BACKGROUND:

As organ donation registration rates remain low, especially among lower-educated people, it is important to support this group in making their registration decision. To prepare lower-educated students in the Netherlands for making a well-informed decision, an interactive educational program was developed. We aim to understand both the (quality of) implementation as well as to contextualize the effects of this program in a lower-educated school setting.

METHODS:

The process evaluation was part of a Cluster Randomized Controlled Trial, in which 11 schools for Intermediate Vocational Education throughout the Netherlands participated. Teachers who taught a course on Citizenship delivered three intervention elements (i.e. video fragments and discussion, quizzes with tailored feedback and an exercise filling out a registration form) to their students. Implementation was assessed by interviews with teachers, questionnaires from students, logbooks from teachers and user data from Google Analytics.

RESULTS:

The program was well received and implemented, but on-the-spot adaptations were made by teachers to fit their students better. Within the lower-educated target group, differences between students are high in terms of active participation, reading abilities, knowledge and attention span. The program fit well within their regular teaching activities, but the topic of organ donation is not always prioritized by teachers.

CONCLUSIONS:

We see opportunities to disseminate the program on a larger scale and reach a group that has been neglected in organ donation education before. Within the program, there are possibilities to increase the effectiveness of the program, such as alternative delivery methods for the elements with a lot of text, the addition of booster sessions and guidelines for teachers to adapt the program to students of different levels within Intermediate Vocational Education. Moreover, in order to have an impact on a national level, strategies need to be employed to reach high numbers of students and, therefore, support on a higher level is needed (both within schools and at policy level).

TRIAL REGISTRATION:

Dutch Trial Register, NTR6771. Prospectively registered on 24 October 2017.

Solid-organ transplantation is the treatment of choice for end-stage organ failure. Parents of pediatric transplant recipients who reported a lack of readiness for discharge had more difficulty coping and managing their child's medically complex care at home. In this paper, we describe the protocol for the pilot study of a mHealth intervention (myFAMI). The myFAMI intervention is based on the Individual and Family Self-Management Theory and focuses on family self-management of pediatric transplant recipients at home. The purpose of the pilot study is to test the feasibility of the myFAMI intervention with family members of pediatric transplant recipients and to test the preliminary efficacy on postdischarge coping through a randomized controlled trial. The sample will include 40 family units, 20 in each arm of the study, from three pediatric transplant centers in the United States. Results from this study may advance nursing science by providing insight for the use of mHealth to facilitate patient/family-nurse communication and family self-management behaviors for family members of pediatric transplant recipients.

BACKGROUND AND AIMS:

This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein.

MATERIALS AND METHODS:

Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout.

RESULTS:

The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7).

CONCLUSIONS:

In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation.

BACKGROUND:

Tacrolimus pharmacokinetics are influenced by age and CYP3A5 genotype with CYP3A5 expressors (CYP3A5*1/*1 or *1/*3) being fast metabolizers. However, the benefit of genotype-guided dosing in pediatric solid organ transplantation has been understudied.

OBJECTIVE:

To determine whether age and CYP3A5 genotype-guided starting dose of tacrolimus result in earlier attainment of therapeutic drug concentrations.

SETTING:

Single hospital-based transplant center.

METHODS:

This was a randomized, semi-blinded, 30-day pilot trial. Between 2012 and 2016, pediatric patients listed for solid organ transplant were consented and enrolled into the study. Participants were categorized as expressors, CYP3A5*1/*1 or CYP3A5*1/*3, and nonexpressors, CYP3A5*3/*3. Patients were stratified by age (≤ or > 6 years) and randomized (2:1) after transplant to receive genotype-guided (n = 35) or standard (n = 18) starting dose of tacrolimus for 36-48 hours and were followed for 30 days.

RESULTS:

Median age at transplant in the randomized cohort was 2.1 (0.75-8.0) years; 24 (45%) were male. Participants in the genotype-guided arm achieved therapeutic concentrations earlier at a median (IQR) of 3.4 (2.5-6.6) days compared to those in the standard dosing arm of 4.7 (3.5-8.6) days (P = 0.049), and had fewer out-of-range concentrations [OR (95% CI) = 0.60 (0.44, 0.83), P = 0.002] compared to standard dosing, with no difference in frequency of adverse events between the two groups.

CONCLUSIONS:

CYP3A5 genotype-guided dosing stratified by age resulted in earlier attainment of therapeutic tacrolimus concentrations and fewer out-of-range concentrations.

Children who have undergone SOT mount a lower immune response after vaccination with TIV compared to healthy controls. HD or SD TIV in pediatric SOT was given to subjects 3-17 yr and at least six months post-transplant. Subjects were randomized 2:1 to receive either the HD (60 μg) or the SD (15 μg) TIV. Local and systemic reactions were solicited after each vaccination, and immune responses were measured before and after each vaccination. Thirty-eight subjects were enrolled. Mean age was 11.25 yr; 68% male, 45% renal, 26% heart, 21% liver, 5% lung, and 5% intestinal. Twenty-three subjects were given HD and 15 SD TIV. The median time since transplant receipt was 2.2 yr. No severe AEs or rejection was attributed to vaccination. The HD group reported more tenderness and local reactions, fatigue, and body ache when compared to the SD cohort, but these were considered mild and resolved within three days. Subjects in the HD group demonstrated a higher percentage of four-fold titer rise to H3N2 compared to the SD group. HD influenza vaccine was well tolerated and may have increased immunogenicity. A phase 2 trial is needed to confirm.

OBJECTIVE:

To determine whether collaborative requesting increases consent for organ donation from the relatives of patients declared dead by criteria for brain stem death.

DESIGN:

Unblinded multicentre randomised controlled trial using a sequential design. Centralised 24 hour telephone randomisation based on randomised permuted blocks of 10.

SETTING:

79 general, neuroscience, and paediatric intensive care units in the United Kingdom.

PARTICIPANTS:

201 relatives of patients meeting criteria for brain stem death. Relatives were blind to the intervention and to the trial; all other participants were necessarily unblinded.

INTERVENTIONS:

Collaborative requesting for consent for organ donation by the potential donor's clinician and a donor transplant coordinator (organ procurement officer) compared with routine requesting by the clinical team alone.

MAIN OUTCOME MEASURE:

Proportion of relatives consenting to organ donation.

RESULTS:

101 relatives were randomised to routine requesting and 100 to collaborative requesting. All were analysed on an intention to treat basis. In the routine requesting group, 62 relatives consented to organ donation. In the collaborative requesting group, 57 relatives consented. After correction for the ethnicity, age, and sex of the potential donors the risk adjusted ratio of the odds of consent in the collaborative requesting group relative to the routine group was 0.80 (95% confidence interval 0.43 to 1.53), with a P value of 0.49 adjusted for interim analysis and trial over-running. The conversion rate (donors with consent from whom any organs were retrieved) was 92% (57/62) in the routine requesting group and 79% (45/57) in the collaborative requesting group (P=0.043). There were 140 approaches to relatives in the per protocol analysis, leading to 60.3% (44/73) consent after routine and 67.2% (45/67) after collaborative requesting (risk adjusted odds ratio of consent 1.47, 0.67 to 3.20, P=0.33).

CONCLUSION:

There is no increase in consent rates for organ donation when collaborative requesting is used in place of routine requesting by the patient's clinician.

TRIAL REGISTRATION:

ISRCTN01169903.

BACKGROUND:

Transplant recipients who are Epstein-Barr virus (EBV)-seronegative and receive organs from seropositive donors (EBV D+/R-) are at increased risk for posttransplant lymphoproliferative disorder (PTLD) and may benefit from antiviral prophylaxis. We performed a multi-center trial assessing two different antiviral regimens and their effect on EBV replication.

METHODS:

EBV D+/R- solid organ transplant recipients were randomized to receive either ganciclovir and placebo or ganciclovir and immunoglobulin (IG) for 3 months. Following this, patients were unblinded and IG patients received additional IG therapy until 6 months. EBV viral loads were done at least monthly. RESULTS.: Thirty-four patients (25 pediatric, 9 adult) completed the protocol (16 placebo; 18 IG). The incidence of a detectable viral load within the first year posttransplant was 13/16 (81.3%) in the ganciclovir arm vs. 13/18 (72.2%) in the ganciclovir and IG arm (P=0.8). Time to first detectable viral load, and time to high-level viral load were not significantly different. By repeated measures ANOVA analysis, and by estimation of viral load AUC, no significant effect of randomization group was observed on EBV viral loads. PTLD developed in 3 (8.8%) patients (all in IG arm; P=0.23).

CONCLUSIONS:

No significant difference in EBV viral load suppression was observed when ganciclovir was compared with ganciclovir and IG in high-risk EBV D+/R- patients.

BACKGROUND:

Acute tacrolimus toxicity is manifest by oliguria and elevated serum creatinine. Various vasoregulatory molecules have been implicated in calcineurin inhibitor-mediated nephrotoxicity, including calcium, adenosine and endothelin. Theophylline (THEO), a non-specific adenosine-receptor antagonist prevents renal dysfunction from various nephrotoxins which mediate vasoconstriction. In the setting of acute tacrolimus toxicity, we demonstrated that administration of THEO along with a loop diuretic (LD) enhanced diuresis. This randomized, controlled trial was undertaken to confirm these earlier findings under more rigorous conditions.

METHODS:

Children with non-renal visceral transplant(s) and evidence of tacrolimus nephrotoxicity oliguria with a 25% increase in serum creatinine concentration from baseline, a whole blood tacrolimus concentration >20 ng/dl and oliguria resistant to therapy with a LD were randomized to receive either THEO (n = 10) or normal saline placebo (n = 8). Using pre and post (6 h) timed urine collections and coincident plasma concentrations the following were measured or calculated: urine flow rate, net fluid balance, creatinine clearance, fractional excretion of chloride, free water clearance and distal delivery of chloride.

RESULTS:

These patients had markedly impaired creatinine clearance at the onset of tacrolimus toxicity. Urine flow increased in the LD + THEO group by 110% over baseline, but was unchanged in the LD + NS group. An increase in creatinine clearance did not reach statistical significance (P = 0.09). Fractional excretion of chloride and distal solute delivery increased after THEO treatment.

CONCLUSIONS:

THEO induced a solute diuresis during furosemide-resistant oliguric tacrolimus toxicity in paediatric patients with a trend towards improved renal function.

OBJECTIVE:

Nosocomial infection is an important contributor to morbidity and mortality in pediatric solid organ transplantation. The relative effect of protective gown and glove isolation was compared with strict handwashing in pediatric intensive care unit (PICU) patients with solid organ transplantation.

DESIGN/SETTING:

A prospective, randomized design was used; children in a 23-bed PICU with solid organ transplantation were enrolled into a gown and glove protective isolation protocol or a strict handwashing protocol.

PATIENTS:

All children admitted to the PICU immediately after solid organ transplantation, excluding renal transplantation, and at subsequent readmissions to the PICU were eligible for the study. Children with current infection or known exposure to varicella were excluded from the study initially or at readmission.

INTERVENTIONS:

By using a block randomization design based on organ transplanted, age, and initial admission vs. readmission, each patient was randomized to either strict handwashing or protective gown and glove isolation intervention groups.

MEASUREMENTS:

We analyzed demographics, infection outcomes (defined according to Centers for Disease Control criteria), and monitoring of patient contacts in compliance with protocols.

RESULTS:

The infection rate in the overall PICU population did not change significantly from the year before the study compared with during the study (2.1 per 100 vs. 1.95 per 100 patient days; p =.4) The infection rate in the gown and glove group (2.3 per 100 patient days) was reduced significantly compared with the prestudy infection rate in the transplant population (4.9 per 100 patient days; p =.0008). Strict handwashing also significantly reduced the infection rate in the transplant population (3.0 per 100 patient days; p =.008). Compliance with gowning and gloving was 82% and compliance with handwashing was 76% (compared with 22% before study [p <.0001] and 52% after the study [p <.0001]). Despite an increased mean length of stay in the PICU in the gown and glove group (p =.014), there was a trend toward reduction in the incidence of infection (Fisher's exact test, p =.07; odds ratio,.76) in the gown and glove group.

CONCLUSIONS:

Increased compliance with handwashing was associated with a reduction in nosocomial infections, and gown and glove isolation appeared to have an additional protective effect. Some nosocomial infections may be preventable in the pediatric solid organ transplantation population.