Developing a Tailored eHealth Self-Management Intervention for Patients With Chronic Kidney Disease in China: Intervention Mapping Approach.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern. Adequate self-management skills are vital to reduce CKD burden, optimize patient health outcomes, and control health care expenditures. Using eHealth to support CKD self-management has the potential to promote healthy behaviors and improve health outcomes of patients with CKD. However, knowledge of the implementation of such interventions in general, and in China specifically, is still limited. OBJECTIVE: This study aims to develop a tailored eHealth self-management intervention for patients with CKD in China based on the Dutch Medical Dashboard (MD) eHealth self-management intervention. METHODS: We used an intervention mapping approach. In phase 1, a systematic review and 2 qualitative studies were conducted to examine the needs, beliefs, and perceptions of patients with CKD and health care professionals regarding CKD self-management and eHealth interventions. Afterward, key factors gathered from the aforementioned studies were categorized following the 5 domains of the Consolidated Framework for Implementation Research (CFIR). In phase 2, we specified program outcomes, performance objectives, determinants, theory-based methods, and practical strategies. Knowledge obtained from previous results was combined to complement core components of the MD self-management intervention and adapt them for Chinese patients with CKD. Additionally, the CFIR-Expert Recommendations for Implementing Change Matching Tool was pragmatically used to generate a list of potential implementation strategies to address the key factors influencing the implementation of eHealth CKD self-management interventions, and implementation strategies were discussed and finalized with the intervention monitoring group. RESULTS: An overview of the CFIR domains showed the essential factors influencing the implementation of eHealth CKD self-management interventions in Chinese settings, including "knowledge and beliefs" in the domain "individual characteristics," "quality and advantage of eHealth intervention" in the domain "intervention characteristics," "compatibility" in the domain "inner setting," and "cultural context" in the domain "outer setting." To ensure the effectiveness of the Dutch MD-based self-management intervention, we did not change the core self-management intervention components of MD that underlie its effectiveness, such as self-monitoring. We identified surface-level cultural adaptations involving customizing intervention content, messages, and approaches to the observable cultural characteristics of the local population to enhance the intervention's appeal, receptivity, and feasibility, such as providing video or voice call options to support interactions with health care professionals. Furthermore, the adapted modules such as Knowledge Center and My Self-Monitoring were developed in a mobile health app. CONCLUSIONS: Our study resulted in the delivery of a culturally tailored, standardized eHealth self-management intervention for patients with CKD in China that has the potential to optimize patients' self-management skills and improve health status and quality of life. Moreover, our study's research approach and results can inform future research on the tailoring and translation of evidence-based, eHealth self-management interventions to various contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT04212923; https://classic.clinicaltrials.gov/ct2/show/NCT04212923.

Impact of a Public Health Emergency on Behavior, Stress, Anxiety and Glycemic Control in Patients With Pancreas or Islet Transplantation for Type 1 Diabetes.

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (ß-cell Tx; n = 51) to control T1D patients (n = 272). Fear of coronavirus infection was higher in those with ß-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p < 0.001). A previous ß-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with ß-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), p = 0.038). Fewer patients with ß-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with ß-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).

Ellipro scores of donor epitope specific HLA antibodies are not associated with kidney graft survival.

In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants.

Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation.

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope-specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan-Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre-transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA-DR, and 1 of HLA-DQ, and most antibodies were directed to HLA-B (47%). Fifty-three patients (69.7%) had DESA against one donor epitope (range 1-5). Long-term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84-3.25) in deceased donation, and 2.22 (1.25-3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA-based risk analysis on antigen level.

Meltdose Tacrolimus Population Pharmacokinetics and Limited Sampling Strategy Evaluation in Elderly Kidney Transplant Recipients.

BACKGROUND: Meltdose tacrolimus (Envarsus®) has been marketed as a formulation achieving a more consistent tacrolimus exposure. Due to the narrow therapeutic window of tacrolimus, dose individualization is essential. Relaxation of the upper age limits for kidney transplantations has resulted in larger numbers of elderly patients receiving tacrolimus. However, due to the physiological changes caused by aging, the tacrolimus pharmacokinetics (PK) might be altered. The primary aim was to develop a population PK model in elderly kidney transplant recipients. Secondary aims were the development and evaluation of a limited sampling strategy (LSS) for AUC estimation. METHODS: A total of 34 kidney transplant recipients aged ≥65 years, starting on meltdose tacrolimus directly after transplantation, were included. An eight-point whole blood AUC0-24h and an abbreviated dried blood spot (DBS) AUC0-24h were obtained. The PK data were analyzed using nonlinear mixed effect modeling methods. RESULTS: The PK data were best described using a two-compartment model, including three transit compartments and a mixture model for oral absorption. The best three-sample LSS was T = 0, 2, 6 h. The best four-sample LSSs were T = 0, 2, 6, 8 h and T = 0, 1, 6, 8 h. CONCLUSIONS: The developed population PK model adequately described the tacrolimus PK data in a population of elderly kidney transplant recipients. In addition, the developed population PK model and LSS showed an adequate estimation of tacrolimus exposure, and may therefore be used to aid in tacrolimus dose individualization.