The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis.
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SUBMITTER: Perito ER
PROVIDER: S-EPMC6428603 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis.
Perito Emily R ER Mogul Douglas B DB VanDerwerken Douglas D Mazariegos George G Bucuvalas John J Book Linda L Horslen Simon S Kim Heung B HB Miloh Tamir T Ng Vicky V Reyes Jorge J Rodriguez-Davalos Manuel I MI Valentino Pamela L PL Gentry Sommer S Hsu Evelyn E
Journal of pediatric gastroenterology and nutrition 20190401 4
<h4>Objective</h4>The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two "SharePeds" allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Org ...[more]
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Project description:BACKGROUND & AIM:The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. METHODS:Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ?40 were followed for 30days or until the earliest occurrence of death or transplant. RESULTS:Of 65,776 waitlisted patients, 3.3% had MELD ?40 at registration, and an additional 7.3% had MELD scores increase to ?40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ?40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2-1.6) for patients with MELD 41-44, 2.6 (95% CI 2.1-3.1) for MELD 45-49, and 5.0 (95% CI 4.1-6.1) for MELD ?50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. CONCLUSIONS:Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.
| S-EPMC7735955 | biostudies-literature
Project description:Offer acceptance practices may cause geographic variability in allocation Model for End-Stage Liver Disease (aMELD) score at transplant and could magnify the effect of donor supply and demand on aMELD variability. To evaluate these issues, offer acceptance practices of liver transplant programs and donation service areas (DSAs) were estimated using offers of livers from donors recovered between January 1, 2016, and December 31, 2016. Offer acceptance practices were compared with liver yield, local placement of transplanted livers, donor supply and demand, and aMELD at transplant. Offer acceptance was associated with liver yield (odds ratio, 1.32; P < 0.001), local placement of transplanted livers (odds ratio, 1.34; P < 0.001), and aMELD at transplant (average aMELD difference, -1.62; P < 0.001). However, the ratio of donated livers to listed candidates in a DSA (ie, donor-to-candidate ratio) was associated with median aMELD at transplant (r = -0.45; P < 0.001), but not with offer acceptance (r = 0.09; P = 0.50). Additionally, the association between DSA-level donor-to-candidate ratios and aMELD at transplant did not change after adjustment for offer acceptance. The average squared difference in median aMELD at transplant across DSAs was 24.6; removing the effect of donor-to-candidate ratios reduced the average squared differences more than removing the effect of program-level offer acceptance (33% and 15% reduction, respectively). Offer acceptance practices and donor-to-candidate ratios independently contributed to geographic variability in aMELD at transplant. Thus, neither offer acceptance nor donor-to-candidate ratios can explain all of the geographic variability in aMELD at transplant. Liver Transplantation 24 478-487 2018 AASLD.
| S-EPMC5869092 | biostudies-literature
Project description:Sarcopenia is a clinical condition characterized by a reduction in muscle mass, which typically affects adult patients; however, it has recently been recognized in pediatric literature. Few studies in children with chronic liver disease (CLD) undergoing liver transplantation (LT) have investigated the role of sarcopenia, with controversial results. The aim of our study was to assess the prevalence and impact of sarcopenia among children with CLD who are candidates for LT. We conducted a retrospective, single-center study at Bambino Gesù Children's Hospital (Rome, Italy) from July 2016 to July 2021, evaluating all children (0-16 years old) with CLD listed for LT with an abdomen computed tomography imaging available before LT. The total psoas muscle surface area (t-PMSA) was defined as the sum of left and right psoas muscle surface area measured at L4-L5 on axial images. The t-PMSA z-score was calculated according to reference data, and sarcopenia was defined as a t-PMSA z-score of ≤-2 (1-16 years) or a psoas muscle index [PMI; PMI = t-PMSA/(100 × BSA)] of <50th percentile of the population examined (<1 year). Clinical, laboratory, and LT outcome data were collected from all the patients with CLD. 27 out 48 (56%) of the patients aged 1-16 years were sarcopenic. No differences were noted in anthropometrics, nutritional support, liver function tests, model for ESLD (MELD), or pediatric ESLD (PELD) scores between patients with and without sarcopenia. The former showed a higher prevalence of respiratory complications (66.7% vs. 42.1%) and need for inotropes (40.7% vs. 10.8%) after LT. Among patients aged 0-1 years (n: 36), those with reduced muscle mass (50%) had a longer hospitalization time (44 vs. 24 days) and higher incidences of multi-organ failure syndrome (38.9% vs. 0%) and intensive care unit-related infections (61.1% vs. 27.8%) compared to those with greater muscle mass. t-PMSA and PMI were statistically significant predictors of LT outcomes. Sarcopenia is a reliable index of frailty in children with CLD, as its presence is associated with the risk of a more challenging LT. Future studies will have to investigate the functional aspects of sarcopenia and conceive preventive measures of muscle wasting in CLD patients.
| S-EPMC9891232 | biostudies-literature
Project description:ImportanceLiver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex.ObjectiveTo use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment.Design, setting, and participantsA retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant waiting list data from the liver simulated allocation modeling system. Patients who regularly used VUMC with measurements for any MELDNa component laboratory were included in the analyses. Analysis took place from November 2019 to March 2021.ExposuresElectronic health record-reported sex.Main outcomes and measureCreatinine, bilirubin, international normalized ratio, and sodium levels.ResultsThe VUMC sample was composed of 623 931 individuals (359 976 [57.7%] female) with a median (IQR) age of 44 (23-61) years. All component MELDNa laboratory values and calculated MELDNa scores yielded significant sex differences within VUMC (mean [SD] creatinine: male, 0.99 [0.39] mg/dL; female, 0.79 [0.30] mg/dL; P < .001; bilirubin: male, 0.76 [0.83] mg/dL; female, 0.58 [0.64] mg/dL; P < .001; international normalized ratio of prothrombin rate: male, 1.24 [0.42]; female, 1.20 [0.40]; P < .001; sodium: male, 139.00 [2.36] mEq/L; female, 139.03 [2.28] mEq/L; P < .001), resulting in MELDNa scoring that disadvantaged female individuals. This pattern persisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD]: male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD]: male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death.Conclusions and relevanceThese results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.
| S-EPMC9118088 | biostudies-literature
Project description:Background & aimsPortal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters.MethodsNutrition (subjective global assessment), handgrip strength, dietary intake (energy, protein), frequency of paracentesis and severity of liver disease (model for end-stage liver disease score) were prospectively recorded at terlipressin commencement and follow-up (transplantation, cessation or census date).ResultsNineteen patients were included (89% male, median age 59.6 years, median model for end-stage liver disease score 24), of whom 12 had hepatorenal syndrome and 7 had refractory ascites. All patients were malnourished at baseline, 63% (n = 12) had sarcopenic-range grip strength, and mean paracentesis frequency was 2.86 ± 1.62/month. Median duration of terlipressin was 51 days (interquartile range 29-222). Fourteen patients (74%) were transplanted, 2 delisted (10%) and 3 (16%) continued terlipressin. Energy and protein intake improved significantly following terlipressin, from 17.94 ± 5.43 kcal/kg to 27.70 ± 7.48 kcal/kg, and 0.74 ± 0.28 g/kg to 1.16 ± 0.31 g/kg, respectively (both p < 0.001). Handgrip strength increased from 25.36 ± 8.13 kg to 28.49 ± 7.63 kg (p = 0.001). Linear regression analysis demonstrated hand grip strength increased 0.075% for every 1-day of terlipressin (p = 0.005). The frequency of large-volume paracentesis reduced by 46%, to 1.57 ± 1.51/month (p = 0.001).ConclusionContinuous terlipressin infusion reduces the complications of portal hypertension and is associated with an improvement in nutritional and muscle parameters in patients on the liver transplant waiting list, in whom such characteristics usually demonstrate progressive decline. This validates both the aetiological role of portal hypertension in malnutrition and represents a promising new anabolic therapy.Lay summaryMalnutrition and poor muscle strength are common in liver disease and often get worse while patients await liver transplant. Terlipressin is a medication used to treat portal hypertension in patients with hepatorenal syndrome. It is usually given for a few days or weeks in patients confined to hospital. Our centre provides outpatient terlipressin for weeks to months as a bridge to liver transplant. In patients treated with terlipressin at our hospital, we observed a substantial increase in their dietary intake and muscle strength, which may improve their quality of life and outcomes after liver transplant.
| S-EPMC7001556 | biostudies-literature
Project description:BackgroundSensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods.MethodsTransfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ? 2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA).ResultsIn the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ? 10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ? 30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ? 3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients.ConclusionsAmong prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.
| S-EPMC3811060 | biostudies-literature
Project description:The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency.Wait-list data from adult primary liver transplantation candidates from the Organ Procurement and Transplantation Network were divided into a model derivation set (2005-2006; n=14,214) and validation set (2007-2008; n=13,945). Cox regression analysis was used to derive and validate an optimized model that updated coefficients and upper and lower bounds for MELD components and included serum levels of sodium. Main outcomes measure was ability to predict 90-day mortality of patients on the liver transplantation wait list.Optimized MELD score updated coefficients and implemented new upper and lower bounds for creatinine (0.8 and 3.0 mg/dL, respectively) and international normalized ratio (1 and 3, respectively). Serum sodium concentrations significantly predicted mortality, even after adjusting for the updated MELD model. The final model, based on updated fit of the 4 variables (ie, bilirubin, creatinine, international normalized ratio, and sodium) had a modest yet statistically significant gain in discrimination (concordance: 0.878 vs 0.865; P<.01) in the validation dataset. Utilization of the new score could affect up to 12% of patients (based on changed score for 459 of 3981 transplants in the validation set).Modification of MELD score to update coefficients, change upper and lower bounds, and incorporate serum sodium levels improved wait-list mortality prediction and should increase efficiency of allocation of donated livers.
| S-EPMC4546828 | biostudies-literature
Project description:ImportanceLiving-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC).ObjectiveTo investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription.Design, setting, and participantsThis multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020.Main outcomes and measuresIntention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created.ResultsA total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated.Conclusions and relevanceThis study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.
| S-EPMC8281041 | biostudies-literature
Project description:BackgroundAllocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment.MethodsPublished and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context.FindingsPublished and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes.InterpretationDefining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.
| S-EPMC7779078 | biostudies-literature
Project description:BackgroundWhenever vaccines for a new pandemic or widespread epidemic are developed, demand greatly exceeds the available supply of vaccine doses in the crucial, initial phases of vaccination. Rationing protocols must then fulfill a number of ethical principles balancing equal treatment of individuals and prioritization of at-risk and instrumental subpopulations. For COVID-19, actual rationing methods used a territory-based first allocation stage based on proportionality to population size, followed by locally-implemented prioritization rules. The results of this procedure have been argued to be ethically problematic.MethodsWe use a formal-analytical approach arising from the mathematical social sciences which allows to investigate whether any allocation methods (known or unknown) fulfill a combination of (ethical) desiderata and, if so, how they are formulated algorithmically.ResultsStrikingly, we find that there exists one and only one method that allows to treat people equally while giving priority to those who are worse off. We identify this method down to the algorithmic level and show that it is easily implementable and it exhibits additional, desirable properties. In contrast, we show that the procedures used during the COVID-19 pandemic violate both principles.ConclusionsOur research delivers an actual algorithm that is readily applicable and improves upon previous ones. Since our axiomatic approach shows that any other algorithm would either fail to treat people equally or fail to prioritize those who are worse off, we conclude that ethical principles dictate the adoption of this algorithm as a standard for the COVID-19 or any other comparable vaccination campaigns.
| S-EPMC9792380 | biostudies-literature