Measuring and monitoring equity in access to deceased donor kidney transplantation.

The Organ Procurement and Transplantation Network monitors progress toward strategic goals such as increasing the number of transplants and improving waitlisted patient, living donor, and transplant recipient outcomes. However, a methodology for assessing system performance in providing equity in access to transplants was lacking. We present a novel approach for quantifying the degree of disparity in access to deceased donor kidney transplants among waitlisted patients and determine which factors are most associated with disparities. A Poisson rate regression model was built for each of 29 quarterly, period-prevalent cohorts (January 1, 2010-March 31, 2017; 5 years pre-kidney allocation system [KAS], 2 years post-KAS) of active kidney waiting list registrations. Inequity was quantified as the outlier-robust standard deviation (SDw ) of predicted transplant rates (log scale) among registrations, after "discounting" for intentional, policy-induced disparities (eg, pediatric priority) by holding such factors constant. The overall SDw declined by 40% after KAS implementation, suggesting substantially increased equity. Risk-adjusted, factor-specific disparities were measured with the SDw after holding all other factors constant. Disparities associated with calculated panel-reactive antibodies decreased sharply. Donor service area was the factor most associated with access disparities post-KAS. This methodology will help the transplant community evaluate tradeoffs between equity and utility-centric goals when considering new policies and help monitor equity in access as policies change.

OPTN/SRTR 2015 Annual Data Report: Intestine.

Intestine and intestine-liver transplant remains important in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2015, 196 new patients were added to the intestine transplant waiting list, with equal numbers waiting for intestine and intestine-liver transplant. Among prevalent patients on the list at the end of 2015, 63.3% were waiting for an intestine transplant and 36.7% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was notably higher for intestine-liver than for intestine transplant candidates (respectively, 19.9 vs. 2.8 deaths per 100 waitlist years in 2014-2015). By age, pretransplant mortality was highest for adult candidates, at 19.6 per 100 waitlist years, and lowest for children aged younger than 6 years, at 3.6 per 100 waitlist years. Pretransplant mortality by etiology was highest for candidates with non-congenital types of short-gut syndrome. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 70 in 2015. Intestine-liver transplants increased from a low of 44 in 2012 to 71 in 2015. Short-gut syndrome (congenital and non-congenital) was the main cause of disease leading to intestine and to intestine-liver transplant. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

OPTN/SRTR 2015 Annual Data Report: Liver.

Several notable developments in adult liver transplantation in the US occurred in 2015. The year saw the largest number of liver transplants to date, leading to reductions in median waiting time, in waitlist mortality for all model for end-stage liver disease categories, and in the number of candidates on the waiting list at the end of the year. Numbers of additions to the waiting list and of liver transplants performed in patients with hepatitis C virus infection decreased for the first time in recent years. However, other diagnoses, such as non-alcoholic fatty liver disease and alcoholic cirrhosis, became more prevalent. Despite large numbers of severely ill patients undergoing liver transplant, graft survival rates continued to improve. The number of new active candidates added to the pediatric liver transplant waiting list in 2015 was 689, down from a peak of 826 in 2005. The number of prevalent pediatric candidates (on the list on December 31 of the given year) continued to decline, to 373 active and 195 inactive candidates. The number of pediatric liver transplants peaked at 613 in 2008 and was 580 in 2015. The number of living donor pediatric liver transplants increased to its highest level, 79, in 2015; most were from donors closely related to the recipients. Pediatric graft survival rates continued to improve.

Liver.

The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers.

Intestine.

Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

OPTN/SRTR 2013 Annual Data Report: liver.

During 2013, 10,479 adult candidates were added to the liver transplant waiting list, compared with 10,185 in 2012; 5921 liver transplants were performed, and 211 of the transplanted organs were from living donors. As of December 31, 2013, 15,027 candidates were registered on the waiting list, including 12,407 in active status. The most significant change in allocation policy affecting liver waitlist trends in 2013 was the Share 35 policy, whereby organs from an entire region are available to candidates with model for end-stage liver disease scores of 35 or higher. Median waiting time for such candidates decreased dramatically, from 14.0 months in 2012 to 1.4 months in 2013, but the effect on waitlist mortality is unknown. The number of new active pediatric candidates added to the liver transplant waiting list increased to 693 in 2013. Transplant rates were highest for candidates aged younger than 1 year (275.6 per 100 waitlist years) and lowest for candidates aged 11 to 17 years (97.0 per 100 waitlist years). Five-year graft survival was 71.7% for recipients aged younger than 1 year, 74.9% for ages 1 to 5 years, 78.9% ages 6 to 10 years, and 77.4% for ages 11 to 17 years.

OPTN/SRTR 2013 Annual Data Report: intestine.

Despite improvements in medical and surgical treatment of intestinal failure over the past decade, intestine transplant continues to play an important role. Of 171 new patients added to the intestine transplant waiting list in 2013, 49% were listed for intestine-liver transplant and 51% for intestine transplant alone or with an organ other than liver. The pretransplant mortality rate decreased dramatically over time for all age groups, from 30.3 per 100 waitlist years in 2002-2003 to 6.9 for patients listed in 2012-2013. The number of intestine transplants decreased from 91 in 2009 to 51 in 2013; intestine-liver transplants decreased from 135 in 2007 to a low of 44 in 2012, but increased slightly to 58 in 2013. Ages of intestine and intestineliver transplant recipients have changed substantially; the number of adult recipients was double the number of pediatric recipients in 2013. Graft survival improved over the past decade. Graft failure in the first 90 days posttransplant occurred in 14.1% of intestine recipients and in 11.2% of intestine-liver recipients in 2013. The number of recipients alive with a functioning intestine graft has steadily increased since 2002, to 1012 in 2013; almost half were pediatric intestine-liver transplant recipients.

A scientific registry of transplant recipients bayesian method for identifying underperforming transplant programs.

In response to recommendations from a recent consensus conference and from the Committee of Presidents of Statistical Societies, the Scientific Registry of Transplant Recipients explored the use of Bayesian hierarchical, mixed-effects models in assessing transplant program performance in the United States. Identification of underperforming centers based on 1-year patient and graft survival using a Bayesian approach was compared with current observed-to-expected methods. Fewer small-volume programs (<10 transplants per 2.5-year period) were identified as underperforming with the Bayesian method than with the current method, and more mid-volume programs (10-249 transplants per 2.5-year period) were identified. Simulation studies identified optimal Bayesian-based flagging thresholds that maximize true positives while holding false positive flagging rates to approximately 5% regardless of program volume. Compared against previous program surveillance actions from the Organ Procurement and Transplantation Network Membership and Professional Standards Committee, the Bayesian method would have reduced the number of false positive program identifications by 50% for kidney, 35% for liver, 43% for heart and 57% for lung programs, while preserving true positives for, respectively, 96%, 71%, 58% and 83% of programs identified by the current method. We conclude that Bayesian methods to identify underperformance improve identification of programs that need review while minimizing false flags.

OPTN/SRTR 2012 Annual Data Report: liver.

Liver transplant in the us remains a successful life-saving procedure for patients with irreversible liver disease. In 2012, 6256 adult liver transplants were performed, and more than 65,000 people were living with a transplanted liver. The number of adults who registered on the liver transplant waiting list decreased for the first time since 2002; 10,143 candidates were added, compared with 10,359 in 2011. However, the median waiting time for active wait-listed adult candidates increased, as did the number of candidates removed from the list because they were too sick to undergo transplant. The overall deceased donor transplant rate decreased to 42.3 per 100 patient-years, and varied geographically from 18.9 to 228.0 per 100 patient-years. Graft survival continues to improve, especially for donation after circulatory death livers. The number of new active pediatric candidates added to the waiting list also decreased. Almost 75% of pediatric candidates listed in 2009 underwent transplant within 3 years; the 2012 rate of deceased donor transplants among active pediatric wait-listed candidates was 136 per 100 patient-years. Graft survival for deceased donor pediatric transplants was 92.8% at 30 days. Medicare paid for some or all of the care for more than 30% of liver transplants in 2010.

OPTN/SRTR 2012 Annual Data Report: intestine.

Advances in the medical and surgical treatments of intestinal failure have led to a decrease in the number of transplants over the past decade. In 2012, 152 candidates were added to the intestinal transplant waiting list, a new low. Of these, 64 were listed for intestine-liver transplant and 88 for intestinal transplant alone or with an organ other than liver. Historically, the most common organ transplanted with the intestine was the liver; this practice decreased substantially from a peak of 52.9% in 2007 to 30.0% in 2012. Short-gut syndrome, which encompasses a large group of diagnoses, is the most common etiology of intestinal failure. The pretransplant mortality rate decreased dramatically over time for all age groups, from 51.0 per 100 wait-list years in 1998-1999 to 6.7 for patients listed in 2010-2012. Numbers of intestinal and intestine-liver transplants steadily decreased from 198 in 2007 to 106 in 2012. By age, intestinal transplant recipients have changed substantially; the number of adult recipients now approximately equals the number of pediatric recipients. Graft survival has improved over the past decade. Graft failure in the first 90 days after transplant occurred in 15.7% of 2011-2012 intestinal transplant recipients, compared with 21% in 2001-2002.

OPTN/SRTR 2011 Annual Data Report: liver.

The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait-listed candidates and median waiting times were immediately reduced. However, the total number of adult wait-listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.

OPTN/SRTR 2011 Annual Data Report: intestine.

Since 2006, the number of new intestinal transplant candidates listed each year has declined, likely reflecting increased medical and surgical treatment for intestinal failure. Historically, intestinal transplant occurred primarily in the pediatric population; in 2011, 41% of prevalent candidates on the waiting list were aged 18 years or older. The most common etiology of intestinal failure remains short-gut syndrome, which encompasses several diagnoses. The proportion of candidates with high medical urgency status decreased and time on the waiting list increased in 2011. The overall rate of transplant decreased from a peak of 92.7 transplants per 100 wait-list years in 2005 to 49.2 in 2011. The number of intestines recovered and transplanted per donor has decreased since 2007, possibly due to fewer listed patients. Almost 50% of deceased donor intestines were transplanted with another organ in 2011. Historically, the most common organ transplanted with the intestine was the liver, but in 2011 it was the pancreas. Graft survival has continued to improve over the past decade, and the number of recipients alive with a functioning intestinal graft has steadily increased since 1998. Hospitalization is common, occurring in 84.8% of recipients by 6 months posttransplant and in almost all by 4 years.

Liver and intestine transplantation in the United States 1998-2007.

Liver transplantation numbers in the United States remained constant from 2004 to 2007, while the number of waiting list candidates has trended down. In 2007, the waiting list was at its smallest since 1999, with adults > or =50 years representing the majority of candidates. Noncholestatic cirrhosis was most commonly diagnosed. Most age groups had decreased waiting list death rates; however, children <1 year had the highest death rate. Use of liver allografts from donation after cardiac death (DCD) donors increased in 2007. Model for end-stage liver disease (MELD)/pediatric model for end-stage liver disease (PELD) scores have changed very little since 2002, with MELD/PELD <15 accounting for 75% of the waiting list. Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%. Hepatocellular carcinoma exceptions increased slightly. The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old. Death rates improved, but remain unacceptably high. Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality. In addition to evaluating trends in liver and intestine transplantation, we review in depth, issues related to organ acceptance rates, DCD, living donor transplantation and MELD/PELD exceptions.

Waiting list removal rates among patients with chronic and malignant liver diseases.

Equitable liver allocation should ensure that nonelective removal rates are fairly distributed among waiting candidates. We compared removal rates for adults entered with nonmalignant (NM) (N = 9379) and hepatocellular cancer (HCC) (N = 2052) diagnoses on the Organ Procurement and Transplantation Network (OPTN) list between April 30, 2003, and December 31, 2004. Unadjusted removal rates for NM vs. HCC diagnoses were 9.4% vs. 8.7%, 13.5% vs. 16.9% and 19.1% vs. 31.8% at 90, 180 and 365 days, respectively after listing. For NM candidates, model for end-stage liver disease (MELD) score (RR = 1.16), age (RR = 1.03) and metabolic disease diagnoses (RR = 1.66) had higher risks of removal; and PSC (RR = 0.62) and alcoholic cirrhosis (RR = 0.82) had lower risks of removal. For HCC candidates, MELD score at listing (RR = 1.09), AFP (RR = 1.02), maximum tumor size (RR = 1.16) and age at listing (RR = 1.02) had increased risks of removal. The equation 1 - 0.920 exp[0.09369 (MELD at listing - 12.48) + 0.00193 (AFP - 97.4) + 0.1505 (maximum tumor size - 2.59) defined the probability of dropout for HCC candidates within 90 days of listing. We conclude that factors associated with the risk of removal for HCC are different from NM candidates, although MELD score at listing remains the most predictive for both groups. Liver transplant candidates with HCC may be prioritized using a risk score analogous to the MELD score.

Excellent liver transplant survival rates under the MELD/PELD system.

The MELD/PELD (M/P) system for liver allocation was implemented on February 27, 2002, in the United States. Since then sufficient time has elapsed to allow for assessment of posttransplant survival rates under this system. We analyzed 4163 deceased donor liver transplants performed between February 27, 2002, and December 31, 2003, for whom follow-up reporting was 95% and 67% complete at 6 and 12 months, respectively. Kaplan-Meier survival analysis revealed 1-year patient and graft survival rates for status 1 of 76.9% and 70.4%, respectively, and 87.3% and 82.9% for patients prioritized by M/P (P < .0001 for status 1 vs M/P). When adult candidates were stratified by MELD score quartile at transplant, 1-year survival rates were 89.5%, 88.3%, 86.6%, and 78.1% for lowest to highest quartile (P = .0002) and graft survival rates were similarly distributed (85.0%, 84.5%, 82.7%, 73.0%, P < .0001). Candidates with hepatocellular cancer (89.6%) and other MELD score exceptions (88.8%) had slightly higher 1-year survival rates compared with standard MELD recipients (86.0%), which did not reach statistical significance (P = .089). Pediatric recipients had slightly better patient (88.7%) and graft (86.5%) survival rates at 1 year than adults but there were no significant differences among the PELD strata due to small numbers of patients in each PELD quartile. We conclude that patient and graft survival have remained excellent since implementation of the MELD/PELD system. Although recipients with MELD scores in the highest quartile have reduced survival compared with other quartiles, their 1-year survival rate is acceptable when their extreme risk of dying without a transplant is taken into consideration.

Can energetic expenditure be minimized by performing activity intermittently?

Previous research has shown that the energetic expense per unit distance traveled for one bout of short-duration activity is much greater than the energetic expense associated with long-duration activity. However, animals are often seen moving intermittently, with these behaviors characterized by brief bouts of activity interspersed with brief pauses. We hypothesized that, when multiple bouts of brief activity are performed intermittently, the energetic cost per unit distance is less than when only one short bout is performed. Mice were run 1, 2, 3, 5, 9 or 13 times for 15 s at their maximal speed within a 375 s period while enclosed in an open-flow respirometry system on a treadmill. The mice were also run continuously for 375 s. Following the last sprint and the continuous run, the mice remained in the respirometry chamber until their vO2 reached resting levels. Excess exercise oxygen consumption (EEOC), the excess volume of oxygen consumed during the exercise period, increased from 0.03+/-0.01 to 0.40+/-0.02 ml O2g(-)(1) (mean +/- s.e.m., N=9) with activity frequency. However, the excess post-exercise oxygen consumption (EPOC), or volume of oxygen consumed during the recovery period, was independent of activity frequency (range 0.91-1.16 ml O2g(-)(1)) and accounted for more than 80 % of the total metabolic cost when activity was performed intermittently. Lactate concentration was measured at rest, immediately after running and immediately after recovering from running 1, 5 and 13 times within the 375 s period. After running, [lactate] was significantly higher than resting values, but following recovery, [lactate] had reached resting values. The net cost of activity, C(act), calculated by summing EEOC and EPOC and then dividing by the distance run, decreased significantly from 132+/-38 to 6+/-1 ml O2g(-)(1 )km(-)(1) as activity frequency increased. When these values for C(act) were compared with the cost of running continuously for the same amount of time, the values were identical. Therefore, we conclude that animals can minimize energetic expenditure by performing brief behaviors more frequently, just as they can minimize these costs if they increase the duration of continuous behaviors.

Application of a continuous disease severity score to the OPTN liver waiting list.

In a move to establish measurable, objective criteria for cadaveric liver allocation, the United Network for Organ Sharing OPTN will implement the Model for End Stage Liver Disease (MELD) system in early 2002 as a replacement for the current Child-Turcotte-Pugh (CTP)-based Status 2A, 2B, and 3 categories for patients waiting for a cadaver donor liver transplant. The MELD is a continuous mortality risk score based on serum creatinine, bilirubin, and INR. Although originally developed in patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure, analysis of OPTN data shows that the components of MELD (in particular, bilirubin) have a very strong correlation with mortality in liver transplant candidates. Univariate analyses showed that pretransplant mortality significantly increased when the MELD score was > 1.8. In the study cohort, 25% of the patients had a MELD score > 1.8. Multivariate analysis showed that the MELD score was an independent predictor of mortality, with a 2-unit increase multiplying the risk of mortality by a factor of 5.6. The MELD and CTP scores were correlated, but MELD scores varied widely for any given CTP score, indicating that some patients could be disadvantaged with the status-based system. The MELD score was validated in an independent dataset; concordance with 3-month mortality was 0.88. We conclude that the MELD score is a good indicator of disease severity and that implementation of this system should direct more livers to those patients in greatest need of transplantation.

The OPTN waiting list, 1988-2000.

More patients in the United states are waiting for organ transplants that at any time in the past and the remarkable growth of the UNOS waiting list has become a key issue for the transplant community. 1. On October 31, 2001, there were 84,277, registrations on the combined UNOS waiting list. Among these, 63% were awaiting kidney transplantation, and 22% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 2000, were of blood type O (52%), white (55%) and male (58%), and awaiting their first transplant (87%). 3. The percentage transplanted within one year of listing has been declining for most organs, although that percentage has been somewhat stable for heart and lung between 1998-2000. 4. Blood type and medical urgency have a significant impact upon the percent transplanted within one year of listing for most organ types. Patients awaiting heart, pancreas, and intestinal transplants experience the highest probability of receiving a transplant within one year. 5. Deaths per patients waiting have declined since 1988 for most patients awaiting life-saving organs and have remained relatively low for those awaiting a kidney, pancreas, or kidney-pancreas transplant. Deaths were highest for lung and heart-lung patients, but appear to be declining.

Improved graft survival of pediatric liver recipients transplanted with pediatric-aged liver donors.

BACKGROUND: Improving graft survival after liver transplantation is an important goal for the transplant community, particularly given the increasing donor shortage. We have examined graft survivals of livers procured from pediatric donors compared to adult donors. METHODS: The effect of donor age (<18 years or > or =18 years) on graft survivals for both pediatric and adult liver recipients was analyzed using data reported to the UNOS Scientific Registry from January 1, 1992 through December 31, 1997. Graft survival, stratified by age, status at listing, and type of transplant was computed using the Kaplan-Meier method. In addition, odds ratios of graft failure at 3 months, 1 year, and 3 years posttransplant were calculated using a multivariate logistic regression analysis controlling for several donor and recipient factors. Modeling, using the UNOS Liver Allocation Model investigated the impact of a proposed policy giving pediatric patients preference to pediatric donors. RESULTS: Between 1992 and 1997 pediatric recipients received 35.6% of pediatric aged donor livers. In 1998 the percent of children dying on the list was 7.4%, compared with 7.3% of adults. Kaplan-Meier graft survivals showed that pediatric patients receiving livers from pediatric aged donors had an 81% 3-year graft survival compared with 63% if children received livers from donors > or =18 years (P<0.001). In contrast, adult recipients had similar 3-year graft survivals irrespective of donor age. In the multivariate analysis, the odds of graft failure were reduced to 0.66 if pediatric recipients received livers from pediatric aged donors (P<0.01). The odds of graft failure were not affected at any time point for adults whether they received an adult or pediatric- aged donor. The modeling results showed that the number of pediatric patients trans planted increased by at most 59 transplants per year. This had no significant effect on the probability of pretransplant death for adults on the waiting list. Waiting time for children at status 2B was reduced by as much as 160 days whereas adult waiting time at status 2B was increased by at most 20 days. CONCLUSION: A policy that would direct some livers procured from pediatric- aged donors to children improves the graft survival of children after liver transplantation. The effect of this policy does not increase mortality of adults waiting. Such a policy should increase the practice of split liver transplantation, which remains an important method to increase the cadaveric donor supply.