Keepers of the House: A documentary.

BACKGROUND: Our documentary, Keepers of the House, highlights ways that hospital housekeepers, typically unnoticed care team members, provide emotional support for patients and their families. This film addresses a gap in education by emphasizing the importance of valuing and reflecting on the unique lived experiences of others. APPROACH: We created this documentary to expose students to the experiences and perceptions of hospital housekeepers. A focus group with six hospital housekeepers informed an interview script for the film's creation. Nine additional housekeepers were then interviewed, which developed into a 15-min documentary. Healthcare students and educators from five disciplines viewed the documentary during their institution's Medical Education Day. EVALUATION: To expose students and educators to housekeepers' experiences, we designed our post-viewing survey to address whether the housekeepers' stories impacted their understanding of the role and value of these workers. Viewers were surprised by the depth and breadth of patient-housekeeper interactions, the trauma housekeepers experienced from patient loss and the pride housekeepers take in their work. The stories that touched the viewers varied but centred on connections between housekeepers and patients. Lessons learned focused on recognizing the contributions of unseen team members. IMPLICATIONS: This innovative documentary amplifies the perspectives of voices rarely heard in healthcare. We aim to use this film, alongside its associated learning session, in education and grand round settings to foster discussion around empathy, valuing underrecognised team members and applying these insights in practice. This work can be disseminated to other institutions, further amplifying underrepresented narratives in healthcare.

The Utility of Verbal Therapy for Pediatric Cancer Patients and Survivors: Expressive Writing, Video Narratives, and Bibliotherapy Exercises.

Childhood cancer is a stressful experience. No pediatric patient, however, should be made to feel as if their concerns and feelings about their cancer experience must be bottled up inside. Importantly, talking and writing about one's illness has myriad implications for young cancer patients and survivors. The most salient of these may include increased understanding of one's condition as well as improved physical and cognitive symptoms (e.g., lowered depression, decreased anxiety, and an enhanced quality of life overall). This literature review explores three promising avenues for verbal therapy in the pediatric oncology setting: expressive writing, video narratives, and bibliotherapy exercises. Several recent studies, covering verbal therapy methods from illness blogging to book interventions, are referenced and discussed. Ultimately, we conclude that expressive writing, video narratives, and bibliotherapy exercises are valuable, feasible, inexpensive, and acceptable tools for patients and survivors of childhood cancer to facilitate self-expression-and to find meaning in the uncertainty and anxiety that cancer inherently fosters. We recommend that future studies investigate this theme so that we may improve quality of life and mental health for pediatric cancer patients and survivors worldwide.

Human Flourishing in Adolescents with Cancer: Experiences of Pediatric Oncology Health Care Professionals.

PURPOSE: This study explores human flourishing (HF) in adolescents with cancer (AC) as witnessed by their health care providers, and it develops a list of critical attributes associated with HF to describe the positive outcomes witnessed. DESIGN AND METHODS: Our study used a qualitative descriptive design incorporating data from an open-ended electronic survey and semi-structured individual interviews with 17 pediatric oncology health care providers. RESULTS: We found 3 major themes (positive forward motion, connectedness, and self-character) representing 11 critical attributes of human flourishing in AC: (1) initiative and enterprise, (2) positivity and evocativeness, (3) tranquility and maturity, (4) perseverance and tenacity, (5) compassion and empathy, (6) social engagement and connection, (7) wisdom and translation into life, (8) supportive background, (9) self-awareness and self-agency, (10) transcendence and full potential, and (11) meaning-making. CONCLUSIONS: Understanding the concept of HF as it applies to the needs of AC is a step toward establishing it as a comprehensive health care goal and toward developing care provider guidelines for its promotion. PRACTICE IMPLICATIONS: Given the attributes of HF in AC, nurses can consider HF as an ultimate nursing care outcome and should focus on goals of care beyond disease treatment and symptoms mitigation when providing care for this population. Holistic, individualized assessment, timely care during each phase of treatment, and developmentally tailored intervention should be provided.

Ethical considerations of using a single minor donor for three bone marrow harvests for three HLA-matched siblings with primary immunodeficiency.

Allogeneic hematopoietic stem cell transplantation is curative for primary immunodeficiencies. Bone marrow from an unaffected human leukocyte antigen (HLA)-identical sibling donor is the ideal graft source. For minor donors, meaningful consent or assent may not be feasible, and permission from parents or legal guardians is considered acceptable. Adverse events, albeit extremely small, can be associated with bone marrow harvest in pediatric donors. Donor safety concerns potentially increase with multiple bone marrow harvests. Very little is known about multiple bone marrow harvests from pediatric donors. We describe the ethical considerations and clinical decision-making in an unusual clinical situation where three patients with the same primary immunodeficiency were HLA identical to one another and their younger sibling, who underwent bone marrow harvests three times between 1.3 and 4 years of age, resulting in successful transplantation for all three patients. We hope that this experience will provide guidance to providers and families in a similar situation.

Exploring the vagueness of Religion & Spirituality in complex pediatric decision-making: a qualitative study.

BACKGROUND: Medical advances have led to new challenges in decision-making for parents of seriously ill children. Many parents say religion and spirituality (R&S) influence their decisions, but the mechanism and outcomes of this influence are unknown. Health care providers (HCPs) often feel unprepared to discuss R&S with parents or address conflicts between R&S beliefs and clinical recommendations. Our study sought to illuminate the influence of R&S on parental decision-making and explore how HCPs interact with parents for whom R&S are important. METHODS: A longitudinal, qualitative, descriptive design was used to (1) identify R&S factors affecting parental decision-making, (2) observe changes in R&S themes over time, and (3) learn about HCP perspectives on parental R&S. The study sample included 16 cases featuring children with complex life-threatening conditions. The length of study for each case varied, ranging in duration from 8 to 531 days (median = 380, mean = 324, SD = 174). Data from each case included medical records and sets of interviews conducted at least monthly with mothers (n = 16), fathers (n = 12), and HCPs (n = 108). Thematic analysis was performed on 363 narrative interviews to identify R&S themes and content related to decision-making. RESULTS: Parents from 13 cases reported R&S directly influenced decision-making. Most HCPs were unaware of this influence. Fifteen R&S themes appeared in parent and HCP transcripts. Themes most often associated with decision-making were Hope & Faith, God is in Control, Miracles, and Prayer. Despite instability in the child's condition, these themes remained consistently relevant across the trajectory of illness. R&S influenced decisions about treatment initiation, procedures, and life-sustaining therapy, but the variance in effect of R&S on parents' choices ultimately depended upon other medical & non-medical factors. CONCLUSIONS: Parents consider R&S fundamental to decision-making, but apply R&S concepts in vague ways, suggesting R&S impact how decisions are made more than what decisions are made. Lack of clarity in parental expressions of R&S does not necessarily indicate insincerity or underestimation of the seriousness of the child's prognosis; R&S can be applied to decision-making in both functional and dysfunctional ways. We present three models of how religious and spiritual vagueness functions in parental decision-making and suggest clinical applications.

Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids.

Ethical decision making about end-of-life care issues by pediatric oncologists in economically diverse settings.

PURPOSE: Pediatric cancer represents 1% to 4% of all cancers worldwide, with the majority of diagnoses in developing countries where mortality remains much higher than that in high-income countries. We sought to describe differences in ethical decision-making at the end of life among an international sample of pediatric oncologists practicing in countries with a variety of income levels and resource settings. METHODS: Pediatric oncologists subscribing to an educational international oncology Web site were invited to complete a 38-item web-based survey investigating ethical domains related to end-of-life care: level of care, fiduciary responsibility, decision making, and justice. RESULTS: Responses were received from 401 physicians in 83 countries, with most respondents practicing in middle-income or high-income countries. Significant differences in attitudes toward ethical issues existed across the national developmental indices. CONCLUSIONS: Further education on ethical principles is warranted in pediatric oncology, particularly among oncologists practicing in low-income or middle-income countries.

Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma.

PURPOSE: The addition of immunotherapy, including a combination of anti-GD2 monoclonal antibody (mAb), ch14.18, and cytokines, improves outcome for patients with high-risk neuroblastoma. However, this therapy is limited by ch14.18-related toxicities that may be partially mediated by complement activation. We report the results of a phase I trial to determine the maximum-tolerated dose (MTD), safety profile, and pharmacokinetics of hu14.18K322A, a humanized anti-GD2 mAb with a single point mutation (K322A) that reduces complement-dependent lysis. PATIENTS AND METHODS: Eligible patients with refractory or recurrent neuroblastoma received escalating doses of hu14.18K322A ranging from 2 to 70 mg/m(2) per day for 4 consecutive days every 28 days (one course). RESULTS: Thirty-eight patients (23 males; median age, 7.2 years) received a median of two courses (range, one to 15). Dose-limiting grade 3 or 4 toxicities occurred in four of 36 evaluable patients and were characterized by cough, asthenia, sensory neuropathy, anorexia, serum sickness, and hypertensive encephalopathy. The most common non-dose-limiting grade 3 or 4 toxicities during course one were pain (68%) and fever (21%). Six of 31 patients evaluable for response by iodine-123 metaiodobenzylguanidine score had objective responses (four complete responses; two partial responses). The first-course pharmacokinetics of hu14.18K322A were best described by a two-compartment linear model. Median hu14.18K322A α (initial phase) and ß (terminal phase) half-lives were 1.74 and 21.1 days, respectively. CONCLUSION: The MTD, and recommended phase II dose, of hu14.18K322A is 60 mg/m(2) per day for 4 days. Adverse effects, predominately pain, were manageable and improved with subsequent courses.

64Cu-p-NH2-Bn-DOTA-hu14.18K322A, a PET radiotracer targeting neuroblastoma and melanoma.

UNLABELLED: The hu14.18K322A variant of the GD2-targeting antibody hu14.18 has been shown to elicit a level of antibody-dependent cell-mediated cytotoxicity toward human neuroblastoma cells similar to that of the parent antibody. However, hu14.18K322A exhibited a decreased complement activation and associated pain, the dose-limiting toxicity in neuroblastoma immunotherapy. PET with a radiolabeled analog of the same antibody used in treatment will provide insight into the ability of hu14.18K322A to reach its target, as well as nontarget uptake that may cause side effects. Such antibody radiotracers might also provide a method for measuring GD2 expression in tumors, thus enabling the prediction of response to anti-GD2 therapy for individual patients. METHODS: The conjugation of hu14.18K322A with p-NH(2)-Bn-DOTA was accomplished using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide with subsequent (64)Cu radiolabeling at 37°C for 30 min. Immunoreactivity of the conjugate was assessed by a dose-escalation blocking experiment measuring binding to purified GD2 versus GD1b as a negative control. Cell uptake and biodistribution studies in M21 (GD2-positive) and PC-3 (GD2-negative) tumor models were performed, as was small-animal PET/CT of M21 and PC-3 tumor-bearing mice. RESULTS: The labeling of (64)Cu-p-NH(2)-Bn-DOTA-hu14.18K322A was achieved at more than 95% radiochemical purity and a specific activity of 127-370 MBq/mg (3.4-10 mCi/mg) after chromatographic purification. Preliminary in vitro data demonstrated a greater than 6-fold selectivity of binding to GD2 versus GD1b and dose-dependent inhibition of binding by unmodified hu14.8K322A. In vivo data, including small-animal PET/CT, showed significant GD2-positive tumor-targeting ability, with a persistent 2-fold-higher uptake of radiotracer than in GD2-negative tumors. CONCLUSION: (64)Cu-p-NH(2)-Bn-DOTA-hu14.18K322A represents a novel PET radiotracer to facilitate clinical investigations of anti-GD2 immunotherapies and to complement other imaging modalities in the staging and treatment of neuroblastoma.

Addressing parental bereavement support needs at the end of life for infants with complex chronic conditions.

INTRODUCTION: Health care providers' understandings of parental bereavement needs before and in the acute period following the death of an infant with a complex chronic condition are based upon models that outline the process of grief and provide direction for possible points of intervention. These models do not address prospective factors along the illness trajectory that may contribute to the depth and debilitating nature of grief, and fail to clarify the influence of social structures on parents' experience and construct of grief, loss, and mourning. The purpose of this study was to prospectively describe the bereavement experience of parents whose infants die in acute care settings with a complex chronic condition. METHODS: A longitudinal, qualitative, descriptive design was used to explore the process of parental bereavement. Extreme case sampling with variation on race, socioeconomic status, prenatal diagnosis, and multiple gestations was used to select 7 cases represented by over 72 narrative interviews with parents. RESULTS: Findings are organized into five broad categories: Having Expectations, Continuity of Care, Memory Making, Wide Network of Support, and Altruism. Themes under each category were developed based upon examples given in the parental interviews. CONCLUSION: This study provides an exploration of the complex and longitudinal nature of bereavement. Anticipatory support initiated prior to the death of an infant can help parents experience a smoother transition from caring for their very ill child to coping with the actual death event and its aftermath.

Association of IL-1ß -511 polymorphism with severe veno-occlusive disease in pediatric-matched allogeneic hematopoietic stem cell transplantation.

Single nucleotide polymorphisms (SNPs) of the interleukin 1 (IL-1) family have been implicated in acute graft-versus-host disease and mortality postallogeneic hematopoietic stem cell transplantation (HSCT) in adults. Hepatic veno-occlusive disease (VOD) is a well-known complication of HSCT and can result in an increased risk of mortality. In this study, we sought to investigate the association of both patient and donor genotypes at the IL-1ß -511 cytidine/thymidine (C/T) polymorphic site with hepatic VOD and mortality in an exclusive pediatric cohort undergoing matched myeloablative allogeneic HSCT. Donor TT genotype was associated with higher cumulative incidence of grade III-IV hepatic VOD at 3 months after transplantation relative to donor CT and CC genotypes (25±13.1% in TT, 2.9±2.9% in CT, and 3.6±3.6% in CC; P=0.024). Neither recipient nor donor IL-1ß -511 single nucleotide polymorphisms genotypes were associated with mortality or relapse. Our findings suggest that donor, rather than host, genotype at the IL-1ß -511 polymorphic site may associate with higher risk for severe VOD after matched allogeneic HSCT. Our findings challenge the assumption that host factors are exclusively responsible for VOD and suggest a novel role for the donor inflammasome pathway in inducing injury and microvascular disease after HSCT, which merits further study in a larger cohort analysis.

The nursing dimension of providing palliative care to children and adolescents with cancer.

Palliative care for children and adolescents with cancer includes interventions that focus on the relief of suffering, optimization of function, and improvement of quality of life at any and all stages of disease. This care is most effectively provided by a multidisciplinary team. Nurses perform an integral role on that team by identifying symptoms, providing care coordination, and assuring clear communication. Several basic tenets appear essential to the provision of optimal palliative care. First, palliative care should be administered concurrently with curative therapy beginning at diagnosis and assuming a more significant role at end of life. This treatment approach, recommended by many medical societies, has been associated with numerous benefits including longer survival. Second, realistic, objective goals of care must be developed. A clear understanding of the prognosis by the patient, family, and all members of the medical team is essential to the development of these goals. The pediatric oncology nurse is pivotal in developing these goals and assuring that they are adhered to across all specialties. Third, effective therapies to prevent and relieve the symptoms of suffering must be provided. This can only be accomplished with accurate and repeated assessments. The pediatric oncology nurse is vital in providing these assessments and must possess a working knowledge of the most common symptoms associated with suffering. With a basic understanding of these palliative care principles and competency in the core skills required for this care, the pediatric oncology nurse will optimize quality of life for children and adolescents with cancer.

Ethical considerations for pharmacogenomic testing in pediatric clinical care and research.

The information gained from pharmacogenomic testing is becoming increasingly recognized as an opportunity to improve our current dosing strategies for children. The identification of gene polymorphisms that influence drug disposition and effect can be used to help predict a child's susceptibility to toxicity and/or response to a particular drug or therapeutic regimen. However, the potential consequences of performing genomic analysis in children raise important ethical considerations. Although the level of risk introduced remains partially hypothetical, awareness of the ethical concerns and protective legislation will be an important part of fully informing patients, families, clinicians, and researchers about the risks and benefits of pharmacogenomic testing in children. Where it can be done without loss of benefit, risk reduction is a moral imperative, and so the ethical complexities related to pharmacogenomics must be addressed in an ongoing way as we continue to learn more about the value of the technology to children.

Spontaneous resolution of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative disorder of the immune system resulting in lymphohistiocytic proliferation, hemophagocytosis, and cytokine dysregulation. The most common infectious trigger in sHLH is Epstein-Barr virus (EBV-HLH). Current treatment protocols for EBV-HLH have a cure rate of approximately 75%; however, there are significant toxicities associated with these therapies. We present two patients with EBV-HLH who experienced spontaneous resolution of their disease prior to the initiation of therapy, suggesting there may be a subgroup of patients with EBV-HLH who do well with conservative management and can avoid potentially toxic therapies.

Impact of continuous renal replacement therapy on oxygenation in children with acute lung injury after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute lung injury (ALI) continues to carry a high mortality rate in children after allogeneic hematopoietic stem cell transplant (HSCT). Continuous renal replacement therapy (CRRT) is often used for these patients for various indications including renal failure and fluid overload, and may have a beneficial effect on oxygenation and survival. Therefore, we sought to determine the effect of CRRT on oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI, and to document survival to intensive care unit discharge in this at-risk population receiving both mechanical ventilation and CRRT. PROCEDURE: Retrospective analysis of a pediatric allogeneic HSCT cohort admitted to intensive care unit of a single pediatric oncology center from 1994 to 2006 who received CRRT during a course of mechanical ventilation for ALI. RESULTS: Thirty post-HSCT mechanically ventilated children with ALI who underwent CRRT were included. There was a significant improvement in PaO(2)/FiO(2) with median increase of 31 and 43 in the 24 and 48 hr intervals after initiation of CRRT compared with the 24 hr interval before CRRT (P = 0.0008 and 0.0062, respectively). This improvement in PaO(2)/FiO(2) correlated significantly with reduction of fluid balance achieved after initiation of CRRT (P = 0.0001). There was a trend not reaching statistical significance in improvement in mean airway pressure 48 hr after CRRT in survivors compared to non-survivors. CONCLUSIONS: CRRT improved oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI.

Availability of palliative care services for children with cancer in economically diverse regions of the world.

PURPOSE: We assessed the availability and quality of palliative care for children with cancer according to national income per capita. METHODS: We surveyed physicians who care for children with cancer using the Cure4Kids website (http://www.cure4kids.org). Queries addressed oncology practice site; reimbursement; specialised palliative care, pain management and bereavement care; location of death; decision-making support and perceived quality of care. Responses were categorised by low-, middle- and high-income country (LIC, MIC and HIC). RESULTS: Of 262 completed questionnaires from 58 countries (response rate, 59.8%), 242 were evaluable (55%). Out-of-pocket payment for oncology (14.8%), palliative care (21.9%) and comfort care medications (24.3%) was most likely to be required in LIC (p<0.001). Availability of specialised palliative care services, pain management, bereavement care and institutional or national decision-making support was inversely related to income level. Availability of high-potency opioids (p=0.018) and adjuvant drugs (p=0.006) was significantly less likely in LIC. Physicians in LIC were significantly less likely than others to report high-quality pain control (p<0.001), non-pain symptom control (p=0.003) and emotional support (p=0.001); bereavement support (p=0.035); interdisciplinary care (p<0.001) and parental participation in decisions (p=0.013). CONCLUSION: Specialised palliative care services are unavailable to children with cancer in economically diverse regions, but particularly in LIC. Access to adequate palliation is associated with national income. Programme development strategies and collaborations less dependent on a single country's economy are suggested.

Outcomes of hematopoietic stem cell transplant patients who received continuous renal replacement therapy in a pediatric oncology intensive care unit.

OBJECTIVES: To assess the long-term benefits of continuous renal replacement therapy (CRRT) in this patient population and to analyze factors associated with survival. Hematopoietic stem cell transplantation is being utilized as curative therapy for a variety of disorders. However, organ dysfunction is commonly associated with this therapy. Continuous renal replacement therapy (CRRT) is increasingly being used in the treatment of this multiorgan dysfunction. DESIGN: Retrospective cohort study. SETTING: A free-standing, tertiary care, pediatric oncology hospital. PATIENTS: Twenty-nine allogeneic hematopoietic stem cell transplantation patients who underwent 33 courses of CRRT in the intensive care unit between January 2003 and December 2007. INTERVENTIONS: Cox proportional hazards regressions models were used to examine the relationship between demographic and clinical variables and length of survival. MEASUREMENTS AND MAIN RESULTS: The median length of survival post CRRT initiation was 31 days; only one patient survived >6 mos. Factors associated with increased risk of death included: higher bilirubin and blood urea nitrogen levels before and at 48 hrs into CRRT, lower Pao2/Fio2 ratios at 48 hrs of CRRT, and higher C-reactive protein levels, as well as lower absolute neutrophil counts at CRRT end. CONCLUSION: In this single-center study, CRRT was not associated with long-term survival in pediatric allogeneic hematopoietic stem cell transplantation patients. Clinical data exist, both before and during CRRT, that may be associated with length of survival. Lower C-reactive protein levels at CRRT end were associated with longer survival, suggesting that the ability to attenuate inflammation during CRRT may afford a survival advantage. These findings require confirmation in a prospective study.

Anti-GD2 antibody therapy for GD2-expressing tumors.

In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also expressed on several other high-risk tumors, including those of neuroectodermal or epithelial origin, virtually all melanomas, and approximately 50% of tumor samples from osteosarcoma and soft-tissue sarcomas. Because of the tumor-selective expression of this molecule, it is an attractive target for tumor-specific therapies such as antibody therapy. Over the last 2 decades, several anti-GD2 antibodies have been developed. To reduce both the toxicity of the antibody and the development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that have progressively more human elements while at the same time reducing the mouse components. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with GD2-expressing tumors.