Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia.

BACKGROUND: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life-threatening complications, including septic shock (SS). An area-based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS-associated death (SS-death). METHODS: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS-death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front-line therapy, death, relapse, or removal from study. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. RESULTS: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI-5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI-1; SDI-2: HR, 0.84 [95% confidence interval (CI), 0.51-1.41]; SDI-3: HR, 0.70 [95% CI, 0.42-1.16]; SDI-4: HR, 0.97 [95% CI, 0.61-1.53]; SDI-5: HR, 0.72 [95% CI, 0.45-1.14]). Nine patients (4.4%) with SS experienced SS-death; seven of these patients (78%) were in SDI-4 or SDI-5. CONCLUSIONS: In a large, nationally representative cohort of trial-enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS.

Designing Support to help Health Communication Professionals Convey Numbers Clearly to the Public - A Needs Assessment and Formative Usability Evaluation.

Communicating health-related probabilities to patients and the public presents challenges, although multiple studies have demonstrated that we can promote comprehension and appropriate application of numbers by matching presentation formats (e.g., percentage, bar charts, icon arrays) to communication goal (e.g., improving recall, decreasing worry, taking action). We used this literature to create goal-driven, evidence-based guidance to support health communicators in conveying probabilities. We then conducted semi-structured interviews with 39 health communicators to understand: communicators' goals for expressing probabilities, formats they choose to convey probabilities, and perceptions of prototypes of our "communicating numbers clearly" guidance. We found that communicators struggled to articulate granular goals for their communication, impeding their ability to select appropriate guidance. Future work should consider how best to support health communicators in selecting granular, differentiable goals to support broadly comprehensible information design.

Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

BACKGROUND: Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials. METHODS: We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided. RESULTS: In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group. CONCLUSIONS: Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.

Vaccine Hesitancy and Concerns About Vaccine Safety and Effectiveness in Shanghai, China.

INTRODUCTION: Rapidly urbanizing communities in middle-income countries could be sources of vaccine hesitancy, and may create hot spots of low vaccination coverage. This study characterizes vaccine hesitancy in Shanghai and identifies disparities in vaccine safety and efficacy concerns by residency status-a marker for recent migration into the city. METHODS: Parents of children aged ≤18 years from immunization clinics in Shanghai were enrolled in summer 2019, with the data analyzed during winter 2019-2020. The paper questionnaire used the Parental Attitudes towards Childhood Vaccines scale, which included questions about vaccine safety and efficacy concerns. The primary independent variable was residency-whether an individual was a Shanghai local or a recent migrant (i.e., non-local). Linear regression models assessed the relationship between residency and vaccine safety and efficacy concerns. RESULTS: Among 1,021 participants, 65.4% had local residency, and the remainder were urban non-locals (13.1%) or rural non-locals (21.5%). A majority of parents expressed concerns about vaccine side effects (73.8%), vaccine safety (63.9%), and vaccine effectiveness (52.4%). Compared with locals, rural non-locals were more concerned about vaccine side effects (ß=0.26, 95% CI=0.07, 0.46), vaccine safety (ß=0.42, 95% CI=0.19, 0.65), and vaccine effectiveness (ß=0.37, 95% CI=0.16, 0.58). CONCLUSIONS: Differences in vaccine hesitancy by residency could lead to geographical and sociodemographic disparities in vaccination coverage and outbreaks of vaccine-preventable disease. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Global Vaccination Equity, which is sponsored by the Global Institute for Vaccine Equity at the University of Michigan School of Public Health.

Assessment of the impact of inpatient infectious events in pediatric patients with newly diagnosed acute leukemia at Dr. Robert Reid Cabral Children's Hospital, Dominican Republic.

Survival rates for pediatric acute leukemia vary dramatically worldwide. Infections are a leading cause of morbidity and mortality, and the impact is amplified in low and middle-income countries. Defining the epidemiology of infection in a specific health care setting is paramount to developing effective interventions. This study aimed to define the epidemiology of and outcomes from infection in children with acute leukemia treated in a large public pediatric hospital in the Dominican Republic. A retrospective cohort was assembled of children newly diagnosed with acute leukemia between July 1, 2015 to June 30, 2017 at Hospital Infantil Dr. Robert Reid Cabral in Santo Domingo. Patients were identified from the Pediatric Oncology Network Database (PONDTM) and hospital admissions from the Oncology admissions logbook. Medical records and microbiology results were reviewed to identify all inpatient invasive infections. Distance from a child's home to the hospital was determined using ArcGIS by Esri. Infection rates were described in discrete time periods after diagnosis and risk factors for invasive infection were explored using negative binomial regression. Overall, invasive infections were common and a prominent source of death in this cohort. Rates were highest in the first 60 days after diagnosis. Gastroenteritis/colitis, cellulitis, and pneumonia were most frequent, with bacteremia common early on. Multidrug resistant bacteria were prevalent among a small number of positive cultures. In a multivariate negative binomial regression model, age ≥ 10 years and distance from the hospital > 100 km were each protective against invasive infection in the first 180 days after diagnosis, findings that were unexpected and warrant further investigation. Over one-third of patient deaths were related to infection. Interventions aimed at reducing infection should target the first 60 days after diagnosis, improved supportive care inside and outside the hospital, and increased antimicrobial stewardship and infection prevention and control measures.

Older adults' strategies for obtaining medication refills in hypothetical scenarios in the face of COVID-19 risk.

OBJECTIVE: To determine whether older adults would avoid going to the pharmacy (e.g., by restricting medications or requesting delivery) due to the risk of coronavirus disease (COVID-19). Our secondary objectives were to determine the types of medications that the older adults are more likely to restrict and to determine the factors that influence these decisions. DESIGN: Cross-sectional survey experiment in which participants read 6 scenarios, each stating that they had a 3-day supply of a particular medication remaining. SETTING AND PARTICIPANTS: National Web-based survey distributed to 1457 U.S. adults aged 65 years and older by Dynata from March 25, 2020, to April 1, 2020. OUTCOME MEASURES: Participants reported whether they would go to a pharmacy, have a medication delivered, or restrict the use of each medication. They reported their perceptions and experiences with COVID-19, health risk factors, preferences for more or less care (medical maximizer-minimizer), medication attitudes (beliefs about medicines questionnaire), health literacy, prescription insurance status, and demographics. RESULTS: Most participants (84%) were told to shelter in place, but only 12% reported attempting to obtain extra medications. Participants most often reported that they would go to the pharmacy to obtain each medication (ranging from tramadol 48.9% to insulin 64.9%) except for zolpidem, which they were most likely to restrict (45.4%). Participants who reported comorbidities that increased their risk of COVID-19 were just as likely to go to the pharmacy as those without. In multinomial logistic regression analyses, women and the oldest participants were more likely to seek delivery of medications. Restricting medications was most common for 2 symptom-focused medications (tramadol and zolpidem), and both demographic factors (e.g., gender) and beliefs (e.g., medical maximizing-minimizing preferences) were associated with such decisions. CONCLUSION: Many older adults intend to continue to go to the pharmacy to obtain their medications during a pandemic, even those who have health conditions that further increase their risk for COVID-19.

Assessment of Patient Nondisclosures to Clinicians of Experiencing Imminent Threats.

Importance: Patient disclosure to their clinician about experiencing an imminent threat is a critical step toward receiving support or assistance. Objective: To examine the frequency of patients not disclosing their experience of imminent threats to their clinician and their reasons for doing so. Design, Setting, and Participants: Survey study incorporating results from 2 national, nonprobability samples of 2011 US adults recruited from Amazon's Mechanical Turk (MTurk) from March 16 to 30, 2015, and 2499 recruited from Survey Sampling International (SSI) from November 6 to 17, 2015. Data analysis was conducted from December 20 to 28, 2018. Main Outcomes and Measures: Self-reported nondisclosure of 4 types of imminent threats (depression, suicidality, abuse, and sexual assault) to their clinician and reasons for nondisclosure. Results: There were 2011 participants in the MTurk sample (1210 [60.3%] female; 1696 [60.2%] white; mean [SD] age, 35.7 [12.4] years; age range, 18-79 years) and 2499 participants (1273 [51.0%] female; 1968 [78.8%] white; mean [SD] age, 61.0 [7.6] years; age range, 50-91 years) in the SSI sample. Among those who reported experiencing at least 1 of the 4 imminent threats, 613 of 1292 MTurk participants (47.5%) and 581 of 1453 SSI participants (40.0%) withheld information from their clinician. The most commonly endorsed reasons for withholding this information included being embarrassed (MTurk: 72.7%; SSI: 70.9%), not wanting to be judged or lectured (MTurk: 66.4%; SSI: 53.4%), and not wanting to engage in a difficult follow-up behavior (MTurk: 62.4%; SSI: 51.1%). Respondents who experienced at least 1 of the 4 imminent threats had significantly higher odds of nondisclosure in both samples if they were female (MTurk: odds ratio [OR], 1.66 [95% CI, 1.30-2.11]; and SSI: OR, 1.33 [95% CI, 1.07-1.67]) or younger (MTurk: OR, 0.99 [95% CI, 0.98-1.00]; and SSI: OR, 0.98 [95% CI, 0.97-1.00]). Worse self-rated health was also associated with nondisclosure, but only in the SSI sample (OR, 0.85 [95% CI, 0.74-0.96]). Conclusions and Relevance: This study suggests that many people withhold information from their clinicians about imminent health threats that they face. A better understanding of how to increase patients' comfort with reporting this information is critical to allowing clinicians to help patients mitigate these potentially life-threatening risks.

Cost comparison by treatment arm and center-level variations in cost and inpatient days on the phase III high-risk B acute lymphoblastic leukemia trial AALL0232.

The Children's Oncology Group (COG) develops and implements multi-institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients. In addition, high-dose methotrexate (HD-MTX) led to better survival than escalating doses of methotrexate (C-MTX). Cost data from the Pediatric Health Information System database were merged with clinical data from the COG AALL0232 trial. Total and component costs were compared between treatment arms and across hospitals. Inpatient costs were higher in the HD-MTX and DEX arms when compared to the C-MTX and PRED arms at the end of therapy. There was no difference in cost between these arms at last follow-up. Considerable variation in total costs existed across centers to deliver the same therapy that was driven by differences in inpatient days and pharmacy costs. The more effective regimens were found to be more expensive during therapy but were ultimately cost-neutral in longer term follow-up. The variations in cost across centers suggest an opportunity to standardize resource utilization for patients receiving similar therapies, which could translate into reduced healthcare expenditures.

Perceptions of measles, pneumonia, and meningitis vaccines among caregivers in Shanghai, China, and the health belief model: a cross-sectional study.

BACKGROUND: In China, the measles vaccine is offered for free whereas the pneumococcal vaccine is a for-fee vaccine. This difference has the potential to influence how caregivers evaluate whether a vaccine is important or necessary for their child, but it is unclear if models of health behavior, such as the Health Belief Model, reveal the same associations for different diseases. This study compares caregiver perceptions of different diseases (measles, pneumonia and meningitis); and characterizes associations between Health Belief Model constructs and both pneumococcal vaccine uptake and perceived vaccine necessity for pneumonia, measles, and meningitis. METHODS: Caregivers of infants and young children between 8 months and 7 years of age from Shanghai (n = 619) completed a written survey on their perceptions of measles, pneumonia, and meningitis. We used logistic regression models to assess predictors of pneumococcal vaccine uptake and vaccine necessity. RESULTS: Only 25.2% of children had received a pneumococcal vaccine, although most caregivers believed that pneumonia (80.8%) and meningitis (92.4%), as well as measles (93.2%), vaccines were serious enough to warrant a vaccine. Perceived safety was strongly associated with both pneumococcal vaccine uptake and perceived vaccine necessity, and non-locals had 1.70 times higher odds of pneumonia vaccine necessity than non-locals (95% CI: 1.01, 2.88). CONCLUSIONS: Most factors had a similar relationship with vaccine necessity, regardless of disease, indicating a common mechanism for how Chinese caregivers decided which vaccines are necessary. Because more caregivers believed meningitis needed a vaccine than pneumonia, health care workers should emphasize pneumococcal vaccination's ability to protect against meningitis.

Apply or Die: On the Role and Assessment of Application Papers in Visualization.

Application-oriented papers provide an important way to invigorate and cross-pollinate the visualization field, but the exact criteria for judging an application paper's merit remain an open question. This article builds on a panel at the 2016 IEEE Visualization Conference entitled "Application Papers: What Are They, and How Should They Be Evaluated?" that sought to gain a better understanding of prevalent views in the visualization community. This article surveys current trends that favor application papers, reviews the benefits and contributions of this paper type, and discusses their assessment in the review process. It concludes with recommendations to ensure that the visualization community is more inclusive to application papers.

Perceived Barriers to Implementing Individual Choosing Wisely® Recommendations in Two National Surveys of Primary Care Providers.

BACKGROUND: While some research has examined general attitudes about efforts to reduce overutilization of services, such as the Choosing Wisely® (CW) initiative, little data exists regarding primary care providers' attitudes regarding individual recommendations. OBJECTIVE: We sought to identify whether particular CW recommendations were perceived by primary care providers as difficult to follow, difficult for patients to accept, or both. DESIGN: Two national surveys, one by mail to a random sample of 2000 U.S. primary care physicians in November 2013, and the second electronically to a random sample of 2500 VA primary care providers (PCPs) in October-December 2014. PARTICIPANTS: A total of 603 U.S. primary care physicians and 1173 VA primary care providers. Response rates were 34 and 48 %, respectively. MAIN MEASURES: PCP ratings of whether 12 CW recommendations for screening, testing and treatments applicable to adult primary care were difficult to follow and difficult for patients to accept; and ratings of potential barriers to reducing overutilization. KEY RESULTS: For four recommendations regarding not screening or testing in asymptomatic patients, less than 20 % of PCPs found the CW recommendations difficult to accept (range 7.2-16.6 %) or difficult for patients to follow (12.2-19.3 %). For five recommendations regarding testing or treatment for symptomatic conditions, however, there was both variation in reported difficulty to follow (9.8-32 %) and a high level of reported difficulty for patients to accept (35.7-87.1 %). The most frequently reported barriers to reducing overuse included malpractice concern, patient requests for services, lack of time for shared decision making, and the number of tests recommended by specialists. CONCLUSIONS: While PCPs found many CW recommendations easy to follow, they felt that some, especially those for symptomatic conditions, would be difficult for patients to accept. Overcoming PCPs' perceptions of patient acceptability will require approaches beyond routine physician education, feedback and financial incentives.

The role of acuity of illness at presentation in early mortality in black children with acute myeloid leukemia.

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.

Associations between health literacy and preventive health behaviors among older adults: findings from the health and retirement study.

BACKGROUND: While the association between inadequate health literacy and adverse health outcomes has been well documented, less is known about the impact of health literacy on health perceptions, such as perceptions of control over health, and preventive health behaviors. METHODS: We identified a subsample of participants (N = 707) from the Health and Retirement Study (HRS), a nationally representative sample of older adults, who participated in health literacy testing. Self-reported health literacy was measured with a literacy screening question, and objective health literacy with a summed score of items from the Test of Functional Health Literacy. We compared answers on these items to those related to participation in health behaviors such as cancer screening, exercise, and tobacco use, as well as self-referencing health beliefs. RESULTS: In logistic regression models adjusted for gender, education, race, and age, participants with adequate self-reported health literacy (compared to poorer levels of health literacy) had greater odds of participation in mammography within the last 2 years (Odds ratio [OR] = 2.215, p = 0.01) and participation in moderate exercise two or more times per week (OR = 1.512, p = 0.03). Participants with adequate objective health literacy had reduced odds of participation in monthly breast self-exams (OR = 0.369, p = 0.004) and reduced odds of current tobacco use (OR = 0.456, p = 0.03). In adjusted linear regression analyses, self-reported health literacy made a small but significant contribution to explaining perceived control of health (ß 0.151, p = <0.001) and perceived social standing (ß 0.112, p = 0.002). CONCLUSION: In a subsample of older adult participants of the HRS, measures of health literacy were positively related to several health promoting behaviors and health-related beliefs and non-use of breast self-exams, a screening behavior of questionable benefit. These relationships varied however, between self-reported and objectively-measured health literacy. Further investigation into the specific mechanisms that lead higher literacy people to pursue health promoting actions appears clearly warranted.

Early discharge as a mediator of greater ICU-level care requirements in patients not enrolled on the AAML0531 clinical trial: a Children's Oncology Group report.

Previous data suggest that patients enrolled on clinical trials for treatment of cancer have better overall survival than patients who do not enroll; however, short-term outcomes relative to trial enrollment and corresponding mediators have not been assessed. A cohort of pediatric patients with newly-diagnosed acute myeloid leukemia was assembled from the Pediatric Health Information System. We evaluated whether patients not enrolled onto Children's Oncology Group trial AAML0531 had greater intensive care unit (ICU)-level requirements than enrolled patients and whether early discharge after chemotherapy administration mediated this association. Patients not enrolled on AAML0531 were more likely to be discharged early (aOR = 1.40, 95% confidence interval [CI]: 1.02, 1.90) and to require ICU-level care (aOR = 2.00, 95% CI: 1.06, 3.78) than enrolled patients, but early discharge explained only a small proportion (12.3%) of the absolute difference in ICU-level care risk. The direct effect of nonenrollment on the need for ICU-level care was significant (aOR = 1.89, 95% CI: 1.00, 3.94), whereas the indirect effect mediated through early discharge was not (aOR = 1.07, 95% CI: 0.95, 1.19). Factors other than postchemotherapy discharge strategy drive the difference in ICU utilization by trial enrollment status.

Volume-Outcome Relationships in Pediatric Acute Lymphoblastic Leukemia: Association Between Hospital Pediatric and Pediatric Oncology Volume With Mortality and Intensive Care Resources During Initial Therapy.

BACKGROUND: There are few contemporary studies of volume-outcome relationships in pediatric oncology. Children with acute lymphoblastic leukemia (ALL) are treated at a wide variety of hospitals. We investigated if inpatient hospital volume influences outcomes. The objective of this study was to evaluate the relationship between inpatient pediatric and pediatric oncology volume and mortality and intensive care resources (ICU care). We hypothesized an inverse relationship between volume and these outcomes. PATIENTS AND METHODS: This was a retrospective cohort study. Patients 0 to 18 years of age in the Pediatric Health Information System or Perspective Premier Database from 2009 to 2011 with ALL were included. Exposures were considered as the average inpatient pediatric and pediatric oncology volume. The primary outcome was inpatient mortality; secondary outcome was need for ICU care. RESULTS: The included population comprised 3350 patients from 75 hospitals. The inpatient mortality rate was 0.86% (95% confidence interval, 0.58%-1.2%). In the unadjusted analysis, mortality increased as pediatric oncology volume increased from low (0%) to high volume (1.3%) (P = .009). The small number of deaths precluded multivariable analysis of this outcome. Pediatric and pediatric oncology volume was not associated with ICU care when we controlled for potential confounders. CONCLUSION: Induction mortality was low. We did not observe an inverse relationship between volume and mortality or ICU care. This suggests that in a modern treatment era, treatment at a low-volume center might not be associated with increased mortality or ICU care in the first portion of therapy. This relationship should be evaluated in other oncology populations with higher mortality rates and with longer-term outcomes.

Classification of treatment-related mortality in children with cancer: a systematic assessment.

Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause-of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (κ=0·83, 95% CI 0·60-1·00) and paediatric oncologists (0·84, 0·63-1·00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0·92, 0·78-1·00). Our approach should allow comparison of treatment-related mortality across trials and across time.