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Cramm S.L.,University of Michigan | Waits S.A.,University of Michigan | Englesbe M.J.,University of Michigan | Bucuvalas J.C.,Pediatric Liver Care Center | And 5 more authors.
Transplantation | Year: 2016

Background. Significant intercenter variation exists inmortality and death-censored graft loss (DCGL) after transplantation. Failure to rescue (FTR, death after a major complication) is an emerging tool in quality improvement and may underlie this variation. This study is the first effort to investigate the relationship between FTR and outcomes in transplantation to assess its utility in care improvement. Methods. Using the Studies of Pediatric Liver Transplantation database, we identified 2330 children undergoing primary liver transplants at 21 centers. Centers were ranked by risk-adjusted mortality and sorted into tertiles.We then compared mortality, complications, and FTR across tertiles. Results. Overall mortality was 4.9%, ranging from 1.4%to 8.1%in the low and highmortality tertiles (P < 0.01). The low mortality tertile had significantly lower rates of complications (30.9%vs 38.5%and 40.4%, P < 0.01) as well as FTR (4.6% vs 9.9% and 14.3%, P < 0.01). A similar trend was seen in the DCGL analysis. Conclusions. Our results demonstrate that although centers with higher mortality and DCGL have more frequent major complications, they exhibit 3-fold the rate of FTR. Efforts to standardize perioperative care, and thus minimize FTR, will have value to pediatric liver transplantation recipients. This preliminary study indicates that FTR may provide a useful quality improvement tool for the field of transplantation and warrants further investigation. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Sorensen L.G.,Child and Adolescent Psychiatry | Neighbors K.,Pediatrics | Martz K.,EMMES Corporation | Zelko F.,Child and Adolescent Psychiatry | And 2 more authors.
American Journal of Transplantation | Year: 2011

This multicenter study examined prevalence of cognitive and academic delays in children following liver transplant (LT). One hundred and forty-four patients ages 5-7 and 2 years post-LT were recruited through the SPLIT consortium and administered the Wechsler Preschool and Primary Scale of Intelligence, 3rd Edition (WPPSI-III), the Bracken Basic Concept Scale, Revised (BBCS-R), and the Wide Range Achievement Test, 4th edition (WRAT-4). Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants performed significantly below test norms on intelligence quotient (IQ) and achievement measures (Mean WPPSI-III Full Scale IQ = 94.7 ± 13.5; WRAT-4 Reading = 92.7 ± 17.2; WRAT-4 Math = 93.1 ± 15.4; p < 0001). Twenty-six percent of patients (14% expected) had 'mild to moderate' IQ delays (Full Scale IQ = 71-85) and 4% (2% expected) had 'serious' delays (Full Scale IQ = 70; p < 0.0001). Reading and/or math scores were weaker than IQ in 25%, suggesting learning disability, compared to 7% expected by CDC statistics (p < 0.0001). Executive deficits were noted on the BRIEF, especially by teacher report (Global Executive Composite = 58; p < 0.001). Results suggest a higher prevalence of cognitive and academic delays and learning problems in pediatric LT recipients compared to the normal population. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Sorensen L.G.,Child and Adolescent Psychiatry | Neighbors K.,Pediatrics | Martz K.,EMMES Corporation | Zelko F.,Child and Adolescent Psychiatry | And 2 more authors.
Journal of Pediatrics | Year: 2014

Objective To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. Study design Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤.10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). Results Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P =.0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P <.002), parent education (P <.01), weight z-score at liver transplantation (P <.03), and transfusion volume during liver transplantation (P <.0001) as predictors of FSIQ. Conclusions More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome. © 2014 Elsevier Inc. All rights reserved.

Pescovitz M.D.,Indiana University | Ettenger R.B.,University of California at Los Angeles | Strife C.F.,Medical Center | Sherbotie J.R.,University of Utah | And 6 more authors.
Transplant Infectious Disease | Year: 2010

In an open-label, prospective, pharmacokinetic assessment, we evaluated total drug exposure (area under the curve [AUC]) of intravenous (IV) ganciclovir (GCV) and oral (p.o.) valganciclovir when normalized for body surface area (BSA) in pediatric liver (n=20) and renal (n=26) transplant patients Reference doses for IV GCV (200 mg/m2) and p.o. valganciclovir (520 mg/m 2) were based on adult doses, and adjusted for BSA initially, and BSA and renal function (estimated via creatinine clearance [CrCL]) thereafter. Renal transplant patients received GCV on days 1-2, valganciclovir 260 mg/m 2 on day 3, and valganciclovir 520 mg/m2 on day 4. Liver transplant patients received twice daily GCV from enrollment to day 12, and then valganciclovir twice daily on days 13-14. GCV pharmacokinetics were described using a population pharmacokinetic approach. Type of solid organ transplant (kidney or liver) had no effect on GCV pharmacokinetics. Median GCV exposure following valganciclovir 520 mg/m2 was similar to that with IV GCV, and to that reported in adults. Patients <5 years of age had AUC values approximately 50% of those compared with older age ranges; dosing based on both BSA and CrCL increased drug exposure in younger patients. A dosing algorithm based on BSA and CrCL should be tested in future studies. © 2009 John Wiley & Sons A/S.

Ng V.L.,University of Toronto | Alonso E.M.,Northwestern University | Bucuvalas J.C.,Pediatric Liver Care Center | Cohen G.,EMMES Corporation | And 6 more authors.
Journal of Pediatrics | Year: 2012

Objectives: To determine clinical and health-related quality of life outcomes, and to derive an "ideal" composite profile of children alive 10 years after pediatric liver transplantation (LT) performed in the US and Canada. Study design: This was a multicenter cross-sectional analysis characterizing patients enrolled in the Studies of Pediatric Liver Transplantation database registry who have survived >10 years from LT. Results: A total of 167 10-year survivors were identified, all of whom received daily immunosuppression therapy. Comorbidities associated with the post-LT course included post-transplantation lymphoproliferative disease (in 5% of patients), renal dysfunction (9%), and impaired linear growth (23%). Health-related quality of life, as assessed by the PedsQL 4.0 Generic Core Scales, revealed lower patient self-reported total scale scores for 10-year survivors compared with matched healthy children (77.2 ± 12.9 vs 84.9 ± 11.7; P <.001). At 10 years post-LT, only 32% of patients achieved an ideal profile of a first allograft stable on immunosuppression monotherapy, normal growth, and absence of common immunosuppression-induced sequelae. Conclusion: Success after pediatric LT has moved beyond patient survival. Availability of an ideal composite profile at follow-up provides opportunities for patients, families, and healthcare providers to identify broader sets of outcomes at earlier stages, ultimately contributing to improved outcomes after pediatric LT. © 2012 Mosby Inc.

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