Belinda N. Mandrell

Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL

BACKGROUND Dexamethasone contributes to high cure rates in paediatric acute lymphoblastic leukaemia (ALL) but significantly and adversely alters sleep and fatigue. Herein we explored three mechanisms (pharmacokinetics, serum albumin and pharmacogenetics) through which dexamethasone may cause debilitating fatigue and disrupted sleep. METHODS We enrolled 100 patients on a 10-d study: 5-d of no dexamethasone (OFF DEX) followed by 5-d of dexamethasone (ON DEX) during continuation chemotherapy. Sleep variables were collected with continuous actigraphy on days 1 through 5, both OFF DEX and ON DEX. On days 2 and 5 of each 5-d period, parents and patients 7 years of age and older completed a sleep diary and Fatigue Scale questionnaire. Blood was collected at 0 (pre-dexamethasone), 1, 2, 4 and 8 h after the first oral dexamethasone dose for pharmacokinetic analysis. Serum albumin concentration was retrospectively analysed in stored samples. Patient DNA was genotyped for 99 polymorphic loci in candidate genes associated with glucocorticoid metabolism. RESULTS Dexamethasone clearance was significantly greater in younger patients than in older ones and in lower risk patients. In multiple regression models, risk group was significantly related to pharmacokinetic parameters. We found that polymorphisms in three genes (AHSG, IL6, POLDIP3) were significantly associated with sleep measures but not with fatigue. CONCLUSION Risk group had the most significant relationship with disrupted sleep in patients while on dexamethasone. Serum albumin levels had neither a direct relationship with sleep or fatigue variables nor an indirect relationship through systemic exposure to dexamethasone. We identified candidate genes that may help explain the adverse events of disrupted sleep in paediatric patients receiving dexamethasone.

Research Priorities in Pediatric Palliative Care

OBJECTIVE To synthesize the perspectives of a broad range of pediatric palliative care (PPC) clinicians and parents, to formulate a consensus on prioritization of the PPC research agenda. STUDY DESIGN A 4-round modified Delphi online survey was administered to PPC experts and to parents of children who had received PPC. In round 1, research priorities were generated spontaneously. Rounds 2 and 3 then served as convergence rounds to synthesize priorities. In round 4, participants were asked to rank the research priorities that had reached at least 80% consensus. RESULTS A total of 3093 concepts were spontaneously generated by 170 experts and 72 parents in round 1 (65.8% response rate [RR]). These concepts were thematically organized into 78 priorities and recirculated for round 2 ratings (n = 130; 53.7% RR). Round 3 achieved response stability, with 31 consensus priorities oscillating within 10% of the mode (n = 98; 75.4% RR). Round 4 resulted in consensus recognition of 20 research priorities, which were thematically grouped as decision making, care coordination, symptom management, quality improvement, and education. CONCLUSIONS This modified Delphi survey used professional and parental consensus to identify preeminent PPC research priorities. Attentiveness to these priorities may help direct resources and efforts toward building a formative evidence base. Investigating PPC implementation approaches and outcomes can help improve the quality of care services for children and families.

Psychometric and Clinical Assessment of the 13-Item Reduced Version of the Fatigue Scale–Adolescent Instrument:

Fatigue is one of the most common and distressing symptoms experienced by adolescents during and after treatment for cancer. The lack of reliable and valid instruments has prevented an accurate assessment of the trajectory of fatigue among adolescent oncology patients. The purposes of this study were to identify the items on the Fatigue Scale–Adolescent (FS-A) that distinguished adolescents with high fatigue and to identify the most sensitive and specific score (“cut score”) in order to identify those in need of a fatigue intervention. Rasch methods were used to identify FS-A items that distinguished adolescents with high cancer-related fatigue, and results indicated that the 14-item FS-A could be reduced to 13 items. The 13-item FS-A was assessed for its psychometric properties, with application of the receiver operating characteristics curve analysis to the responses from 75 adolescents. The internal consistency coefficient was .87, and a 4-factor confirmatory analysis achieved good fit coefficients. The identified cut score was 31, with 66.6% sensitivity and 82.6% specificity; 16 (21.33%) of the patients scored 31 or higher. The 13-item FS-A has acceptable psychometric properties and is able to identify adolescent oncology patients with high fatigue.

Patients’ and Parents’ Needs, Attitudes, and Perceptions About Early Palliative Care Integration in Pediatric Oncology

Importance Early palliative care integration for cancer patients is now touted as the optimal care model, yet significant barriers often prevent its implementation. A perceived barrier, especially for pediatric oncology patients, is the notion that patients and their families may not need or want palliative care involvement early in the disease trajectory. Objective To determine the perception of symptom burden early in treatment and assess attitudes toward early integration of palliative care in pediatric oncology patient-parent pairs. Design, Setting, and Participants Novel but pretested survey tools were administered to 129 patient-parent dyads of hospital-based pediatric oncology ambulatory clinics and inpatient units between September 2011 and January 2015. All patient participants were aged between 10 and 17 years and were diagnosed as having an oncologic condition 1 month to 1 year before enrollment. Both the patient and the parent in the dyad spoke English, and all participating parents provided written informed consent. A convenience sample was used for selection, with participants screened when otherwise presenting at a participating site. A total of 280 eligible participants were approached for study inclusion, 258 of whom were enrolled in the study (92.1% positive response-rate). Main Outcomes and Measures Degree of perceived suffering from early symptom-related causes, attitudes toward early palliative care integration, and patient-parent concordance. Statistical analysis included descriptive statistics, calculation of concordance, McNemar test results, and Cochran-Armitage trend test results. Results Of the 129 patients in the dyads, 68 were boys, and 61 girls; of the 129 parents, 15 were men, and 114 women. Patients reported the following symptoms in the first month of cancer therapy: nausea (n = 109; 84.5%), loss of appetite (n = 97; 75.2%), pain (n = 96; 74.4%), anxiety (n = 77; 59.7%), constipation (n = 69; 53.5%), depression (n = 64; 49.6%), and diarrhea (n = 52; 40.3%). A large proportion of those reporting suffering indicated substantial suffering severity from specific symptoms (ie, a great deal or a lot) including nausea, 52.3% (57 of 109), loss of appetite, 50.5% (49 of 97), constipation 30.4% (21 of 69), pain 30.2% (29 of 96), anxiety 28.6% (22 of 77), depression 28.1% (18 of 64), and diarrhea 23.1% (12 of 52). Few children and parents expressed opposition to early palliative care involvement (2 [1.6%] and 8 [6.2%]) or perceived any detrimental effects on their relationship with their oncologist (6 [4.7%] and 5 [3.9%]), loss of hope (3 [2.3%] and 10 [7.8%]), or therapy interference (3 [2.3%] and 2 [1.6%], respectively). Intradyad concordance was low overall: 26% to 29% for exact concordance and 40% to 69% for agreement within 1 response category. Significant differences in patient-parent attitudes toward aspects of early palliative care included child participants being more likely than their parents (40.3% [n = 52] vs 17.8% [n = 23]) to indicate that palliative care would have been helpful for treating their symptoms (P < .001). Conclusions and Relevance Pediatric oncology patients experience a high degree of symptom-related suffering early in cancer therapy, and very few patients or parents in this study expressed negative attitudes toward early palliative care. Our findings suggest that pediatric oncology patients and families might benefit from, and are not a barrier to, early palliative care integration in oncology.

Excessive daytime sleepiness and sleep-disordered breathing disturbances in survivors of childhood central nervous system tumors.

Improvements in treatment and management for pediatric central nervous system (CNS) tumors have increased survival rates, allowing clinicians to focus on long‐term sequelae, including sleep disorders. The objective of this study was to describe a series of CNS tumor survivors who had sleep evaluations that included polysomnography (PSG) with attention to sleep disorder in relation to the tumor site.

Aluminum toxicity following intravesical alum irrigation for hemorrhagic cystitis

Mental status changes in an immunosuppressed child can be due to a variety of causes; aluminum toxicity is rarely considered. We report a teenage girl with acute lymphoblastic leukemia who developed mental status changes, speech disturbance, coarse tremor, and abnormal EEG findings following intravesical 1% alum irrigation and administration of aluminum-containing antacids. Her serum aluminum levels were mildly elevated (14-22 milligram(s), normal 0-6 milligram(s)), and bone marrow biopsy specimens demonstrated aluminum deposition on special staining (Kruegers method). All abnormalities resolved after a nine-week course of intravenous deferoxamine.

Does phase 1 trial enrollment preclude quality end-of-life care? Phase 1 trial enrollment and end-of-life care characteristics in children with cancer.

End‐of‐life care (EOLC) discussions and treatment‐related decisions, including phase 1 trial enrollment, in patients with incurable disease are complex and can influence the quality of EOLC received. The current study was conducted in pediatric oncology patients to determine whether end‐of‐life characteristics differed between those who were and were not enrolled in a phase 1 trial.

Pediatric HIV disclosure: a process-oriented framework.

As children with vertically transmitted human immunodeficiency virus (HIV) infection live into adulthood, caregivers face the stressful process of informing their children about their infection. Although developmentally guided disclosure of HIV status is widely recommended, there are few specific frameworks to guide caregivers, families, and health care providers through the disclosure process. The authors propose a process-oriented framework for the disclosure of HIV in children and adolescents. This educational framework incorporates Piagets cognitive development theory in an attempt to disclose and assist children and adolescents in understanding their HIV status. The framework is organized into 10 sequential stages of disclosure and three assessment stages in which health care providers discuss HIV health concepts with the child and caregiver, based on the childs developmental readiness. The described framework can be easily replicated by health care providers in disclosing disease status to children with HIV.

Development of a respite care program for caregivers of pediatric oncology patients and their siblings.

Children with chronic health care needs, including those with cancer, require complex care under direct caregiver supervision. This intensive care management may result in increased stress and psychological distress for the caregiver and family. Respite care services are needed in providing alleviation of caregiver stress among families of children with complex health care needs. This report describes the feasibility of a pilot hospital-based respite care program for caregivers of pediatric oncology patients and their siblings and development of a permanent, expanded service to include both inpatient and outpatient units under the supervision of hospital volunteer services. During the feasibility pilot, 39 respite care requests were made by caregivers for care of patients, with 67% of these requests for care of infants and toddlers. The respite care providers were hospital volunteers. Reasons for the caregiver respite care request included a need to leave the hospital for running an errand, eating a meal, taking a mental break, or talking with the medical team. At the completion of the pilot, caregivers and staff were surveyed and expressed a strong desire for continuation of the service. The success of the pilot led to the implementation of a formal respite care program, Helping Hands, which provides services 7 days a week for inpatients, outpatients, and their siblings. Although this respite care service is specific to children with cancer, the program model is feasible within most pediatric care facilities.

Disturbed Sleep in Pediatric Patients With Leukemia: The Potential Role of Interleukin-6 (-174GC) and Tumor Necrosis Factor (-308GA) Polymorphism

PURPOSE/OBJECTIVES To explore an association between sleep quality in children and adolescents undergoing therapy for acute lymphoblastic leukemia (ALL) and polymorphisms in two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor (TNF). DESIGN Retrospective exploratory analysis using data from a multi-institutional prospective study comparing objective sleep measures by actigraphy over 10 days with retrospective genotyping of IL-6 (-174GC) and TNF (-308GA). SETTING Pediatric oncology centers in the southeastern and southwestern United States and in Canada. SAMPLE 88 children or adolescents with ALL. METHODS Secondary analysis of 88 patients (ages 5-18) with sleep quality measured by actigraphy over 10 days in their home environment and retrospective DNA genotyping. MAIN RESEARCH VARIABLES Sleep variables and genotype. FINDINGS IL-6 promoter (-174G>C) C allele was associated with fewer total daily sleep minutes (p = 0.028) and fewer daily nap minutes (p < 0.01). Patients with the TNF genotype AA had 28.2 more minutes of wake after sleep onset (p = 0.015), 3.4 more nocturnal wake episodes (p = 0.026), and a 5% lower sleep efficiency rate (p = 0.03) than their GA genotype counterparts. CONCLUSIONS Patients with the TNF (-308G>A) or IL-6 (-174G>C) polymorphisms demonstrated disturbed sleep. This study is the first to find a relationship between these two cytokines and disturbed sleep in children and adolescents with cancer. IMPLICATIONS FOR NURSING Disturbed sleep among pediatric patients with cancer is multifactoral and includes interactions among environment, medications, and genotype. Additional research should explore serum proinflammatory cytokine levels and the influence of mood and worry on sleep.