title: Change of Outcomes in Pediatric Intestinal Failure: Use of Time-Series Analysis to Assess the Evolution of an Intestinal Rehabilitation Program.
abstract: The clinical picture of pediatric intestinal failure has changed over the past 15 years, while effectiveness evolving treatment options remains unclear. This study explored evolution in care and quantified independent effects of new treatment options.
  
  
  
  Consecutive patients (n = 196) with neonatal or infantile intestinal failure, born between July 1996 and December 2011, were derived from an intestinal rehabilitation program (IRP) patient registry. Change over time was analyzed using multivariable Box-Jenkins method-based autoregressive integrative moving average models (ARIMA), robust linear regression, and nonparametric trend analysis. Four systematically introduced treatment options (IRP, serial transverse enteroplasty, omega-3 lipid emulsions, and ethanol locks) were evaluated. Analyses were adjusted for patient characteristics and disease severity. The primary outcome was disease-specific mortality from liver failure and sepsis. Secondary outcomes included parenteral nutrition weaning, transplantations, catheter complications, and liver disease.
  
  
  
  Patient characteristics remained unchanged over time, except for decreasing small bowel length (-0.5%/quarter; 95% CI -0.85, -0.16) and ICU admission time (-0.6 days/quarter; 95% CI -1.03, -0.18). Disease-specific mortality diminished significantly over time (-0.02 deaths/quarter; 95% CI -0.03, -0.01) by IRP and omega-3 lipids introduction (-0.6 deaths/quarter each, 95% CI -1.23, -0.02 and -0.77, -0.45, respectively). Serial transverse enteroplasty and ethanol locks had no significant impact. Parenteral nutrition weaning and transplantations remained unchanged, while catheter sepsis and complication rates decreased by 0.3 episodes/1,000 catheter-days each (95% CI -0.43, -0.2 and -0.45, -0.24, respectively).
  
  
  
  Introduction of IRP and omega-3 lipids independently decreased disease-specific mortality. For the first time, time series analysis was applied to evaluate effectiveness of treatment options in intestinal rehabilitation.
authors.affiliation: Group for Improvement of Intestinal Function and Treatment Program (GIFT), The Hospital for Sick Children, Toronto, Canada; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Canada; Child Health Evaluative Sciences (CHES) Program, The Hospital for Sick Children, Toronto, Canada; The Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Oliveira
authors.affiliation: Group for Improvement of Intestinal Function and Treatment Program (GIFT), The Hospital for Sick Children, Toronto, Canada; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Nicole T
authors.initials: NT
authors.lastname: de Silva
authors.affiliation: Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Canada; Child Health Evaluative Sciences (CHES) Program, The Hospital for Sick Children, Toronto, Canada; The Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stanojevic
authors.affiliation: Group for Improvement of Intestinal Function and Treatment Program (GIFT), The Hospital for Sick Children, Toronto, Canada; Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Avitzur
authors.affiliation: The Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada; Centre for Research on Inner City Health, Li Ka Shing Knowledge Institute and Division of General Internal Medicine, St Michael's Hospital, Toronto, Canada.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Bayoumi
authors.affiliation: Child Health Evaluative Sciences (CHES) Program, The Hospital for Sick Children, Toronto, Canada; The Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada.
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Ungar
authors.affiliation: The Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada; Centre for Excellence in Economic Analysis Research (CLEAR), St Michael's Hospital, Toronto, Canada.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hoch
authors.affiliation: Group for Improvement of Intestinal Function and Treatment Program (GIFT), The Hospital for Sick Children, Toronto, Canada; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Canada; Child Health Evaluative Sciences (CHES) Program, The Hospital for Sick Children, Toronto, Canada; The Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, Canada. Electronic address: paul.wales@sickkids.ca.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wales
mesh_terms: D003131:Combined Modality Therapy; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012778:Short Bowel Syndrome / Q000401:mortality / Q000534:rehabilitation*; D016896:Treatment Outcome
chemical_list: D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3