1. Gastroesophageal Reflux Disease in Children with Neurological Impairment Raj Srivastava, MD, FRCP(C), MPH Center for Pediatric Clinical Effectiveness, Children’s Hospital of Philadelphia, Dec 5th, 2008

2. Overview Children with neurologic impairment –Why this population? –High resource utilization Nutritional and respiratory conditions Current Studies Future Steps –Care process model –Multi-center studies

3. Why This Population? Children with NI are living longer and use increasing resources of the health care system NI results from many different conditions but they share several common clinical issues (e.g. nutritional and respiratory conditions) Lack of sufficient evidence base due to small numbers Idiosyncratic practices within institutions Lack of a clear medical group that studies outcomes in this population Opportunity for further study (generalists and specialists, multidisciplinary)

4. High Resource Utilization

5. Agency for Healthcare Research Quality –Kid’s Inpatient Database –1997, 2000, 2003 National estimates of hospitalizations –Children ages 0-18 years –Clustered, stratified, weighted sample 2.9 million hospital discharges 3,400 hospitals 38 states

6. Total Number of Hospitalizations Children with Neurologic Impairment Year 33% increase, p <.01

7. Year Hospital Type199720002003 All Hospitals* 3.9% 4.6%5.1% Children’s Hospitals* 9.0% 11.9% 12.6% Percentage of All Hospitalizations Children with Neurologic Impairment *p < 0.01

8. Nutritional and Respiratory Conditions Children with neurological impairment (NI) and severe functional limitations have dysfunctional swallowing and gastroesophageal reflux disease (GERD) placing them at risk for aspiration pneumonia (AP) AP leads to repeated hospitalization, respiratory failure, compromised quality of life, and death. Initial GERD management consists of medications

9. Nutritional and Respiratory Conditions Some children with NI and GERD fail medical management There are competing management approaches for treating the GERD in order to prevent AP and subsequent respiratory failure Few published studies comparing treatment efficacy and quality of life outcomes with long- term follow-up for treating these conditions in this population

10. Fundoplication Fundoplication is an anti-reflux procedure used to treat GERD in children who have failed medical management. Fundoplication is the third most common procedure performed by pediatric surgeons in the U.S. Half of these procedures are performed on children with NI

11. Gastrojejunal feeding tubes GJ tubes are an anti-reflux procedure used to treat GERD in children who have failed medical management. GJ tubes are frequently used in children with NI

12. Background and Rationale Multi-center randomized control trial (RCT) is the best approach to answering questions about GERD management in this population: –Equipoise –Outcomes –Sufficient number of patients –Expertise to conduct study

13. Clinical Question In children with neurodevelopmental disabilities who have GERD and have failed medical management, what is the next best management option? –Compare time to develop AP and survival –Treatment with first fundoplication compared to first gastrojejunal feeding tube (change from gastrostomy to GJ feeding tube in radiology)

14. Study Design and Timeline Enrollment Period for Cohort Pre- Enrollment Period Jan 1997 Oct 2006 Born Outcomes Dec 2005 Post- Enrollment and F/U Period Retrospective cohort followed for outcomes Excluded medical management only patients First Fundo or First GJT GERD NI AP Death Inclusion criteria

15. Enterprise Data Warehouse Integrated Reporting and Analysis A single source for complex data analysis and reporting EDW Financial Data Financial Data Clinical Data Clinical Data Claims& Eligibility Claims& Eligibility Slide Courtesy of Brent James, Intermountain Healthcare

16. Study Groups Fundoplication N = 323 Gastrojejunal Feeding Tube N = 43 p-value Age at time of procedure (mean) 16 months (S.D. 16 months) 24 months (S.D. 20 months) 0.008 Gender (female)146 (45%)13 (30%)0.07 Previous AP50 (15%)9 (21%)0.36 Tracheostomy21(7%)9 (21%)<0.001 Cerebral Spinal Fluid Shunt38 (12%)12 (28%)0.004 Chronic Lung Disease50 (15%)7 (16%)0.89 Seizures117 (36%)21 (49%)0.11 Relative surgical contraindications¶ 28 (9%)12 (28%)<0.001 Complex Chronic Condition CCC* - Cardiovascular27 (63%)139 (43%)0.014 CCC* – Other congenital or genetic defect 124 (38%)24 (56%)0.028 Reason for Neurological Impairment▲ Cerebral Palsy165 (42%)20 (47%)0.55 Brain or Spinal Cord Anomaly122 (38%)20 (47%)0.26 Chromosomal Anomalies50 (15%)11 (26%)0.09

17. Survival Fundoplication vs. Gastrojejunal Tube

18. Aspiration Pneumonia Free Fundoplication vs. Gastrojejunal Tube

19. Comparative Studies FundoplicationGJ tubep-value Albanese et al 1993 (n =112) Mortality 4 (8.8%)Mortality 2 (5.9%)Non- significant Wales et al 2001 (n =111) Mortality 11 (17.5%) AP 23 (36.5%) Mortality 6 (12.5%) AP 15 (31.3%) Non- significant Srivastava et al in press (n=366) Mortality 40 (12%) AP 48 (15%) Mortality 9 (21%) AP 7 (16%) Non- significant

20. Objectives To examine child and caregiver quality of life for children with NI who received a first fundoplication for treatment of GERD

21. Eligible:  NI or at risk  GERD  0 – 21 years old  At time of procedure Screening + Entry Fundoplication Gastrojejunal Feeding Tube 1) Baseline Functional Status – (WeeFIM®) 2) Child QoL – PedQL®/CHQ 3) Caregiver QoL – PSI/SF36 4) Nutrition Outcomes Repeat all assessments Primary Outcome = Child QoL, Caregiver QoL (1 year post- procedure) Secondary Outcome = Nutrition, Mortality, Adverse Events, Costs, Long-Term Outcomes 1 month post procedure 6 month post procedure Repeat all assessments Prospective Study

22. Study Enrollment

23. Reason for NI Genetic Syndrome34 (57%) Developmental Delay29 (48%) Seizures20 (33%) Hypotonia18 (30%) Microcephaly 10 (17%) Cerebral Palsy10 (17%) Brain Injury8 (13%) Hydrocephalus7 (12%) Anoxic Brain injury6 (10%) Neurodegenerative Disease5 (8%) Brain Abnormality5 (8%) Spinal Muscular Atrophy3 (5%) Myotonic Dystrophy2 (3%) CNS Infection2 (3%)

24. Characteristics Variables Study Patients N = 60 Age (years)2.2 Complete Dependence on mobility, communication and self-care 54 (90%) Indications for Fundoplication Vomiting 32 (52%) Feeding related 32 (52%) Failure to thrive 25 (42%) Failure of medical therapy59 (98%)

25. 6 month Outcomes VariablesStudy Patients N = 60 Ongoing Symptoms – vomiting, gagging or aspiration26 (43%) ED visits* post-fundoplication14 children; 18 visits Admissions* post-fundoplication15 children; 25 admits Revision of fundoplication4 (6.7%) Weight (increase)1.8 kg Weight for z score (increase)-2.15 to -1.44, p <0.001 Death – none related to complication of surgery 5 (8%) *Visits related to a complication, the gastrostomy tube, AP or GERD symptoms

26. Child HRQoL Baseline6 monthsp-value General Health30.230.90.81 Physical Functioning 19.622.30.72 Behavior73.783.90.03 Parent Time Impact 46.657.60.09 Family Activities44.454.30.15

27. Bodily Pain

28. Caregiver Quality of Life

31. Total Stress remains high during study period Significantly higher stress than parental norms 1 in 3 parents expressed clinically significant levels of stress (scores > 90, 90th percentile)

32. Caregiver Quality of Life Total Stress remains high during study period Significantly higher stress than parental norms 1 in 3 parents expressed clinically significant levels of stress (scores > 90, 90th percentile) 1 in 3 parents of children with TBI, 1 in 5 parents of children with CHD

33. Goals of Caregivers Symptom Reduction –Stop vomiting –Decrease gagging –No more aspiration Nutrition –Gain weight –Eat by mouth Medical –Stay healthy –Keep out of hospital

34. Cohort Identification

37. Median Time to RRH

38. Next Steps Evidence-based best practice care process model for GERD and dysphagia evaluation, medical management and when to refer

39. Medical Management n=60 all with NI who received a Fundoplication Various medications had been tried and were considered to have failed in these patients –39% had been treated with acid suppressive agents –80% with acid blocking agents –61% with prokinetic agents Duration? Dose? Impact on Symptoms?

40. Diagnosis of GERD

42. Next Steps R03 for Oct 2009 – Two hospital study –Pilot data for GJ tubes –Equipoise –Two hospitals (feasibility of multi-center study) Pilot study –Using evidence-based best practices guideline

44. Next Steps R01 for June 2009 – Multi-center study –Which first procedure? –Feasibility and Inclusion criteria –Outcomes –Number of sites, patients, power –DCC –Protocol –Investigator Meeting or at APSA/other meetings

45. Acknowledgements Child Health Research Center, Primary Children’s Medical Center Foundation Eunice Kennedy Shriver National Institute for Child Health and Human Development K23 HD 052553

46. Future Steps Prospective, multidisciplinary Specifically defined patient population Clear cut diagnostic criteria for GERD Uniform implementation of medical therapy Stringent documentation throughout the course of diagnosis and therapy with objective data Feedback to providers regarding outcomes of children Study comparing surgical therapies: fundoplication/GT vs GJ tube placement