Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation.

With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor.

Determining the impact of timing and of clinical factors during end-of-life decision-making in potential controlled donation after circulatory death donors.

Controlled donation after circulatory death (cDCD) occurs after a decision to withdraw life-sustaining treatment and subsequent family approach and approval for donation. We currently lack data on factors that impact the decision-making process on withdraw life-sustaining treatment and whether time from admission to family approach, influences family consent rates. Such insights could be important in improving the clinical practice of potential cDCD donors. In a prospective multicenter observational study, we evaluated the impact of timing and of the clinical factors during the end-of-life decision-making process in potential cDCD donors. Characteristics and medication use of 409 potential cDCD donors admitted to the intensive care units (ICUs) were assessed. End-of-life decision-making was made after a mean time of 97 hours after ICU admission and mostly during the day. Intracranial hemorrhage or ischemic stroke and a high APACHE IV score were associated with a short decision-making process. Preserved brainstem reflexes, high Glasgow Coma Scale scores, or cerebral infections were associated with longer time to decision-making. Our data also suggest that the organ donation request could be made shortly after the decision to stop active treatment and consent rates were not influenced by daytime or nighttime or by the duration of the ICU stay.

Appointing nurses trained in organ donation to improve family consent rates.

BACKGROUND: One of the most important bottlenecks in the organ donation process worldwide is the high family refusal rate. AIMS AND OBJECTIVES: The main aim of this study was to examine whether family guidance by trained donation practitioners increased the family consent rate for organ donation. DESIGN: This was a prospective intervention study. METHODS: Intensive and coronary care unit nurses were trained in communication about donation (ie, trained donation practitioners) in two hospitals. The trained donation practitioners were appointed to guide the families of patients with a poor medical prognosis. When the patient became a potential donor, the trained donation practitioner was there to guide the family in making a well-considered decision about donation. We compared the family consent rate for donation with and without the guidance of a trained donation practitioner. RESULTS: The consent rate for donation with guidance by a trained donation practitioner was 58.8% (20/34), while the consent rate without guidance by a trained donation practitioner was 41.4% (41/99, P = 0.110) in those patients where the family had to decide on organ donation. CONCLUSIONS: Our data suggest that family guidance by a trained donation practitioner could benefit consent rates for organ donation. RELEVANCE TO CLINICAL PRACTICE: Trained nurses play an important role in supporting the families of patients who became potential donors to guide them through the decision-making process after organ donation request.

Interventions aimed at healthcare professionals to increase the number of organ donors: a systematic review.

BACKGROUND: The last decade, there have been many initiatives worldwide to increase the number of organ donors. However, it is not clear which initiatives are most effective. The aim of this study is to provide an overview of interventions aimed at healthcare professionals in order to increase the number of organ donors. METHODS: We systematically searched PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Library for English language studies published until April 24, 2019. We included studies describing interventions in hospitals aimed at healthcare professionals who are involved in the identification, referral, and care of a family of potential organ donors. After the title abstract and full-text selection, two reviewers independently assessed each study's quality and extracted data. RESULTS: From the 18,854 records initially extracted from five databases, we included 22 studies in our review. Of these 22 studies, 14 showed statistically significant effects on identification rate, family consent rate, and/or donation rate. Interventions that positively influenced one or more of these outcomes were training of emergency personnel in organ donation, an electronic support system to identify and/or refer potential donors, a collaborative care pathway, donation request by a trained professional, and additional family support in the ICU by a trained nurse. The methodological quality of the studies was relatively low, mainly because of the study designs. CONCLUSIONS: Although there is paucity of data, collaborative care pathways, training of healthcare professionals and additional support for relatives of potential donors seem to be promising interventions to increase the number of organ donors. TRIAL REGISTRATION: PROSPERO, CRD42018068185.

Physician Experiences with Communicating Organ Donation with the Relatives: A Dutch Nationwide Evaluation on Factors that Influence Consent Rates.

BACKGROUND: The aim of this nationwide observational study is to identify modifiable factors in communication about organ donation that influence family consent rates. METHODS: Thirty-two intensivists specialized in organ donation systematically evaluated all consecutive organ donation requests with physicians in the Netherlands between January 2013 and June 2016, using a standardized questionnaire. RESULTS: Out of 2528 consecutive donation requests, 2095 (83%) were evaluated with physicians. The questionnaires of patients registered with consent or objection in the national donor registry were excluded from analysis. Only those questionnaires, in which the family had to make a decision about donation, were analyzed (n = 1322). Independent predictors of consent included: requesting organ donation during the conversation about futility of treatment (OR 1.8; p = 0.004), understanding of the term 'brain death' by the family (OR 2.4; p = 0.002), and consulting a donation expert prior to the donation request (OR 3.4; p < 0.001). CONCLUSIONS: Our study showed that decoupling the organ donation conversation from the conversation about futility of treatment was associated with lower family consent rates. Comprehension of the concept of brain death by the family and consultation with a transplant coordinator before the organ donation request by the physician could positively influence consent rates.

Are all tissue donors recognised? A cohort study in three Dutch hospitals.

Nowadays, the demand for tissue transplantation has significantly increased. To optimize donor recruitment, the potential availability of tissue donors has to be evaluated. In 2011 we conducted a cohort study in three Dutch hospitals in the Netherlands. The potential amount of eligible tissue donors found, based on medical records in these hospitals is compared to the physician's donation form report. In total 1,342 patient records were analysed. From these records, the donation officers considered 484 patients as a potential tissue donor (36.1 %). Despite the absence of contra-indication, the physician did not recognise 25 % (n = 123/484) of potential tissue donors. Physicians' lack of sufficient knowledge of tissue donation was the main cause of adequately identifying tissue donors. A higher percentage of tissue donors in these Dutch hospitals should be feasible through creating awareness and education regarding tissue donation.

Disparities in kidney transplantation accessibility among immigrant populations in Europe: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Disparities in access to healthcare for patients with an immigration background are well-known. The aim of this study was to determine whether disparities among immigrant populations translate into a relative difference in the number of kidney transplants (KT) performed in documented immigrant patients (first and second generation) relative to native-born patients in Europe. METHODS: A literature search was performed in PubMed from inception to 11-10-2022. Studies were eligible if: (1) written in English, (2) included immigrant and native-born KT patients, (3) performed in countries registered as Council of Europe members, (4) focused on documented first- and second-generation immigrant populations [1]. Systematic reviews, literature reviews, and case reports or articles about emigration, non-KT, and undocumented immigrants were excluded. The outcome measurement was a relative percentage of KTs to the total population per 100.000 residents. By dividing the immigrant percentages by the native-born resident percentages, the odds ratio (OR) was calculated in a meta-analysis. The risk of bias was assessed; articles with high risk of bias were excluded in a second meta-analysis. RESULTS: Out of 109 articles, 5 were included (n = 24,614). One Italian study (n = 24,174) had a ratio below 1, being 0.910 (95%CI 0.877-0.945). The other four articles (n = 196, n = 283, n = 77, n = 119) had ratios above 1: 1.36 (95%CI 0.980-1.87), 2.04 (95%CI 1.56-2.68), 2.23 (95%CI 1.53-3.25) and 2.64 (95%CI 1.68-4.15). After performing a meta-analysis, the OR did not show a significant difference: 1.68 (95%CI 1.03-2.75). After bias correction, this remained unchanged: 1.78 (95%CI 0.961-3.31). CONCLUSIONS: In our meta-analysis we did not find a significant difference in the relative number of KTs performed in immigrant versus native-born populations in Europe. However, a lesser likelihood for immigrants to receive a pre-emptive kidney transplantation was found. Large heterogeneity between studies (e.g. different sample size, patient origins, study duration, adult vs children patients) was a shortcoming to our analysis. Nevertheless, our article is the first review in this understudied topic. As important questions (e.g. on ethnicity, living donor rate) remain, future studies are needed to address them.

Imprecise definitions of starting points in retrospectively reviewing potential organ donors causes confusion: call for a reproducible method like 'imminent brain death'.

Low donor supply and the high demand for transplantable organs is an international problem. The efficiency of organ procurement is often expressed by donor conversion rates (DCRs). These rates differ among countries, but a uniform starting point for defining a potential heart-beating donor is lacking. Imprecise definitions cause confusion; therefore, we call for a reproducible method like imminent brain death (IBD), which contains criteria in detail to determine potential heart-beating donors. Medical charts of 4814 patients who died on an ICU in Dutch university hospitals between January 2007 and December 2009 were reviewed for potential heart-beating donors. We compared two starting points: 'Severe Brain Damage' (SBD) (old definition) and IBD (new definition), which differ in the number of absent brainstem reflexes. Of the potential donors defined by IBD 45.6% fulfilled the formal brain death criteria, compared with 33.6% in the larger SBD group. This results in a higher DCR in the IBD group (40% vs. 29.5%). We illustrated important differences in DCRs when using two different definitions, even within one country. To allow comparison among countries and hospitals, one universal definition of a potential heart-beating donor should be used. Therefore, we propose the use of IBD.

Appointing 'trained donation practitioners' results in a higher family consent rate in the Netherlands: a multicenter study.

The consent process for organ and tissue donation is complex, both for families and professionals. To help professionals in broaching this subject we performed a multicenter study. We compared family consent to donation in three hospitals between December 2007 and December 2009. In the intervention hospital, trained donation practitioners (TDP) guided 66 families throughout the time in the ICU until a decision regarding donation had been reached. In the first control hospital, without any family guidance or training, 107 families were approached. In the second control hospital 'hostesses', who were not trained in donation questions, supported 99 families during admittance. A total of 272 families were requested to donate. We primarily compared consent rates, but also asked families about their experiences through a questionnaire. Family consent rate was significantly higher in the intervention hospital: 57.6% (38/66), than in the control hospitals: 34.6% (37/107) and 39.4% (39/99). The 69% response rate to the questionnaire -~5 months after death - showed no confounding variables that could have influenced the consent rate. Appointing TDPs in the intervention hospital to guide families during admittance and the donation decision-making process, results in higher family consent rates.

Organ donation performance in the Netherlands 2005-08; medical record review in 64 hospitals.

BACKGROUND: The Netherlands has a low number of deceased organ donors per million population. As long as there is a shortage of suitable organs, the need to evaluate the donor potential is crucial. Only in this way can bottlenecks in the organ donation process be detected and measures subsequently taken to further improve donation procedures. METHODS: Within a time frame of 4 years, 2005-08, medical charts of all intensive care deaths in 64 hospitals were reviewed by transplant coordinators and donation officers. Data were entered in a web-based application of the Dutch Transplant Foundation, both to identify the number of potential organ donors (including donation after cardiac death), as well as to analyse the reasons for potential donor loss. RESULTS: In total, 23 508 patients died in intensive care units, of which 64% were younger than 76 years. The percentage of all potential organ donors out of the total number of deaths decreased from 8.2% in 2005 to 7.1% in 2008. Donor detection increased from 96% in 2005 to 99% in 2008. Of the potential donors, 17-21% recorded consent and 17-18% recorded objection in the national Donor Register. If the Donor Register was not decisive, the consent rate of families approached for organ donation was 35% in 2005, 29% in 2006, 41% in 2007 and 31% in 2008. The overall conversion rate (the number of actual donors divided by the number of potential donors) was 30%, 26%, 35% and 29% in these years. In the group of potential donor losses, objection by families accounted for about 60% during this study. CONCLUSIONS: This study showed that the maximal number of potential organ donors is about three times higher than the number of effective organ donors. The main reason accounting for approximately 60% of the potential donor losses was the high family refusal rate. The year 2007 showed that a higher percentage of deceased organ donors can be procured from the pool of potential donors. All improvements should focus on decreasing the unacceptably high family refusal rates.

Prediction Model for Timing of Death in Potential Donors After Circulatory Death (DCD III): Protocol for a Multicenter Prospective Observational Cohort Study.

BACKGROUND: Controlled donation after circulatory death (cDCD) is a major source of organs for transplantation. A potential cDCD donor poses considerable challenges in terms of identification of those dying within the predefined time frame of warm ischemia after withdrawal of life-sustaining treatment (WLST) to circulatory arrest. Several attempts have been made to develop models predicting the time between treatment withdrawal and circulatory arrest. This time window determines whether organ donation can occur and influences the quality of the donated organs. However, the selected patients used for these models were not always restricted to potential cDCD donors (eg, patients with cancer or severe infections were also included). This severely limits the generalizability of those data. OBJECTIVE: The objectives of this study are the following: (1) to develop a model predicting time to death within 60 minutes in potential cDCD patients; (2) to validate and update previous prediction models on time to death after WLST; (3) to determine timing and patient characteristics that are associated with prognostication and the decision-making process that leads to initiating end-of-life care; (4) to evaluate the impact of timing of family approach on organ donation approval; and (5) to assess the influence of variation in WLST processes on postmortem organ donor potential and actual postmortem organ donors. METHODS: In this multicenter observational prospective cohort study, all patients admitted to the intensive care unit of 3 university hospitals and 3 teaching hospitals who met the criteria of the cDCD protocol as defined by the Dutch Transplant Foundation were included. The target of enrolment was set to 400 patients. Previously developed models will be refitted in our data set. To further update previous prediction models, we will apply least absolute shrinkage and selection operator (LASSO) as a tool for efficient variable selection to develop the multivariable logistic regression model. RESULTS: This protocol was funded in August 2014 by the Dutch Transplant Foundation. We expect to have the results of this study in July 2020. Patient enrolment was completed in July 2018 and data collection was completed in April 2020. CONCLUSIONS: This study will provide a robust multimodal prediction model, based on clinical and physiological parameters, that can predict time to circulatory arrest in cDCD donors. In addition, it will add valuable insight in the process of WLST in cDCD donors and will fill an important knowledge gap in this essential field of health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04123275; https://clinicaltrials.gov/ct2/show/NCT04123275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16733.

A plea for uniform European definitions for organ donor potential and family refusal rates.

Conversion of potential organ donors to actual donors is negatively influenced by family refusals. Refusal rates differ strongly among countries. Is it possible to compare refusal rates in order to be able to learn from countries with the best practices? We searched in the literature for reviews of donor potential and refusal rates for organ donation in intensive care units. We found 14 articles pertinent to this study. There is an enormous diversity among the performed studies. The definitions of potential organ donors and family refusal differed substantially. We tried to re-calculate the refusal rates. This method failed because of the influence caused by the registered will on donation in the Donor Register. We therefore calculated the total refusal rate. This strategy was also less satisfactory considering possible influence of the legal consent system on the approach of family. Because of lack of uniform definitions, we can conclude that the refusal rates for organ donation can not be used for a sound comparison among countries. To be able to learn from well-performing countries, it is necessary to establish uniform definitions regarding organ donation and registration of all intensive care deaths.

The Implementation of a Multidisciplinary Approach for Potential Organ Donors in the Emergency Department.

BACKGROUND: The aim of this study was to evaluate the implementation process of a multidisciplinary approach for potential organ donors in the emergency department (ED) in order to incorporate organ donation into their end-of-life care plans. METHODS: A new multidisciplinary approach was implemented in 6 hospitals in The Netherlands between January 2016 and January 2018. The approach was introduced during staff meetings in the ED, intensive care unit (ICU), and neurology department. When patients with a devastating brain injury had a futile prognosis in the ED, without contraindications for organ donation, an ICU admission was considered. Every ICU admission to incorporate organ donation into end-of-life care was systematically evaluated with the involved physicians using a standardized questionnaire. RESULTS: In total, 55 potential organ donors were admitted to the ICU to incorporate organ donation into end-of-life care. Twenty-seven families consented to donation and 20 successful organ donations were performed. Twenty-nine percent of the total pool of organ donors in these hospitals were admitted to the ICU for organ donation. CONCLUSIONS: Patients with a devastating brain injury and futile medical prognosis in the ED are an important proportion of the total number of donors. The implementation of a multidisciplinary approach is feasible and could lead to better identification of potential donors in the ED.

[Legislative amendment legitimises current organ donation practices]. / Wetswijziging legitimeert de huidige donatiepraktijk.

On 23rd April 2013, the Dutch Senate unanimously approved a proposal from Minister Schippers of the Ministry of Health for an amendment of the Organ Donation Act.

Higher refusal rates for organ donation among older potential donors in the Netherlands: impact of the donor register and relatives.

BACKGROUND: The availability of donor organs is considerably reduced by relatives refusing donation after death. There is no previous large-scale evaluation of the influence of the Donor Register (DR) consultation and the potential donor's age on this refusal in The Netherlands. METHODS: This study examines 2101 potential organ donors identified in intensive care units between 2005 and 2008 and analyzes the association of DR consultation and subsequent refusal by relatives and the relationship with the potential donor's age. RESULTS: Of the 1864 potential donor cases where the DR was consulted, the DR revealed no registration in 56%, 20% registration of consent, and 18% objection. In the other 6.5% of cases, where the DR indicated that relatives had to decide, the relatives' refusal rate was significantly lower than in the absence of a DR registration (46% vs. 63%). In 6% of the cases where the DR recorded donation consent, relatives still refused donation. DR registration, objection in the DR, and the relatives' refusal rate if the DR was not decisive increased with donor age. CONCLUSIONS: Despite the introduction of a DR, relatives still play an equally important role in the final decision for organ donation. The general public should be encouraged to register their donation preferences in the DR and also to discuss their preferences with their families. The higher refusal rate of older potential donors means that this group should receive more information about organ donation, especially because the cohort of available donors is ageing.

Imminent brain death: point of departure for potential heart-beating organ donor recognition.

PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.