Allied health and nursing practices in pediatric solid organ transplantation: An international survey.

INTRODUCTION: With improved survival in pediatric solid organ transplantation (SOT) care has focused on optimizing functional, developmental, and psychosocial outcomes, roles often supported by Allied Health and Nursing professionals (AHNP). However, there is a scarcity of research examining frameworks of clinical practice. METHODS: The International Pediatric Transplant Association AHNP Committee developed and disseminated an online survey to transplant centers as a quality improvement project to explore AHNP practice issues. Participant responses were characterized using descriptive statistics, and free-text comments were thematically analyzed. Responses were compared across professional groups; Group 1: Advanced Practice Providers, Group 2: Nursing, Group 3: Allied Health. RESULTS: The survey was completed by 119 AHNP from across the globe, with responses predominantly (78%) from North America. Half of respondents had been working in pediatric transplant for 11+ years. Two-thirds of respondents were formally funded to provide transplant care; however, of these not funded, over half (57%) were allied health, compared to just 6% of advance practice providers. Advanced practice/nursing groups typically provided care to one organ program, with allied health providing care for multiple organ programs. Resource constraints were barriers to practice across all groups and countries. CONCLUSION: In this preliminary survey exploring AHNP roles, professionals provided a range of specialized clinical care. Challenges to practice were funding and breadth of care, highlighting the need for additional resources, alongside the development of clinical practice guidelines for defining, and supporting the role of AHNP within pediatric SOT. Professional organizations, such as IPTA, can offer professional advocacy.

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.

Significant Effects of Renal Function on Mycophenolic Acid Total Clearance in Pediatric Kidney Transplant Recipients with Population Pharmacokinetic Modeling.

BACKGROUND AND OBJECTIVES: Mycophenolic acid (MPA) is an immunosuppressant commonly prescribed in pediatric kidney transplantation to prevent graft rejection. Large variabilities in MPA plasma exposures have been observed in this population, which could result in severe adverse effects. The majority of the MPA pharmacokinetic data have been reported in adult populations, whereas information in pediatric patients is still very limited. The objective of this study was to establish a novel, nonlinear mixed-effects model for MPA and investigate the clinical variables affecting MPA population pharmacokinetics in pediatric kidney transplant recipients. METHODS: Data were collected retrospectively from pediatric kidney transplant patients (≤ 18 years when MPA concentrations were initially collected; on oral administration of mycophenolate mofetil) in Calgary, Alberta, Canada. Nonlinear mixed-effect modeling was conducted using stochastic approximation expectation-maximization in Monolix 2021R2 (Lixoft SAS, France) to determine population pharmacokinetic estimates, interindividual variabilities, and interoccasional variabilities. Covariate models were constructed using the Model Proposal function in Monolix in conjunction with a systematic stepwise inclusion/elimination protocol. The best model was selected based on objective function values, relative standard errors, goodness-of-fit plots, prediction-corrected visual predictive checks, and numerical predictive checks. RESULTS: A total of 50 pediatric kidney transplant patients (25 female) with 219 MPA plasma concentration-time profiles were included. The average age (± standard deviation) and posttransplant time for the sample population were 12.8 ± 4.8 years and 762 ± 1160 days, respectively. The majority of study subjects (i.e., > 85% based on all occasions) were co-administered tacrolimus. A two-compartment, first-order absorption with lag time and linear elimination structural model with lognormal distributed proportional residual errors best described the MPA concentration-time data. The absorption rate constant (2.52 h-1 or 0.042 min-1), lag time (0.166 h or 9.96 min), volumes of distributions of the central (22.8 L) and peripheral (216 L) compartments, and intercompartment clearance (17.6 L h-1 or 0.293 L min-1) were consistent with literature values; whereas total MPA clearance (0.72 L h-1 or 0.012 L min-1) was relatively reduced, likely due to the general lack of cyclosporine interactions and the stabilized graft functions from significantly longer posttransplant time in our sample population. Of the clinical variables tested, only estimated glomerular filtration rate (eGFR) was identified a significant covariate affecting total MPA clearance with a positive, exponential relationship. The final population pharmacokinetic model was successfully evaluated/validated using a variety of complementary methods. CONCLUSION: We have successfully constructed and validated a novel population pharmacokinetic model of MPA in pediatric kidney transplant patients. A positive, nonlinear relationship between eGFR and total MPA clearance identified in our model is likely attributed to multiple concurrent mechanisms, which warrant further systematic investigations.

An international survey of allied health & nursing professionals during the COVID-19 pandemic: Perspectives on facilitators of & barriers to care.

BACKGROUND: Allied health and nursing professionals (AHNP) are integral members of transplant teams. During the COVID-19 pandemic, they were required to adapt to changes in their clinical practices. The goal of the present study was to describe AHNP perceptions concerning the impact of the pandemic on their roles, practice, and resource allocation. METHODS: An online survey was distributed globally via email by the International Pediatric Transplant Association to AHNP at transplant centers from September to December 2020. Responses to open-ended questions were collected using an electronic database. Using a thematic analysis approach, coding was conducted by three independent coders who identified patterns in responses, and discrepancies were resolved through discussion. RESULTS: The majority of respondents (n = 119) were from North America (78%), with many other countries represented (e.g., the United Kingdom, Europe, Australia, New Zealand, South Africa, and Central and South America). Four main categories of impacts were identified: (1) workflow changes, (2) the quality of the work environment, (3) patient care, and (4) resources. CONCLUSIONS: Participants indicated that the pandemic heightened existing barriers and resource challenges frequently experienced by AHNP; however, the value of team connections and opportunities afforded by technology were also highlighted. Virtual care was seen as increasing healthcare access but concerns about the quality and consistency of care were also expressed. A notable gap in participant responses was identified; the vast majority did not identify any personal challenges connected with the pandemic (e.g., caring for children while working remotely, personal stress) which likely further impacted their experiences.

A Randomized Controlled Trial of a Pretransplant Educational Intervention in Kidney Patients.

Poor patient knowledge about transplantation is a significant problem following kidney transplant. A video-based educational intervention was developed to supplement standard education provided by transplant teams. METHODS: A multicenter randomized controlled trial tested the intervention delivered to patients undergoing assessment or waitlisted for kidney transplant. Adult participants were randomized to the control (standard education) or the intervention group, consisting of electronic access to the videos (or digital video disks if no internet) plus standard education. Differences between groups in changes in transplant knowledge (measured by the Kidney Transplant Understanding Tool), education satisfaction, self-efficacy, and quality of life (secondary outcomes) were evaluated by a preintervention and postintervention survey. Video viewing habits were tracked and described for patients in the intervention group. RESULTS: One hundred sixty-two patients were enrolled, with 132 completing both questionnaires (n = 64 intervention and n = 68 control), with similar enrollment from 3 Canadian sites. Video viewing statistics in the complete cases indicated that 78% (50/64) watched the videos, with 70% (45/64) viewing them electronically, while 8% (5/64) received digital video disks and self-reported participation. Baseline knowledge scores in the intent-to-treat population were 55.4 ± 6.5 and 55.7 ± 7.1 in the intervention and control, respectively. The mean knowledge change in the intervention (2.1 ± 3.6) was significantly higher than in the control group (0.8 ± 3.4, P < 0.02). In the per-protocol analysis (patients with objective evidence of watching at least 80% of the videos), the knowledge improvements were 3.4 ± 3.8. Video group participants reported higher satisfaction with education (P < 0.02) and expressed positive comments in open-ended feedback. CONCLUSIONS: Electronic video education in the pretransplant setting improved knowledge and satisfaction.

Time in Therapeutic Range Using a Nomogram for Dose Adjustment of Warfarin in Patients on Hemodialysis With Atrial Fibrillation.

BACKGROUND: Patients treated with hemodialysis and prescribed warfarin typically have lower time in therapeutic range (TTR) compared to the general population. This may result in less benefit or increased risk of over anticoagulation in these patients. OBJECTIVE: To assess effectiveness of use of an electronic nomogram for the management of warfarin therapy in patients treated with hemodialysis. DESIGN: Retrospective chart review. SETTING: Adult patients treated with hemodialysis. PATIENTS: Patients on hemodialysis receiving warfarin for the management of atrial fibrillation (AF) with therapy managed by nursing led electronic nomogram. MEASUREMENTS: Time in therapeutic range (as fraction and Rosendaal). METHODS: Retrospective chart review over 1 year of international normalized ratio (INR) results was completed, and TTR was calculated. Comparison of patients with TTR greater than 60% to those less than 60% was completed using chi-square analysis. RESULTS: Of 43 patients with warfarin therapy managed by the nomogram, the mean TTR was 55.2% (calculated by fraction method) or 61.2% (calculated by Rosendaal method). More than half of the patients (63.5%) had moderate to good control, defined as TTR greater than 60%. Female sex, liver disease, or history of substance use and more medication holds were associated with lower TTR. LIMITATIONS: Small sample size and retrospective nature of review. CONCLUSIONS: The results of this review supports the use of an electronic, nursing-led nomogram for the maintenance management of warfarin therapy in stable patients treated with hemodialysis, as use results in TTR greater than 60% for more than half of patients.

CONTEXTE: La marge thérapeutique (TTR­time in therapeutic range) des patients sous hémodialyse qui reçoivent de la warfarine est habituellement inférieure à celle de la population générale; ce qui pourrait se traduire par de moindres bénéfices sur la santé de ces patients ou par un risque accru de surtraitement anticoagulant. OBJECTIFS: Évaluer l'efficacité d'un nomogramme électronique pour la prise en charge du traitement à la warfarine chez les patients sous hémodialyse. TYPE D'ÉTUDE: Examen rétrospectif des dossiers médicaux. CADRE: Des patients adultes traités par hémodialyse. SUJETS: Des patients sous hémodialyse recevant de la warfarine pour la prise en charge de la fibrillation auriculaire (FA) et dont le traitement était administré à l'aide d'un nomogramme électronique géré par le personnel infirmier. MESURES: Temps dans la marge thérapeutique (par fraction et par Rosendaal). MÉTHODOLOGIE: L'analyze rétrospective des dossiers médicaux a été réalisée sur une année de résultats ratio international normalisé (RIN) et le temps dans la marge thérapeutique a été calculé. Une analyze du chi carré a servi à comparer les patients présentant une TTR de plus de 60 % à ceux qui présentaient une TTR inférieure à 60 %. RÉSULTATS: Pour les 43 patients recevant de la warfarine administrée par nomogramme, le temps moyen passé dans la marge thérapeutique était de 55,2 % (méthode de fraction) ou 61,2 % (méthode Rosendaal). Plus de la moitié des patients (63,5 %) montraient une maîtrise de la FA modérée à bonne, définie comme une TTR supérieure à 60 %. Être une femme, présenter une maladie hépatique ou avoir des antécédents de toxicomanie ou de consommation d'un grand nombre de médicaments figurait parmi les facteurs associés à une faible TTR. LIMITES: La faible taille de l'échantillon et la nature rétrospective de l'étude. CONCLUSION: Ces résultats appuient l'utilization d'un nomogramme électronique géré par le personnel infirmier pour administrer le traitement d'entretien par warfarine chez les patients stables traités par hémodialyse, car elle a permis d'atteindre une marge thérapeutique supérieure à 60 % chez plus de la moitié des patients.

Patient Factors Associated with Prescribing of Iron for IV Administration: A Descriptive Study.

BACKGROUND: IV administration of iron is appropriate for the treatment of iron deficiency anemia (IDA) when orally administered iron has not been effective, tolerated, or clinically appropriate. In Calgary, Alberta, high levels of IV iron utilization required review, because of significant health care resource utilization, high cost, and reduced accessibility. OBJECTIVES: The primary objective was to describe the population of adult patients in Calgary with estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73 m2 for whom IV iron was dispensed from acute care facilities, in terms of pretreatment laboratory data, previous use of oral iron, and treatment location, as well as to characterize dose and product selection for IV iron. The secondary objective was to determine the proportion of inpatients whose treatment was in alignment with the Toward Optimized Practice clinical practice guideline for IDA. METHODS: A retrospective review of electronic charts was used to obtain data about patients with a first dose of IV iron dispensed in Calgary hospitals between March 1 and December 31, 2018. The data were analyzed descriptively. RESULTS: A total of 1352 patients met the inclusion criteria. These patients received a total of 3532 doses of IV iron, 97.1% of which were iron sucrose, at a median of 300 mg per infusion. Laboratory indices assessed before the first infusion were hemoglobin (mean 92, standard deviation [SD] 19.6 g/L), mean corpuscular volume (mean 81 [SD 10.3] fL), and ferritin (median 18 [interquartile range 9-48] µg/L). Among the included patients, 233 (17.2%) had oral iron dispensed within 90 days before their first IV dose of iron. Only 146 (20.1%) of the 726 inpatients had treatment that was in alignment with the Toward Optimized Practice IDA guideline. CONCLUSIONS: There was substantial variation in baseline hemoglobin, mean corpuscular volume, and ferritin, and in the use of oral iron before initiation of IV iron treatment. Provision of educational tools and stewardship initiatives may help in ensuring alignment of iron prescribing with current guidelines.

CONTEXTE: L'administration de fer par intraveineuse (IV) convient au traitement de l'anémie ferriprive lorsque son administration par voie orale n'a pas été efficace, tolérée ou appropriée d'un point de vue clinique. À Calgary (Alberta), il a fallu réviser les quantités de fer administrées par IV en raison de la mobilisation importante des ressources de soins de santé et des coûts élevés que cela exigeait ainsi que de l'accessibilité réduite au produit. OBJECTIFS: L'objectif principal consistait à décrire la population de patients adultes, dont le taux estimé de filtration glomérulaire était supérieur ou égal à 30 mL/min/1,73 m2 et à qui on administrait du fer par IV dans des installations de soins intensifs de Calgary. La description devait se faire en termes de données de laboratoire préalables au traitement, d'administration antérieure de fer par voie orale et de lieu du traitement; il s'agissait aussi de décrire la dose et la sélection du produit pour l'administration de fer par IV. L'objectif secondaire consistait à déterminer la proportion de patients hospitalisés, dont le traitement s'alignait sur les directives de pratique clinique Toward Optimized Practice relatives à l'anémie ferriprive. MÉTHODES: Un examen rétrospectif des tableaux électroniques a permis d'obtenir des données sur les patients, ayant reçu une première dose de fer par IV dans les hôpitaux de Calgary, entre le 1er mars et le 31 décembre 2018. Les données ont fait l'objet d'une analyse descriptive. RÉSULTATS: Au total, 1352 patients répondaient au critère d'inclusion. Ils ont reçu 3532 doses de fer par IV, dont 97,1 % de saccharose de fer à raison d'une médiane de 300 mg par perfusion. Les indices de laboratoire évalués avant la première perfusion concernaient l'hémoglobine (moyenne 92, écart-type [ET] 19,6 g/L), le volume corpusculaire moyen (moyenne 81 [ET 10,3] fL) et la ferritine (moyenne 18 [écart interquartile 9­48] µg/L). Parmi les patients de l'étude, 233 (17,2 %) avaient reçu du fer par voie orale 90 jours avant la première dose de fer administrée par IV. Seuls 146 (20,1 %) des 726 patients hospitalisés avaient reçu un traitement conforme aux directives de pratique clinique Toward Optimized Practice relatives à l'anémie ferriprive. CONCLUSIONS: On a constaté une variation importante de l'hémoglobine de base, du volume corpusculaire moyen et de la ferritine, ainsi que de l'utilisation du fer par voie orale avant le début du traitement par IV. Des outils pédagogiques et des initiatives de gestion pourraient aider à assurer l'alignement de la prescription de fer sur les directives actuelles.

Predictability of Capillary Blood Spot Toward Venous Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus in Solid Organ Transplant Recipients.

Therapeutic drug monitoring (TDM) of tacrolimus in whole blood obtained from venipuncture is routinely practiced. Dried blood spotting (DBS) may act as a suitable alternative for tacrolimus TDM due to relative ease of sampling and processing. The objective of this literature review was to provide a critical evaluation on the feasibility (i.e., accuracy and precision) of DBS for predicting tacrolimus whole blood concentrations in solid organ transplant recipients. A comprehensive systematic literature search using PubMed, Scopus, EMBASE, and Google Scholar was conducted. The primary objective was to extract the bias and precision data from the identified papers. In addition, the collection, storage, and analysis protocols were also summarized. Both adult and pediatric data were included. The reported bias data (primarily based on individual concentrations) in the majority of studies were within acceptable limits (< 15%). However, the precision data were not consistently reported. The area under the concentration-time curve of tacrolimus derived from DBS appeared to be a better predictor of whole blood compared to single concentrations based on a limited number of studies. No apparent differences in prediction were observed between pediatric and adult patients. Small sample sizes and the lack of complete description of the study population were common limitations. DBS is a promising approach for tacrolimus TDM. However, in order for DBS to become a useful substitute for tacrolimus whole blood monitoring in solid organ transplant patients, further systematic studies with sufficient power and comprehensive prediction error analyses are required.

Randomised controlled trial of a video intervention and behaviour contract to improve medication adherence after renal transplantation: the VECTOR study protocol.

INTRODUCTION: Non-adherence after kidney transplantation contributes to increased rejections, hospitalisations and healthcare expenditures. Although effective adherence interventions are sorely needed, increasing education and support to transplant recipients demands greater use of care providers' time and resources in a healthcare system that is stretched. The objective of this clinical trial is to determine the effectiveness of an electronically delivered video series and adherence behaviour contract on improving medication adherence to immunosuppressant medications. METHODS AND ANALYSIS: A multicentre, parallel arm, randomised controlled trial will be conducted with four sites across North America (Saskatoon, Calgary, Halifax, Chicago). Adult patients will be randomised (1:1) to either the intervention (ie, home-based video education +behaviour contract plus usual care) or usual care alone. De novo transplant recipients will be enrolled prior to their hospital discharge and will be provided with electronic access to the video intervention (immediately) and adherence contract (1 month post-transplant). Follow-up electronic surveys will be provided at 3 and 12 months postenrolment. The primary outcome will be adherence at 12 months post-transplant, as measured by self-report Basel Assessment of Adherence to Immunosuppressive medications and immunosuppressant levels. Secondary outcomes include the difference in knowledge score between the intervention and control in groups (measured by the Kidney Transplant Understanding Tool); differences in self-efficacy (Generalised Self-efficacy Scale), Beliefs of Medicine Questionnaire (BMQ), quality of life (Short Form-12), patient satisfaction and cost utilisation. The study aims to recruit at least 200 participants across participating sites. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Saskatchewan Behavioural Ethics Committee (Beh 18-63), and all patients provide informed consent prior to participating. This educational intervention aims to improve information retention and self-efficacy, leading to improved medication adherence after kidney transplantation, at low cost, with little impact to existing healthcare personnel. If proven beneficial, delivery can be easily implemented into standard of care. TRIAL REGISTRATION NUMBER: NCT03540121; Pre-results.

Generic immunosuppression in solid organ transplantation: a Canadian perspective.

The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data. Cyclosporine, tacrolimus, and sirolimus are designated as "critical dose drugs" and are held to stricter criteria. However, whether this provides sufficient guarantee of therapeutic equivalence in SOTR remains controversial, and failure to maintain an appropriate balance of immunosuppression may have serious consequences, including rejection, graft loss, and death. Published evidence supporting therapeutic equivalence of generic formulations in SOTR is lacking. Moreover, in the setting of multiple generic formulations the potential for uncontrolled product switching is a major concern, since generic preparations are not required to demonstrate bioequivalence with each other. Although close monitoring is recommended with any change in formulation, drug product switches are likely to occur without prescriber knowledge and may pose a significant patient safety risk. The advent of generic immunosuppression will require new practices including more frequent therapeutic drug and clinical monitoring, and increased patient education. The additional workload placed on transplant centers without additional funding will create challenges and could ultimately jeopardize patient outcomes. Until more robust clinical data are available and adequate regulatory safeguards are instituted, caution in the use of generic immunosuppressive drugs in solid organ transplantation is warranted.