Search

Foundation models are transforming artificial intelligence (AI) in healthcare by providing modular components adaptable for various downstream tasks, making AI development more scalable and cost-effective. Foundation models for structured electronic health records (EHR), trained on coded medical records from millions of patients, demonstrated benefits including increased performance with fewer training labels, and improved robustness to distribution shifts. However, questions remain on the feasibility of sharing these models across hospitals and their performance in local tasks. This multi-center study examined the adaptability of a publicly accessible structured EHR foundation model (FMSM), trained on 2.57 M patient records from Stanford Medicine. Experiments used EHR data from The Hospital for Sick Children (SickKids) and Medical Information Mart for Intensive Care (MIMIC-IV). We assessed both adaptability via continued pretraining on local data, and task adaptability compared to baselines of locally training models from scratch, including a local foundation model. Evaluations on 8 clinical prediction tasks showed that adapting the off-the-shelf FMSM matched the performance of gradient boosting machines (GBM) locally trained on all data while providing a 13% improvement in settings with few task-specific training labels. Continued pretraining on local data showed FMSM required fewer than 1% of training examples to match the fully trained GBM's performance, and was 60 to 90% more sample-efficient than training local foundation models from scratch. Our findings demonstrate that adapting EHR foundation models across hospitals provides improved prediction performance at less cost, underscoring the utility of base foundation models as modular components to streamline the development of healthcare AI. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about the impact of coronavirus disease 2019 (COVID‐19) on healthcare professional emotional health in pediatric hematology/oncology. Primary objective was to describe anxiety, depression, positive affect, and perceived stress among pediatric hematology/oncology healthcare professionals following a COVID‐19 outbreak. Secondary objectives were to compare these outcomes based on contact with a positive person, and to identify risk factors for worse outcomes. Materials and methods: We included 272 healthcare professionals working with pediatric hematology/oncology patients. We determined whether respondents had direct or indirect contact with a COVID‐19‐positive individual and then measured outcomes using the Patient‐Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, and positive affect measures, and the Perceived Stress Scale. Results: Among eligible respondents, 205 agreed to participate (response rate 75%). Sixty‐nine (33.7%) had contact with a COVID‐19‐positive person. PROMIS anxiety, depression, and positive affect scores were similar to the general United States population. Those who had contact with a COVID‐19‐positive individual did not have significantly different outcomes. In multiple regression, non‐physicians had significantly increased anxiety (nurses: p = 0.013), depression (nurses: p = 0.002, pharmacists: p = 0.038, and other profession: p = 0.021), and perceived stress (nurses: p = 0.002 and other profession: p = 0.011) when compared to physicians. Conclusions: Pediatric hematology/oncology healthcare professionals had similar levels of anxiety, depression, and positive affect as the general population. Contact with a COVID‐19‐positive individual was not significantly associated with outcomes. Non‐physician healthcare professionals had more anxiety, depression, and perceived stress when compared to physicians. These findings may help to develop programs to support healthcare professional resilience. [ABSTRACT FROM AUTHOR]

Background: Objectives were to describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation.Methods: We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators prior to randomization to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of the COVID-19 pandemic on clinical research. The Wilcoxon rank sum test was used to compare characteristics of institutions that agreed that their department supported the implementation of symptom management care pathways vs. institutions that did not agree.Results: Of the 25 sites, one withdrew because of resource constraints and one did not respond, leaving 23 institutions. Among the seven CFIR constructs, the least supported was implementation climate; 57% agreed there was support, 39% agreed there was recognition and 39% agreed there was prioritization for symptom management care pathway implementation at their institution. Most common barriers were lack of person-time to create care pathways and champion their use (35%), lack of interest from physicians (30%) and lack of information technology resources (26%). Most sites reported no negative impact of the COVID-19 pandemic across research activities. Sites with fewer pediatric cancer patients were more likely to agree that staff are supported to implement symptom management care pathways (P = 0.003).Conclusions: The most commonly reported barriers to implementation were lack of support, recognition and prioritization. The COVID-19 pandemic may not be a major barrier to clinical research activities in pediatric oncology. [ABSTRACT FROM AUTHOR]

There is accumulating evidence that vitamin E may have different roles in the prevention and treatment of cancer. The purpose of this review is to summarize and evaluate this evidence and to suggest future avenues of research. A comprehensive literature review of vitamin E and cancer was conducted. Articles were organized into the following categories: 1) cancer prevention, 2) direct antineoplastic activity, 3) augmentation of chemotherapy effects, and 4) attenuation or treatment of chemotherapy toxicity. The evidence was systematically evaluated using guidelines developed by the U.S. Preventative Services Task Force. There is evidence to suggest that those individuals with higher serum vitamin E levels and those receiving vitamin E supplementation have a decreased risk of some cancers, including lung, prostate, stomach, and gastrointestinal carcinoma. However, these results differed depending on the study design and the population studied. There is insufficient evidence to support anticancer activity and attenuation of chemotherapy toxicity by vitamin E. Vitamin E is likely to be important in the prevention of some cancers. The therapeutic role of vitamin E is poorly understood. Further research will be required before routine use of vitamin E in patients with cancer can be advocated in the clinical setting. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. PARTICIPANTS AND METHODS. We e-mailed a cross-sectional survey to pediatric hematopoietic cell transplantation physicians in the United States and Canada; 93 of 152 potentially eligible physicians (93 of 130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed by using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. RESULTS. Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36 of 40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alter- native stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with 1 healthy sibling when both parents were of northern European descent; 11 % would recommend banking when parents were of different minority ethnicities. CONCLUSIONS. Few transplants have been performed by using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric hematopoietic cell transplantation physicians endorse private cord blood banking in the absence of an identified recipient, even for mixed-ethnicity children for whom finding a suitably matched unrelated donor may be difficult. [ABSTRACT FROM AUTHOR]

Context: The National Cancer Institute created the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to allow direct input on symptomatic adverse events (AEs) from adult patients in oncology trials.Objectives: This study sought to determine the youngest age to complete the PRO-CTCAE, evaluated comprehension of PRO-CTCAE among adolescents, tested new items not currently in PRO-CTCAE, and tested a parent-proxy version.Methods: From seven pediatric cancer hospitals, 51 adolescents (13-20 years) receiving cancer treatment participated, along with 40 parent proxies. We evaluated 55 AEs from the PRO-CTCAE library (97 questions) and seven new AEs not in PRO-CTCAE that assess symptom frequency, severity, interference, or presence. Questions were distributed across three forms to reduce burden. Cognitive interviews with retrospective probing were completed in age groups of 13-15 and 16-20 year olds. Proxies were interviewed independently.Results: In general, the 16-20 year olds and the parent proxies were able to understand and complete the PRO-CTCAE and newly designed AE questions. Five PRO-CTCAE terms (bloating of the abdomen, anxiety, flashing lights in front of your eyes, hot flashes, and bed sores) and the wording of the questions about AE severity were challenging for a few adolescents and proxies. The 13-15 year olds had greater challenges completing the PRO-CTCAE.Conclusion: This study extends use of the adult PRO-CTCAE for adolescents as young as 16 years and proposes new questions for seven new symptomatic AEs and a parent-proxy version of PRO-CTCAE. Additional testing of the new questions and alternative language for more challenging PRO-CTCAE items is recommended in adults. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare improvement in survival from 1986 to 2009 for acute lymphoblastic leukemia (ALL) patients 1–14, 15–19 and 20–29 years in Ontario and United States. Methods: This population-based analysis used data from Ontario Cancer Registry (OCR) and Surveillance Epidemiology and End Results (SEER). Results: In OCR, there was steady improvement in survival by period of diagnosis in all three age groups. In SEER, there was no improvement in survival for patients aged 20–29 years. Conclusions: Survival in Ontario and the United States has improved for patients with ALL aged 1–19 years. However, survival has improved among patients aged 20–29 years only in Ontario. [Copyright &y& Elsevier]

Existing standards for screening and management of late effects occurring in children who have undergone hematopoietic cell transplantation (HCT) include recommendations from pediatric cancer networks and consensus guidelines from adult-oriented transplantation societies applicable to all HCT recipients. Although these approaches have significant merit, they are not pediatric HCT-focused, and they do not address post-HCT challenges faced by children with complex nonmalignant disorders. In this article we discuss the strengths and weaknesses of current published recommendations and conclude that pediatric-specific guidelines for post-HCT screening and management would be beneficial to the long-term health of these patients and would promote late effects research in this field. Our panel of late effects experts also provides recommendations for follow-up and therapy of selected post-HCT organ and endocrine complications in pediatric patients. [ABSTRACT FROM AUTHOR]

The National Cancer Institute (NCI) has a 40-year history of initiatives to encourage the participation of community oncology sites into clinical trials research and clinical care. In 2014, the NCI re-organized to form the NCI Community Oncology Research Program (NCORP) network across seven research bases, including the Children's Oncology Group (COG), and numerous community sites. The COG portfolio for Cancer Care Delivery Research (CCDR), mirroring the larger NCORP network, has included two studies addressing guideline congruence, as an important marker of quality cancer care, and another focusing on financial toxicity, addressing the pervasive problems of healthcare cost. CCDR is a cross-cutting field that frequently examines intersectional aspects of healthcare delivery. With that in mind, we explicitly define domains of CCDR to propel our research agenda into the next phase of the NCORP CCDR program while acknowledging the complex and dynamic fields of clinical care, policy level decisions, research findings, and needs of communities served by the NCORP network that will inform the subsequent research questions. To ensure programmatic success, we will engage a broad interdisciplinary group of investigators and clinicians with expertise and dedication to community oncology and the populations they serve., (© 2023 Wiley Periodicals LLC.)

Background: The study purpose is to describe trajectories of financial distress for parents of children (ages 1-14.9 years) with newly diagnosed acute lymphoblastic leukemia (ALL). The secondary aim is to identify multilevel factors (child, parent, household, treating institution) that influence change in financial distress over time., Methods: The study uses a prospective cohort design, repeated measurements, and mixed methods. The settings are Children's Oncology Group (COG) institutions participating in the National Cancer Institute Community Oncology Research Program (NCORP). Eligible participants are English- and/or Spanish-speaking parents or legal guardians (hereafter "parents") of index children. Parents are asked to complete a survey during their child's induction (T1) and maintenance therapy (T2), and near treatment completion (T3). Study surveys include items about (a) the child's cancer and clinical course, (b) parental socio-economic status, financial distress and financial coping behaviors, and (c) household material hardships. At least 15 parents will be invited to participate in an optional semi-structured interview. NCORP institutions that enroll at least one parent must complete an annual survey about institution resources that could influence parental financial distress., Discussion: The results will inform future interventions to mitigate financial distress for parents of children diagnosed with ALL and could be instructive beyond this disease group., Trial Registration: This trial was initially registered with the NCI Clinical Trial Reporting Program ID: NCI-2021-03,567 on June 16, 2021. The study can be found on clinicaltrials.gov, Identifier NCT04928599 ., (© 2022. The Author(s).)

Background: Although it is well documented that adolescents and young adults (AYAs) with cancer have low participation in cancer clinical trials (CCTs), the underlying reasons are not well understood. We used the National Cancer Institute Community Oncology Research Program (NCORP) network to identify barriers and facilitators to AYA CCT enrollment, and strategies to improve enrollment at community-based and minority and/or underserved sites., Methods: We performed one-on-one semistructured qualitative interviews with stakeholders (NCORP site principle investigators, NCORP administrators, physicians involved in enrollment, lead clinical research associates or clinical research nurses, nurse navigators, regulatory research associates, patient advocates) in the AYA CCT enrollment process. NCORP sites that included high and low AYA-enrolling affiliate sites and were diverse in geography and department representation (eg, pediatrics, medical oncology) were invited to participate. All interviews were recorded and transcribed. Themes related to barriers and facilitators and strategies to improve enrollment were identified., Results: We conducted 43 interviews across 10 NCORP sites. Eleven barriers and 13 facilitators to AYA enrollment were identified. Main barriers included perceived limited trial availability and eligibility, physician gatekeeping, lack of provider and research staff time, and financial constraints. Main facilitators and strategies to improve AYA enrollment included having a patient screening process, physician endorsement of trials, an "AYA champion" on site, and strong communication between medical and pediatric oncology., Conclusions: Stakeholders identified several opportunities to address barriers contributing to low AYA CCT enrollment at community-based and minority and/or underserved sites. Results of this study will inform development and implementation of targeted interventions to increase AYA CCT enrollment., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Associations between body mass index (BMI), outcome, and leukemia-related factors in children with acute myeloid leukemia (AML) remain unclear. We investigated associations between pretherapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML., Methods: We included patients, age 2-17 years, diagnosed with de novo AML from the five Nordic countries (2004-2016), Hong Kong (2007-2016), the Netherlands and Belgium (2010-2016), and Canada and USA (1995-2012). BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Kaplan-Meier estimator, Cox regression, and logistic regression were used to investigate associations., Results: In total, 867 patients were included. The median age was 10 years (range 2-17 years). At diagnosis, 32 (4%) were underweight, 632 (73%) were healthy weight, 127 (15%) were overweight, and 76 (9%) were obese. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age, and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1-3.4) and 2.8 (95% CI 1.3-5.8), respectively, compared to healthy weight patients., Conclusions: This study did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Timely medication access in pediatric oncology is important; yet barriers are poorly described. We surveyed pediatric oncology health care providers at National Cancer Institute Community Oncology Research Program sites on their experience with the impact of drug acquisition difficulties, prior authorization (PA) requests, insurance denials, and patient copays leading to deviations or delays from prescribed treatment for their pediatric/adolescent/young adult patients in calendar year 2016. PA requests, the most frequently cited issue, created a deviation or delay from planned chemotherapy and supportive care treatment in at least 61% of respondents. Half of the respondents believed that PA-induced delays had a negative impact on care. Two-thirds of respondents felt that delays in starting therapy due to barriers in medication access created psychologic or emotional distress for the patient or family. Pediatric cancer patients may be receiving inferior care as a result of barriers to medication access.

Background: It is questionable whether enrollment on clinical trials offers any survival advantage at the population level over standard-of-care treatment. The objectives of this study were to describe the impact of trial enrollment on event-free survival and overall survival in pediatric acute myeloid leukemia (AML) using the Cancer in Young People in Canada (CYP-C) database., Methods: Children were included if they had had AML newly diagnosed between ages birth and 14 years from 2001 to 2012. CYP-C is a national pediatric cancer population-based database that includes all cases of pediatric cancer diagnosed and treated at 1 of the 17 tertiary pediatric oncology centers in Canada. Univariate and Cox proportional hazards models were used to evaluate the impact of initial trial enrollment on survival., Results: In total, 397 eligible children with AML were included in the analysis, of whom 94 (23.7%) were enrolled on a clinical trial at initial diagnosis. The most common reason for non-enrollment was that no trial was available. The event-free survival rate at 5 years was 57.8% ± 5.2% for those enrolled versus 54.8% ± 2.9% for those not enrolled (P = .75). The overall survival rate at 5 years was 70.1% ± 4.9% for those enrolled versus 66.3% ± 2.8% for those not enrolled (P = .58). Enrollment on a trial was not associated with improved event-free or overall survival in multiple regression analyses., Conclusions: Enrollment on a clinical trial was not associated with improved survival for children with AML in a population-based cohort. Rationale for trial enrollment should not include the likelihood of benefit compared with non-enrollment., (© 2018 American Cancer Society.)

Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self-report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least "a little") and those who rated the degree of bother as severe ("a lot" or "extremely"). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15-18 and 11-14 years vs. 8-10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1-4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (β = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This article highlights key findings from the "Comprehensive Cancer Care for Children and Their Families" March 2015 joint workshop by the Institute of Medicine (IOM) and the American Cancer Society. This initiative convened more than 100 family members, clinician investigators, advocates, and members of the public to discuss emerging evidence and care models and to determine the next steps for optimizing quality-of-life outcomes and well-being for children and families during pediatric cancer treatment, after treatment completion, and across the life spectrum. Participants affirmed the triple aim of pediatric oncology that strives for every child with cancer to be cured; provides high-quality palliative and psychosocial supportive, restorative, and rehabilitative care to children and families throughout the illness course and survivorship; and assures receipt of high-quality end-of-life care for patients with advancing disease. Workshop outcomes emphasized the need for new pediatric cancer drug development and identified critical opportunities to prioritize palliative care and psychosocial support as an integral part of pediatric cancer research and treatment, including the necessity for adequately resourcing these supportive services to minimize suffering and distress, effectively address quality-of-life needs for children and families at all stages of illness, and mitigate the long-term health risks associated with childhood cancer and its treatment. Next steps include dismantling existing silos and enhancing collaboration between clinical investigators, disease-directed specialists, and supportive care services; expanding the use of patient-reported and parent-reported outcomes; effectively integrating palliative and psychosocial care; and clinical communication skills development. CA Cancer J Clin 2016;66:398-407. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: Little is known about emergency department (ED) use among pediatric patients with cancer. We explored reasons prompting ED visits and factors associated with hospital admission., Procedure: A retrospective cohort analysis of pediatric ED visits from 2006 to 2010 using the Nationwide Emergency Department Sample, the largest all-payer database of United States ED visits. Pediatric patients with cancer (ages ≤19 years) were identified using Clinical Classification Software. Proportion of visits and disposition for the top ten-ranking non-cancer diagnoses were determined. Weighted multivariate logistic regression was performed to analyze factors associated with admission versus discharge., Results: There were 294,289 ED visits by pediatric patients with cancer in the U.S. over the study period. Fever and fever with neutropenia (FN) were the two most common diagnoses, accounting for almost 20% of visits. Forty-four percent of pediatric patients with cancer were admitted to the same hospital, with admission rates up to 82% for FN. Risk factors for admission were: FN (odds ratio (OR) 8.58; 95% confidence interval (CI) 5.97-12.34); neutropenia alone (OR 7.28; 95% CI 5.08-10.43), ages 0-4 years compared with 15-19 years (OR 1.19; 95% CI 1.08-1.31) and highest median household income ZIP code (OR 1.27; 95% CI 1.08-1.49) compared with lowest. "Self-pay" visits had lower odds of admission (OR 0.42; 95% CI 0.35-0.51) compared with public payer., Conclusion: FN was the most common reason for ED visits among pediatric patients with cancer and is the condition most strongly associated with admission. Socioeconomic factors appear to influence ED disposition for this population., (© 2014 Wiley Periodicals, Inc.)

Purpose: To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification., Patients and Methods: Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children’s Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three)., Results: There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v. 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P.04) but not OS (3 years: 69.4% v. 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v. 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v. 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v. 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v. 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07)., Conclusion: GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML.

The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM., (© 2014 by The American Society of Hematology.)

Objective: Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care., Design: Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality., Setting: Forty-three children's hospitals contributing data to the Pediatric Health Information System database., Patients: Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied., Interventions: None., Measurements and Main Results: One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64-3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89-1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999-2003 vs 16.4% in 2004-2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999-2003 vs 6.5% in 2004-2010 in the nononcology cohort, p < 0.0001)., Conclusions: Pediatric patients with acute myeloid leukemia frequently required intensive care resources, with mortality rates substantially lower than previously reported. Mortality also decreased over the time studied. Pediatric acute myeloid leukemia patients with sepsis who required intensive care had a mortality comparable to children without oncologic diagnoses; however, overall mortality and mortality for each category of organ failure studied was higher for the acute myeloid leukemia cohort compared with the nononcology cohort.

Background: Candida species are the third most common cause of pediatric health care-associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis., Methods: From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis., Results: Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes., Conclusions: We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.

The purpose of this manuscript is to summarize issues relevant to health-related quality of life (HRQL), physical function, and neurocognitive function for survivors of pediatric hematopoietic stem cell transplantation (HCT). The physiologic and psychological demands of HCT and its sequelae have the potential to substantially alter HRQL. When compared with research on adult HCT recipients, research in pediatric HRQL following HCT has lagged considerably. Initially, this lag was because of limited validated questionnaires, small numbers of affected patients, and a general lack of salience for the topic relative to traditional endpoints, such as transplant-related toxicity and potential mortality. The percentage of childhood HCT survivors with physical disability ranges from 7% to 17% in studies where the outcome was based on clinician or self-report measures, to over 40% in studies where the outcome was based on a directly measured physical performance task. Direct and comprehensive measures of physical performance may help further clarify the proportion of individuals who have subclinical problems amenable to intervention before apparent functional loss becomes a problem. There is a need to include longer term survivors in such an assessment. In terms of neurocognitive function, the majority of reports demonstrate relatively good function in survivors. However, it is clear that little or no data on outcomes beyond 5 years posttransplant have been obtained, and clinicians working with this population remain concerned regarding the cognitive functions of these survivors. Research focused on these domains should attempt to better understand the prevalence of the problem using child self-report and direct measurements of function, standardize measurement methods, and tools across trials, obtain longer term evaluations and begin to consider interventional trials., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls., Methodology/principal Findings: To obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56-0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34-0.36). High intake of antioxidants (OR 0.67-0.86, p = 0.04-0.05) and carotenoids (OR 0.68-0.86, p = 0.03-0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42-0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19-1.67, p = 0.07-0.17) to breast cancer., Conclusions/significance: Based on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet.