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Clinical Outcomes of Pediatric Intestinal Failure Management After Implementation of a Multidisciplinary Intestinal Rehabilitation Program

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Clinical Outcomes of Pediatric Intestinal Failure Management After Implementation of a Multidisciplinary Intestinal Rehabilitation Program Clinical Outcomes of Pediatric Intestinal Failure Management after Implementation of a Multidisciplinary Intestinal Rehabilitation Program by Carol Oliveira A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Institute of Health Policy, Management and Evaluation University of Toronto © Copyright by Carol Oliveira 2016 Clinical Outcomes of Pediatric Intestinal Failure Management after Implementation of a Multidisciplinary Intestinal Rehabilitation Program Carol Oliveira Doctor of Philosophy Institute of Health Policy, Management and Evaluation University of Toronto 2016 Abstract The objective of this thesis was to evaluate the effect of implementation of a multidisciplinary intestinal rehabilitation program (IRP) on clinical outcomes of pediatric intestinal failure (IF). This was attained by two comprehensive reviews and three related research projects that contribute both clinical and methodological knowledge. Pediatric IF is a complex medical condition. Advances have been made clinically in recent years, but research in the field has suffered from methodological challenges and poor quality. Many of these were outlined and solutions suggested in this thesis. The first project compared clinical outcomes of three eras of pediatric IF-management using univariate categorical and time-to-event analysis. While IRP-introduction led to an increased transplantation rate and improved clinical outcomes, further progress was made and the ii natural course of the disease changed with IRP-maturation and adoption of novel treatment strategies. The second project quantified the continuous change over time of pediatric IF over a 15-year time period and tested systematically introduced treatments using novel methods. Multivariate time series analysis was applied to assess the relationship between new treatment options and change in clinical outcomes. The study showed that IRP-introduction and omega-3 lipid emulsions independently decreased disease-specific mortality from liver failure and sepsis when adjusted for disease severity, while serial transverse enteroplasty and ethanol locks did not impact mortality significantly. With improved mortality of pediatric IF, assessment of morbidity became imperative. After having identified a severe lack in methodology to measure neonatal and infant health-related quality of life (NIHRQOL) in a systematic literature review, the conceptual meaning of NIHRQL was explored in the final project. It concluded that NIHRQOL is a multidimensional, multilayered and interconnected concept, in which the child’s needs are fundamental factors, and the caregiver’s and society’s ability to meet those needs characterize the interdependence between the child and its caregiving environment. In summary, the complexity of pediatric IF and related methodological challenges were identified. Methodological solutions were described and illustrated. Clinical advancements of pediatric IF were quantified, and IRP-introduction and omega-3 lipid emulsions recognized as strongest contributors. Finally, the meaning of NIHRQOL was explored and organized in a conceptual framework in this thesis. iii Acknowledgments I am grateful to a number of people who provided me with support, guidance and encouragement, without which this thesis would not have been possible. My thanks go: To my supervisor, Dr. Paul Wales, for his insight, guidance and mentorship; To my thesis committee, Drs. Ahmed Bayoumi, Wendy Ungar, Jeffrey Hoch and Yaron Avitzur, for their guidance and inspiration; To the surgeons of the Division of General and Thoracic Surgery at the Hospital for Sick Children, Drs. Jacob Langer, Annie Fecteau, Sharifa Himidan, Priscilla Chiu, Georges Azzie, Ted Gerstle, Peter Kim and Agostino Pierro for their support, mentorship and dedication to my academic development; To the Group for Improvement of Intestinal Function and Treatment (GIFT), Karen Steinberg, Christina Kosar, Glenda Courtney-Martin, Alain Rogers, Stephanie So, Catherine Patterson, Dr. Anna Gold, Carina Silva, Megan Carricato, Kathryin Chambers, Andrea Carpenter, Debra Harrison and Jane Darch for their help with any questions and requests I had, and specially to Julia Maxwell, for her assistance with the focus groups. To Nicole de Silva, for her important help and support with my thesis and non-thesis projects; To the administrative staff of the Division of General and Thoracic Surgery at the Hospital for Sick Children, in particular Janice Bowers, Catherine Day, Anne Apong, Jennifer Ionson, Shannon Hannah and Tanya Kovaleva, for all their help with my administrative questions and organizational requests; To Dr. Sanja Stanojevic, for helping me understand time series analysis. To the director of Bioethics at the Hospital for Sick Children, Dr. Randi Zlotnik, for her insight into neonatal and infant quality of life; iv To the director of the library at the Hospital for Sick Children, Elizabeth Uleryk, for her assistance with literature searches; To the program director of the Division of General Surgery at the University of Toronto, Dr. Najma Ahmed, for her invaluable support; To the surgeons of the Department of Pediatric Surgery at the University Children’s Hospital Zurich, Switzerland, in particular Drs. Martin Meuli and Clemens Schiestl, who supported my wish to pursue graduate studies at the University of Toronto, committed to my academic endeavors and provided me with mentorship; To the Child Health Evaluative Sciences (CHES) Program at the Hospital for Sick Children, for providing a nurturing environment that cultivates academic productivity and success; To the Institute of Health Policy, Management and Evaluation (IHPME), in particular past and present program directors, Drs. Ahmed Bayoumi, Sharon Dell and Robert Fowler, and program coordinators, Amber Gertzbein and Jennifer James, for their guidance and administrative support throughout my PhD studies; To the Swiss National Science Foundation, the Stiefel-Zangger Foundation and the Walter and Gertrud Siegenthaler Foundation of the University of Zurich, and the Research Training Center at the Hospital For Sick Children for their financial support; And finally to my family and friends, for their continuous support and encouragement, without which I could not have attained this achievement. v Table of Contents Abstract ................................................................................................................................ ii Acknowledgments ............................................................................................................... iv Table of Contents ............................................................................................................... vi List of Tables ..................................................................................................................... xiii List of Figures ................................................................................................................... xiv List of Appendices ............................................................................................................. xv List of Abbreviations ........................................................................................................ xvi Thesis Overview ................................................................................................................ xxi Chapter 1 .............................................................................................................................. 1 1 Overview of Pediatric Intestinal Failure ..................................................................... 1 1.1 Definition .................................................................................................................. 1 1.2 History ...................................................................................................................... 1 1.3 Epidemiology ............................................................................................................ 4 1.4 Etiology ..................................................................................................................... 5 1.5 Pathophysiology ....................................................................................................... 6 1.5.1 Jejunal Resection ............................................................................................... 6 1.5.2 Ileal Resection ................................................................................................... 7 1.5.3 Colonic Resection .............................................................................................. 9 1.5.4 Adaptation .......................................................................................................... 9 1.6 Clinical Management .............................................................................................. 11 1.6.1 Multidisciplinary Intestinal Rehabilitation ...................................................... 11 1.6.2 Medical Management ...................................................................................... 12 1.6.2.1 Parenteral Nutrition .................................................................................... 12 1.6.2.2 Enteral Nutrition ........................................................................................ 15 vi 1.6.2.3 Hormone Therapy ...................................................................................... 16 1.6.2.4 Other Medication Frequently Used ...........................................................
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