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
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
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)
High Resource Utilization
High Resource Utilization
• 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
Total Number of HospitalizationsChildren with Neurologic Impairment
Year
0
50000
100000
150000
200000
250000
300000
350000
1997 2000 2003
33% increase, p <.01
Year
Hospital Type 1997 2000 2003
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
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
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
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
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
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
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)
Study Design and Timeline
Enrollment Period for Cohort
Pre-
Enroll
men
t
Period
Jan
1997
Oct 20
06
Born
Outcomes
Dec 2
005
Post-
Enroll
men
t
and
F/U
Period
• Retrospective cohort followed for outcomes • Excluded medical management only patients
First Fundo or First GJT
GERDNI
AP Death
Inclusion criteria
Enterprise Data WarehouseIntegrated Reporting and Analysis
A single source for complex data analysis and reporting
EDWEDWFinancial
Data
FinancialData
Clinical Data
Clinical Data
Claims&Eligibility
Claims&Eligibility
Slide Courtesy of Brent James, Intermountain Healthcare
Study GroupsFundoplication
N = 323Gastrojejunal Feeding Tube
N = 43p-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 AP 50 (15%) 9 (21%) 0.36
Tracheostomy 21(7%) 9 (21%) <0.001
Cerebral Spinal Fluid Shunt 38 (12%) 12 (28%) 0.004
Chronic Lung Disease 50 (15%) 7 (16%) 0.89
Seizures 117 (36%) 21 (49%) 0.11
Relative surgical contraindications¶
28 (9%) 12 (28%) <0.001
Complex Chronic Condition
CCC* - Cardiovascular 27 (63%) 139 (43%) 0.014
CCC* – Other congenital or genetic defect
124 (38%) 24 (56%) 0.028
Reason for Neurological Impairment▲
Cerebral Palsy 165 (42%) 20 (47%) 0.55
Brain or Spinal Cord Anomaly 122 (38%) 20 (47%) 0.26
Chromosomal Anomalies 50 (15%) 11 (26%) 0.09
SurvivalFundoplication vs. Gastrojejunal Tube
Aspiration Pneumonia FreeFundoplication vs. Gastrojejunal Tube
Comparative Studies
Fundoplication GJ tube p-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
Objectives
• To examine child and caregiver quality of life for children with NI who received a first fundoplication for treatment of GERD
Eligible: NI or at risk GERD0 – 21 years old
At time of procedure
Screening +
Entry
Fundoplication
Gastrojejunal Feeding Tube
1) Baseline Functional Status – (WeeFIM®)2) Child QoL – PedQL®/CHQ3) Caregiver QoL – PSI/SF364) 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
Study EnrollmentChildren with a
Fundoplication at PCMC Jan 2005 – Feb 2007
N = 236
Eligible Patients with FIRST Fundoplication
N =95
Excluded Patients N = 137
-Procedure Not Done-G Tube Only-No NI Diagnoses -Redo Fundoplication-Spanish speaking-Unknown
Excluded Patients N = 42
-Declined-Unable to Consent-Materials Not Retrieved-DiedStudy Cohort
N = 53Baseline Data
Reason for NI
Genetic Syndrome 34 (57%)
Developmental Delay 29 (48%)
Seizures 20 (33%)
Hypotonia 18 (30%)
Microcephaly 10 (17%)
Cerebral Palsy 10 (17%)
Brain Injury 8 (13%)
Hydrocephalus 7 (12%)
Anoxic Brain injury 6 (10%)
Neurodegenerative Disease 5 (8%)
Brain Abnormality 5 (8%)
Spinal Muscular Atrophy 3 (5%)
Myotonic Dystrophy 2 (3%)
CNS Infection 2 (3%)
Characteristics
VariablesStudy 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 therapy 59 (98%)
6 month OutcomesVariables Study Patients
N = 60
Ongoing Symptoms – vomiting, gagging or aspiration 26 (43%)
ED visits* post-fundoplication 14 children; 18 visits
Admissions* post-fundoplication 15 children; 25 admits
Revision of fundoplication 4 (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
Child HRQoL
Baseline 6 months p-value
General Health 30.2 30.9 0.81
Physical Functioning
19.6 22.3 0.72
Behavior 73.7 83.9 0.03
Parent Time Impact
46.6 57.6 0.09
Family Activities 44.4 54.3 0.15
Bodily Pain
Caregiver Quality of Life
Domain of Quality of Life Study Group
Mean Study Group S.D
U.S. Norm Population Mean
U.S. Norm S.D.
p-value
Physical Functioning 86.74 18.15 84.15 23.28 0.54 Role Physical 84.78 26.60 80.96 34.00 0.43 Bodily Pain 82.92 19.95 75.15 23.69 0.02 General Health 70.19 19.98 71.95 20.34 0.55 Vitality¶ 45.58 19.04 60.86 33.04 0.001 Social Functioning 74.02 26.20 83.28 22.69 0.005 Role Emotional 77.24 28.32 81.26 33.04 0.39 Mental Health 65.58 19.5 1 74.74 18.05 0.001 ¶ Comparisons of study cohort to adults with clinical depression in the domains of Vitality mean score 40 S.D 21.08, p = 0.72.
Caregiver Quality of Life
Domain of Quality of Life Study Group
Mean Study Group S.D
U.S. Norm Population Mean
U.S. Norm S.D.
p-value
Physical Functioning 86.74 18.15 84.15 23.28 0.54 Role Physical 84.78 26.60 80.96 34.00 0.43 Bodily Pain 82.92 19.95 75.15 23.69 0.02 General Health 70.19 19.98 71.95 20.34 0.55 Vitality¶ 45.58 19.04 60.86 33.04 0.001 Social Functioning 74.02 26.20 83.28 22.69 0.005 Role Emotional 77.24 28.32 81.26 33.04 0.39 Mental Health 65.58 19.5 74.74 18.05 0.001 ¶ Comparisons of study cohort to adults with clinical depression in the domains of Vitality mean score 40 S.D 21.08, p = 0.72.
Caregiver Quality of Life
Domain of Quality of Life Study Group
Mean Study Group S.D
U.S. Norm Population Mean
U.S. Norm S.D.
p-value
Physical Functioning 86.74 18.15 84.15 23.28 0.54 Role Physical 84.78 26.60 80.96 34.00 0.43 Bodily Pain 82.92 19.95 75.15 23.69 0.02 General Health 70.19 19.98 71.95 20.34 0.55 Vitality¶ 45.58 19.04 60.86 33.04 0.001 Social Functioning 74.02 26.20 83.28 22.69 0.005 Role Emotional 77.24 28.32 81.26 33.04 0.39 Mental Health 65.58 19.5 1 74.74 18.05 0.001 ¶ Comparisons of study cohort to adults with clinical depression in the domains of Vitality mean score 40 S.D 21.08, p = 0.72.
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)
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
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
Cohort Identification
Birth cohort (2000-2005)N = 955,285
>1 Neuro CodeN = 144,749 (15.2%)
No Neuro CodeN = 810,536 (84.8%)
FundoN = 6,716 (24.3%)
No FundoN = 21,004 (75.7%)
GERDN = 27,720 (19.2%)
No GERDN = 117,029 (80.8%)
Died N = 264 (4.1%)
AliveN = 6,452 (95.9%)
Birth cohort (2000-2005)N = 955,285
>1 Neuro CodeN = 144,749 (15.2%)
No Neuro CodeN = 810,536 (84.8%)
FundoN = 6,716 (24.3%)
No FundoN = 21,004 (75.7%)
GERDN = 27,720 (19.2%)
No GERDN = 117,029 (80.8%)
Died N = 264 (4.1%)
AliveN = 6,452 (95.9%)
Table 3. Unadjusted rates per yearPre Post IRR* p
AP 0.12 (0.1, 0.14) 0.1 (0.08, 0.13) 0.86 (0.76, 0.97) 0.0138GERD 0.75 (0.66, 0.85) 0.67 (0.56, 0.79) 0.9 (0.85, 0.94) <.0001Esophagitis 0.01 (0.01, 0.02) 0 (0, 0.01) 0.29 (0.16, 0.53) <.0001Mechanical Vent 0.35 (0.31, 0.39) 0.27 (0.24, 0.3) 0.73 (0.68, 0.79) <.0001Pneumonia 0.19 (0.17, 0.23) 0.27 (0.24, 0.32) 1.35 (1.25, 1.47) <.0001Asthma 0.16 (0.13, 0.2) 0.25 (0.2, 0.32) 1.58 (1.45, 1.73) <.0001Any RREs 1.63 (1.45, 1.81) 1.63 (1.43, 1.86) 0.98 (0.95, 1.02) 0.3443*Incidence Rate Ratio (Post:Pre)
Table 4. Adjusted IRR using Table 1 covariates.IRR* p
AP 0.72 (0.63, 0.82) <.0001GERD 0.62 (0.59, 0.65) <.0001Esophagitis - -Mechanical Vent 0.42 (0.39, 0.46) <.0001Pneumonia 1.07 (0.98, 1.17) 0.1465Asthma 1.51 (1.37, 1.65) <.0001Any RREs 0.7 (0.68, 0.73) <.0001*Incidence Rate Ratio (Post:Pre)
Median Time to RRH
Next Steps
• Evidence-based best practice care process model for GERD and dysphagia evaluation, medical management and when to refer
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?
Diagnosis of GERD
Child with Neurological Impairment (A) who presents with a
Feeding Concern or Nutritional Aberration (B)
Clinical Evaluation reveals cause other than
GERD or Dysphagia(C)
YES Protocol Does Not Apply
GERD Positive?
Evaluate for Dysphagia (D)Go to Page 2
YES Dysphagia Positive?
YES
NO
NO
Dysphagia Positive?
YES
NO
GERD flow diagram (July 9, 2008) Page 1
1
23
Evaluate for GERD (D)Go to Page 3
(AND)
GERD PositiveDysphagia Positive
Go to Page 4B Box 42
GERD PositiveDysphagia Negative
Go to Page 4A Box 41
GERD NegativeDysphagia Positive
Go to Page 5D Box 58
GERD Negative Dysphagia Negative
Go to Page 5C Box 57
NO
4
5
6 7 8
9
10
11
12
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
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
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
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