A scoping review of pediatric transplant education.

BACKGROUND: Education is crucial for pediatric patients and caregivers throughout the transplant continuum, yet data are lacking around which interventions are effective and in what circumstances. METHODS: We undertook a scoping review with the objectives of (a) describing the types, effects, and outcomes of patient-focused educational interventions before and after pediatric transplant and (b) understanding the educational experiences of patients and caregivers. Five scientific databases were explored for relevant literature using the JBI methodology. Educational interventions published in English, targeting pediatric solid organ transplant patients (0-25 years) and their caregivers were included. Relevant data from eligible articles (n = 27) were extracted and summarized. RESULTS: Eighteen articles describing 17 educational interventions were identified for objective A, and nine articles qualitatively assessing patient or parental learning needs were identified for objective B. Most interventions were directed toward teenage patients and their caregivers post kidney transplant, primarily focusing on medication self-management and adherence, or providing general information on transplant using multicomponent delivery formats. Most interventions achieved statistically significant improvements in knowledge (n = 8/9) and patients or caregivers expressed satisfaction with the intervention (n = 7/7) but health-related outcomes such as medication adherence (n = 2/6) or behavior change (n = 1/3) rarely achieved statistically significant results. In objective B, patients and caregivers described the transplant process as overwhelming, but indicated that social supports and education helped them cope. Participants consistently wanted more information than they received. CONCLUSION: Caregivers and pediatric patients value transplant education, but high-quality studies are limited. Since education is a fundamental part of the transplant process, future research in this area should be prioritized.

Fluid overload and acute kidney injury in children with tumor lysis syndrome.

AIM: Tumor lysis syndrome (TLS) is a common oncologic emergency among patients with pediatric hematologic malignancies. The mainstay of TLS management is aggressive intravenous hydration. However, the epidemiology of fluid overload (FO) and acute kidney injury (AKI) in this population is understudied. In this study, we aimed to describe the incidence, severity, and complications of FO and AKI among pediatric patients with TLS. METHODS: We completed a single-center retrospective cohort study of pediatric patients with a new diagnosis of hematologic malignancy over a 10-year period. Patients with TLS were analyzed in two groups based on the severity of AKI and FO. Charts were reviewed for complications associated with AKI and FO including hypoxemia, mechanical ventilation, hyponatremia, pulmonary edema, pediatric intensive care (PICU) admission, and need for renal replacement therapy (RRT). RESULTS: We analyzed 56 patients with TLS for FO and AKI. We found severe FO (≥10%) occurred in 35.7% (n = 20). PICU admission occurred in 35% of patients with severe FO compared to 8.3% in those with mild/moderate FO <10% (p = .013). Complications of hypoxemia (30% vs. 5.6%, p = .012) and pulmonary edema (25% vs. 2.8%, p = .010) were more common among those with severe FO. AKI occurred in 37.5% (n = 21) patients and resulted in a significant increase in PICU admission and requirement for RRT (p = .001 and <.001, respectively). CONCLUSION: Our results show FO and AKI are common, and often unrecognized complications of TLS associated with increased morbidity. Prospective, multicenter studies are needed to further dissect the burden of FO and AKI within this vulnerable population.

Implementation and Evaluation of a Diabetic Ketoacidosis Order Set in Pediatric Type 1 Diabetes at a Tertiary Care Hospital: A Quality-Improvement Initiative.

OBJECTIVES: Despite published clinical practice guidelines in pediatrics for the use of a standardized diabetic ketoacidosis (DKA) protocol, our centre lacked an accepted, evidence-informed protocol for pediatric DKA management. Our primary aim was to attain broad clinical uptake of a DKA order set. Secondary aims included improved standard-of-care DKA management principles regarding fluid, potassium and dextrose administration. METHODS: A pediatric multidisciplinary collaborative was created to examine evidence for the development and implementation of a DKA order set. A modified plan-do-study-act cycle guided by end-user feedback and early clinical outcomes allowed progressive order-set modifications and hospitalwide implementation. RESULTS: We achieved 83% uptake of the order set for patients presenting to our tertiary centre and 67% uptake for patients transferred from peripheral centres. Following the implementation of the DKA order set, we observed improvements in DKA management, which included more appropriate intravenous (IV) replacement fluid rates (30% vs. 55.1%; p=0.03); earlier administration of potassium to IV fluids (66% vs. 93.1%; p=0.006); more appropriate potassium chloride dosing to IV fluid (40% vs. 79.3%; p=0.0007) and earlier addition of IV dextrose (67.4% vs. 93.1%; p=0.009). CONCLUSIONS: Implementation of a DKA order set in a tertiary hospital required identification of key stakeholders, formation of a multidisciplinary team and the development of an evaluation process. There was an observed increase in physician order-set uptake and DKA management practice improvements. Future goals involve expanding the implementation and evaluation process to provincial regional and remote centres and analyzing the impact on resource utilization.

Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein.

Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays key roles in cell death or apoptosis. It is an integral partner to the tumor suppressor protein, Ras association domain family 1A (RASSF1A), and functions to activate the Bcl-2 family pro-apoptotic protein Bax. Although RASSF1A is now considered a bona fide tumor suppressor protein, the role of MOAP-1 as a tumor suppressor protein has yet to be determined. In this study, we present several lines of evidence from cancer databases, immunoblotting of cancer cells, proliferation, and xenograft assays as well as DNA microarray analysis to demonstrate the role of MOAP-1 as a tumor suppressor protein. Frequent loss of MOAP-1 expression, in at least some cancers, appears to be attributed to mRNA down-regulation and the rapid proteasomal degradation of MOAP-1 that could be reversed utilizing the proteasome inhibitor MG132. Overexpression of MOAP-1 in several cancer cell lines resulted in reduced tumorigenesis and up-regulation of genes involved in cancer regulatory pathways that include apoptosis (p53, Fas, and MST1), DNA damage control (poly(ADP)-ribose polymerase and ataxia telangiectasia mutated), those within the cell metabolism (IR-α, IR-ß, and AMP-activated protein kinase), and a stabilizing effect on microtubules. The loss of RASSF1A (an upstream regulator of MOAP-1) is one of the earliest detectable epigenetically silenced tumor suppressor proteins in cancer, and we speculate that the additional loss of function of MOAP-1 may be a second hit to functionally compromise the RASSF1A/MOAP-1 death receptor-dependent pathway and drive tumorigenesis.