Barriers to ideal outcomes after pediatric liver transplantation.

Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.

Initial assessment of the infant with neonatal cholestasis-Is this biliary atresia?

INTRODUCTION: Optimizing outcome in biliary atresia (BA) requires timely diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses (Non-BA). Identification of clinical features of neonatal cholestasis that would expedite decisions to pursue subsequent invasive testing to correctly diagnose or exclude BA would enhance outcomes. The analytical goal was to develop a predictive model for BA using data available at initial presentation. METHODS: Infants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2 mg/dl [34.2 µM]) were enrolled prior to surgical exploration in a prospective observational multi-centered study (PROBE-NCT00061828). Clinical features (physical findings, laboratory results, gallbladder sonography) at enrollment were analyzed. Initially, 19 features were selected as candidate predictors. Two approaches were used to build models for diagnosis prediction: a hierarchical classification and regression decision tree (CART) and a logistic regression model using a stepwise selection strategy. RESULTS: In PROBE April 2004-February 2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis identified 13 features that were significantly different between BA and Non-BA. Using a CART predictive model of BA versus Non-BA (significant factors: gamma-glutamyl transpeptidase, acholic stools, weight), the receiver operating characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as BA. Stepwise logistic regression identified seven factors in a predictive model (ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357) yielded an 81% true positive rate for BA; <0.2 (n = 120) yielded an 11% false negative rate. CONCLUSION: Despite the relatively good accuracy of our optimized prediction models, the high precision required for differentiating BA from Non-BA was not achieved. Accurate identification of BA in infants with neonatal cholestasis requires further evaluation, and BA should not be excluded based only on presenting clinical features.

Organ Donation Attitudes and Practices among African Americans: An Adapted Measurement Instrument.

UNLABELLED: This study reports the psychometric properties and correlates of a measure of organ donation attitudes and practices for African Americans. METHODS: We surveyed 736 members from 14 alumni chapters of historically African American sororities and fraternities in Michigan. We constructed subscales and compared subscale values with two variables related to donation status: 1) enrollment status in the state donor registry, and 2) intentions for future enrollment. RESULTS: Psychometric analyses indicated our measure tapped four distinct domains of attitudes concerning donation. The four subscales identified-General Benefits, Race Benefits, General Barriers, and Disparity Barriers-had good psychometric properties. For all four scales the more positive the attitudes toward donation held by the respondent, the more likely they were to report having signed up to be an organ donor. DISCUSSION: An understanding of attitudes toward donation may help development of effective culturally sensitive intervention messages targeting the African American community.

Patient selection and volume in the era surrounding implementation of Medicare conditions of participation for transplant programs.

OBJECTIVE: To evaluate evidence of practice changes affecting kidney transplant program volumes, and donor, recipient and candidate selection in the era surrounding the introduction of Centers for Medicare and Medicaid Services (CMS) conditions of participation (CoPs) for organ transplant programs. DATA: Scientific Registry of Transplant Recipients; CMS ESRD and Medicare claims databases. DESIGN: Retrospective analysis of national registry data. METHODS: A Cox proportional hazards model of 1-year graft survival was used to derive risks associated with deceased-donor kidney transplants performed from 2001 to 2010. FINDINGS: Among programs with ongoing noncompliance with the CoPs, kidney transplant volumes declined by 38 percent (n = 766) from 2006 to 2011, including a 55 percent drop in expanded criteria donor transplants. Volume increased by 6 percent (n = 638) among programs remaining in compliance. Aggregate risk of 1-year graft failure increased over time due to increasing recipient age and obesity, and longer ESRD duration. CONCLUSIONS: Although trends in aggregate risk of 1-year kidney graft loss do not indicate that the introduction of the CoPs has systematically reduced opportunities for marginal candidates or that there has been a systematic shift away from utilization of higher risk deceased donor kidneys, total volume and expanded criteria donor utilization decreased overall among programs with ongoing noncompliance.

Development of a scale to measure African American attitudes toward organ donation.

African American attitudes toward organ donation differ from other racial and ethnic groups. However, existing measures of organ donation attitudes do not adequately address ethnic identity and cultural factors. We examined the psychometric properties of a new 18-item organ donation scale among 1225 members of 21 African American churches in Southeast Michigan. We identified three factors: (1) Barriers; (2) Family/Race Benefits; and (3) Altruism. More positive donation attitudes on each subscale were observed for individuals who reported being enrolled as a donor. Among individuals not enrolled, higher scores were observed on scales two and three for those with stronger intentions to enroll.

Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy.

BACKGROUND & AIMS: Pathologists participating in the National Institutes of Health-sponsored Biliary Atresia Research Consortium (BARC) developed and then evaluated a standardized system for histologic reporting of liver biopsies from infants with cholestasis. METHODS: A set of 97 anonymous liver biopsy samples was sent to 10 pathologists at BARC centers. A semiquantitative scoring system that had 16 histologic features was developed and then used by the pathologists, who had no knowledge of clinical history, imaging results, or laboratory data. Interobserver agreement was evaluated statistically. Agreement on scoring of each feature and on the pathologists' diagnosis, compared with the final clinical diagnosis, was evaluated by using weighted kappa statistics. RESULTS: There was moderate to substantial interobserver agreement in identification of bile plugs in ducts, giant-cell transformation, extramedullary hematopoiesis, and bile duct proliferation. The pathologists' diagnosis of obstruction in clinically proven cases of biliary atresia (BA) ranged from 79%-98%, with a positive predictive value of 90.7%. Histologic features that best predicted BA, on the basis of logistic regression, included bile duct proliferation, portal fibrosis, and absence of sinusoidal fibrosis (each P<.0001). CONCLUSIONS: The BARC histologic assessment system identified features of liver biopsies from cholestatic infants, with good interobserver agreement, that might be used in diagnosis and determination of prognosis. The system diagnosed BA with a high level of sensitivity and identified infants with biliary obstruction with reasonable interobserver agreement. However, distinguishing between BA and disorders such as total parenteral nutrition-associated liver disease and alpha(1)-antitrypsin deficiency is not possible without adequate clinical information.

Randomized trial using hair stylists as lay health advisors to increase donation in African Americans.

OBJECTIVE: To test the efficacy of using hair stylists as lay health advisors to increase organ donation among African American clients. DESIGN: This study was a randomized, controlled intervention trial where we randomized 52 salons (2,789 clients) to receive a 4 session, stylist-delivered health education program (comparison) or a four session brief motivational intervention that encouraged organ donation (intervention). Intervention stylists received a four-hour training in organ donation education and counseling. Organ donation was measured by self-report questionnaire at 4-month posttest as well as by verified enrollment in the Michigan Organ Donor Registry. SETTING: Hair salons in Michigan urban areas. PARTICIPANTS: Blacks (n = 2,449), non-Blacks (n = 261) in Michigan. MAIN OUTCOME MEASURES: Self-reported donation status, registration in Michigan Organ Donor Registry. RESULTS: At posttest, rates of self-reported positive donation status were 19.8% in the intervention group and 16.0% in the comparison group. In multivariate analyses, intervention participants were 1.7 times (95% Cl = 0.98-2.8) more likely than comparison participants to report positive donation status at posttest. Based on verified organ registry data, enrollment rates were 4.8% and 2%, respectively for the intervention and comparison groups. In multivariate analyses, intervention group members were 4.4 (95% CI = 1.3-15.3) more likely to submit an enrollment card than comparison participants. CONCLUSION: Clients of hair stylists trained to provide brief motivational intervention for organ donation were approximately twice as likely to enroll in the donor registry as comparison clients. Use of lay health advisors appears to be a promising approach to increase donation among African Americans.

Assessment of transition readiness skills and adherence in pediatric liver transplant recipients.

To examine transition readiness, adherence, and health outcomes in pediatric liver transplant recipients using a clinically administered screening measure. Seventy-one pediatric liver transplant recipients (11-20 yr) and 58 parents completed a clinic-based TRS measuring perceived and demonstrated self-management skills, AoR for health-related tasks, regimen knowledge, and psychosocial adjustment. Adherence was measured using s.d. of immunosuppressants, proportion of immunosuppressant blood levels out of target range, and clinic attendance. Health outcomes included liver test panels, biopsies, rejection episodes, and hospitalizations. Results indicate that all domains of transition readiness, with the exception of demonstrated skills, and non-adherence were positively correlated with age. Proportion of immunosuppressant blood levels below target range was positively correlated with self-management skills and increased responsibility for medication tasks. Parent regimen knowledge was associated with clinic attendance. Health outcomes were significantly related to medication non-adherence, but not to transition readiness domains. Medication adherence is considered to be a key factor in the transition from pediatric to adult-centered transplant care. Non-adherence is associated with an increased risk for medical complications and is potentially modifiable. Interventions to promote self-management skills and adherence should be an essential component of transition planning.

Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. MEASUREMENTS AND MAIN RESULTS: Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, p<0.001). Fifty percent of rejection episodes in the no induction group required hospitalization, and 46% of rejection episodes required TMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). CONCLUSION: Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

Early urologic complications after pediatric renal transplant: a single-center experience.

BACKGROUND: Urologic complications cause substantial morbidity in the pediatric population after renal transplantation, but their impact on graft survival and transplant costs is poorly understood. In this retrospective review, we evaluated the records of all pediatric renal transplant recipients at our center from 1995 to 2004. METHODS: Patient demographics, presence of urinary leak, stricture, compression, or vesicoureteral reflux, and hospital costs were analyzed. Univariable analysis identified predictors of complications and of need for reoperation, and Kaplan-Meier analysis was used to assess graft survival in relation to urinary complications. RESULTS: One hundred forty-seven children received renal transplants; mean follow-up was 1478+/-965 days. Nine (6.1%) patients had urologic complications and seven (4.8%) patients developed vesicoureteral reflux requiring reoperation. Sex, ischemia time, race, previous transplant, donor type, nephrectomy technique, and stent use did not affect the incidence of urologic complications. Previous urologic reconstruction and pretransplant ureteral pathologic conditions increased the risk of urologic complication and vesicoureteral reflux. Patients with urologic complications had equivalent graft survival, but triple the hospital costs of unaffected recipients. CONCLUSIONS: Prior urologic surgery is associated with increased risk of urologic complications posttransplant. Posttransplant urologic complications are associated with substantially increased costs in the first year after transplant, but not with decreased graft survival.

Financial implications of surgical complications in pediatric liver transplantation.

Surgical complications following pediatric liver transplantation are common and expensive. We examined the incremental costs of surgical complications and determined who pays for these complications (center or payer). We reviewed the records of 36 pediatric liver transplant patients aged

Pre-transplant risk factors for chronic renal dysfunction after pediatric heart transplantation: a 10-year national cohort study.

BACKGROUND: Chronic renal dysfunction may develop after pediatric heart transplantation (PHTx). We examined the incidence of end-stage renal disease (ESRD) and chronic renal insufficiency (CRI) after PHTx, the associated pre-transplant patient characteristics, and impact of renal disease on survival. METHODS: Data sources included the Scientific Registry of Transplant Recipients, Centers for Medicare and Medicaid Services and the Social Security Death Master File. All PHTx recipients (age <18 years) in the USA from 1990 to 1999 who survived >1 year were included. ESRD was defined as long-term dialysis and/or kidney transplant. CRI was defined as creatinine >2.5 mg/dl, including those with ESRD. Relationships between pre-transplant characteristics and time to ESRD and CRI were analyzed using Cox proportional hazards models. The effect of renal disease on survival was analyzed using time-dependent Cox models. RESULTS: During the mean follow-up of 7 years (range 1 to 14 years), 61 of 2,032 (3%) PHTxs developed ESRD. Ten-year actuarial risks for ESRD and CRI were 4.3% and 11.8%, respectively. In a multivariate analysis, significant risk factors for ESRD were: hypertrophic cardiomyopathy; African-American race; intensive care unit (ICU) stay or extracorporeal membrane oxygenation (ECMO) at time of transplant; and pre-transplant diabetes. Risk factors for CRI were: pre-transplant dialysis; hypertrophic cardiomyopathy; African-American race; and previous transplant. Adjusted risk of death in those who developed CRI was 9-fold higher than in those who did not (p < 0.0001). CONCLUSIONS: After PHTx there is an increasing risk for CRI and ESRD over time. Recipients with the characteristics identified in this study may be at greater risk. Development of renal disease significantly increases the risk of post-transplant mortality.