, of whom 36% did not have an apparent indication for therapy.
    Subject(s): Pediatrics ; General aspects ; Viral diseases of the respiratory system and ent viral diseases ; Infectious diseases ; Viral diseases ; Biological and medical sciences ; Medical sciences ; Human viral diseases ; Community-Acquired Infections - diagnosis ; Community-Acquired Infections - epidemiology ; Hospitals, Pediatric - statistics & numerical data ; Bacterial Infections - drug therapy ; Comorbidity ; Humans ; Child, Preschool ; Infant ; Influenza, Human - epidemiology ; Male ; Drug Utilization ; Young Adult ; Anti-Bacterial Agents - therapeutic use ; Child, Hospitalized - statistics & numerical data ; Community-Acquired Infections - drug therapy ; Adolescent ; Bacterial Infections - epidemiology ; Female ; Influenza, Human - diagnosis ; Retrospective Studies ; Influenza, Human - drug therapy ; Child ; Cohort Studies ; Pediatric pharmacology ; Medical colleges ; Bacterial infections ; Influenza ; Cross infection ; Nosocomial infections ; Children ; Health aspects ; Antibacterial agents ; Diseases ; Index Medicus ; Abridged Index Medicus
    ISSN: 0022-3476
    E-ISSN: 1097-6833
    Source: Backfile Package - All of Back Files EBS [ALLOFBCKF]
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Blood, 2019-11-13, Vol.134 (Supplement_1), p.4753-4753
    Description: Introduction: CML accounts for 15-20% of leukemias. Tyrosine kinase inhibitor (TKI) therapy has led to significant improvement in survival rates, approaching the life expectancy of the general public in some settings, with less than three life years lost in a recent Swedish registry study.[1] Understanding cost associated with CML care compared to HEM in the setting of long-term survival on prolonged therapy can aid with resource allocation and clinical decision making. Methods: A retrospective cohort was constructed from OptumLabs® Data Warehouse using claims data between 2000-16. Eligible patients had ≥2 claims for CML and were continuously enrolled for ≥6m prior to diagnosis and ≥1y afterwards. CML patients were compared with HEM and general patients without history of cancer (GEN). As the CML group was the primary group of interest, the HEM and GEN groups were each frequency-matched on an approximate 4:1 ratio to the CML group on the basis of age (10-year increments), sex, year of diagnosis (3-year increments), geographic region (10 US census divisions), and insurance (commercial vs. Medicare Advantage). Follow-up data were available for this analysis through October 31, 2017. The primary outcome was total mean annualized health care costs including medical and outpatient drugs paid by health plan and patient (inflation adjusted to 2017). We used generalized linear models (GLM) to assess the variation in total costs in the three cohorts, using a gamma distribution and a log link. Models were adjusted for frequency-matched factors (sex, age, year of diagnosis, geographic region, insurance). Within the CML cohort, GLM was also used to examine the influence of factors hypothesized to be associated with costs: sex, age at index year, index year, race/ethnicity, insurance, modified Charlson comorbidity index, percent (%) days with TKI prescription, stem cell transplant, and number of inpatient and ambulatory days per year. Results: We identified 1909 enrollees with CML; mean diagnosis age 56y. They were matched with 7,268 HEM patients and 7,636 GEN patients. Mean annualized costs for CML were $82,054, $25,000 more than HEM and approximately $75,000 more than GEN (p〈0.001 in 3-way and pairwise comparisons; Table 1). This difference persisted after multivariate adjustment, with cost $25,471 higher in the CML population versus the HEM (95% CI: $20,808 to 30,133). Costs for CML care increased over each 5-year diagnostic interval until 2015 ($64,158 in 2000-04, peaking at $91,990 in 2010-14) (Table 1). Following index date, the trend in costs differ by cancer with HEM costs decreasing after the first six months post index date (Figure 1). In multivariable analysis, % days on a tyrosine kinase inhibitor had the greatest influence on cost among CML treatment factors. After adjustment for additional demographic and treatment factors, there was an association with increased cost by percent of days on a TKI (trend p〈0.001); for those with 75% of days on a TKI, the cost was $110,790 more than those without TKIs. Other factors associated with cost included receipt of stem cell transplant compared to no transplant ($55,549, 95% CI: $30,077 to 81,021), greater number of inpatient days ($148,664 for greater than 7 days versus none, 95% CI: $120,628 to 176,699) and greater number of ambulatory visits (20+ visits in one year versus 〈5, $62,255, 95% CI $52,969 to 71,541) Conclusions: Contemporary CML costs exceed the cost of treatment for other hematologic malignancies. This is primarily driven by the use of TKIs. The plateau in CML costs in those diagnosed between 2015-16 needs further evaluation for associations with TKI availability and the introduction of generics. [1] Bower H et al. JCO 2016 Aug 20; 34(24):2851-7 Disclosures Lyman: G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific Affairs, LLC: Research Funding; Amgen Inc.: Other: Research support, Research Funding.
    ISSN: 0006-4971
    E-ISSN: 1528-0020
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: American Society of Hematology
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  • 9
    Language: English
    In: Cancer, 2021-01-19
    Description: Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures. Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer-related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log-link modeled average monthly health-plan-paid (HPP) expenditures and amount owed by the patient (out-of-pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non-CCC). Incidence rate ratios (IRRs) compared CCC and non-CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled. Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non-CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P 〈 .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non-CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P 〈 .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable. Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long-term cost savings. Health care expenditures in young adults (aged 22-39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) than those at non-CCCs. The CCC/non-CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs. Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care. Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events.
    Subject(s): Index Medicus ; Abridged Index Medicus
    E-ISSN: 1097-0142
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Journal of clinical oncology, 2020-05-20, Vol.38 (15_suppl), p.7081-7081
    Description: 7081 Background: Patients diagnosed with HL between 22-39y have worse outcomes than younger patients (≤21y); we previously reported that treatment at a CCC mitigates these disparities [Wolfson, Leukemia 2017]. While there is general consensus that CCC care is expensive, expenditures for managing young adults with HL in CCC vs. non-CCC are not known. Methods: Cancer-related expenditures were examined in HL patients diagnosed between 2001-2014 at age 22-39y and treated at CCC and non-CCC sites using commercial insurance claims data (OptumLabs Data Warehouse). Multivariable generalized linear models with log link modeled average monthly health plan paid expenditures, adjusting for sociodemographics, stage, adverse events, pre-existing comorbidities, and diagnostic era. Results: Of the 1501 HL patients, 33% (n = 489) were treated at a CCC. Patients treated at CCC vs. non-CCC did not differ with respect to race, sex, income, diagnostic era or comorbidities (p≥0.3). Mean duration of enrollment was longer in CCC than non-CCC (25 vs. 23 mos; p 〈 0.001) patients. During the first year after HL diagnosis, total average monthly expenditures were higher in CCC ($9,111) than non-CCC ($7,834, p = 0.001), including those related to inpatient (CCC: $1,790 vs. non-CCC: $1,011; p = 0.001) and outpatient (CCC: $6,971 vs. non-CCC: $6,487; p = 0.001) expenditures. The higher CCC expenditures were associated with higher monthly rates of inpatient admissions (IRR = 1.3, p = 0.001) and outpatient visits (IRR = 1.1, p = 0.02) at CCC. Rates of chemotherapy-related inpatient admissions were higher (IRR = 2.3, p = 0.001) in CCC than non-CCC patients, while outpatient chemotherapy visit rates were lower (IRR = 0.9, p = 0.001) in CCC. During Years 2-3, total average monthly expenditures were higher in CCC ($19,259) than non-CCC ($4,145, p = 0.002) patients. Outpatient expenditures were higher in CCC ($10,164) vs. non-CCC ($2,901, p = 0.001), with higher monthly outpatient visit rates (IRR = 1.7, p = 0.001) at CCC. Conclusions: Inpatient and outpatient cancer-related expenditures in young adults with HL were higher at CCC than non-CCCs. Higher outpatient expenditures at CCC were associated with only higher monthly visit rates. Higher inpatient expenditures were in the setting of higher admission rates, including those related to chemotherapy. Additional work is necessary to understand whether these higher expenditures at CCC are related to supportive care and/or differences in facility structure and billing practices.
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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