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Background There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. Methods Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications. Results Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection. Conclusions Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes. Trial registration clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1.

While care pathways based upon clinical practice guidelines (CPGs) are important, little is known about optimal approaches to development and adaptation in pediatric oncology. Objectives were to develop care pathway templates for pediatric cancer supportive care that are based upon CPGs and to adapt an infection management care pathway for use at a single institution.Study phases were as follows: (1) creation of care pathway templates across multiple supportive care topics; (2) refinement of the infection management care pathway template by interviewing pediatric oncology clinicians at a single institution; and (3) adaptation of the infection management care pathway template for use at a different institution.Informed by seven CPGs, an initial iteration of the infection management care pathway template was created. This template was then refined based upon 20 interviews with pediatric oncology clinicians. Adaptation of the infection management care pathway template for use at a different institution required many changes to improve its clinical usability. Specificity and additional information not considered by the source CPGs were incorporated.We developed a process to create care pathway templates across multiple supportive care topics in pediatric oncology and to refine and adapt the infection management care pathway. While we found that the process was feasible, we also identified the need to substantially modify the care pathway during the adaptation process to consider scenarios not addressed by the source CPGs. Future work should measure implementation success.

Objective Primary objective was to determine the feasibility of three times weekly symptom reporting by pediatric cancer patients for eight weeks. Methods We included English-speaking patients 8–18 years of age with cancer. Patients were sent reminders by text or email to complete Symptom Screening in Pediatrics Tool (SSPedi) three times weekly for eight weeks. When patients reported at least one severely bothersome symptom, the symptom report was emailed to the primary healthcare team. Patient-reported outcomes were obtained at baseline, week 4 ± 1 and week 8 ± 1. Symptom documentation, intervention provision for symptoms and unplanned healthcare encounters were determined by chart review at weeks 4 and 8. The primary endpoint was feasibility, defined as at least 75% patients achieving adherence with at least 60% of SSPedi evaluations. We planned to enroll successive cohorts until this threshold was met. Results Two cohorts consisting of 30 patients (cohort 1 (n = 20) and cohort 2 (n = 10)) were required to meet the feasibility threshold. In cohort 1, 11/20 (55%) met the SSPedi completion threshold. Interventions applied after cohort 1 included engaging parents to facilitate pediatric patient self-report, offering mechanisms to remember username and password and highlighting potential benefits of symptom feedback to clinicians. In cohort 2, 9/10 (90%) met the SSPedi completion threshold and thus feasibility was met. Patient-reported outcomes and chart review outcomes were obtained for all participants in cohort 2. Conclusions Three times weekly symptom reporting by pediatric patients with cancer for eight weeks was feasible. Mechanisms to enhance three times weekly symptom reporting were identified and implemented. Future studies of longitudinal symptom screening can now be planned.

Children with cancer commonly experience distressing symptoms such as pain, fatigue and nausea. Improvements in patient outcomes have been associated with implementation of clinical practice guideline-consistent care across several domains. The objective of this study was to develop a process to identify symptom management clinical practice guidelines (CPGs) applicable to children and adolescents receiving cancer treatments. We focused on identifying CPGs to manage 15 symptoms. The process defined three Tiers of CPGs based upon applicability to pediatric cancer patients and ease of identification: Tier 1: endorsed by the Children’s Oncology Group; Tier 2: housed in the Emergency Care Research Institute repository, or developed by the American Society of Clinical Oncology or National Institute for Health and Care Excellence; and Tier 3: identified by systematic review. We first searched for CPGs published 2015–2020 and identified Tiers 1 or 2 CPGs. If unavailable or scope was too narrow, we proceeded to Tier 3. If CPGs were not identified, we repeated these steps for CPGs published 2010–2014. There were six Tier 1 and 13 Tier 2 CPGs published 2015–2020 across the 15 symptoms. Four symptoms required progression to Tier 3 because CPGs were absent (anger) or because scope was too narrow (pain, anorexia/excessive hunger and diarrhea). The systematic review identified three CPGs for pain and none for the other three symptoms. In total, CPGs were identified for 14 of 15 symptoms. None were identified for anger. We created a process to identify supportive care CPGs for pediatric cancer symptom management and were able to identify CPGs that addressed 14 of 15 symptoms. Future work should focus on evaluating implementation techniques for these CPGs and determining the impact of these CPGs on provider and patient outcomes.

To qualitatively describe reasons for disagreement in ratings of bothersome symptoms between child self-report and parent proxy-report. We enrolled child and parent dyads, who understood English and where children (4–18 years of age) were diagnosed with cancer or were hematopoietic stem cell transplantation (HSCT) recipients. Each child and parent separately reported symptoms using self-report or proxy-report Symptom Screening in Pediatrics Tool (SSPedi). We then used semi-structured interviews to elicit reasons for discrepancies in symptom reporting. We enrolled 12 dyads in each of four age cohorts, resulting in 48 dyads. Forty-one dyads (85.4%) had disagreement in rating the presence or absence of at least one symptom. Themes identified as reasons for disagreement included (1) perception, differing perception of symptom or availability or palatability of intervention; (2) understanding, difficulty orienting to time frame or concept of bother; (3) lack of communication, including child not acknowledging or talking about experiences; (4) projection, of how the parent felt or how they assumed the child would feel; and (5) discrepancy, in how the amount of symptom bother that was initially reported on SSPedi, by either child or parent, did not align with what was reported during the dyad discussion. We identified themes that explained disagreement in ratings of bothersome symptoms between child self-report and parent proxy-report. Some disagreement may be reduced by enhancing communication about symptom reporting between child and parent. Future research should focus on methods of symptom screening that encourage communication between children with cancer and their caregivers.

Change in hunger is a common and bothersome symptom among pediatric patients receiving cancer treatments. Objectives were to describe how children and adolescents receiving cancer treatments experience changes in hunger, factors associated with both increases and decreases in hunger, and coping strategies used by these patients. We enrolled children and adolescents 4–18 years of age with cancer or hematopoietic stem cell transplantation (HSCT) recipients who were actively receiving treatment or who had completed therapy. Using a single, qualitative, semi-structured interview, we asked participants about the experience of increases or decreases in hunger, including characteristics of the change and identified coping strategies. There were 50 children enrolled; 25 (50%) were 4–10 years of age and 33 (66%) were boys. Most often, patients associated an increase in hunger with corticosteroid administration, while other treatments, accompanying symptoms, inactivity, and the hospital environment were associated with a decrease in hunger. Many reported that no coping strategies were successful. For those who did report successful strategies to manage an increase in hunger, these included sleep and having food available. Strategies used to manage a decrease in hunger included anti-emetic medications, increased caloric intake, varied food choices, encouragement to eat, scheduling or tracking of meals, and physical activity. Both increases and decreases in hunger were commonly described. Some coping strategies were reported to be successful. Further research should identify and test interventions to manage changes in hunger in pediatric cancer patients.

PURPOSE: Prescribing guideline-recommended anti-emetics is an effective strategy to prevent CINV. However, the rate of guideline-concordant care is not well-understood. The purpose of this study was to describe the proportion of pediatric, adolescent, and young adult patients receiving HEC or MEC who received guideline-concordant antiemetic prophylaxis for acute CINV, and to identify potential predictors of guideline-concordant antiemetic prophylaxis. METHODS: Using electronic health record data from 2016 through 2018, a retrospective single-institution cohort study was conducted to investigate how often patients less than 26 years of age receiving moderately or highly emetogenic chemotherapy receive guideline-concordant prophylaxis for acute CINV. Guideline-concordant care was defined according to guidelines from the Pediatric Oncology Group of Ontario for patients < 18 years and the American Society of Clinical Oncology for those ≥ 18 years. Independent variables included: sex, age, insurance status, race, ethnicity, cancer type, chemotherapy regimen, clinical setting, chemotherapy emetogenicity, and patient location. Predictors of receiving guideline-concordant care were determined using multiple logistic regression. RESULTS: Of 180 eligible patients, 65 (36.1%) received guideline-concordant care. In multivariable analysis, being treated in adult oncology setting (aOR: 14.3, CI(95): 5.3 – 38.6), with a cisplatin-based regimen (aOR: 3.5, CI(95):1.4 – 9.0), solid tumor diagnosis (aOR: 2.2, CI(95): 1.0 – 4.8), and commercial insurance (aOR: 2.4, CI(95): 1.1 – 5.2) were associated with significantly higher likelihood of receiving guideline-concordant care. CONCLUSIONS: Multi-level factors were associated with receiving guideline concordant care for prevention of CINV in children, adolescents, and young adults receiving emetogenic chemotherapy. These findings can inform current efforts to optimize implementation strategies for supportive care guidelines

There is growing recognition of the degree to which symptoms negatively impact on children receiving cancer treatments. A recent study described that almost all inpatient pediatric oncology patients are experiencing at least one bothersome symptom and almost 60% are experiencing at least one severely bothersome symptom. Poor symptom control occurs because of challenges with communication of bothersome symptoms to clinicians, lack of clinical practice guidelines (CPGs) for most of these symptoms, and failure to administer preventative and therapeutic interventions known to be effective for symptom control. This article reviews approaches used to improve symptom control for children receiving cancer treatments. Areas addressed include systematic symptom screening and creation of CPGs for symptom management. Challenges with electronic health integration are also addressed. Several multi-symptom assessment scales have been developed but none have yet been used to directly influence patient management. The number of CPGs applicable to symptom control in pediatric oncology is increasing but remains small. Improving the creation of and adherence to CPGs for symptom management is an important priority. Finally, identifying ways that symptom management systems can be integrated into clinical work flows is essential; these will likely need to focus on electronic health records.

Changes in taste is a common bothersome symptom in children receiving cancer treatments. However, little is known about how pediatric cancer patients experience this symptom. The objective was to describe how children receiving cancer treatments experience taste alterations and the approaches they use to address the issue. In this qualitative study, we included English-speaking children 4–18 years of age with cancer or hematopoietic stem cell transplantation recipients who were actively receiving cancer treatment or who had completed therapy. Using a semi-structured questionnaire, we asked questions about the experience of altered taste sensation. We asked about its characteristics, impacts and identified coping strategies. We included 50 children. Children experienced changes in taste in a heterogeneous fashion although commonly described food as tasting “different”, “not right” or “funny”. While change in food preferences due to taste alterations was common, specific choices varied. Many found changes started with treatment initiation or mid-way through treatment, and some found that symptoms persisted up to 9 months following treatment completion. Actions taken to address taste changes were sucking on candy, brushing teeth and modifying food choices. The experience of changes in taste was common yet highly variable in its presentation and resultant changes in food preferences. Taste changes did not always resolve soon after treatment completion. Future research should identify ways to manage this symptom in pediatric cancer patients.

Little evidence exists regarding the emetogenicity of chemotherapy in pediatric patients. This study describes the prevalence of chemotherapy-induced nausea and vomiting (CINV) in pediatric patients receiving etoposide plus ifosfamide over 5 days, a common pediatric regimen. English-speaking, non-chemotherapy-naive patients aged 4 to 18 years about to receive etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day over 5 days participated. Antiemetic prophylaxis was determined by each patient’s care team. Emetic episodes were recorded and nausea severity was assessed by patients beginning with the first chemotherapy dose, continuing until 24 h after the last chemotherapy dose (acute phase) and ending 7 days later (delayed phase). The proportion of patients experiencing complete acute CINV control (no nausea, no vomiting, and no retching), the primary study endpoint, was described. The prevalence of complete chemotherapy-induced vomiting (CIV) and chemotherapy-induced nausea (CIN) during the acute, delayed, and overall (acute plus delayed) phases; complete delayed and overall CINV control; and anticipatory CINV were also determined. Twenty-four patients participated; acute CINV was evaluable in 22. Most (75%; 18/24) received a 5-HT3 antagonist plus dexamethasone for antiemetic prophylaxis. Few (23%; 5/22) experienced complete acute CINV control. Complete acute CIV and CIN control were experienced by 57% (13/23) and 27% (6/22) of patients, respectively. Complete delayed CINV, CIV, and CIN control rates were 42% (8/19), 70% (14/20), and 42% (8/19), respectively. Our findings support the classification of etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day IV over 5 days as highly emetogenic. This information will optimize antiemetic prophylaxis selection and CINV control in pediatric patients.

Objectives were to describe bothersome fatigue in children with cancer and hematopoietic stem cell (HSCT) recipients and to identify factors associated with severely bothersome fatigue. We included children ages 8–18 years treated for cancer or HSCT recipients from three groups: [1] receiving active cancer treatment and admitted to hospital for at least 3 days, [2] attending outpatient clinic for acute lymphoblastic leukemia maintenance therapy, and [3] attending outpatient clinic following treatment completion. Fatigue was measured using the Symptom Screening in Pediatrics Tool (SSPedi); severely bothersome fatigue was defined as a lot or extremely bothersome fatigue (score of 3–4 on 0–4 scale). Factors associated with severely bothersome fatigue were examined using univariate and multiple logistic regression. Of 502 children included, 414 (82.5%) reported some degree of bothersome fatigue (scores 1–4), and 123 (24.5%) reported severely bothersome fatigue (score 3 or 4). In multiple regression analysis, factors significantly associated with severely bothersome fatigue were child age 11–14 and 15–18 years vs 8–10 years (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.21–3.77 and OR 2.96, 95% CI 1.66–5.44), and inpatients receiving cancer treatment vs outpatients who had completed therapy (OR 3.85, 95% CI 2.17–7.27). We found that 82.5% of children with cancer or HSCT recipients reported bothersome fatigue and 24.5% of children reported severely bothersome fatigue. Risk factors for severely bothersome fatigue were older age and inpatients receiving active cancer treatment. Future work should evaluate systematic symptom screening in clinical practice and apply interventions to reduce fatigue.

Objectives were to describe bothersome self-reported changes in taste in pediatric oncology and hematopoietic stem cell (HSCT) patients and to identify patient and treatment-related factors associated with bothersome taste changes. We prospectively enrolled children and adolescents with cancer or pediatric HSCT recipients 8–18 years of age from three groups: inpatients receiving cancer treatments; outpatients in maintenance therapy for acute lymphoblastic leukemia (ALL); and outpatients in survivorship. Bothersome changes in taste was self-reported using the Symptom Screening in Pediatrics Tool (SSPedi); nausea was self-reported using the Pediatric Nausea Assessment Tool (PeNAT). Among the 502 children included, 226 (45.0%) reported bothersome taste changes and 48 (9.6%) reported severely bothersome taste changes. In multiple regression, factors independently associated with severely bothersome taste changes were: inpatients receiving cancer treatments vs outpatients in survivorship (odds ratio (OR) 12.28, 95% confidence interval (CI) 2.50–222.27), ALL in maintenance vs outpatients in survivorship (OR 7.43, 95% CI 1.06–147.77), current nausea (OR 1.59, 95% CI 1.04–2.42), vomiting (OR 2.18, 95% CI 1.06–4.38), and first language not English (OR 2.09, 95% CI 0.97–4.28). We found that 45% of children with cancer and pediatric HSCT recipients reported bothersome changes in taste and these were severely bothersome in 9.6% of children. Inpatients receiving cancer treatment, those experiencing more nausea and vomiting and children whose first language was not English were at greater risk of severely bothersome changes in taste. Future work should evaluate systematic symptom screening in clinical practice and identify interventions focused on addressing bothersome taste changes.

Survival for high-risk neuroblastoma patients is still suboptimal. Although stem cell transplantation (SCT) is used, there is no consensus as to which conditioning regimen has the greatest efficacy and fewest toxicities. We assessed the incidence of and risk for hepatic veno-occlusive disease (VOD) for neuroblastoma patients who underwent autologous SCT with busulfan and melphalan (BuMel) at eight centers following Children's Oncology Group (COG)-based induction chemotherapy. Data regarding the patients, SCT characteristics, busulfan steady-state concentrations, incidence of VOD, and survival were evaluated. VOD was defined using the modified Seattle criteria. Possible factors associated with VOD (age, busulfan-pharmacokinetic parameters, history of hepatic dysfunction, and day of neutrophil engraftment) were evaluated. Seventy five patients were included and 23 children (31%) developed VOD at a median of 19 days after SCT (range 14-27 days). VOD was the cause of death in 4 patients (5%). In a multivariable analysis, young age (OR 1.7 (95% CI: 1.16-2.56; p = 0.012)) and early day of neutrophil engraftment (OR 1.4 (95% CI: 1.08-2.14; p = 0.041) were associated with the development of VOD. Initial or cumulative busulfan steady-state concentration were not associated with VOD. We found that despite the use of intravenous busulfan with adjusted serum levels, the incidence of VOD remains high in pediatric neuroblastoma patients.

Background Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web application focused on improving symptom control. It enables pediatric cancer and hematopoietic stem cell transplant (HSCT) patients to self-report and track symptoms, and allows healthcare professionals to access guidelines for symptom management. Objective was to determine the feasibility of longitudinal collection of symptom data. Methods In this longitudinal, single-armed feasibility study, respondents were children 8–18 years of age with cancer or pediatric HSCT recipients. Participants completed symptom reporting daily for 5 days. Cognitive interviews were conducted on day 5. Quantitative evaluation included SPARK ease of use and understandability of SPARK reports. Qualitative feedback on facilitators and barriers to daily symptom screening was solicited. Feasibility was defined as ≥75% of participants completing symptom screening on at least 60% of on-study days during the five-day study. Results Among the 30 children enrolled, the median number of days SSPedi was completed at least once was 5 (range 3 to 5). Overall, 28/29 (96.6%) thought completing symptom screening using SPARK was easy or very easy. All participants understood SPARK symptom reports. Severe symptoms was the most common barrier to daily reporting while an alarm reminder system was the most commonly identified facilitator. Conclusions Daily completion of symptom screening using SPARK over 5 days was feasible in children aged 8 to 18 years with cancer and pediatric HSCT recipients. SPARK is now appropriate for use in randomized trials to evaluate the effect of symptom screening and symptom feedback.

Prochlorperazine is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV). The objective of this review was to describe its safety in children when given for any indication to help define its role for CINV control in children. Electronic searches of MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials were performed as of 9 March 2015. All studies in English reporting adverse effects (AEs) associated with prochlorperazine in children (≤18 years) were included. AEs were synthesized for prospective studies. Forty-nine (15 prospective) studies evaluating the use of prochlorperazine in 758 children were included. The most commonly reported AEs in prospective studies of prochlorperazine in children were sedation (multiple-dose studies: 10 %, 95 % CI 5–21) and extrapyramidal symptoms (EPS) (single-dose studies: 9 %, 95 % CI 3–29; multiple-dose studies: 4 %, 95 % CI 1–11). Serious AEs (seizure, neuroleptic malignant syndrome, autonomic collapse, tardive dyskinesia) were rarely associated with prochlorperazine use in children. Five fatalities were reported in children receiving prochlorperazine. The limitations of this systematic review and meta-analysis were that the AEs reported in the included studies were heterogeneous, the prospective use of systematic clinical tools to identify AEs was rare, and the risk of bias in most prospective studies was moderate. The most common AEs reported with the pediatric use of prochlorperazine are EPS and sedation. Fatalities, life-threatening, and persistent AEs have also been reported.

Background To describe a process for adapting a supportive care clinical practice guideline (CPG) for use in a middle income country setting. Method We reviewed different approaches for CPG adaptation and created a straight-forward approach for adapting supportive care guidelines for use in Shenzhen, China. The initial CPG to be adapted was for the empiric management of fever and neutropenia (FN) in children with cancer and hematopoietic stem cell transplantation recipients. Results The steps to be used in adaptation were as follows: review of local guideline; understanding local clinical pathways and contexts through interviews; development of worksheets to facilitate adaptation decisions; deliberation of guideline recommendations in focus groups; and drafting of the adapted FN CPG. After several iterations, stakeholders agreed upon a final adapted guideline. Conclusions We described an approach to adaptation of a supportive care CPG for the middle income country setting of Shenzhen, China. Although we believe this work has broad applicability, this approach requires rigorous evaluation, both in terms of methodology and the validity of the adapted guideline. Future work will evaluate implementation of the adapted CPG.

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. English-speaking children (4 to 18 years) receiving intermediate-dose (ID-MTX: >1 to

Corticosteroids such as methylprednisolone (MP) remain the primary therapy for acute GVHD (aGVHD). Patients who are refractory to standard treatment (MP 2 mg/kg/day) may be treated with high-dose MP. This study evaluated the response to high-dose MP in children with aGVHD refractory to standard dose MP. Children who underwent hematopoietic SCT (HSCT) at our hospital between 1 June 2002 and 31 July 2006 and were treated with high-dose MP upon developing steroid-refractory aGVHD were included. Response to aGVHD therapy, adverse effects attributed to MP and overall outcomes were documented. Ten children received high-dose MP (≥ 20mg/kg/day) on 3-5 consecutive days followed by a tapering dose for steroid-refractory aGVHD, at a median of 12 days after starting standard treatment. Nine patients had ≥ grade III aGVHD. Only one patient with grade III aGVHD had a complete response. Two patients had a partial response but flared when MP was tapered. Complications included hypertension (100%), hyperglycemia requiring insulin therapy (33%) and four documented severe infections. Five children (50%) died (median follow-up: 5.9 years). Salvage therapy other than high-dose MP should be considered in children who fail to respond to MP 2 mg/kg/day.

Existing guidelines for the prevention of antineoplastic chemotherapy-induced nausea and vomiting (CINV) in children are constrained by the lack of robust evidence. Current guidelines recommend the use of a serotonin 5-HT3 receptor antagonist plus a corticosteroid to prevent acute CINV. Consequently, antiemetic agents that are recommended for use in adult cancer patients do not appear in the current pediatric guidelines. In addition, there is no information to guide the selection of alternative antiemetic agents for children who either cannot receive the recommended agents or who do not respond adequately to the treatment. Possible barriers to adherence to the pediatric antiemetic selection guidelines that are currently available are discussed, and published pediatric experience with antiemetic agents recommended in the current adult antiemetic selection guidelines (dolasetron, tropisetron, palonosetron, aprepitant) is summarized in this review. The use of novel and emerging antiemetic therapeutic interventions {metopimazine, diphenhydramine (Benadryl®)-lorazepam (Avitan®)-dexamethasone (Decadron®) [BAD], nabilone, acupuncture, midazolam, olanzapine, mirtazapine, gabapentin, droperidol} in children are explored.

We aimed to develop an instrument to assess cancer-treatment-related adverse effects that parents believe children find most bothersome and use it to solicit the opinions of parents regarding this issue. Parents of children 4 to 18 years of age who had received intravenous antineoplastic therapy in the last month were asked to rank prevalence, severity, and degree of bother of each symptom on behalf of their child using a questionnaire. One hundred fifty-eight of 200 (82%) questionnaires were evaluable. The most prevalent symptoms identified were mood swings (85%), fatigue (80%), and disappointment at missing activities with friends/peers (74%). These symptoms were also most commonly identified as being significantly severe. Symptoms most commonly identified as the most bothersome were disappointment at missing activities with friends/peers (50%) and feeling worried about receiving treatment, procedures, or side effects (43%). Symptoms most commonly identified as the most severe and bothersome were disappointment at missing activities with friend/peers (46%); feeling worried about receiving treatment, procedures, or side effects (40%); and painful, aching, or stiff bones, joints, or muscles (36%). This information can be used when explaining the effects of cancer treatment to patients/families, creating policies regarding pediatric cancer care and framing research hypotheses in pediatric supportive care.

Aprepitant is currently recommended for the prevention of acute antineoplastic-induced nausea and vomiting in adults receiving highly emetogenic therapy. The lack of an oral liquid dosage form is one barrier to its use in children. The purpose of this study was to develop a stable oral liquid formulation of aprepitant using the marketed aprepitant capsules.Aprepitant 20-mg/mL oral liquid was prepared from 125-mg capsule contents in Orablend(R). Twelve test samples were prepared: six packaged in amber glass and six in polyethylene terephthalate (PET) containers, three of each stored at either 23 degrees C or 4 degrees C. The physical characteristics of the oral aprepitant liquid stored in amber glass bottles were evaluated at the time of compounding and on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, and 91. The aprepitant content of three test solutions of each container type and storage temperature was determined using a stability-indicating assay at 5, 9, 14, 29, 48, 62, 73, and 111 days after compounding.All samples stored in glass demonstrated suitable physical characteristics and those stored in either glass or PET retained more than 94.0% of the initial concentration. Based on the higher limit of the 95% confidence interval of the degradation rate, suspensions stored at 23 degrees C achieved 10% loss within 66 to 85 days, compared to greater than 100 days when stored at 4 degrees C.The extemporaneous aprepitant oral suspension formulation described is physically and chemically stable for at least 90 days when refrigerated. The bioavailability of this formulation is unknown.

In solid organ transplantation, CYA dosing is based on the area under the concentration vs time curve (AUC(inf)). This study aimed to develop a guideline for the initial i.v. CYA dose for pediatric hematopoietic SCT (HSCT) patients to achieve the target AUC(inf) recommended in solid organ transplantation. Whole-blood CYA concentrations were determined in 24 patients (0.5-16.9 years) after the first i.v. dose given over 2 h, 1 day before HSCT. The i.v. CYA dose predicted to achieve an AUC(inf) of 4200 microg x h/l was calculated for each patient and expressed as a function of each patient's actual weight and body surface area (BSA). In patientsor=9 and9 years of age, the mean i.v. CYA dose predicted to achieve the target AUC was 2.6+/-0.94 and 2.1+/-1.21 mg/kg, respectively. When these doses were expressed in terms of BSA, the mean dose was 65+/-23.1 and 68+/-35.0 mg/m(2) in childrenor=9 and9 years of age, respectively. In children 0.5-17 years of age undergoing HSCT, we recommend an initial i.v. CYA dose of 65 mg/m(2) infused over 2 h to achieve an AUC(inf) of approximately 4200 microg x h/l.

Objective: To describe the provision of pediatric drug safety information in a national formulary of manufacturers’ drug product monographs. Methods: We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. Results: A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. Conclusion: We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1–11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32–6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15–3.14, probability of rate ratio

Children with cancer often cite procedural pain as the most distressing part of their disease. Pharmacologic interventions that decrease the pain and anxiety of invasive procedures have been shown to be beneficial, particularly when these interventions are a routine part of every procedure. However, despite the known benefits of analgesia and sedation, guidelines for the management of pediatric pain and stress during oncology procedures have not been established. Thus, children may not be receiving optimal pain relief. Various drugs have been investigated in pediatric populations to provide local anesthesia, systemic analgesia, conscious sedation, deep sedation, and general anesthesia. These agents include lidocaine-prilocaine, amethocaine, lidocaine, methohexital, propofol, midazolam, meperidine, nitrous oxide, fentanyl, ketamine, and diazepam. Local anesthesia with lidocaine-prilocaine and amethocaine decreases pain from accessing centrally placed venous devices (ports) and venipuncture; however, neither, is sufficient as a sole intervention for bone marrow aspirations (BMA), bone marrow biopsies (BMB) or lumbar punctures (LP). Transient local skin reactions are common with the use of lidocaine-prilocaine and amethocaine. Deep sedation or general anesthesia can be achieved with a variety of agents and are ideal interventions if pain and movement are to be prevented during more invasive procedures such as LP, BMA, and BMB. Titration of doses and monitoring to detect early adverse effects increase the safety of these interventions. Systemic analgesia with fentanyl or nitrous oxide in combination with local anesthesia may be appropriate for older children more comfortable and familiar with these procedures; conscious sedation may also be an option for these children, but deep sedation and general anesthesia should always be made available if it is the child’s preferred method of pain relief.

Background The objective was to describe symptom assessment scales that have been used in children with cancer. Methods We conducted electronic searches of OVID Medline and EMBASE in order to identify all symptom assessment scales that have been used in pediatric cancer. Two reviewers abstracted information from each identified study. Data collected included study demographics and information related to the instrument and children enrolled. We also collected information about the purpose of instrument administration and whether treatment was altered as a result of this information. Results Fourteen studies were identified which evaluated eight different symptom assessment scales. Eight studies used child self-report and all studies included children on active treatment for cancer although 4 studies also included children following completion of treatment. The most common purpose of instrument administration was to measure the prevalence of symptom burden (n = 8). None of the 14 studies used the scale to screen for symptoms and none changed patient management on the basis of identified symptoms. Conclusions We failed to identify any symptom assessment scales that were used as a symptom screening tool. There is a need to develop such a tool for use in children with cancer.