A Prediction Model for Bacteremia and Transfer to Intensive Care in Pediatric and Adolescent Cancer Patients With Febrile Neutropenia

Objectives:Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. Methods: We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009-2015) and prospective validation (2015-2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. Results: A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn’t have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1,2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden’s Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Conclusions: Our prediction model has a good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduce length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.

Young Survivors at KSA: registry for standardised assessment of long-term and late-onset health events in survivors of childhood and adolescent cancer—a study protocol

IntroductionA high proportion of survivors of childhood and adolescent cancer experience chronic medical conditions — late effects. Most studies on late effects have a retrospective or questionnaire-based design, which leads to unavoidable limitations such as missing data or different severity coding and grading of late effects. We, therefore, need prospective data, including standardised severity coding and grading. ‘Young Survivors at KSA’ aims to close this gap by assessing frequency, severity, risk factors and longitudinal changes of late effects in childhood cancer survivors prospectively and in a standardised way.Methods and analysisWithin the ‘Young Survivors at KSA’ registry, we collect data from regular follow-up visits in a comprehensive database prospectively and repeatedly from start of the study and retrospectively at most until January 2016. We classify and grade the severity of late effects according to the Common Terminology Criteria for Adverse Events version 4.0 modified by Hudson et al. The outcome variables correspond to results from risk-stratified organ examinations, performed according to the Children’s Oncology Group guidelines version 5.0 and the recommendations by the International Guideline Harmonization Group. We collect the exposure variables from the patients’ medical history, including detailed information on cancer diagnosis and treatment. We analyse the data in an exposure-driven and organ system-driven approach. We start recruitment with patients treated at the Kantonsspital Aarau, Switzerland. However, our design allows the inclusion of additional national centres later.Ethics and dissemination‘Young Survivors at KSA’ is approved by the Ethikkommission Nordwest- und Zentralschweiz, reference number AO_2020–00012. The results of this study will be presented at scientific meetings, including meetings with childhood cancer survivors and published in peer-reviewed and if possible open access journals. New insights gained from the study will be used directly in clinical practice.Trial registration numberClinicalTrials.gov NCT04811794; https://clinicaltrials.gov/ct2/show/study/NCT04811794

Development and use of an innovative Gap Finding Tool to create Pharmaceutical Care Model within a paediatric oncology setting

Introduction A paediatric cancer ward is a setting where pharmacists participate in direct patient care, acting as coordinators between the patient, caregivers and healthcare professionals. The aim of the study was to develop a Gap Finding Tool to support the setting up of a pharmaceutical care model at a Paediatric-Adolescent Cancer Ward. Methods The Standards of Practice for Clinical Pharmacy Services by the Society of Hospital Pharmacists of Australia Committee of Specialty Practice in Clinical Pharmacy (2013), the American College of Clinical Pharmacy (2014) and the European Association of Hospital Pharmacists (2014) were used to compile the Gap Finding Tool. The developed Tool was tested for content validity by a panel of experts and subsequently implemented over 2 months. Results The Gap Finding Tool comprised of nine sections with an average of eight statements each about pharmacy services that should be provided at ward level. For each statement, the rater indicates whether these contributions are provided. When the Tool was implemented at the Paediatric-Adolescent Cancer Ward, four major gaps were identified, namely, absence of a clinical pharmacist, lack of medicines information, vetting of chemotherapy prescriptions by pharmacist with limited access to patient data and lack of pharmacist-input on medicines availability. Processes requiring optimisation included discharge medication advice and documentation processes. Conclusion The developed Gap Finding Tool is an innovative tool which is versatile and can be used in ward or ambulatory clinical settings to identify gaps in pharmaceutical processes and services and compare national or regional practices to international standards.

Keeping Connected With School: Implementing Telepresence Robots to Improve the Wellbeing of Adolescent Cancer Patients

Background: Adolescent cancer patients experience considerable absence from their education, contributing to poorer academic attainment and isolation from peers, and impacting wellbeing. Telepresence robots have been used to support the educational and social needs of young people with chronic illness. This article presents the results of the development and pilot-testing of a telepresence robot service in schools for adolescent cancer patients – the TRECA (Telepresence Robots to Engage CAncer patients in education) service.Methods: Phase I used semi-structured interviews (n = 25) to assess the views of patients, parents, schools and clinicians on the benefits, acceptability, barriers, and enablers of utilizing robots in schools for adolescent cancer patients. Results from Phase I informed the development of the TRECA service. Phase II used semi-structured interviews (n = 22) to assess the implementation experiences of adolescent cancer patients, and their families, schools, and keyworkers who pilot-tested the TRECA service.Results: Phase I demonstrated the need for telepresence technology in connecting adolescent cancer patients to school. Given the variable support during treatment, a telepresence robot service was considered an acceptable method of facilitating a school-patient connection. The recommendations provided in Phase I, such as the need for provision of ongoing education, training, and support to the patient and school, informed the development of the TRECA service. In Phase II, the themes of The necessity of stakeholder buy-in, A facilitator of meaningful connection, and One size does not fit all were generated. The TRECA service’s flexibility in meeting the needs of its users helped facilitate meaningful connections. Participants reported that these connections provided patients an enhanced sense of agency and wellbeing. The importance of stakeholder buy-in and taking an individualized approach to service delivery were also highlighted. Stakeholder miscommunication and lack of knowledge were key aspects of implementation needing improvement as the service is rolled out on a larger scale.Conclusion: Using telepresence robots to connect adolescents to school during cancer treatment was regarded as highly acceptable, facilitating peer and academic connection. By making stakeholder-recommended improvements to the TRECA service’s existing processes, the service will continue to grow in effectiveness and capacity.

Hearing the Adolescents' Voice: a Study Evaluating the Use of Conjoint Analysis for Use with Adolescents to Determine Preferences for Inpatient Hospital Facilities

<p>Some adolescents spend considerable time in hospital in environments that are designed either with adults or with younger children in mind. This research used the economic technique of conjoint analysis and an informal discussion to canvas opinions regarding ideal combination of inpatient facilities and, because of the changing youth culture, the use of cell phones in hospital. The content of the conjoint analysis was, with the exception of the inclusion of the question regarding the use of cell phones, derived from the literature. Because conjoint analysis does not appear to have been used with adolescents one of the questions to be answered was whether this was a method of research that could be used with adolescents. The research was undertaken with 29 young people, most of who were from CanTeen (the adolescent cancer support group) in Wellington. The conjoint analysis, and discussion with the adolescents supported the general findings from the literature that adolescents do not want to be nursed in either overtly paediatric or, in their words, ‘dull adult wards’, as they enjoy bright lively surrounds. Ideally they would like to be nursed with their peer group and so have the opportunity to interact with young people of their age. The research demonstrated that adolescents are able to understand the concept of conjoint analysis and also supported findings from overseas that these healthcare consumers value having their opinions canvassed and are well able to give constructive and well thought out opinions. A report on the findings of this research will be presented to Capital and Coast District Health Board with the expectation that it will be considered when the final decisions are made regarding the upgrading of Wellington Hospital’s present facilities as it is anticipated that these facilities will contain dedicated adolescent beds within the paediatric unit.</p>

Hearing the Adolescents' Voice: a Study Evaluating the Use of Conjoint Analysis for Use with Adolescents to Determine Preferences for Inpatient Hospital Facilities

<p>Some adolescents spend considerable time in hospital in environments that are designed either with adults or with younger children in mind. This research used the economic technique of conjoint analysis and an informal discussion to canvas opinions regarding ideal combination of inpatient facilities and, because of the changing youth culture, the use of cell phones in hospital. The content of the conjoint analysis was, with the exception of the inclusion of the question regarding the use of cell phones, derived from the literature. Because conjoint analysis does not appear to have been used with adolescents one of the questions to be answered was whether this was a method of research that could be used with adolescents. The research was undertaken with 29 young people, most of who were from CanTeen (the adolescent cancer support group) in Wellington. The conjoint analysis, and discussion with the adolescents supported the general findings from the literature that adolescents do not want to be nursed in either overtly paediatric or, in their words, ‘dull adult wards’, as they enjoy bright lively surrounds. Ideally they would like to be nursed with their peer group and so have the opportunity to interact with young people of their age. The research demonstrated that adolescents are able to understand the concept of conjoint analysis and also supported findings from overseas that these healthcare consumers value having their opinions canvassed and are well able to give constructive and well thought out opinions. A report on the findings of this research will be presented to Capital and Coast District Health Board with the expectation that it will be considered when the final decisions are made regarding the upgrading of Wellington Hospital’s present facilities as it is anticipated that these facilities will contain dedicated adolescent beds within the paediatric unit.</p>

The matrisome contributes to the increased rigidity of the bovine ovarian cortex and provides a source of new bioengineering tools to investigate ovarian biology

The gonadotoxic effects of some cancers significantly increase the risk of developing infertility and cessation of ovary hormones (premature ovarian insufficiency, POI). Fertility preservation in the form of ovarian tissue cryopreservation (OTC) is offered to pediatric and adolescent cancer patients who cannot undergo oocyte retrieval and egg cryopreservation. The cryopreserved ovarian tissue can be transplanted back and has been found to restore fertility in 20 - 40% of transplants and restore hormone function for an average of 3 to 5 years. However, some individuals have primary or metastatic disease within their ovarian tissue and would not be able to transplant it back in its native form. Therefore, there is a need for additional methods for hormone and fertility restoration that would support a safe transplant with increased successful livebirths and long-term hormone restoration. To support this goal, we sought to understand the contribution of the ovarian microenvironment to its physical and biochemical properties to inform bioprosthetic ovary scaffolds that would support isolated follicles. Using atomic force microscopy (AFM), we determined that the bovine ovarian cortex was significantly more rigid than the medulla. To determine if this difference in rigidity was maintained in isolated matrisome proteins from bovine ovarian compartments, we cast, and 3D printed hydrogels created from decellularized bovine ovarian cortex and medulla slices. The cast gels and 3D printed bioprosthetic ovary scaffolds from the cortex was still significantly more rigid than the medulla biomaterials. To expand our bioengineering toolbox that will aide in the investigation of how biochemical and physical cues may affect folliculogenesis, we sought to confirm the concentration of matrisome proteins in bovine ovarian compartments. The matrisome proteins, COL1, FN, EMILIN1 and AGRN were more abundant in the bovine ovarian cortex than the medulla. Whereas VTN was more abundant in the medulla than the cortex and COL4 was present in similar amounts within both compartments. Finally, we removed proteins of interest, EMILIN1 and AGRN, from decellularized bovine ovarian cortex materials and confirmed that this specifically depleted these proteins without affecting the rigidity of cast or 3D printed hydrogels. Taken together our results indicate the existence of a rigidity gradient in the bovine ovary, that this rigidity gradient is maintained in resulting engineered materials strongly implicating a role for matrisome proteins in contributing to the physical properties of the bovine ovary. By establishing additional engineering tools, we will continue to explore mechanisms behind matrisome-follicle interactions.