Training pediatric hematologist/oncologists for capacity building in Ethiopia.

PURPOSE: A considerable barrier to global pediatric oncology efforts has been the scarcity and even absence of trained professionals in many low- and middle-income countries, where the majority of children with cancer reside. In 2013, no dedicated pediatric hematology-oncology (PHO) programs existed in Ethiopia despite the estimated annual incidence of 6000-12000 cases. The Aslan Project initiative was established to fill this gap in order to improve pediatric cancer care in Ethiopia. A major objective was to increase subspecialty PHO-trained physicians who were committed to practicing locally and empowered to lead programmatic development. METHODS: We designed and implemented a PHO training curriculum to provide a robust educational and clinical experience within the existing resource-constrained environment in Ethiopia. Education relied on visiting PHO faculty, a training attachment abroad, and extraordinary initiative from trainees. RESULTS: Four physicians have completed comprehensive PHO subspecialty training based primarily in Ethiopia, and all have remained local. Former fellows are now leading two PHO centers in Ethiopia with a combined capacity of 64 inpatient beds and over 800 new diagnoses per year; an additional former fellow is developing a pediatric cancer program in Nairobi, Kenya. Two fellows currently are in training. Program leadership, teaching, and advocacy are being transitioned to these physicians. CONCLUSIONS: Despite myriad challenges, a subspecialty PHO training program was successfully implemented in a low-income country. PHO training in Ethiopia is approaching sustainability through human resource development, and is accelerating the growth of dedicated PHO services where none existed 7 years ago.

Tolerance and effectiveness of nivolumab after pediatric T-cell replete, haploidentical, bone marrow transplantation: A case report.

To date, there has been a lack of pediatric experience regarding the efficacy and tolerability of immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present the case of a 22-year-old female with multiple-relapsed Hodgkin lymphoma (HL) who presented with a new relapse after haploidentical (post-haplo) HSCT. Anti-PD-1 therapy with nivolumab resulted in significant objective disease response and clinical improvement without notable side effects, including the absence of a graft-versus-host disease (GVHD). This case report suggests that immune checkpoint inhibition may be safely tolerated even in the setting of haploidentical HSCT, without triggering overt GVHD.

Safety, Tolerability, and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients.

The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections. The pharmacokinetic parameters of L-AMB were measured as those of amphotericin B by high-performance liquid chromatography and calculated by noncompartmental methods. There were nine adverse-event-related discontinuations, four of which were related to infusions. Infusion-related side effects occurred for 63 (11%) of 565 infusions, with 5 patients experiencing acute infusion-related reactions (7.5- and 10-mg/kg dosage levels). Serum creatinine levels increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dl in the overall population (P = 0.003), with significant increases in dosage cohorts receiving 5.0 and 10 mg/kg/day. At the higher dosage level of 10 mg/kg, there was a trend toward greater hypokalemia and vomiting. The area under the concentration-time curve from 0 to 24 h (AUC0-24) values for L-AMB on day 1 increased from 54.7 ± 32.9 to 430 ± 566 µg · h/ml in patients receiving 2.5 and 10.0 mg/kg/day, respectively. These findings demonstrate that L-AMB can be administered to pediatric patients at dosages similar to those for adults and that azotemia may develop, especially in those receiving ≥5.0 mg/kg/day.

Validation of a milk consumption stage of change algorithm among adolescent survivors of childhood cancer.

OBJECTIVE: To assess the construct validity of a milk consumption Stages of Change (SOC) algorithm among adolescent survivors of childhood cancer ages 11 to 21 years (n = 75). METHODS: Baseline data from a randomized controlled trial designed to evaluate a health behavior intervention were analyzed. Assessments included a milk consumption SOC algorithm and hypothesized theoretical and behavioral predictors of SOC. RESULTS: Compared with survivors who expressed no readiness to change, those expressing readiness to change behavior for both 2 and 4 daily servings of milk reported more frequent milk consumption (P < .001), greater dietary calcium intake (P = .006), and were more likely to meet age-specific recommendations for daily calcium intake (P = .01). CONCLUSIONS AND IMPLICATIONS: Results provide support for the construct validity of the milk consumption SOC algorithm relative to behavioral criteria. Research is needed to further examine algorithm validity with respect to theoretical predictors of SOC.

Survey of consumer informatics for palliation and hospice care.

CONTEXT: Palliation in patient care is under-utilized in part because many patients have insufficient knowledge about this management option. Information technology can improve awareness by providing access to numerous sources of trustworthy information. EVIDENCE ACQUISITION: To estimate what a patient interested in palliation might find online, online resources were searched in July 2010, using terms relevant to palliation. PubMed was searched for publications relevant to discussed topics. EVIDENCE SYNTHESIS: Search engines returned vast numbers of hits, and identifying trustworthy sites was difficult. Products judged as trustworthy were classified as information, decision tool, or extended interaction tool. Sites with useful educational material were relatively plentiful; decision guides or interactive tools were much rarer. Available consumer informatics did not address some terminal illnesses very well, and some subpopulations such as children, nor was there sufficient attention to literacy levels or principles of instructional design. Online or published information about usage numbers, effectiveness, and cost/benefit considerations was scant. Many sectors, including commercial, government, healthcare, research, and wellness/advocacy groups, have created consumer informatics for palliation. CONCLUSIONS: Online information about palliation is available, although identifying trustworthy sources can be problematic. General information sites are relatively plentiful, but more tools for decision making, and interaction would increase value of web resources. More attention to literacy levels, instructional principles, and needs of special populations would improve products. Research to measure usage of such tools, ability to influence behavior, and cost/benefit issues is needed.

Pediatric palliative care and eHealth opportunities for patient-centered care.

BACKGROUND: Pediatric palliative care currently faces many challenges including unnecessary pain from insufficiently personalized treatment, doctor-patient communication breakdowns, and a paucity of usable patient-centric information. Recent advances in informatics for consumer health through eHealth initiatives have the potential to bridge known communication gaps, but overall these technologies remain under-utilized in practice. PURPOSE: This paper seeks to identify effective uses of existing and developing health information technology (HIT) to improve communications and care within the clinical setting. METHODS: A needs analysis was conducted by surveying seven pediatric oncology patients and their extended support network at the Lombardi Pediatric Clinic at Georgetown University Medical Center in May and June of 2010. Needs were mapped onto an existing inventory of emerging HIT technologies to assess what existing informatics solutions could effectively bridge these gaps. RESULTS: Through the patient interviews, a number of communication challenges and needs in pediatric palliative cancer care were identified from the interconnected group perspective surrounding each patient. These gaps mapped well, in most cases, to existing or emerging cyberinfrastructure. However, adoption and adaptation of appropriate technologies could improve, including for patient-provider communication, behavioral support, pain assessment, and education, all through integration within existing work flows. CONCLUSIONS: This study provides a blueprint for more optimal use of HIT technologies, effectively utilizing HIT standards-based technology solutions to improve communication. This research aims to further stimulate the development and adoption of interoperable, standardized technologies and delivery of context-sensitive information to substantially improve the quality of care patients receive within pediatric palliative care clinics and other settings.

Improving short-term sun safety practices among adolescent survivors of childhood cancer: a randomized controlled efficacy trial.

INTRODUCTION: Skin cancer is one of the most common secondary neoplasms among childhood cancer survivors. However, little evidence exists for effective interventions to promote sun safety behaviors within this population. METHODS: This small-scale randomized controlled trial examined the efficacy of the Survivor Health and Resilience Education (SHARE) Program intervention, a multiple health behavior change intervention designed to increase sun safety practices among adolescent survivors of childhood cancer. Adolescent survivors of childhood cancer (11-21 years) were randomly allocated to a group-based behavioral intervention (n = 38) or wait-list control (n = 37). Self-reported sun safety behaviors were assessed using a valid, 8-item scale at baseline and 1-month post-intervention. RESULTS: Controlling for baseline sun safety, gender, and seasonal influences, intervention participants reported significantly more sun safety practices (e.g., using sunscreen, reapplying sunscreen regularly) at 1-month post-intervention than control participants (B = 2.64, 95% CI = 1.02, 4.27, p = 0.002). CONCLUSIONS: The results suggest that SHARE was efficacious in producing improvements in short-term self-reported sun safety practices among adolescent survivors of childhood cancer. Future research is needed to build upon this work by incorporating objective measures of sun safety behaviors and examining intervention durability. IMPLICATIONS FOR CANCER SURVIVORS: Behavioral interventions addressing lifestyle factors, including sun safety behaviors, among adolescent survivors of childhood cancer should be integrated into long-term care to reduce the risk for secondary malignancies and diseases.

Efficacy of the Survivor Health and Resilience Education (SHARE) program to improve bone health behaviors among adolescent survivors of childhood cancer.

PURPOSE: The purpose of this study is to test the efficacy of the Survivor Health and Resilience Education Program intervention--a manualized, behavioral intervention focusing on bone health behaviors among adolescent survivors of childhood cancer. METHODS: Participants were 75 teens aged 11-21 years, one or more years post-treatment, and currently cancer-free. Teens were randomized to a group-based intervention focusing on bone health or a wait-list control. Bone health behaviors were assessed at baseline and 1-month post-intervention. RESULTS: Controlling for baseline outcome measures and theoretical predictors, milk consumption frequency (p=0.03), past month calcium supplementation (p<0.001), days in the past month with calcium supplementation (p<0.001), and dietary calcium intake (p=0.04) were significantly greater at 1-month follow-up among intervention participants compared with control participants. CONCLUSIONS: The intervention had a significant short-term impact on self-reported bone health behaviors among adolescent survivors of childhood cancer. Research examining long-term intervention effectiveness is warranted.

Development and evaluation of an educational interactive CD-ROM for teens with cancer.

BACKGROUND: Cancer is the number one disease killer of children and adolescents in North America. For adolescents, this diagnosis comes at a particularly vulnerable stage. Educating adolescents with cancer from diagnosis through treatment teaches and empowers them. Increasing evidence shows that these adolescents want more information. Few educational tools exist for young cancer patients; none are interactive; therefore, a CD-ROM was developed to meet this need. PROCEDURE: Animation, voiceover, music, videos, and games were combined to develop a comprehensive multimedia CD-ROM to teach 12- to 18-year-olds with solid tumors about their disease, treatment, coping skills, and late effects in an interactive and non-threatening way. The CD-ROM was evaluated in a pre-post design with 65 subjects recruited from four pediatric oncology centers randomized to the CD-ROM or a "Handbook" containing analogous information. Pre-post questionnaires measured coping strategies, health locus of control, quality of life, cancer knowledge, and self-efficacy; post-test variables also included acceptability and use by teens, their families, and healthcare professionals. RESULTS: Teens receiving the CD-ROM were significantly more likely to increase their internal locus of control scores; however, no significant differences were observed on other measures, attributable in part to the study sample size. Among teens, acceptability was higher in the CD-ROM versus the Handbook group, but not different between the two parent groups. Pediatric oncology healthcare providers gave positive feedback on the CD-ROM. CONCLUSIONS: This CD-ROM is an innovative and engaging educational tool--the first portable interactive product with access on demand for adolescents with solid tumors.

Pediatric acute lymphoblastic leukemia and exposure to pesticides.

Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) program.

BACKGROUND: Health-compromising behaviors among survivors of childhood cancer may increase their risks of cancer recurrence and the onset of chronic disease in adulthood. Regardless of whether such behaviors occur singly or in combination with one another, multiple behavioral risk factors must be identified and addressed early to promote better health outcomes within this special population. Adolescent survivors may be especially vulnerable, as reported rates of smoking and other risky behaviors are at or near levels of their healthy peers. The psychological literature suggests stress may play a role in risk behavior initiation and maintenance, including multiple behavioral risks, and that adolescent survivors are stress-prone. This report focuses on the prevalence and co-occurrence of three behavioral risk factors (cigarette use, insufficient physical activity, and non-adherence to sun protection recommendations) and describes stress-health behavior relationships in this special population. PROCEDURE: All patients in this study (n = 75) were adolescent survivors of childhood cancer and completed a baseline assessment of their health behaviors and stress as part of a randomized controlled trial of health promotion. RESULTS: Twenty-eight percent of the patients reported one of three risk factors, 12% reported two of three risk factors, and 7% reported all three risk factors. Non-adherence to sun protection was the single most common risk factor; physical inactivity and non-adherent sun protection were the most common co-occurring risk factors. Greater age and stress were significantly associated with the presence of more behavioral risk factors. CONCLUSIONS: The evidence suggests interventions to reduce multiple health-compromising behaviors in these patients are warranted, and that efforts to address these patients' personal and family stress levels are important as well.

Identifying, recruiting, and enrolling adolescent survivors of childhood cancer into a randomized controlled trial of health promotion: preliminary experiences in the Survivor Health and Resilience Education (SHARE) Program.

OBJECTIVE: To report on the identification, recruitment, and enrollment of adolescent survivors of childhood cancer into an ongoing randomized controlled trial (RCT) of health promotion. METHODS: A total of 244 adolescents were contacted by mail and telephone to assess their trial eligibility. Data were collected with respect to each adolescent's demographics and trial recruitment efforts (frequency and intensity of telephone call contact); exclusion and randomization status were tracked throughout. RESULTS: Thirty-one percent of adolescents were ultimately randomized in the trial and 69% were excluded from randomization (13% were ineligible, 33% refused to participate, 22% were unreachable or nonresponsive, that is, did not respond to trial mailings or telephone calls, and less than 1% were withdrawn prior to randomization). Among all eligible adolescents, the trial's consent rate was 49%. Adolescents excluded owing to refusal resided the farthest away from the intervention site and experienced the least amount of telephone call contact time. The primary reasons for trial refusal were lack of interest in health promotion (28%) and lack of time to participate (23%). CONCLUSIONS: Health promotion RCTs among adolescent survivors of childhood cancer may help prevent and control the onset and severity cancer-treatment-related late effects. However, trial success may be contingent upon tracing nonresponsive adolescents and reducing and eliminating barriers to participation.

Treatment of immune thrombocytopenic purpura in children : current concepts.

Treatment of immune thrombocytopenic purpura (ITP), the most common bleeding disorder of childhood, is a controversial subject for most practitioners. Diagnosis and management of ITP has historically been based primarily on expert opinion rather than on evidence. Due to a paucity of carefully conducted clinical trials in children, the management of ITP varies widely, ranging from observation only, to aggressive management with intravenous immunoglobulin (IVIG), intravenous anti-D rhesus (Rh)0 immunoglobulin (IV RhIG), corticosteroids, and splenectomy. To address the controversies, the American Society of Hematology (ASH) and the British Society for Hematology (BSH) have developed ITP practice guidelines. These guidelines, based on expert opinion, differ in their recommendations for treatment. The ASH guidelines favor therapy based on a low platelet count, and the more current BSH guidelines recommend a more conservative 'wait and watch' approach. In addition to treating children with severe bleeding symptoms, there is a tendency (not evidence based) to treat early in order to prevent a life-threatening bleeding episode, including intracerebral hemorrhage. Corticosteroids are a highly effective therapy, inexpensive, and can usually increase the platelet count within hours to days. However, chronic or prolonged use is associated with toxicity. In the US, based on the knowledge of known toxicities of corticosteroids, as well as the efficacy of alternative treatments (IV RhIG, IVIG), many pediatricians prefer to treat with IVIG and IV RhIG, reserving corticosteroid treatment for serious bleeding or refractory disease. However, in the UK, for the most part, corticosteroids are used as first-line therapy in children with ITP. Splenectomy is rarely indicated in children except for those with life-threatening bleeding and chronic, severe ITP with impairment of quality of life. For children who develop chronic or refractory ITP, immunosuppressive drugs and/or chemotherapy agents may offer some promise. However, the long-term effects of these drugs in children are unknown and they should not be considered unless there is unequivocal evidence that the patient is refractory to IV RhIG, IVIG, and corticosteroids. To date, virtually all of the randomized clinical trials conducted in children with ITP have focused on platelet counts as the sole outcome measure. Only carefully designed, multicenter, randomized clinical trials comparing the effects of different treatment modalities in terms of bleeding, quality of life, adverse effects, and treatment-related costs will be able to address the controversies surrounding childhood ITP treatment and allow management of this condition to be based on scientific data rather than treatment philosophy.

Brief report: health beliefs among survivors of childhood cancer.

OBJECTIVE: To describe interest in cancer screening and tobacco-control procedures (nicotine-addiction susceptibility testing) among survivors of childhood cancer and to identify psychosocial modifying and readiness factors associated with survivors' interest, based on the children's health belief model. METHODS: Twenty-eight survivor-mother dyads were interviewed as part of a preliminary study (mean age of survivors = 15.4 years at time of interview, 10.1 years at time of diagnosis, and 12.0 years at end of treatment); interviews consisted of well-validated self-report items and measures of health beliefs. RESULTS: In sum, 57% and 61% of survivors were interested in screening and susceptibility testing, respectively. Survivors who rated themselves as more competent, more concerned about cancer, and more vulnerable to cancer were more interested in participating in screening. Regarding interest in nicotine-addiction susceptibility testing, survivors were more interested when they perceived greater vulnerability to the harm of smoking and when they had mothers who perceived themselves to be in better health. CONCLUSIONS: Preliminary data suggest that psychosocial modifying and readiness factors are associated with survivors' interest in cancer screening and tobacco-control procedures and that additional research in this area is warranted.

Comparison of intermittent versus continuous infusion of propofol for elective oncology procedures in children.

OBJECTIVE: To compare the effects of administering propofol as a continuous infusion vs. bolus dosing in children undergoing ambulatory oncologic procedures in the pediatric intensive care unit (PICU). DESIGN: Prospective, randomized study. SETTING: Tertiary PICU in a university hospital. PATIENTS: Ambulatory oncology patients scheduled for diagnostic or therapeutic procedures with propofol anesthesia in the PICU were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive either continuous infusion or bolus administration of propofol in a protocol-driven manner. All patients received an initial bolus of 1.5 mg/kg, with additional 0.5 mg/kg doses until complete induction. Continuous infusions were started at 0.1 mg/kg/min and, if needed, increased 20% after a bolus of 0.5 mg/kg. Bolus group patients were given doses of 0.5 mg/kg if needed. Ramsay scores of < 5 were used as criteria for additional dosing. MEASUREMENTS AND MAIN RESULTS: Eighteen patients undergoing 40 separate procedures were enrolled during the study period. Twenty procedures each were performed with continuous or bolus administration of propofol. No differences were present between groups in demographic characteristics, induction dose and time, procedure and recovery times, or adverse events. All patients had adequate anesthesia and favorable satisfaction scores. More boluses were needed in the bolus group (8.5 +/- 4.6 vs. 5.4 +/- 2.9; p < .05). Average systolic blood pressure decreased more in the continuous infusion group (26.4% +/- 12 vs. 19.3% +/- 10; p < .05). Total propofol dose was higher in the continuous infusion group (8.0 mg/kg +/- 3.8 vs. 5.7 mg/kg +/- 2.4; p < .05). CONCLUSION: Both continuous and bolus administration of propofol provided conditions for conducting oncologic procedures that were satisfying to patients, their families, and physicians. Continuous infusions were associated with a larger total dose and greater decreases in systolic blood pressure. Physician preference is likely to dictate which method is used.