Pilot Randomized Trial of a Three Times Weekly Heparin Flushing Intervention in Children, Adolescents, and Young Adults With Cancer With Tunneled Central Venous Catheters.

Background: Children and adolescents with cancer often undergo aggressive treatment and receive supportive care requiring a long-term tunneled central venous catheter (TCVC). Regular flushing promotes TCVC patency when not in use (i.e., noninfusing). However, TCVC flushing guidelines and the current practice of daily flushing are not based on high-quality evidence. Few studies have compared the effect of less frequent flushing on TCVC patency. The purpose of this study was to evaluate the feasibility of a three times weekly heparin flushing intervention, as compared to daily heparin flushing, in children and adolescents and young adults (AYAs) with noninfusing TCVCs. Methods: Twenty children and AYAs were randomized to one of two groups, standard of care (SOC) (i.e., daily heparin flushing) or intervention (three times weekly heparin flushing) for 8 weeks. Feasibility data (recruitment, retention, acceptability, TCVC patency, and complications) were analyzed descriptively. Results: Twenty of 22 eligible patients were enrolled in the study (90% recruitment rate). Four participants discontinued the study early due to TCVC removal (20% attrition rate). One participant in each group had their TCVC removed due to a central line-associated bloodstream infection, one SOC group participant had their TCVC removed due to damage, and one intervention group participant had their TCVC removed due to discontinuation of treatment. No participants were withdrawn for safety concerns or because they did not find the protocol acceptable. Conclusions: It is feasible to conduct a large-scale randomized controlled trial to investigate a three times weekly heparin flushing intervention in children and AYAs with TCVCs.

Quality of Life and Pain Experienced by Children and Adolescents With Cancer at Home Following Discharge From the Hospital.

An exploratory study was conducted to examine the quality of life and pain experienced by patients with pediatric cancer at home after discharge. Physical, cognitive, social, and emotional aspects of quality of life were measured and how these may be affected by age, sex, diagnosis, and pain status. The authors also characterized intensity, location, and quality of pain experienced. A sample of 33 patients participating in a larger study was selected on the basis of having pain on the day of discharge and having completed the Pediatric Quality of Life Inventory Generic, Cancer Module, Multidimensional Fatigue Scale, and the Adolescent Pediatric Pain Tool at home. Cancer diagnoses were leukemias/lymphomas (42.4%), brain/central nervous system tumors (27.3%), sarcomas (24.2%), or other (6.1%). More than half of patients reported pain (n=17; 51.5%). Patients with pain had more fatigue affecting the quality of life (P=0.01), and lower physical and emotional functioning, leading to lower overall health-related quality of life scores (P=0.011). Female individuals and adolescents reported worse emotional functioning (P=0.02 and P=0.05, respectively). Physical, cognitive, and social functioning were lowest among patients diagnosed with sarcomas (P=0.00, P=0.01, and P=0.04, respectively). It is important to understand the symptom experience of patients at home as a first step in moving towards optimal discharge teaching and treatment.

Frequency, Severity, and Distress Associated With Physical and Psychosocial Symptoms at Home in Children and Adolescents With Cancer.

Malignancy- and cancer-related treatments lead to multiple symptoms. Although treatments focus on cure, few research studies have examined the symptoms that accompany these aggressive and complicated treatments. The purpose of the study was to evaluate the symptoms experienced by children at home. Children (n = 25) and adolescents (n = 33) diagnosed with cancer completed the Memorial Symptoms Assessment Scale during the 5 days at home after discharge from the hospital. The most frequent physical symptoms were fatigue (52.1%), nausea (50.7%), lack of appetite (43.7%), and pain (42.3%). The most frequent psychological symptoms were difficulty sleeping (21.1%), worrying (18.3%), feeling sad (18.3%), and feeling nervous (16.9%). Significant differences were found in the overall physical and psychosocial symptoms and Global Distress Index in patients with and without pain, fatigue, and nausea. Results indicated that physical and psychosocial symptoms and Global Distress Index increased as severity of pain, nausea, and fatigue increased. Children and adolescents were experiencing many symptoms at home but were often not reporting them.

Community-based participatory research: an innovative approach for improving perioperative care of underserved children.

Pediatric disparities disproportionately affect Latino youth undergoing surgery and their families. As such, there is a critical need for culturally relevant frameworks that can advance perioperative intervention approaches in this population and reduce these disparities. In the following article, we first describe the methodological process of community-based participatory research (CBPR) and next report the results of the CBPR process that was conducted in this population. An interdisciplinary group of investigators, Latina mothers, and various other stakeholders met for a series of CBPR-based structured meetings. Qualitative data collection and analyses of the CBPR process were guided by principles of grounded theory that employs inductive techniques and constant comparison analyses until reaching saturation of data. Barriers identified in the process can be grouped within the following domains: child-related factors, family-related factors, health care provider factors, and hospital system factors. Family system factors category (coded references = 136) had the highest number of coded references; this category was found to be best described by the value of familismo or familism, including a duty to help family members when in need. The health care provider category (coded references = 42) was ranked second by frequency. Within this category, two major themes surfaced: health care provider cultural competence and overestimating health literacy. All barriers identified will be next incorporated in an innovative behavioral intervention that is currently being developed. We conclude that the model of CBPR can be used within the context of perioperative care of children and their families.

Fatigue and Sleep Experiences at Home in Children and Adolescents With Cancer.

PURPOSE/OBJECTIVES: To (a) investigate fatigue and sleep patterns of children and adolescents at home and (b) examine factors associated with fatigue and sleep.. DESIGN: Descriptive with repeated measures
. SETTING: Homes of study participants in Los Angeles and Orange, California
. SAMPLE: 35 children and adolescents with cancer. METHODS: Data were collected using the PedsQL Multidimensional Fatigue Scale, which was completed once at home by each participant, and sleep actigraphs, which were worn for five days at home following discharge from hospitalization
. MAIN RESEARCH VARIABLES: General fatigue, cognitive fatigue, sleep-rest fatigue, sleep duration, sleep quantity, sleep efficiency, and wake after sleep onset
. FINDINGS: More than half of the participants had problems with fatigue at home. Significant correlations were found between sleep/rest fatigue and sleep duration. Factors that affected fatigue were age, gender, and cancer diagnosis. Adolescents had more problems with fatigue than children, and female patients had more problems with fatigue than male patients. Patients with sarcoma had more problems with fatigue than those with leukemia, lymphoma, and other cancer diagnoses. Adolescents slept less than children. CONCLUSIONS: Children and adolescents with cancer have fatigue and sleep problems at home that vary by age, gender, and cancer diagnosis
. IMPLICATIONS FOR NURSING: Data from the current study support the need for nurses to provide teaching about fatigue and sleep at home in children and adolescents with cancer. Future studies are needed to examine interventions that may alleviate fatigue and improve sleep at home
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Clinical Nurse Specialist Collaboration to Recognize, Prevent, and Treat Pediatric Pressure Ulcers.

PURPOSE/OBJECTIVES: The purpose of this quality improvement project was to reduce the incidence of pressure ulcers in a 232-bed, freestanding children's hospital in Western United States. BACKGROUND: Pressure ulcers have been an underappreciated hospital-acquired condition in children. Children have distinct anatomic, physiologic, and developmental factors that alter how pressure ulcers occur, but nurses may not recognize the pediatric patient as at risk because of lack of knowledge and tools to assess skin, identify risk factors, and recognize or stage pressure ulcers. Our initial efforts to develop organizational tools to reduce pediatric pressure ulcers were not sufficient, despite improvements in care. Interprofessional and intraprofessional collaboration, led by clinical nurse specialists, focused on documentation, tracheostomies, respiratory devices, and hemodynamically unstable or extracorporeal life support patients. RATIONALE: Stage 3 and 4 and unstageable pressure ulcers are also "never events" in children. The unique factors involved with infant and pediatric pressure ulcers demand unique solutions. OUTCOME: Our collaborative efforts led to a significant and sustained reduction in pressure ulcer incidence, from 3.3 per 1000 patient days in the first quarter of 2010 to 1.7 per 1000 patient days in the second quarter of 2014. Reportable pressure ulcers were reduced by 60%. Improved awareness and prevention strategies also led to significant reductions in extracorporeal life support patient pressure ulcers and respiratory device-related pressure ulcers. CONCLUSION: Through intraprofessional and interprofessional collaboration, the clinical nurse specialists were able to implement sustained organizational change and improve care for infants and children. IMPLICATIONS: Reduction in pressure ulcers is achievable but requires collaboration and creative solutions that involve multiple disciplines.

Sorafenib treatment following hematopoietic stem cell transplant in pediatric FLT3/ITD acute myeloid leukemia.

BACKGROUND: FLT3/ITD is associated with poor outcomes in adult and pediatric acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) can improve cure rates, however relapse is still common. Recent studies demonstrate the activity of FLT3 inhibitors, including sorafenib, in targeting the underlying mutation. PROCEDURE: We conducted a retrospective study of 15 pediatric patients with FLT3/ITD+ AML treated with sorafenib within 18 months after receiving HSCT. Sorafenib was administered either as prophylaxis in patients considered at very high risk for relapse (n = 6) or at the time of disease recurrence (n = 9). RESULTS: Sorafenib was initiated at a median of 100 days post HSCT. Overall, 11/15 (73%) of patients experienced medically significant toxicities. Among patients who experienced toxicity, 6/11 (55%) received treatment at doses above what was later determined to be the maximum tolerated dose of sorafenib for pediatric leukemia. Importantly, sorafenib did not appear to exacerbate graft versus host disease. Our findings suggest that sorafenib may be of particular efficacy in patients with minimal residual disease (MRD); all patients who received sorafenib for MRD immediately prior to transplant or with emergence post-HSCT are alive and remain in complete remission at a median of 48 months post HSCT. CONCLUSIONS: Our case series suggests that sorafenib administration is feasible and tolerable in pediatric FLT3/ITD+ AML patients early post HSCT. Ongoing prospective controlled studies are needed to further define the dosing of sorafenib in the post-HSCT period and to determine the optimal context for this treatment approach.

A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group.

BACKGROUND: This Phase 2 study tested the tolerability and efficacy of bortezomib combined with reinduction chemotherapy for pediatric patients with relapsed, refractory or secondary acute myeloid leukemia (AML). Correlative studies measured putative AML leukemia initiating cells (AML-LIC) before and after treatment. PROCEDURE: Patients with <400 mg/m(2) prior anthracycline received bortezomib combined with idarubicin (12 mg/m(2) days 1-3) and low-dose cytarabine (100 mg/m(2) days 1-7) (Arm A). Patients with ≥400 mg/m(2) prior anthracycline received bortezomib with etoposide (100 mg/m(2) on days 1-5) and high-dose cytarabine (1 g/m(2) every 12 hours for 10 doses) (Arm B). RESULTS: Forty-six patients were treated with 58 bortezomib-containing cycles. The dose finding phase of Arm B established the recommended Phase 2 dose of bortezomib at 1.3 mg/m(2) on days 1, 4, and 8 with Arm B chemotherapy. Both arms were closed after failure to meet predetermined efficacy thresholds during the first stage of the two-stage design. The complete response (CR + CRp) rates were 29% for Arm A and 43% for Arm B. Counting additional CRi responses (CR with incomplete neutrophil recovery), the overall CR rates were 57% for Arm A and 48% for Arm B. The 2-year overall survival (OS) was 39 ± 15%. Correlative studies showed that LIC depletion after the first cycle was associated with clinical response. CONCLUSION: Bortezomib is tolerable when added to chemotherapy regimens for relapsed pediatric AML, but the regimens did not exceed preset minimum response criteria to allow continued accrual. This study also suggests that AML-LIC depletion has prognostic value.

Phase I/II trial of clofarabine and cytarabine in children with relapsed/refractory acute lymphoblastic leukemia (AAML0523): a report from the Children's Oncology Group.

BACKGROUND: The discovery of effective re-induction regimens for children with more than one relapse of acute lymphoblastic leukemia (ALL) remains elusive. The novel nucleoside analog clofarabine exhibits modest single agent efficacy in relapsed ALL, though optimal combinations of this agent with other active chemotherapy drugs have not yet been defined. Herein we report the response rates of relapsed ALL patients treated on Children's Oncology Group study AAML0523, a Phase I/II study of the combination of clofarabine and cytarabine. PROCEDURE: AAML0523 enrolled 21 children with ALL in second or third relapse, or those refractory to re-induction therapy. The study consisted of two phases: a dose finding phase and an efficacy phase. The dose finding portion consisted of a single dose escalation/de-escalation of clofarabine for 5 days in combination with a fixed dose of cytarabine (1 g/m(2)/day for 5 days). Eight patients received clofarabine at 40 mg/m(2)/day and 13 patients at 52 mg/m(2)/day. RESULTS: Toxicities observed at all doses of clofarabine were typical of intensive chemotherapy regimens for leukemia, with infection being the most common. We did not observe significant hepatotoxicity as reported in other clofarabine combination regimens. The recommended pediatric Phase II dose of clofarabine in combination with cytarabine for the efficacy portion of AAML0523 was 52 mg/m(2). Of 21 patients with ALL, 3 (14%) achieved a complete response (CR). Based on the two-stage design definition of first-stage inactivity, the therapy was deemed ineffective. CONCLUSION: The combination of clofarabine and cytarabine in relapsed/refractory childhood ALL does not warrant further clinical investigation.

Symptoms in children with advanced cancer: child and nurse reports.

BACKGROUND: Systematic studies on the specific symptom experience in children with advanced cancer are limited. OBJECTIVE: The objective of the study was to examine the common symptoms and to explore commonly occurring symptoms over time. METHODS: A prospective and longitudinal study design was used. Data were collected at 10 data points from 60 children over a 5-month period. Children ranged from 6 to 17 years old, spoke English or Spanish, were diagnosed with advanced cancer, and were receiving healthcare in 1 of 4 Southern California hospitals. Nurses' documentations of symptoms were examined. RESULTS: The study sample was composed of children 6 to 12 years old (52%) and 13 to 17 years old (48%); 42% were female, and 58% were male. Fifty-five percent were Latino, and 30% were Caucasian. Pain, nausea, drowsiness, and energy loss were reported by children in more than 50% of the interviews. Children's and nurses' reports of symptoms were similar except children reported significantly more frequency and intensity of pain. CONCLUSION: Children with advanced cancer were able to report and describe their symptoms. There were few differences by gender, age, and ethnicity. IMPLICATIONS FOR PRACTICE: It is important that children's symptoms are clearly communicated to nurses, and these study findings may be used to anticipate and manage the symptoms experienced by children with advanced cancer.

Examining the push-pull method of blood sampling from central venous access devices.

The placement of a central venous access device (CVAD) has revolutionized supportive care for pediatric cancer patients. The CVAD is used to administer chemotherapy/biotherapy, blood products, total parenteral nutrition, antibiotics, and many other supportive medications. CVADs also provide the ability to obtain blood samples without the trauma associated with venipuncture. Frequent blood sampling is often needed to monitor the side effects and response of the cancer treatment. Unfortunately, the most common method requires discarding blood (0.5-10 mL, depending on the institution's protocol) with each lab draws, for various reasons. For pediatric oncology patients, this can result in a large volume of blood being discarded and subsequently increase the need for blood transfusions. Repeated exposure to allogeneic (donor) blood products can put this patient population at additional risk for alloimmunization and febrile reactions. The purpose of this study is to test the limits of agreement between laboratory values (chemistry panel 18 and complete blood count) obtained using the push-pull and standard methods of blood sampling from CVADs in pediatric oncology patients.

The pain experience of children with leukemia during the first year after diagnosis.

BACKGROUND: Children with cancer experience pain related to the disease process, the treatment, and the associated procedures. For children with leukemia, the pain experienced after diagnosis has received scant attention. OBJECTIVE: To examine the pain experience, management strategies, and outcomes during the first year after the diagnosis of acute leukemia. METHODS: A longitudinal descriptive approach was used to collect data at seven data points from 95 English- and Spanish-speaking children, ages 4 to 17 years, receiving care in one of three southern California hospitals, and from their English- and Spanish-speaking parents. Age-appropriate instruments were used to examine the variables of pain intensity, location, pattern over time, and quality, as well as strategies for managing pain, perceived effectiveness of management strategies, and functional status. RESULTS: All the children reported pain over the course of the year. Pain intensity scores incorporated the full range of possible responses. For the children 4 to 7 years old, the highest and lowest mean scores, respectively, were 2 and 1.6 (scale, 0-4). For the children 8 to 17 years old, the highest and lowest mean scores, respectively, were 50.1 and 39.5 (scale, 0-100). The most common location of pain was the legs (26.5%) in all seven interviews. Other frequently noted sites were the abdomen (16.6%), head/neck (16.6%), and back (14.2%). The words used most frequently by the older English- and Spanish-speaking children to describe pain were "uncomfortable" (incómodo) and "annoying" (molesto). According to the interviews, the most frequently used strategy for pain management was stressor modification (e.g., medication, sleep, hot/cold, and massage). The most common coping strategies according to a Likert scale rating were "watch TV" (n = 426), "lie down" (n = 421), "wish for it to go away" (n = 417), and "tell my mother or father" (n = 416). The pain intensity scores after pain management were significantly lower for the younger children in three of the seven interviews and for the older children in all seven interviews. For both the younger and older children, functional status (i.e., the ability to engage in routine activities) was above the median score at the seven interviews. CONCLUSIONS: Children with leukemia experience pain throughout the first year of treatment. In this study, the pain was responsive to the management strategies used by the parents and children.

Pain and leukemia: the stories of three children.

The stories of the pain experience of three children with acute leukemia during the first year after diagnosis are presented in this report. To provide a broad picture, children who represent various characteristics were selected: ages 6, 9, and 15 years; two male and one female; two Latino and one Caucasian; two English-speaking and one Spanish; two with acute lymphocytic leukemia and one with acute myelocytic leukemia. Consideration of the disease, procedures, treatment, and normal childhood pain experiences will provide the nurse who cares for these children guidance in knowing why and when pain may occur, which will lead to timely interventions for the pain.