Transcript Objective - The Children's Hospital of Philadelphia

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 Hospitalizations
Children with Neurologic Impairment
33% increase, p <.01
350000
300000
250000
200000
150000
100000
50000
0
1997
2000
Year
2003
Percentage of All Hospitalizations
Children with Neurologic Impairment
Hospital Type
1997
Year
2000
All Hospitals*
3.9%
4.6%
5.1%
Children’s Hospitals*
9.0%
11.9%
12.6%
*p < 0.01
2003
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 longterm 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
Outcomes
Inclusion
criteria
Born
NI
GERD
First Fundo or First GJT
AP Death
• Retrospective cohort followed for outcomes
• Excluded medical management only patients
Enterprise Data Warehouse
Integrated Reporting and Analysis
EDW
Financial
Data
Claims&
Eligibility
A single source for
complex data analysis
and reporting
Clinical
Data
Slide Courtesy of Brent James, Intermountain Healthcare
Study Groups
Fundoplication
N = 323
Gastrojejunal Feeding Tube
N = 43
p-value
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
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
28 (9%)
12 (28%)
<0.001
Age at time of procedure
(mean)
Tracheostomy
Relative surgical
contraindications¶
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
Survival
Fundoplication vs. Gastrojejunal Tube
Aspiration Pneumonia Free
Fundoplication vs. Gastrojejunal Tube
Comparative Studies
Fundoplication
GJ tube
p-value
Albanese et al
1993 (n =112)
Mortality 4 (8.8%)
Mortality 2 (5.9%)
Nonsignificant
Wales et al
2001 (n =111)
Mortality 11 (17.5%)
AP
23 (36.5%)
Mortality 6 (12.5%) NonAP
15 (31.3%) significant
Srivastava et al
in press (n=366)
Mortality 40 (12%)
AP
48 (15%)
Mortality 9 (21%)
AP
7 (16%)
Nonsignificant
Objectives
• To examine child and caregiver quality of life for
children with NI who received a first fundoplication
for treatment of GERD
Prospective Study
Eligible:
 NI or at risk
 GERD
0 – 21 years
old
At time of
procedure
Fundoplication
1 month
post
procedure
6 month
post
procedure
Screening
+
Entry
Gastrojejunal
Feeding Tube
1) Baseline Functional
Status – (WeeFIM®)
2) Child QoL –
PedQL®/CHQ
3) Caregiver QoL –
PSI/SF36
4) Nutrition Outcomes
Repeat all
assessments
Repeat all
assessments
Primary Outcome = Child QoL,
Caregiver QoL (1 year postprocedure)
Secondary Outcome = Nutrition,
Mortality, Adverse Events, Costs,
Long-Term Outcomes
Study Enrollment
Children with a
Fundoplication at PCMC
Jan 2005 – Feb 2007
N = 236
Eligible Patients with
FIRST Fundoplication
N =95
Study Cohort
N = 53
Baseline Data
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
-Died
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
Variables
Age (years)
Complete Dependence on mobility, communication and
self-care
Study Patients
N = 60
2.2
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 Outcomes
Variables
Ongoing Symptoms – vomiting, gagging or aspiration
ED visits* post-fundoplication
Admissions* post-fundoplication
Revision of fundoplication
Weight (increase)
Weight for z score (increase)
Death – none related to complication of surgery
Study Patients
N = 60
26 (43%)
14 children; 18 visits
15 children; 25 admits
4 (6.7%)
1.8 kg
-2.15 to -1.44, p <0.001
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
Physical Functioning
Role Physical
Bodily Pain
General Health
Vitality¶
Social Functioning
Role Emotional
Mental Health
Study Group
Mean
86.74
84.78
82.92
70.19
45.58
74.02
77.24
65.58
Study Group
S.D
18.15
26.60
19.95
19.98
19.04
26.20
28.32
19.5
1
U.S. Norm
Population Mean
84.15
80.96
75.15
71.95
60.86
83.28
81.26
74.74
U.S. Norm
S.D.
23.28
34.00
23.69
20.34
33.04
22.69
33.04
18.05
p-value
0.54
0.43
0.02
0.55
0.001
0.005
0.39
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
Physical Functioning
Role Physical
Bodily Pain
General Health
Vitality¶
Social Functioning
Role Emotional
Mental Health
Study Group
Mean
86.74
84.78
82.92
70.19
45.58
74.02
77.24
65.58
Study Group
S.D
18.15
26.60
19.95
19.98
19.04
26.20
28.32
19.5
U.S. Norm
Population Mean
84.15
80.96
75.15
71.95
60.86
83.28
81.26
74.74
U.S. Norm
S.D.
23.28
34.00
23.69
20.34
33.04
22.69
33.04
18.05
p-value
0.54
0.43
0.02
0.55
0.001
0.005
0.39
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
Physical Functioning
Role Physical
Bodily Pain
General Health
Vitality¶
Social Functioning
Role Emotional
Mental Health
Study Group
Mean
86.74
84.78
82.92
70.19
45.58
74.02
77.24
65.58
Study Group
S.D
18.15
26.60
19.95
19.98
19.04
26.20
28.32
19.5
1
U.S. Norm
Population Mean
84.15
80.96
75.15
71.95
60.86
83.28
81.26
74.74
U.S. Norm
S.D.
23.28
34.00
23.69
20.34
33.04
22.69
33.04
18.05
p-value
0.54
0.43
0.02
0.55
0.001
0.005
0.39
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 Code
N = 144,749 (15.2%)
GERD
N = 27,720 (19.2%)
Fundo
N = 6,716 (24.3%)
Died
N = 264 (4.1%)
Alive
N = 6,452 (95.9%)
No Neuro Code
N = 810,536 (84.8%)
No GERD
N = 117,029 (80.8%)
No Fundo
N = 21,004 (75.7%)
Table 3. Unadjusted rates per year
AP
GERD
Esophagitis
Mechanical Vent
Pneumonia
Asthma
Any RREs
*Incidence Rate Ratio (Post:Pre)
Pre
0.12 (0.1, 0.14)
0.75 (0.66, 0.85)
0.01 (0.01, 0.02)
0.35 (0.31, 0.39)
0.19 (0.17, 0.23)
0.16 (0.13, 0.2)
1.63 (1.45, 1.81)
Post
0.1 (0.08, 0.13)
0.67 (0.56, 0.79)
0 (0, 0.01)
0.27 (0.24, 0.3)
0.27 (0.24, 0.32)
0.25 (0.2, 0.32)
1.63 (1.43, 1.86)
IRR*
0.86 (0.76, 0.97)
0.9 (0.85, 0.94)
0.29 (0.16, 0.53)
0.73 (0.68, 0.79)
1.35 (1.25, 1.47)
1.58 (1.45, 1.73)
0.98 (0.95, 1.02)
p
0.0138
<.0001
<.0001
<.0001
<.0001
<.0001
0.3443
Table 4. Adjusted IRR using Table 1 covariates.
IRR*
AP
0.72 (0.63, 0.82)
GERD
0.62 (0.59, 0.65)
Esophagitis
Mechanical Vent
0.42 (0.39, 0.46)
Pneumonia
1.07 (0.98, 1.17)
Asthma
1.51 (1.37, 1.65)
Any RREs
0.7 (0.68, 0.73)
*Incidence Rate Ratio (Post:Pre)
p
<.0001
<.0001
<.0001
0.1465
<.0001
<.0001
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
GERD flow diagram (July 9, 2008)
Page 1
1
Child with Neurological Impairment (A)
who presents with a
Feeding Concern or Nutritional Aberration (B)
2
3
Clinical Evaluation
reveals cause other than
GERD or Dysphagia
(C)
YES
Protocol Does Not Apply
NO
4
Evaluate for Dysphagia (D)
Go to Page 2
(AND)
5
Evaluate for GERD (D)
Go to Page 3
6
8
7
GERD Positive?
YES
Dysphagia
Positive?
NO
9
GERD Positive
Dysphagia Negative
Go to Page 4A Box 41
NO
10
11
Dysphagia
Positive?
12
NO
GERD Negative
Dysphagia Negative
Go to Page 5C Box 57
YES
GERD Negative
Dysphagia Positive
Go to Page 5D Box 58
YES
GERD Positive
Dysphagia Positive
Go to Page 4B Box 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
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