Initial development of Supportive care Assessment, Prioritization and Recommendations for Kids (SPARK), a symptom screening and management application.

BACKGROUND: We developed Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK), a web-based application designed to facilitate symptom screening by children receiving cancer treatments and access to supportive care clinical practice guidelines primarily by healthcare providers. The objective was to describe the initial development and evaluation of SPARK from the perspective of children. IMPLEMENTATION: Development and evaluation occurred in three phases: (1) low fidelity focused on functionality, (2) design focused on "look and feel" and (3) high fidelity confirmed functionality and design. Cognitive interviews were conducted with children receiving cancer treatments 8-18 years of age. Evaluation occurred after every five interviews and changes were guided by a Review Panel. Quantitative evaluation included SPARK ease of use and understandability of SPARK reports. RESULTS: The number of children included by phase were: low fidelity (n = 30), design (n = 30) and high fidelity (n = 30). Across phases, the median age was 13.2 (range 8.5 to 18.4) years. During low-fidelity and design phases, iterative refinements to SPARK improved website navigation, usability and likability from the perspective of children and established symptom report design. Among the last 10 children enrolled to high-fidelity testing, all (100%) understood how to complete symptom screening, access reports and interpret reports. Among these 10 respondents, all (100%) found SPARK easy to use and 9 (90%) found SPARK reports were easy to understand. CONCLUSIONS: SPARK is a web-based application which is usable and understandable, and it is now appropriate to use for research. Future efforts will focus on clinical implementation of SPARK.

Relationship between cyclosporine area-under-the curve and acute graft versus host disease in pediatric patients undergoing hematopoietic stem cell transplant: A prospective, multicenter study.

Traditionally in hematopoietic stem cell transplant (HSCT), cyclosporine doses are individualized using cyclosporine trough concentrations (C0) while area under the concentration vs time curve (AUC) is used in solid organ transplant. AUC potentially has an important relationship with the development of acute graft-versus-host-disease (aGVHD). We conducted a prospective study to describe the relationship between severe (grade III-IV) aGVHD and cyclosporine AUC in pediatric HSCT recipients. Pediatric patients who underwent allogeneic myeloablative HSCT and scheduled to receive cyclosporine for aGVHD prophylaxis participated in this multicenter study. Cyclosporine doses were adjusted based on C0 according to each center's standard of care. Cyclosporine AUC was determined weekly until neutrophil engraftment or Day +42, whichever was later. Associations between severe aGVHD and cyclosporine AUC and other patient and treatment-related factors were evaluated. Of the 110 children enrolled, 97 were evaluable. Thirty-seven (38%) children developed aGVHD; 13 (13.4%) had severe aGVHD. On univariate analysis, there was no association between severe aGVHD and cyclosporine AUC at any time point before engraftment. Future research should focus on refinement of C0 targets for cyclosporine therapeutic drug monitoring in HSCT.

Evaluation of the electronic self-report Symptom Screening in Pediatrics Tool (SSPedi).

OBJECTIVE: We previously developed the paper-based Symptom Screening in Pediatrics Tool (SSPedi) designed for paediatric cancer symptom screening. Objectives were to evaluate and refine the electronic mobile application (app) of SSPedi using the opinions of children with cancer. METHODS: Participants were children 8-18 years of age with cancer. Participants completed electronic SSPedi on their own and then responded to semistructured questions to determine whether they found electronic SSPedi easy or difficult to complete and understand, understood and liked the app features (audio and animation), and understood previously difficult to understand concepts with the introduction of a help menu. After each group of 10 children, responses were reviewed to determine whether modifications were required. RESULTS: 20 children evaluated electronic SSPedi. None found electronic SSPedi difficult to complete or understand. All children understood the app features and each of the 4 more difficult to understand concepts after using the help menu. 19 of 20 children thought the app was a good way to communicate with doctors and nurses. CONCLUSIONS: We finalised an electronic version of SSPedi that is easy to use and understand with features specifically designed to facilitate child self-report. Future work will evaluate the psychometric properties of electronic SSPedi.

Poor chemotherapy-induced nausea and vomiting control in children receiving intermediate or high dose methotrexate.

PURPOSE: Chemotherapy emetogenicity is the most important known determinant of chemotherapy-induced vomiting (CIV) in children. However, direct evidence regarding the emetogenic potential of chemotherapeutic agents in children is limited. This study describes the prevalence of complete control of acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in children receiving methotrexate. The prevalence of anticipatory CINV is described, and risk factors for CINV are explored. METHODS: English-speaking children (4 to 18 years) receiving intermediate-dose (ID-MTX: >1 to <12 g/m(2)/dose) or high-dose methotrexate (HD-MTX: ≥12 g/m(2)/dose) participated in this prospective study. Emetic episodes, nausea severity, and antiemetic administration were documented for 24 h from the start of the methotrexate infusion (acute phase) and for up to a further 168 h (delayed phase). CINV prophylaxis was provided at the discretion of the treating physician. Anticipatory CINV was assessed in the 24 h preceding chemotherapy. Complete CINV control was defined as no emetic episodes and no nausea. RESULTS: Thirty children (mean age, 11.8 ± 4 years; ID-MTX, 20; HD-MTX, 10) completed the study. CINV prophylaxis included the following: ondansetron/granisetron plus dexamethasone or nabilone. Few patients experienced complete CINV control (ID-MTX: acute phase 20%, delayed phase 5%; HD-MTX: acute phase 0%, delayed phase 30%). Complete emesis control was higher (ID-MTX: acute phase 70%, delayed phase 50%; HD-MTX: acute phase 70%, delayed phase 60%). Anticipatory CINV was reported by 6/28 patients (21%). Patient age, sex, and history of motion sickness were not significant predictors of CINV. CONCLUSIONS: The poor complete CINV control rate in children receiving methotrexate confirms the classification of HD-MTX as highly emetogenic chemotherapy (HEC) and suggests that ID-MTX be reclassified as HEC.

Cyclosporine-induced pain syndrome in a child undergoing hematopoietic stem cell transplant.

OBJECTIVE: To report a case of calcineurin-induced pain syndrome (CIPS) in a child undergoing his second hematopoietic stem cell transplant (HSCT). CASE SUMMARY: A 6.1-year-old child received cyclosporine and methotrexate for acute graft-versus-host disease (aGVHD) prophylaxis after his first HSCT for acute myeloblastic leukemia. Amlodipine was given for the treatment of hypertension. Symptoms of CIPS were not observed. After the second HSCT at the age of 6.7 years, the child received cyclosporine (target trough whole blood cyclosporine concentration range 150-200 microg/L), starting on day -3, and mycophenolate mofetil for aGVHD prophylaxis. With the first cyclosporine dose, the patient complained of leg pain that was most severe during the cyclosporine infusion. Analgesic agents and a change from intravenous to oral administration of cyclosporine were ineffective in controlling the pain. Magnetic resonance imaging findings on day 10 showed periosteal soft tissue changes and mild bone marrow edema of the femora and tibiae. Tacrolimus was substituted for cyclosporine on day 20; on day 21 amlodipine was initiated to manage hypertension. Trough whole blood tacrolimus concentrations ranged from 1.7 to 6.2 microg/L. Pain was reduced in severity by day 29 and completely resolved once tacrolimus was discontinued on day 42. In this case, CIPS was considered to be probably associated with cyclosporine according to the Naranjo probability scale. DISCUSSION: CIPS is hypothesized to result from calcineurin-induced vascular changes that disturb bone perfusion and permeability, leading to intraosseous vasoconstriction and bone marrow edema. In our patient, symptoms were most acute during the infusion, when whole blood cyclosporine concentrations were likely to be the highest. Our patient's symptoms were resolved when tacrolimus was substituted for cyclosporine and amlodipine was initiated. CONCLUSIONS: Interventions aimed at reducing pain associated with CIPS may include the initiation of calcium-channel blocker therapy and conversion to an alternative calcineurin inhibitor.