Trends in wait-list mortality in children listed for heart transplantation in the United States: era effect across racial/ethnic groups.
ABSTRACT: We sought to evaluate trends in overall and race-specific pediatric heart transplant (HT) wait-list mortality in the United States (US) during the last 20 years. We identified all children <18 years old listed for primary HT in the US during 1989-2009 (N = 8096, 62% White, 19% Black, 13% Hispanic and 6% Other) using the Organ Procurement and Transplant Network database. Wait-list mortality was assessed in four successive eras (1989-1994, 1995-1999, 2000-2004 and 2005-2009). Overall wait-list mortality declined in successive eras (26%, 23%, 18% and 13%, respectively). The decline across eras remained significant in adjusted analysis (hazard ratio [HR] 0.70 in successive eras, 95% confidence interval [CI], 0.67-0.74) and was 67% lower for children listed during 2005-2009 versus those listed during 1989-1994 (HR 0.33; CI, 0.28-0.39). In models stratified by race, wait-list mortality decreased in all racial groups in successive eras. In models stratified by era, minority children were not at higher risk of wait-list mortality in the most recent era. We conclude that the risk of wait-list mortality among US children listed for HT has decreased by two-thirds during the last 20 years. Racial gaps in wait-list mortality present variably in the past are not present in the current era.
Project description:The risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) receiving direct acting antivirals (DAAs) has been debated. This study aims to describe the incidence of HCC among patients listed for liver transplantation (LT) in the DAA era. Individuals with cirrhosis listed for LT from January 2003 to December 2015 were identified using the Scientific Registry for Transplant Recipients database. Patients with HCC at listing or HCC exception within 180 days were excluded. Patients were divided into three eras based on listing date: eras 1 (2003-2010), 2 (2011-2013), and 3 (2014-2015). Incidence rates of HCC were calculated by era and compared using incident rate ratios (IRRs). The association between HCC and listing era was evaluated using Cox regression and competing risk analyses, the latter considering death and LT as competing events. Of the 48,158 eligible wait-list registrants, 3112 (6.5%) received HCC exceptions after a median of 493 days. In 20,039 individuals with HCV, the incidence of HCC was 49% higher in era 3 versus era 1 (IRR 1.49, 95% confidence interval [CI] 1.24-1.79). In multivariate analysis, those in era 3 had a higher hazard of HCC compared with era 1 (hazard ratio 1.22, 95% CI 1.01-1.48). However, in multivariable competing risks analysis, with death and LT considered as competing events for de novo HCC, era was no longer associated with HCC (subdistribution hazard ratio 0.83, 95% CI 0.69-1.00). CONCLUSION:In this large population-based cohort of LT registrants, the incidence of HCC among HCV patients has increased in the DAA era. Competing risks analysis suggests that this may be explained by changes in rates of LT and wait-list mortality in the HCV population during this time. (Hepatology 2018; 00:000-000).
Project description:Access to the renal transplantation (RT) waiting list depends on factors related to lower mortality rates and often occurs after dialysis initiation. The aim of the study was to use a flexible regression model to determine if registration on the RT waiting list is associated with mortality on dialysis, independent of the comorbidities associated with such registration.Data from the French REIN registry on 7138 incident hemodialysis (HD) patients were analyzed. A multi-state model including four states ('HD, not wait-listed', 'HD, wait-listed', 'death', and 'RT') was used to estimate the effect of being wait-listed on the probability of death.During the study, 1392 (19.5%) patients were wait-listed. Of the 2954 deaths observed in the entire cohort during follow-up, 2921 (98.9%) were observed in the not wait-listed group compared with only 33 (1.1%) in the wait-listed group. In the multivariable analysis, the adjusted hazard ratio for death associated with non-registration on the waiting list was 3.52 (95% CI, 1.70-7.30). The risk factors for death identified for not wait-listed patients were not found to be significant risk factors for wait-listed patients, with the exception of age.The use of a multi-state model allowed a flexible analysis of mortality on dialysis. Patients who were not wait-listed had a much higher risk of death, regardless of co-morbidities associated with being wait-listed, and did not share the same risk factors of death as wait-listed patients. Registration on the waiting list should therefore be taken into account in survival analysis of patients on dialysis.
Project description:Young children?<?2 years of age with chronic end-stage liver disease (YC2) are a uniquely vulnerable group listed for liver transplantation, characterized by a predominance of biliary atresia (BA). To investigate wait-list mortality, associated risk factors, and outcomes of YC2, we evaluated United Network for Organ Sharing registry data from April 2003 to March 2013 for YC2 listed for deceased donor transplant (BA?=?994; other chronic liver disease [CLD]?=?221). Overall, wait-list mortality among YC2 was 12.4% and posttransplant mortality was 8%, accounting for an overall postlisting mortality of 19.6%. YC2 demonstrated 12.2%, 18.7%, and 20.6% wait-list mortality by 90, 180, and 270 days, respectively. YC2 with CLD demonstrated significantly higher wait-list mortality compared with BA among YC2 (23.9% versus 9.8%; P?<?0.05). Multivariate analyses revealed that listing Pediatric End-Stage Liver Disease [PELD]?>?21 (hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.6-6.5), lack of exception (HR, 5.8; 95% CI, 2.8-11.8), listing height?<?60.6?cm (HR, 2.1; 95% CI, 1.4-3.1), listing weight ?>?10?kg (HR, 3.8; 95% CI, 1.5-9.2), and initial creatinine?>?0.5 (HR, 6.8; 95% CI, 3.4-13.5) were independent risk factors for YC2 wait-list mortality (P?<?0.005 for all). Adjusting for all variables, the risk of death among CLD patients was 2 (95% CI, 1.3-3.1) times greater than patients with BA?+?surgery (presumed Kasai). Furthermore, the risk of death in BA without surgery was 1.9 (95% CI, 1?3.4) times greater than BA with presumed Kasai. Our data highlight unacceptably high wait-list and early post-liver transplant mortality in YC2 not predicted by PELD and suggest key risk factors deserving of further study in this age group. Liver Transplantation 22 1584-1592 2016 AASLD.
Project description:Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End-Stage Liver Disease (MELD) at WL was ?15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003-2010), protease inhibitor (PI; 2011-2013), and direct-acting antiviral (DAA; 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all).The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804-812).
Project description:BACKGROUND:Determining eligibility for a kidney transplant is one of the most important decisions facing nephrologists. It is assumed that the harm of kidney transplantation is minimal and most will benefit. The purpose of this study was to quantify the probability of 'no benefit' as defined by death on the wait list; 'harm', defined by the probability that a transplanted patient would live less than the average wait listed patient; and 'benefit' for the probability a transplanted patient would outlive the average wait listed patient. METHODS:A computerized model was developed to replicate observed patient survival outcomes in deceased donor kidney transplantation. Three sequential periods of risk for the transplanted recipient compared to the wait listed cohort (increased, equivalent and reduced risk) were modeled. RESULTS:The model predicted that wait listed patients with a baseline mortality of 28 deaths per 100 patient years were equally likely to benefit or be harmed with a transplant. However if 20% of patients on the wait list were on hold (assuming a 2.2-fold higher mortality than those who were transplanted), then the baseline mortality rate for equal harm or benefit decreases to 22 deaths per 100 patient years (equivalent life expectancy 4.5 years). CONCLUSION:Patients with limited life expectancies are more likely to suffer some harm than derive benefit from kidney transplantation.
Project description:The number of patients listed active for kidney transplantation has continued to rise over the last 10 years, leading to significantly increased wait-list time for patients awaiting kidney transplantation in the USA. This increased demand has led to a supply-demand mismatch and should prompt clinicians to seek timely solutions to improve access to available organs. Hepatitis C virus positive [HCV(+)] kidneys continue to be discarded without clear evidence that they lead to poor outcomes in the current era of highly efficacious HCV treatment with direct-acting antiviral agents (DAAs). Increased utilization of HCV(+) donor kidneys will decrease wait-list time and improve availability of donor organs. Emerging data suggests that HCV can be successfully treated with DAAs after kidney transplantation with 100% sustained virologic response rates and no significant changes from baseline kidney function. Utilization of HCV(+) donor kidneys should be considered more liberally in the era of highly effective HCV treatment. Further studies are warranted to assess the long-term effect of HCV(+) donor kidneys in transplant recipients in the new era of DAAs.
Project description:Donor livers are offered to patients with the highest risk of death. How ascites could inform risk models to reduce liver transplant wait-list mortality is unclear. All adult candidates for primary liver transplantation for cirrhosis without exception points who were registered with the Organ Procurement and Transplantation Network from 2005 to 2007 composed our study cohort. Using Cox models and advanced discriminative metrics and paying attention to geographic disparities, we evaluated the additional risk discrimination of moderate ascites over that of the Model for End-Stage Liver Disease (MELD) or the Model for End-Stage Liver Disease plus serum sodium (MELD-Na) alone for the prediction of 90-day wait-list mortality. Additional analyses examined lower mortality risk candidates and those listed in high-demand, low-supply United Network for Organ Sharing regions in which accounting for ascites may most significantly affect wait-list mortality. Between 2005 and 2007, 18,124 subjects were listed for liver transplantation. Mortality was higher in patients with moderate ascites (15.4% versus 6.0%, P < 0.0001), and this risk persisted despite adjustments for MELD (hazard ratio = 1.58, 95% confidence interval = 1.42-1.76) and MELD-Na (hazard ratio = 1.42, 95% confidence interval = 1.28-1.58). The effect of moderate ascites was more prominent with a MELD score <21 (equal to 4.7 MELD units) or with a MELD-Na score <21 (equal to 3.5 MELD-Na units). Wait-list mortality was higher in patients with moderate ascites who were listed in high-demand, limited-supply regions (25.8% versus 17.5% at 1 year, P < 0.01). With the addition of moderate ascites, there was improvement in the overall risk model, particularly with a MELD score <21, as measured by the C index and integrated discrimination improvement. Moderate ascites informed risk prediction, particularly with a MELD score <21 and in high-demand, limited-supply regions. Under the MELD system, the presence of moderate ascites should prompt clinicians to consider strategies to expand access to transplantation, such as the use of extended donor liver grafts.
Project description:Background:Understanding how frailty affects patients listed for transplantation has been identified as a priority research need. Frailty may be associated with a high risk of death or wait-list withdrawal, but this has not been evaluated in a large multicenter cohort of Canadian wait-listed patients. Objective:The primary objective is to evaluate whether frailty is associated with death or permanent withdrawal from the transplant wait list. Secondary objectives include assessing whether frailty is associated with hospitalization, quality of life, and the probability of being accepted to the wait list. Design:Prospective cohort study. Setting:Seven sites with established renal transplant programs that evaluate patients for the kidney transplant wait list. Patients:Individuals who are being considered for the kidney transplant wait list. Measurements:We will assess frailty using the Fried Phenotype, a frailty index, the Short Physical Performance Battery, and the Clinical Frailty Scale at the time of listing for transplantation. We will also assess frailty at the time of referral to the wait list and annually after listing in a subgroup of patients. Methods:The primary outcome of the composite of time to death or permanent wait-list withdrawal will be compared between patients who are frail and those who are not frail and will account for the competing risks of deceased and live donor transplantation. Secondary outcomes will include number of hospitalizations and length of stay, and in a subset, changes in frailty severity over time, change in quality of life, and the probability of being listed. Recruitment of 1165 patients will provide >80% power to identify a relative hazard of ?1.7 comparing patients who are frail to those who are not frail for the primary outcome (2-sided ? = .05), whereas a more conservative recruitment target of 624 patients will provide >80% power to identify a relative hazard of ?2.0. Results:Through December 2019, 665 assessments of frailty (inclusive of those for the primary outcome and all secondary outcomes including repeated measures) have been completed. Limitations:There may be variation across sites in the processes of referral and listing for transplantation that will require consideration in the analysis and results. Conclusions:This study will provide a detailed understanding of the association between frailty and outcomes for wait-listed patients. Understanding this association is necessary before routinely measuring frailty as part of the wait-list eligibility assessment and prior to ascertaining the need for interventions that may modify frailty. Trial Registration:Not applicable as this is a protocol for a prospective observational study.
Project description:BACKGROUND:This study aimed to evaluate the changes in heart transplantation (HTx) waiting list mortality following the introduction of the Berlin Heart EXCOR (BH EXCOR) in the Netherlands, as well as the occurrence of adverse events in these children. METHODS:A retrospective, single-center study was conducted including all pediatric patients (?18 years) awaiting HTx. Patients were grouped in two eras based on availability of the BH EXCOR in our center, era I (1998-2006; not available) and era II (2007 to July 31, 2018; available). RESULTS:In total, 87 patients were included, 15 in era I and 72 in era II. Extracorporeal membrane oxygenator support was required in 1 (7%) patient in era I and in 13 (18%) patients in era II. Overall mortality (7/15 in era I vs 16/72 in era II; 47% vs 22%, P = .06) and transplantation rates (8/15 in era I vs 47/72 in era II; 53% vs 65%, P = .39) did not differ significantly. Eleven (39%) patients of the pediatric ventricular assist device (VAD) population died, with the predominant cause being cerebrovascular accidents (CVAs) in eight (29%) patients. Furthermore, 14 (50%) of the pediatric VAD patients survived to transplantation. Adverse events most frequently occurring in VAD patients included CVA in 14 (50%), mostly (68%) within 30 days after VAD implantation, and bleeding requiring rethoracotomy in 14 (50%), all within 30 days after VAD implantation. CONCLUSIONS:The introduction of the BH EXCOR has positively impacted the survival of pediatric patients with end-stage heart failure in our center. The predominant cause of death changed from end-stage heart failure in era I to CVA in era II. We emphasize the need for large prospective registry-based studies.
Project description:Posttransplant survival in heart transplant recipients has progressively improved during the past 2 decades. It is unknown, however, whether the major racial groups in the United States have benefited equally.We analyzed all primary heart transplant recipients aged ?18 years in the United States from 1987 to 2008. We compared posttransplant survival in white, black, and Hispanic recipients in 5 successive eras (1987 to 1992, 1993 to 1996, 1997 to 2000, 2001 to 2004, 2005 to 2008). Early survival was defined as freedom from death or retransplantation during the first 6 months posttransplant. Longer-term, conditional survival was assessed in patients who survived the first 6 months. There were 29 986 (81.6%) white, 4745 (12.9%) black, and 2017 (5.5%) Hispanic patients in the study cohort. Black patients were at increased risk of early death or retransplant (hazard ratio [HR], 1.15; 95% CI, 1.05 to 1.26) in adjusted analysis. Early posttransplant survival improved (HR, 0.83; 95% CI, 0.80 to 0.87 for successive eras) equally in all 3 groups (black-era interaction, P=0.94; Hispanic-era interaction, P=0.40). Longer-term survival improved in white (HR, 0.95; 95% CI, 0.92 to 0.97 for successive eras) but not in black (HR, 1.04; 95% CI, 0.99 to 1.09) or Hispanic (HR, 1.02; 95% CI, 0.95 to 1.09) recipients, resulting in increased disparities in longer-term survival with time.Early posttransplant survival has improved equally in white, black, and Hispanic heart transplant recipients. Longer-term survival has improved in white but not in black or Hispanic recipients, resulting in a more marked disparity in outcomes in the current era. These disparities warrant further investigation and targeted interventions.