Molecular Profile of Women With and Without Secondary Breast Cancer After the Treatment of Pediatric Hodgkin Lymphoma

dentification of genetic risk factors associated with the development of secondary cancers would facilitate identification of at risk patients and permit modification of therapy and heightened surveillance that may reduce cancer-related morbidity and mortality. Women survivors of pediatric Hodgkin lymphoma (HL) have an increased risk of morbidity and mortality associated with secondary effects of therapy, with a 35-75 fold excess risk of developing breast cancer over the general population. The mechanism for secondary breast cancer among Hodgkin survivors is not understood. Researchers have postulated that the familial characteristics of HL could be associated with mutations found within familial cancer syndromes; however, these mutations have not been identified. This has led to the exploration of inherent polymorphisms that might impair the patient’s capability to detoxify chemotherapy and/or repair DNA damage produced by irradiation. Examinations of candidate polymorphisms indicate that single nucleotide changes may have only a small effect on the development of subsequent cancers. However, multiple studies support the idea that sensitivity to irradiation and the subsequent development of breast cancer is mediated through the interaction of multiple genes or gene complexes. The objective of this case-control study design was to explore the identification of potential candidate genes and polymorphisms that may be risk factors for the development of secondary breast cancer among women who are pediatric HL survivors. Global gene expression and genotyping of women with (n=13) and without (n=36) secondary breast cancer after the treatment of pediatric HL were compared. Differences were found in global gene expression and genotyping between the cases and controls. Additionally, copy number variation in association with gene expression found a locus of interest at 15q11.2 in association with the development of secondary breast cancer

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma

Objective: Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. Methods: Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. Results: EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. Conclusion: Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity

Impact of PEWS on Perceived Quality of Care During Deterioration in Children With Cancer Hospitalized in Different Resource-Settings

BackgroundChildren with cancer are at high risk for clinical deterioration and subsequent mortality. Pediatric Early Warning Systems (PEWS) have proven to reduce the frequency of clinical deterioration in hospitalized patients. This qualitative study evaluates provider perspectives on the impact of PEWS on quality of care during deterioration events in a high-resource and a resource-limited setting.MethodsWe conducted semi-structured interviews with 83 healthcare staff (nurses, pediatricians, oncology fellows, and intensivists) involved in recent deterioration events at two pediatric oncology hospitals of different resource levels: St. Jude Children’s Research Hospital (SJCRH; n = 42) and Unidad Nacional de Oncología Pediátrica (UNOP; n = 41). Interviews were conducted in the participant’s native language (English or Spanish), translated into English, and transcribed. Transcripts were coded and analyzed inductively.ResultsProviders discussed both positive and negative perspectives of clinical deterioration events. Content analysis revealed “teamwork,” “experience with deterioration,” “early awareness,” and “effective communication” as themes associated with positive perception of events, which contributed to patient safety. Negative themes included “lack of communication,” “inexperience with deterioration,” “challenges with technology”, “limited material resources,” “false positive score,” and “objective tool.” Participants representing all disciplines across both institutions shared similar positive opinions. Negative opinions, however, differed between the two institutions, with providers at UNOP highlighting limited resources while those at SJCRH expressing concerns about technology misuse.ConclusionProviders that care for children with cancer find PEWS valuable to improve the quality of hospital care, regardless of hospital resource-level. Identified challenges, including inadequate critical care resources and challenges with technology, differ by hospital resource-level. These findings build on growing data demonstrating the positive impact of PEWS on quality of care and encourage wide dissemination of PEWS in clinical practice

A new measure for multi-professional medical team communication: design and methodology for multilingual measurement development

BackgroundAs implementation science in global health continues to evolve, there is a need for valid and reliable measures that consider diverse linguistic and cultural contexts. A standardized, reproducible process for multilingual measure development may improve accessibility and validity by participants in global health settings. To address this need, we propose a rigorous methodology for multilingual measurement development. We use the example of a novel measure of multi-professional team communication quality, a determinant of implementation efforts.MethodsThe development and translation of this novel bilingual measure is comprised of seven steps. In this paper, we describe a measure developed in English and Spanish, however, this approach is not language specific. Participants are engaged throughout the process: first, an interprofessional panel of experts and second, through cognitive interviewing for measure refinement. The steps of measure development included: (1) literature review to identify previous measures of team communication; (2) development of an initial measure by the expert panel; (3) cognitive interviewing in a phased approach with the first language (English); (4): formal, forward-backward translation process with attention to colloquialisms and regional differences in languages; (5) cognitive interviewing repeated in the second language (Spanish); (6) language synthesis to refine both instruments and unify feedback; and (7) final review of the refined measure by the expert panel.ResultsA draft measure to assess quality of multi-professional team communication was developed in Spanish and English, consisting of 52 questions in 7 domains. This measure is now ready for psychometric testing.ConclusionsThis seven-step, rigorous process of multilingual measure development can be used in a variety of linguistic and resource settings. This method ensures development of valid and reliable tools to collect data from a wide range of participants, including those who have historically been excluded due to language barriers. Use of this method will increase both rigor and accessibility of measurement in implementation science and advance equity in research and practice

sleep, circadian rhythms and fatigue in children with CNS tumors hospitalized for high dose chemotherapy

This study tested a sleep promotion intervention (randomized controlled trial) in children with recently diagnosed central nervous system tumors admitted to the hospital for high dose chemotherapy in preparation for autologous stem cell rescue

Relationship between circadian activity rhythms and fatigue in hospitalized children with CNS cancers receiving high-dose chemotherapy.

PURPOSE:Robust circadian rhythms are increasingly recognized as essential to good health. Adult cancer patients with dysregulated circadian activity rhythms (CAR) experience greater fatigue, lower responsiveness to chemotherapy, and shorter time to relapse. There is scant research describing circadian rhythms and associated outcomes in children with cancer. As part of a larger study examining whether a cognitive-behavioral intervention could preserve sleep in children and adolescents with central nervous system cancers hospitalized for high-dose chemotherapy (HDCT), this study aimed to compare CAR of these children to published values and to investigate the relationship between CAR and fatigue. METHODS:Participants aged 4-19 years wore an actigraph throughout their hospitalization (5 days). From activity counts recorded by actigraphy, six CAR variables were calculated: amplitude, 24-h autocorrelation (r24), dichotomy index (I < O), interdaily stability (IS), intradaily variability (IV), and acrophase. Parent-reported child fatigue and child/adolescent self-reported fatigue measures were collected daily. RESULTS:Thirty-three participants were included. Three CAR variables (amplitude, r24, and I < O) showed dysregulation compared to published values. Older age was significantly associated with later acrophase and greater dysregulation of all other CAR variables. Controlling for age, more dysregulated amplitude (p = 0.001), r24 (p = 0.003), IS (p = 0.017), and IV (p = 0.001) were associated with higher parent-reported fatigue; more dysregulated IV (p = 0.003) was associated with higher child-reported fatigue. CONCLUSIONS:Participants demonstrated dysregulated CAR during hospitalization for HDCT. Greater dysregulation was associated with greater fatigue. Research on circadian dysregulation and its relationship to health-related outcomes in children with cancer, and interventions to support circadian rhythmicity, is urgently needed

A pilot randomized controlled trial to improve sleep and fatigue in children with central nervous system tumors hospitalized for high‐dose chemotherapy

ObjectivesTo determine whether a sleep intervention compared with standard of care (SOC) was successful in preserving nighttime sleep in children with central nervous system cancers hospitalized for high-dose chemotherapy (HDCT) and autologous stem cell rescue, and to explore associations between sleep and fatigue during treatment.MethodsAn unblinded, randomized, controlled, multicomponent intervention (NCT00666614) including evidence-based cognitive and behavioral strategies to improve sleep was implemented in 33 children (age 4-12 years) and adolescents (age 13-19 years) during hospitalization. Children wore an actigraph to measure sleep and wake, and reported fatigue scores daily. Parents concurrently kept a sleep diary and reported fatigue scores for their children.ResultsThe mean age was 9.5 ± 3.9 years, 81.8% were white, and 60.6% were male. Sleep in all children was seriously disturbed throughout the study. Children in the intervention group maintained their longest nighttime sleep across the study, while it declined in children receiving SOC (P = 0.009 for interaction). There were few other differences in sleep between groups. Controlling for age and baseline fatigue, higher nighttime activity score, and lower percent sleep were significantly associated with higher next-day adolescent-reported fatigue (P < 0.05); longest sleep was significantly positively associated with next-day child-reported fatigue (P = 0.018).ConclusionIn this sample of children undergoing HDCT, a multicomponent sleep intervention modestly preserved nighttime sleep duration, although overall sleep was poor in both groups. Sleep is an integral component of health, and may influence outcomes of children receiving HDCT. Further investigation into methods of preserving sleep in children undergoing intensive cancer therapy is warranted

Student/patient: the school perceptions of children with cancer

Childhood cancer incidence is rising, affecting a growing proportion of elementary school students. For most of these children, school attendance can be limited by hospitalisations, treatments and side effects. However, little is yet known about the educational needs and experiences of this population. This phenomenological study explored the school experiences of 10 6- to 12-year-old children with cancer as they underwent chemotherapy. Results revealed perceptions that attending school in the hospital or home during cancer treatment is essentially lonely, confusing and “different”. These perceptions intertwined to illuminate five themes: (1) school should involve fun activities; (2) group educational formats are preferable; (3) old school is the “best school”; (4) being a “good student” is important during treatment; and (5) attending school is complicated during treatment. Therefore, hospital-based and homebound schooling programmes should integrate socially interactive and cognitively engaging curriculum to best support the learning needs of this population