The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities. The results of each working group (Definitions, Prevention, Management, and Epstein-Barr viral [EBV] load/Biomarker Monitoring) are presented in separate manuscripts within this volume of Pediatric Transplantation.

A position statement of the International Pediatric Transplant Association endorsing prioritizing pediatric recipients for deceased donor organ allocation, examining the key ethical arguments that serve as the foundation for that position, and making specific policy recommendations to support prioritizing pediatric recipients for deceased donor organ allocation globally.

BACKGROUND:

Clostridioides difficile is considered an urgent threat to human health by the US Centers for Disease Control and Prevention. In recent years, C. difficile has been reported increasingly as a cause of gastrointestinal disease in children, and the prevalence of hospital-acquired C. difficile infection and community-acquired CDI in children is increasing.

AIM:

To perform a systematic review and meta-analysis of risk factors for CDI in children.

METHODS:

MEDLINE/PubMed, EMBASE, Web of Science, Scopus, OVID, China National Knowledge Infrastructure, Wanfang (Chinese), SinoMed (Chinese) and Weipu (Chinese) were searched from inception to 12th January 2022. Observational studies (cohort, case-control and cross-sectional) on CDI in children were included in the analysis. Data were pooled using a fixed or random-effects model, and odds ratios (OR) were calculated.

FINDINGS:

In total, 25 observational studies were included in the analysis. Prior antibiotic exposure [OR 1.93, 95% confidence interval (CI) 1.25-2.97], prolonged hospitalization (OR 14.68, 95% CI 13.24-16.28), history of hospitalization (OR 3.67, 95% CI 1.91-7.06), gastric acid suppressants (OR 1.96, 95% CI 1.41-2.73), male gender (OR 1.18, 95% CI 1.05-1.32), neoplastic disease (OR 3.40, 95% CI, 2.85-4.07), immunodeficiency (OR 4.18, 95% CI 3.25-5.37), solid organ transplantation (OR 4.56, 95% CI 3.95-5.27) and enteral feeding (OR 2.21, 95% CI 1.05-4.62) were associated with increased risk of CDI.

CONCLUSION:

This systematic review and meta-analysis provides further evidence for the susceptibility factors of CDI to improve clinicians' awareness of CDI, and prevent C. difficile-associated diarrhoea in children.

BACKGROUND:

Non-adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to immunosuppressant therapy is a modifiable patient behaviour, and different approaches to increasing adherence have emerged, including multi-component interventions. There has been limited exploration of the effectiveness of interventions to increase adherence to immunosuppressant therapy.

OBJECTIVES:

This review aimed to look at the benefits and harms of using interventions for increasing adherence to immunosuppressant therapies in solid organ transplant recipients, including adults and children with a heart, lung, kidney, liver and pancreas transplant.

SEARCH METHODS:

We searched the Cochrane Kidney and Transplant Register of Studies up to 14 October 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

SELECTION CRITERIA:

All randomised controlled trials (RCTs), quasi-RCTs, and cluster RCTs examining interventions to increase immunosuppressant adherence following a solid organ transplant (heart, lung, kidney, liver, pancreas) were included. There were no restrictions on language or publication type.

DATA COLLECTION AND ANALYSIS:

Two authors independently screened titles and abstracts of identified records, evaluated study quality and assessed the quality of the evidence using the GRADE approach. The risk of bias was assessed using the Cochrane tool. The ABC taxonomy for measuring medication adherence provided the analysis framework, and the primary outcomes were immunosuppressant medication initiation, implementation (taking adherence, dosing adherence, timing adherence, drug holidays) and persistence. Secondary outcomes were surrogate markers of adherence, including self-reported adherence, trough concentration levels of immunosuppressant medication, acute graft rejection, graft loss, death, hospital readmission and health-related quality of life (HRQoL). Meta-analysis was conducted where possible, and narrative synthesis was carried out for the remainder of the results.

MAIN RESULTS:

Forty studies involving 3896 randomised participants (3718 adults and 178 adolescents) were included. Studies were heterogeneous in terms of the type of intervention and outcomes assessed. The majority of studies (80%) were conducted in kidney transplant recipients. Two studies examined paediatric solid organ transplant recipients. The risk of bias was generally high or unclear, leading to lower certainty in the results. Initiation of immunosuppression was not measured by the included studies. There is uncertain evidence of an association between immunosuppressant medication adherence interventions and the proportion of participants classified as adherent to taking immunosuppressant medication (4 studies, 445 participants: RR 1.09, 95% CI 0.95 to 1.20; I² = 78%). There was very marked heterogeneity in treatment effects between the four studies evaluating taking adherence, which may have been due to the different types of interventions used. There was evidence of increasing dosing adherence in the intervention group (8 studies, 713 participants: RR 1.14, 95% CI 1.03 to 1.26, I² = 61%).  There was very marked heterogeneity in treatment effects between the eight studies evaluating dosing adherence, which may have been due to the different types of interventions used. It was uncertain if an intervention to increase immunosuppressant adherence had an effect on timing adherence or drug holidays. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on persistence. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on secondary outcomes. For self-reported adherence, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants classified as medically adherent to immunosuppressant therapy (9 studies, 755 participants: RR 1.21, 95% CI 0.99 to 1.49; I² = 74%; very low certainty evidence). Similarly, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the mean adherence score on self-reported adherence measures (5 studies, 471 participants: SMD 0.65, 95% CI -0.31 to 1.60; I² = 96%; very low certainty evidence). For immunosuppressant trough concentration levels, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants who reach target immunosuppressant trough concentration levels (4 studies, 348 participants: RR 0.98, 95% CI 0.68 to 1.40; I² = 40%; very low certainty evidence). It is uncertain whether an intervention to increase adherence to immunosuppressant medication may reduce hospitalisations (5 studies, 460 participants: RR 0.67, 95% CI 0.44 to 1.02; I² = 64%; low certainty evidence). There were limited, low certainty effects on patient-reported health outcomes such as HRQoL. There was no clear evidence to determine the effect of interventions on secondary outcomes, including acute graft rejection, graft loss and death. No harms from intervention participation were reported.

AUTHORS' CONCLUSIONS:

Interventions to increase taking and dosing adherence to immunosuppressant therapy may be effective; however, our findings suggest that current evidence in support of interventions to increase adherence to immunosuppressant therapy is overall of low methodological quality, attributable to small sample sizes, and heterogeneity identified for the types of interventions. Twenty-four studies are currently ongoing or awaiting assessment (3248 proposed participants); therefore, it is possible that findings may change with the inclusion of these large ongoing studies in future updates.

INTRODUCTION:

Lay-caregivers in organ transplantation (to candidates, recipients, and donors) are essential to pre- and postoperative care, but report significant caregiving-related stressors. This review aims to summarize studies testing nonpharmacological interventions aimed at improving organ transplant caregiver-reported outcomes.

METHODS:

In accordance with PRISMA, we conducted a systematic review (searched PubMed, Embase, Cochrane Central, PsycInfo, and CINAHL, no start-date restriction through 7/1/2021). Quality of comparative studies assessed by ROBS-2 or ROBINS.

RESULTS:

Twelve studies met inclusion. Study designs, interventions, and outcomes varied. Sample sizes were small across caregivers to adults (nine studies, five with caregiver samples ns≤50) and pediatric patients (three studies, caregiver samples ns≤16). Study designs included seven single-arm interventions, two prepost with comparison cohorts, and three randomized-controlled trials. Eight studies included transplant-specific education as the intervention, an interventional component, or as the comparison group. Outcomes included transplant specific knowledge, mental health, and intervention acceptability. Of the nine prepost caregiver assessments and/or comparison groups, four studies demonstrated no statistically significant intervention effects.

CONCLUSION:

Few interventions addressing the needs of organ transplant caregivers have been empirically evaluated. Existing interventions were well-received by caregivers. Given complexities of care in transplantation, research is needed evaluating interventions using rigorous trial methodology with adequate samples.

PURPOSE:

to develop a care bundle for best practices in conducting the family interview for organ and tissue donation with the families of children and adolescents.

DESIGN AND METHODS:

methodological study, with a qualitative approach, developed in Brazil, in three stages: literature review, qualitative study with professionals and family members, and development of the care bundle.

RESULTS:

Nine studies were selected and 17 health professionals and nine family members were interviewed. With this data, the care bundle was developed in three categories: communication of death, emotional support and information about organ and tissue donation. The recommendations were evaluated by five external professionals and all of them assessed the bundle as having the highest possible quality.

CONCLUSIONS:

the care bundle was built following the stages of integrative literature review and interviews with professionals working in this scenario and family members who have already gone through a family interview for organ and tissue donation of children and adolescents.

PRACTICE IMPLICATIONS:

the use of this material is seen as an important resource to support the professional during the conduction of the family interview in a scenario as sensitive and challenging as the care to family members facing death and the decision of organ and tissue donation of children and adolescents. Furthermore, the care bundle can increase the quality of family interviews and impact the reduction of family refusals.

DESCRIPTORS:

Practice Guideline as Topic. Tissue and Organ Procurement. Patient Care Team. Nursing. Pediatrics. Communication.

Obesity might be associated with mortality and clinical outcomes following transplantation; however, the direction of this relationship has not been well-recognized in youth. The aim of this systematic review and meta-analysis was to investigate the association of obesity with post-transplant mortality and clinical outcomes in children and adolescents. Following a systematic search of observational studies published by December 2018 in PubMed, Scopus, Embase, and Cochrane library, 15 articles with total sample size of 50,498 patients were included in the meta-analysis. The main outcome was mortality and secondary outcomes included acute graft versus host disease (GVHD), acute rejection, and overall graft loss. The pooled data analyses showed significantly higher odds of long term mortality (OR 1.30, 95% CI 1.15-1.48, P < 0.001, I2 = 50.3%), short term mortality (OR 1.79, 95% CI 1.19-2.70, P = 0.005, I2 = 59.6%), and acute GVHD (OR 2.13, 95% CI 1.5-3.02, P < 0.001, I2 = 1.7%) in children with obesity. There were no significant differences between patients with and without obesity in terms of acute rejection (OR 1.07, 95% CI 0.98-1.16, P = 0.132, I2 = 7.5%) or overall graft loss (OR 1.04, 95% CI 0.84-1.28, P = 0.740, I2 = 51.6%). This systematic review and meta-analysis has stated higher post-transplant risk of short and long term mortality and higher risk of acute GVHD in children with obesity compared to those without obesity. Future clinical trials are required to investigate the effect of pre-transplant weight management on post-transplant outcomes to provide insights into the clinical application of these findings. This may in turn lead to establish guidelines for the management of childhood obesity in transplantations.

PURPOSE:

There are conflicting results as to the effect of inhaled nitric oxide (iNO) therapy on the risk of acute kidney injury (AKI). The aim of this study was to perform a meta-analysis to assess the updated data.

METHODS:

We systematically searched Web of Science, the Cochrane Library, Wanfang, and PubMed for relevant randomized control trials between database inception and 9/07/2020. Relative risks (RRs) with 95% confidence intervals (CIs) predicting the risk of AKI were extracted to obtain summary estimates using fixed-effects models. The Trim and Fill method was used to evaluate the sensitivity of the results and adjust for publication bias in meta-analysis.

RESULTS:

15 randomized controlled studies from 14 articles involving 1853 patients were included in the study. Analyzing the eligible studies we found: (1) iNO therapy significantly increased the risk of AKI in acute respiratory distress syndrome patients (RR 1.55, 95% CI 1.15-2.10, p = 0.004; I 2 for heterogeneity 0%; P het = 0.649). (2) The use of iNO was associated with reduced AKI risk in patients undergoing cardiac surgery (RR 0.80, 95% CI 0.64-0.99, p = 0.037; I 2 for heterogeneity 0%; P het = 0.528). (3) For organ transplantation recipients, there was no effect of iNO administration on the risk of AKI (RR 0.50, 95% CI 0.16-1.56, p = 0.233; I 2 for heterogeneity 0%; P het = 0.842). The Trim and Fill analysis showed that the overall effect of this meta-analysis was stable.

CONCLUSIONS:

The effect of iNO on AKI risk might be disease-specific. Future RCTs with larger patient populations should aim to validate our findings.