Eurotransplant

Whenever treatment is scarce, the question of how to allocate resources arises. One option is to allocate based on conditional survival benefit, defined as the contrast between an individual's expected survival with and without treatment. Estimating conditional survival benefit from observational data may present the following three challenges: (i) time-dependent confounding, arising when treatments are assigned based on longitudinal health markers which are in turn affected by past assignments; (ii) multiple time scales, namely time since becoming eligible for treatment, relevant for comparability of patients, and calendar time, representing when treatment decisions are made; and (iii) multiple versions of treatment, leading to multiple counterfactual outcomes with treatment. Building on previous work where cross-sections and inverse probability of treatment weighting were combined to estimate survival benefit on the treated population, we propose a strategy to dynamically estimate conditional survival benefit for all patients awaiting scarce treatment at any time treatment becomes available, accounting for multiple versions of treatment. After delineating identifiability assumptions, we show in a simulation study that our proposed method improves the estimation of conditional survival benefit compared to simpler methods. The proposed method is then applied to liver transplant data from the Eurotransplant region.

Ongoing shortages of organs for transplantation have prompted the critical question of which countries have the highest organ donation rates and how each can increase those rates. The existing metric of donors per million population is flawed because it does not sufficiently account for important differences in the underlying population, including age distributions of deaths in the population. We sought to develop a better approach to analyze country-specific data on organ donation, including deaths stratified by age, to allow assessment of performance across the world. We used death data from the World Health Organization and donation data from 17 countries across 3 continents. We calculated age group-stratified organ donation rates as donors per 1000 deaths and estimated each country's potential to increase donation if the age group-specific donation rate mirrored that of the highest-performing country in each age group. There was a 4-fold difference in overall donation rates, with far greater variability within age strata, including a 10-fold difference in donation rates for the oldest age group (70 y and older). The United States showed the greatest potential to increase donations in absolute terms (>8000 increased donors per year), whereas Argentina, Germany, and Hungary had the greatest potential in relative terms. Although countries may have similar overall donation rates, the breakdown within specific age groups varies widely. Examining age-specific donation rates is a necessary step for accurate international comparisons of transplant systems and can enable targeted interventions to augment donation.

ABSTRACTHighly sensitised kidney transplant candidates face substantial barriers to transplantation due to limited donor compatibility. Delisting unacceptable antigens with detectable HLA‐specific antibodies can improve transplant access. It is, however, challenging to determine which specificities are safe to delist. Assessment of circulating HLA‐specific memory B‐cells may support risk stratification. However, current methodologies are limited by the predominant localisation of memory B‐cells in secondary lymphoid organs and thus by potential false negativity. BAFF inhibitors, such as belimumab, mobilise memory B‐cells into the circulation, which could reduce false‐negative evaluations and improve pretransplant risk stratification. We administered off‐label treatment with 200 mg of subcutaneous belimumab weekly for 4 weeks to seven highly sensitised patients with limited allocation probability. The clinical aim was to safely increase allocation probability by selectively delisting unacceptable HLA‐specificities without detectable B‐cell memory. HLA‐specific memory B‐cell profiles were assessed before and after treatment, revealing significantly broader HLA‐specific memory B‐cell profiles after belimumab in addition to a significant increase of HLA‐antibody MFI in the eluate of stimulated memory B‐cells. This strategy may pave the way for a new paradigm in pretransplant immunological risk‐stratification, allowing improved assessment of HLA‐specific memory B‐cell profiles, which could potentially limit the risk of memory responses.

In liver allocation systems based on the Model for End-stage Liver Disease (MELD) score, sex inequities have been identified in countries with high organ donation rates. Whether similar inequities exist in regions with average to low donation rates remained unclear. We assessed the impact of sex on transplantation rates, waiting list mortality and post-transplant survival in 25,943 patients waitlisted for liver transplantation in Germany between 2003 and 2017 using competing risk analysis. Women are currently underrepresented on the waiting list (33.3%) and among transplant recipients (31.1%) compared to their proportion of severe liver disease cases (35.1%). The introduction of MELD-based allocation has worsened this disadvantage [HR before: 0.89 (0.81-0.98), after: 0.77 (0.74-0.81)]. Three key factors contribute to this disparity: Women have lower creatinine levels despite worse renal function, reducing their MELD score (median 1, 0-3). Second, exceptional MELD points are more frequently granted to men [HR 1.61 (1.54-1.69) compared to regular allocation]. Third, the small height of women has the highest impact on the probability of not being transplanted [adjusted HR 0.85 (0.81-0.9)]. Even in countries with lower organ donation rates, MELD-based allocation leads to sex inequity. Measures are needed to ensure sex-neutral liver allocation in MELD-based systems worldwide.

Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries. The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods. Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y. REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany.

BackgroundPrompt administration of post-exposure prophylaxis (PEP) is crucial to prevent a fatal rabies infection after an animal associated injury (AAI), preferably within 24 h. PEP, especially in case of a type III injury for which rabies immune globulin (RIG) is needed, is difficult to obtain abroad. This, along with the fear of potentially having contracted a lethal disease, might be an important source for anxiety and distress. We investigated the occurrence and extent of self-reported anxiety and distress at different timepoints among Dutch travellers after encountering an AAI, and the involved factors.MethodsA retrospective quantitative observational study was conducted including insured Dutch travellers who actively contacted Eurocross Assistance after encountering an AAI abroad. An online questionnaire was designed to measure anxiety and distress levels, using the HADS (Hospital Anxiety and Depression Scale) and distress thermometer at three time points: departure from home (T1), post-AAI (T2), and treatment administration (T3). Statistical analyses included T-tests, Chi-square tests, and ANCOVA analyses.ResultsWe showed a significant increase in mean anxiety and distress scores at T2, and a significant decrease at T3. Women were more often anxious and distressed. Between T1 and T2, PrEP, and being aware of the risks were positively associated with anxiety levels, and PrEP and WHO region Africa with distress levels. Between T2 and T3, anxiety levels remained higher for monkey-induced injury, thoracic injuries, and WHO region Southeast Asia. PEP-delay between 24–48 h resulted in decreased distress levels at this time period, while type II injury elevated distress levels.ConclusionsThis study showed significant anxiety and distress levels after an AAI among the vast majority of travellers, which is detrimental to their health-related quality of life (HR-QOL). This highlights the importance of proper pre-travel information. In the context of rabies prevention, these results suggest that pre-travel advice and policy makers should also take aspects of HR-QOL into consideration.

Assignment of unacceptable HLA mismatches (UAMs) prevents transplantation of incompatible grafts but potentially prolongs waiting time. Whether this is true in the Eurotransplant Kidney Allocation System (ETKAS) and the Eurotransplant Senior Program in Germany is highly debated and relevant for UAM policies. Donor pool restriction due to UAM was expressed as percent virtual panel-reactive antibodies (vPRAs). Kaplan-Meier estimates and multivariable Cox regression models were used to analyze the impact of vPRA levels on waiting time and transplant probability during a period of 2 y in all patients eligible for a kidney graft unter standard circumstances in Germany on February 1, 2019 (n = 6533). Utility of the mismatch probability score to compensate for sensitization in ETKAS was also investigated. In ETKAS, donor pool restriction resulted in significant prolongation of waiting time and reduction in transplant probability only in patients with vPRA levels above 85%. This was most evident in patients with vPRA levels above 95%, whereas patients in the acceptable mismatch program had significantly shorter waiting times and higher chances for transplantation than nonsensitized patients. In the Eurotransplant Senior Program, vPRA levels above 50% resulted in significantly longer waiting times and markedly reduced the chance for transplantation. Compensation for sensitization by the mismatch probability score was insufficient. Donor pool restriction had no significant impact on waiting time in most sensitized patients. However, despite the existence of the acceptable mismatch program, the majority of highly sensitized patients is currently disadvantaged and would benefit from better compensation mechanisms.

Background.Transplantation activity during the first wave of the coronavirus disease 2019 (COVID-19) pandemic was severely affected worldwide. This retrospective analysis aimed to assess the impact of COVID-19 on organ donations and transplantations in the Eurotransplant region during the first 12 mo of the pandemic. Specifically, we compared donor and transplantation numbers during both waves to determine whether transplant systems adapted to this new reality.Methods.All reported organ donations and transplantations from March 1, 2015, to February 28, 2021, were collected from the Eurotransplant International Foundation registry. The observation period from 2020 to 2021 was divided into three 4-mo periods, which were then compared with the corresponding periods of the preceding 5 y. COVID-19 cases for Eurotransplant countries were retrieved from the OurWorldInData.org database.Results.Overall, the number of organ donors decreased by 18.3% (P < 0.0001) and the number of organ transplantations by 12.5% (P > 0.0001) compared with previous years. Pancreas transplantation was the most affected, followed by kidney, liver, heart, and lung transplant. In detail, during period 1, the number of organ donors decreased by 26.2% (P < 0.0001) and the number of organ transplantations by 16.5% (P < 0.0001), in period 2 by 5.5% (P < 0.0091) and 4.9% (P < 0.0001), and in period 3 by 23.1% (P < 0.0001) and 16.4% (P < 0.0001), respectively.Conclusions.Organ donation and transplantation decreased drastically also during the second wave; however, despite the severity of the second wave, the decline was comparable with that of the first wave.