Yu-Chun Chen, Jau-Ching Wu, Laura Liu, Tzeng-Ji Chen, Wen-Cheng Huang... Henrich Cheng ; originally published online June 20, 2011;

Transcription

Yu-Chun Chen, Jau-Ching Wu, Laura Liu, Tzeng-Ji Chen, Wen-Cheng Huang... Henrich Cheng ; originally published online June 20, 2011;
Correlation Between Ventriculoperitoneal Shunts and Inguinal Hernias in
Children: An 8-Year Follow-up
Yu-Chun Chen, Jau-Ching Wu, Laura Liu, Tzeng-Ji Chen, Wen-Cheng Huang and
Henrich Cheng
Pediatrics 2011;128;e121; originally published online June 20, 2011;
DOI: 10.1542/peds.2010-3906
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/128/1/e121.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Downloaded from pediatrics.aappublications.org by guest on August 22, 2014
ARTICLES
Correlation Between Ventriculoperitoneal Shunts and
Inguinal Hernias in Children: An 8-Year Follow-up
AUTHORS: Yu-Chun Chen, MD, MSc,a Jau-Ching Wu,
MD,b,c,d Laura Liu, MD,e Tzeng-Ji Chen, MD, PhD,f,g
Wen-Cheng Huang, MD, PhD,b,c and Henrich Cheng, MD,
PhDb,c,d
aInstitute for Medical Biometry and Informatics, Heidelberg
University, Heidelberg, Germany; bDepartment of Neurosurgery,
Neurological Institute, Taipei Veterans General Hospital, Taipei,
Taiwan; cSchool of Medicine, National Yang-Ming University,
Taipei, Taiwan; dInstitute of Pharmacology, National Yang-Ming
University, Taipei, Taiwan; eDepartment of Ophthalmology,
Chang-Gung Memorial Hospital, and College of Medicine, ChangGung University, Taoyuan, Taiwan; fInstitute of Hospital and
Health Care Administration, School of Medicine, National YangMing University, Taipei, Taiwan; and gDepartment of Family
Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
WHAT’S KNOWN ON THIS SUBJECT: In the entire English
literature, only 3 studies have associated ventriculoperitoneal
shunt in children with higher incidence of inguinal hernia. The 3
studies were institutional based, so the true incidence and
association between a ventriculoperitoneal shunt and
subsequent inguinal hernia remain unclear.
WHAT THIS STUDY ADDS: This study used a nationwide
longitudinal cohort, the National Health Insurance Research
Database, which contains data on ⬎1.5 million preschool-aged
children across institutions for both hernia surgery and
ventriculoperitoneal shunts in children to determine their
association.
KEY WORDS
ventriculoperitoneal shunt, inguinal hernia, incidence
ABBREVIATIONS
CNS—central nervous system
CSF—cerebrospinal fluid
VPS—ventriculoperitoneal shunt
IH—inguinal hernia
ICD-9—International Classification of Disease, Ninth Revision
HR—hazard ratio
abstract
OBJECTIVE: The goal of this study was to investigate the correlation
between ventriculoperitoneal shunts (VPSs) and inguinal hernias (IHs)
in children.
Drs Chen and Wu provided the conception and design,
acquisition of data, analysis and interpretation of data, and
drafting and revision of the article; Dr Liu performed the
interpretation of data and drafting and revision of the article; Dr
Chen conducted the acquisition and analysis of data; Dr Huang
conducted the acquisition and interpretation of data; and Dr
Cheng performed the acquisition of data. All authors provided
final approval on the manuscript that was submitted.
METHODS: Study subjects were identified from a nationwide cohort of
1 537 843 children aged 0 to 5 years from 1996 to 2000. They were
assigned to the VPS group (n ⫽ 675), who received VPS, or a control
group (n ⫽ 6704) of age- and gender-matched children. Both groups
(N ⫽ 7379) were followed up for 8 years for IH. Kaplan-Meier and Cox
regression analyses were performed.
The views in this article are those of the authors. The
interpretation and conclusions contained herein do not
represent those of the Bureau of National Health Insurance, the
Department of Health, or National Health Research Institutes.
RESULTS: After the 8-year follow-up, 353 of the 7379 study subjects (78
from the VPS group and 275 from the control group) underwent IH
surgery. The 8-year cumulative incidence rate of IH-repair surgery was
13.3% in the VPS group, significantly higher than that in the control
group (4.1%; P ⬍ .001). Children in the VPS group were more likely to
develop IH than the control group (hazard ratio: 3.62; P ⬍ .001), even
after adjusting for age, gender, and comorbidities (adjusted hazard
ratio: 6.63; P ⬍ .001). The average time interval between VPS and IH
surgery was 1.73 years earlier in the VPS group than those in the
control group (1.29 vs 3.02 years; P ⬍ .001).
www.pediatrics.org/cgi/doi/10.1542/peds.2010-3906
doi:10.1542/peds.2010-3906
Accepted for publication Mar 18, 2011
Address correspondence to Jau-Ching Wu, MD, Department of
Neurosurgery, Neurological Institute, Taipei Veterans General
Hospital, Room 509, 17F, No 201, Shih-Pai Road, Sec 2, Beitou,
Taipei 11217, Taiwan. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2011 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
PEDIATRICS Volume 128, Number 1, July 2011
CONCLUSIONS: Children who received a VPS when younger than 5
years were more likely to have IH; the highest risk was during the first
2 years after VPS surgery. A high index of suspicion for inguinal manifestations is recommended during their follow-up. Pediatrics 2011;128:
e121–e126
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e121
Hydrocephalus is a common disease in
pediatric neurosurgery. It can be associated with various diseases of the
central nervous system (CNS), including hemorrhage, infection, congenital
malformations, spinal dysraphism,
and neoplasm. Despite its diverse
etiology, hydrocephalus shares a common pathology of a mismatched production and absorption of cerebrospinal fluid (CSF). Thus, the treatments of
choice are CSF diversion shunts, such
as an internal shunt; endoscopic third
ventriculostomy; or an external shunt
(ventriculoperitoneal shunt [VPS]). In
the past decades, there has been tremendous effort to lower the complication rate and extend the survival of
these shunts.1,2 Currently, a VPS is the
most widely used.
Little attention is given to the extracranial complications of VPS insertion in
children.3 There are case reports implying the association between a VPS
and inguinal complications, such as
hernia, hydrocele, catheter migrations
into the scrotum, and implantation of
glial cells in the hernial sac.4–11 These
inguinal complications after VPS surgery are assumed to be related to increased intraabdominal pressure
caused by the diverted CSF during the
progress of closure of the processus
vaginalis in early childhood.12–14 In the
entire English literature, only 3 studies
have associated VPS placement in children with a higher incidence of inguinal hernia (IH).14–16 However, these previous reports use institution-based
data and are of relatively small numbers. Therefore, the true incidence and
association between VPS surgery and
subsequent IH remain unclear.
To ascertain the correlation between
IH and VPS surgery in children, a high
follow-up rate and a relatively large
number of children who underwent
VPS insertion are both necessary. The
National Health Insurance Research
Database, provided by the National
e122
CHEN et al
Health Research Institutes of Taiwan,
is a national database containing 26
million administered insurants accumulated from January 1996 to December 2008. It covers almost the entire
country, or ⬎99% of the population.
This study used a nationwide longitudinal cohort, the National Health Insurance Research Database, which
uniquely provides an investigation
across institutions for both IH and VPS
surgery in children to determine their
association.
METHODS
Data Source
After the deidentification and encryption processes, the National Health Research Institutes recompiled medical
claims and made them publically available for researchers in Taiwan. To protect privacy, individual and hospital
identifiers were unique to the research database and could not be
used to trace each individual patient
or health service provider. This study
was exempted from full institutional
review board review because of the deidentified feature of the National
Health Insurance Research Database.
The Bureau of National Health Insurance performed cross-checking and
validation on medical charts and
claims to ensure the accuracy of diagnosis coding of the National Health Insurance Research Database.
Study Cohort
The flow of data processing in this retrospective cohort is summarized in Fig
1. During the 5-year enrollment period
(January 1, 1996, to December 31,
2000), 1 537 843 children born were
entered as the study cohort of
preschool-aged (0- to 5-year-old)
children.
Identification of the VPS and
Control Groups
From the study cohort, patients hospitalized with a discharge summary of
first-time containing the International
Classification of Disease, Ninth Revision (ICD-9) procedure code of VPS
(02.34) during the enrollment period
were identified as patients with a
newly inserted VPS (n ⫽ 696) during
the specific admission.
The date of the VPS surgery was designated as the first date of each patient’s
Preschool-aged cohort: population born
between 1/1/1996 to 12/31/2000
(N = 1 537 843)
Systematic sampling
Preschool-aged cohort received VPS
procedure during 1/1/1996 to 12/31/2000
(n = 696)
Sampled preschool-aged cohort
unexposed to VPS procedure
(n = 63 330)
Age and gender matching (1:10)
Exclude: (n = 21)
Any hernia repair before
VPS procedure
Age- and gender-matched
controls (n = 6750)
Exclude: (n = 46)
Any hernia repair before
index date
VPS group (n = 675)
Comparison group (n = 6704)
FIGURE 1
Processing flow of the cohort.
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ARTICLES
specific hospitalization. IH-repair surgery was determined by the outpatient
or hospitalization records with procedure codes of IH repair (ICD-9 procedure code 53.0 –1). The 21 patients who
received any hernia repair surgery
(ICD-9 53.X) before their VPS events
were excluded. Therefore, the VPS
group comprised 675 children
younger than 5 years old who received
a VPS (n ⫽ 675).
A comparison control group was randomly extracted from the remainder of
the original cohort. This group comprised 1 to 10 age-and gendermatched controls for every patient in
the VPS group. An index date was designated as its matched case’s VPS surgery date. After excluding patients who
received IH-repair surgery before their
index date (n ⫽ 46), the control group
had 6704 age- and gender-matched
children (Fig 1).
Determination of IH Surgery and
Covariates
All patients in both groups were
followed-up for 8 years. IH surgery was
determined by the outpatient or hospitalization records. Comorbidities, including hereditary diseases of the CNS
(ICD-9 330 –331, 332.0, 333–337, and
340), congenital anomalies of the nervous system (ICD-9 740.0 –2, 741.00 –3,
741.90 –3, 742.0 – 4, 742.51, 742.53,
742.59, and 742.8 –9), intracranial injury (800 – 804 and 850 – 854), malignant neoplasm of the brain and other
nervous system (ICD-9 191–192), cerebrovascular diseases (ICD-9 430 – 438),
CNS infections (ICD-9 003.21, 036.0 –1,
045– 049, 052.0, 053.0, 054.3, 054.72,
055.0, 056.01, 062– 064, 066.2, 072.1–2,
100.81, 112.83, 114.2, 115.01, 115.11,
115.91, 130.0, 138, 139.0, 320 –324, 326,
and V12.02), and disorders related to
short gestation, low birth weight, and
fetal malnutrition (ICD-9 764.0 –2,
764.9, 765.0 –2, and V21.30 –5) were obtained from discharge codes of hospiPEDIATRICS Volume 128, Number 1, July 2011
tal records from birth date to date of IH
repair or the end of follow-up.
Statistical Analysis
All the data were linked by using SQL
server 2008 (Microsoft Corp, Redmond, WA) and analyzed by using SPSS
software (SPSS Inc, Chicago, IL). ␹2 and
independent t tests were used to assess differences in age, gender, and
comorbidities between the VPS and
control groups. The Kaplan-Meier
method and log-rank test were used to
estimate and compare the 8-year incidence rates of IH-repair surgery after
VPS. The Cox proportional hazard model
was used to compare the incidence rate
of IH-repair surgery between the groups
after adjustment for the covariates. A
2-tailed level of .05 was considered statistically significant.
RESULTS
The mean (SD) age of the VPS group
(index date) was 6.37 (8.33) months. A
total of 353 children received IH surgery at the mean age of 3.1 (2.2) years.
Among them, 78 were from the VPS
group and 275 were from the control
group. By proportion, 11.6% of children in the VPS group and 4.1% of
those in the control group received IH
surgery during follow-up. The mean
time interval between the VPS date (index date) and the IH surgery was 2.63
(2.11) years.
Comparison of Comorbidities
Children in the VPS group had significantly more comorbidities than the
control group, including hereditary
diseases of the CNS, congenital anomalies of the nervous system, intracranial injury, malignant neoplasm of the
brain and other nervous system, cerebrovascular diseases, CNS infections,
and disorders related to short gestation, low birth weight, and fetal malnutrition (P ⬍ .05; Table 1). These comorbidities were the most commonly
identified diagnoses that were likely
associated with the etiologies of hydrocephalus requiring the VPS or related to the IH.
Incidence of IH and Hazard Ratios
During the 8-year study, the average
incidence rate of IH-repair surgery
was 13.3% in the VPS group, significantly higher than that in the control
group (4.1%; log-rank test, P ⬍ .001).
This finding suggests that children in
the VPS group were more likely to develop an IH than those in the control
group (hazard ratio [HR]: 3.62; P ⬍
.001). After adjustments for age, gender, and the aforementioned comorbidities, children in the VPS group
were still more likely to develop an IH
than those in the control group (adjusted HR: 6.63; P ⬍ .001; Table 2).
The incidence rate of IH had a feature
of time dependence during the
follow-up period. The stratified HRs, by
the follow-up time and with adjustments for age, gender, and comorbidities, were different in each period of
time (Table 3). The risk for IH surgery
in the VPS group was at least 11-fold
higher than that of the control group
during the first 2 years after VPS (firstyear adjusted HR: 19.67 [95% CI: 9.89 –
39.12]; P ⬍ .001; second-year adjusted
HR: 11.36 [95% CI: 4.22–30.54]; P ⬍
.001). After 2 years, this risk was similar in both groups (adjusted HR after
the third year of follow-up was not significantly different). As such, in the
control group, the cumulative incidence rate of IH increased in a steady
rate all the way to the end of this cohort, whereas in the VPS group, the cumulative incidence rate of the IH increased at a more rapid rate (steeper
slope; Fig 2) in the first 2 years after
the VPS operation. After 2 years, this
increase slowed down, turning into a
more gradual slope, and became parallel to that of the control group afterward (Fig 2).
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e123
TABLE 1 Demographic Characteristics and Comorbidities of the VPS and Control Groups
(N ⫽ 7379)
Control Group/
No VPS
(N ⫽ 6704)
n
Demographic factors
Gender
Male
Female
Ageb
Neonates
Infants
Toddlers
Preschool-aged
Comorbidities
Hereditary diseases of the CNS
Yes
No
Congenital anomalies of the nervous system
Yes
No
Intracranial injury
Yes
No
Malignant neoplasm of the brain and other
nervous system
Yes
No
Cerebrovascular disease
Yes
No
CNS infection
Yes
No
Disorders related to short gestation, low
birth weight, and fetal growth
retardation
Yes
No
%
Pa
VPS Group
(N ⫽ 675)
n
%
DISCUSSION
.9578
3841
2863
57.3
42.7
388
287
57.5
42.5
1718
4089
809
88
25.6
61.0
12.1
1.3
175
409
82
9
25.9
60.6
12.1
1.3
38
6666
0.6
99.4
491
184
72.7
27.3
25
6679
0.4
99.6
362
313
53.6
46.4
662
6042
9.9
90.1
161
514
23.9
76.1
.9971
⬍.001
⬍.001
⬍.001
⬍.001
13
6691
0.2
99.8
44
631
6.5
93.5
28
6676
0.4
99.6
206
469
30.5
69.5
140
6564
2.1
97.9
219
456
32.4
67.6
⬍.001
⬍.001
⬍.001
184
6520
2.7
97.3
187
488
27.7
72.3
␹2 test.
Neonate, newborn up to first 28 days of life; infant, neonatal period up to 12 months; toddler, 1 to 2 years old; preschoolaged, 3 to 5 years old.
a
b
TABLE 2 Crude and Adjusted HRs for IH Repair During the 8-Year Follow-up Period Among
Preschool-Aged Patients With a VPS, 1996 –2000 (N ⫽ 7379)
8-y follow-up period, n (%)
Yes
No
Crude HR (95% CI)
Adjusted HR (95% CI)b
Total Sample
Control Group (No VPS)
VPS Group
353 (4.8)
7026 (95.2)
—
—
275 (4.1)
6429 (95.9)
1.00
1.00
78 (11.6)
597 (88.4)
3.62 (2.81–4.65)a
6.63 (3.96–11.09)a
P ⬍ .001.
Adjustments were made for the patients’ age, gender, hereditary diseases of the CNS, congenital anomalies of the nervous
system, intracranial injury, malignant neoplasm of the brain and other nervous system, cerebrovascular disease, CNS
infection, and disorders related to short gestation, low birth weight, and fetal growth retardation.
a
b
Timing of IH Surgery
The VPS group received IH surgery earlier than the control group. The mean
age on receiving IH surgery in the VPS
e124
CHEN et al
surgery in the VPS group was 1.73
years shorter than that in the control
group (mean: 1.29 vs 3.02 years; t test,
P ⬍ .001).
group was significantly younger by
1.75 years than that of the control
group (1.71 vs 3.46 years; t test, P ⬍
.001). The average time interval to IH
This study used a nationwide database
to recruit a cohort of children younger
than 5 years of age, who numbered
⬎1.5 million. A group of 675 children
who had VPS surgery was then extracted, together with 6704 age- and
gender-matched children as the control group to make a 1 to 10 comparison. After 8 years of follow-up, children
with a VPS were significantly more
likely to develop an IH (Table 2) than
the controls. The correlation between
VPS in children and subsequent IH is
shown by this cohort study.
In the literature, children who receive
a VPS are postulated to have a higher
risk of subsequent IH-repair surgery.
Few single-institution observational
studies report an increased rate of IH
after VPS placement in children, ranging from 10% to 30%.12,14–16 Grosfeld
and Cooney12 first reported the correlation of the development of IH after
VPS surgery in children in 1974. A
study of 134 patients by Moazam et al16
demonstrated a similar correlation
later in 1984. Clarnette et al14 reported
a 15% rate of developing IH after VPS
insertion in 430 children in 1998,
whereas Celik et al15 reported 23.8% of
88 children developed clinical inguinal
manifestations after VPS surgery in
2005. Compared with the present
study, these studies had smaller patient numbers, shorter follow-up durations, and lower follow-up rates, and
were all single-institution based. Nonetheless, their findings are comparable
and are the bases for the rationale of
the present study. Our study further
corroborates the association between
VPS and subsequent IH-repair surgery
via a cross-institutional, large number,
and controlled longitudinal cohort.
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ARTICLES
TABLE 3 HRs of Subsequent IH-Repair Surgery at Different Time Points During the 8-Year Follow-up
Period in Preschool-Aged Patients With VPS, 1996 –2000 (N ⫽ 7379)
Follow-up Time Point
(Years After VPS Surgery)
Adjusted HR (95% CI)a
P
First year (0–1)
Second year (1–2)
Third year (2–3)
Fourth year (3–4)
Eighth year (4–8)
19.67 (9.89–39.12)
11.36 (4.22–30.54)
0.34 (0.02–5.06)
0.75 (0.06–10.34)
0.48 (0.07–3.25)
⬍.001
⬍.001
.440
.835
.455
a
Adjustments were made for the patients’ age, gender, hereditary diseases of the CNS, congenital anomalies of the nervous
system, intracranial injury, malignant neoplasm of the brain and other nervous system, cerebrovascular disease, CNS
infection, and disorders related to short gestation, low birth weight, and fetal growth retardation.
FIGURE 2
Results of the Kaplan-Meier analysis.a P ⬍ .001.
The time interval from VPS insertion to IH
development in children is a very clinically relevant issue for parents and pediatricians but is seldom reported. It is reportedly 5.3 months for notice of clinical
inguinal manifestation from the experience of by Celik et al15 in 21 patients. The
average time interval in the current
study was ⬃1.29 years. Furthermore,
this study demonstrated for the first
time that the incidence rate of IH after
VPS surgery in children may change because it is time dependent (Fig 2). The
risk of IH development in children after
VPS insertion was more than 10 times
higher than that of the control group
during the first 2 years but became
similar afterward. This implies that the
PEDIATRICS Volume 128, Number 1, July 2011
adverse effect of the VPS on IH has a
duration of ⬃2 years. Such findings
are valuable when consulting family
and general physicians for care of
these children who receive shunts.
This study has several strengths. First,
the nationwide database, provided by
a monopolistic health insurance system operated by the government, permitted the extremely high follow-up
rate attained. Because the universal
insurance system covers 99% of the
population and health care providers,
the chance of loss to follow-up is very
low and only exists if they discontinue
citizenship. Theoretically, all subsequent IH surgery can be identified even
if performed in different hospitals,
which is not uncommon for these
pediatric patients. Thus, the rate of follow-up in our study is higher
than those of previously reported
institution-based studies.12,14–16 Second, the control group of age- and
gender-matched children (n ⫽ 6684)
are also very comparable in terms of ethnicity, geographic location, and access
to health care. Because age and gender
are important factors of IH, the 1-to-10
matchup makes the comparison distinct
and with enhanced statistical power.
These 2 features make the present investigation on such an issue authentic.
However, the study also has several
limitations. First, the VPS group is composed of children with more congenital anomalies or prematurity, which is
evident from the comorbidity comparison (Table 1). These congenital anomalies, and prematurity itself, can substantially predispose children for IH
later in childhood.17–19 Adjustments by
using the Cox proportional hazard
model have been used to address this
inherent issue. Second, a detailed operative note review, both of the VPS insertion or the IH repair, was not conducted in this study. Types of shunting
catheters, including pressure-valve selection, and the severity of hydrocephalus were not taken into account.
These factors may exert influences on
intraabdominal pressure and may
possibly affect the development of IH.
All of these intraoperative findings and
postoperative complications, such as
shunt malfunction and infection, were
not analyzed. The anatomic classification of IH, although assumed to be almost all indirect type,18 was also not
considered. Third, the time of IH-repair
surgery, instead of that of diagnosis, is
regarded as the proxy for the development of IH. Therefore, the actual time
interval between VPS and IH surgery may
be shorter than the results here. However, due to the characteristic easy ac-
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e125
cess to health care services in Taiwan,
especially for children, long treatment
delay is not expected.20,21 Fourth, those
children who had an abdominal operation for the VPS might be under increased scrutiny by family and caregivers, and a hernia is therefore more apt
to be detected and perhaps treated.
The definite cause of increased risk of
IH after VPS insertion in children is unclear. However, it is inferred by several
reports to be due to increased intraabdominal pressure.12,14,15 Our study used
a cohort study design with the fitted
multivariate Cox regression model to
demonstrate a cause-and-effect relationship between VPS surgery and IH,
which seems supportive to the hypothesis. But the high incidence rate of pre-
vious IH in the VPS group (incidence
rate of VPS versus comparison: 3.0% vs
0.7%; ␹2 test, P ⬍ .001) may challenge
the hypothesis and deserves additional analysis. Furthermore, the absorptive capacity of the peritoneal cavity for diverted CSF has not been
quantified and may be compromised by
other comorbidities such as prematurity. It is unknown whether it is the excessive amount of CSF resulting in increased peritoneal pressure or the
irritation of the fluid content itself that
causes IH development. The anatomic
differences between boys and girls can
also make for disparate vulnerabilities
to IH after VPS surgery.14 However, these
issues are beyond the scope of this study
and require future investigations.
CONCLUSIONS
Children receiving a VPS who are
younger than 5 years of age were more
likely to have IH. The risk was highest
during the first 2 years after VPS surgery. There should be a high index of
suspicion for inguinal manifestations
when following-up children after they
receive a VPS.
ACKNOWLEDGMENTS
This study was based partly on data
from the National Health Research Institutes database provided by the Bureau of National Health Insurance, the
Department of Health, and managed by
the National Health Research Institutes
in Taiwan.
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Correlation Between Ventriculoperitoneal Shunts and Inguinal Hernias in
Children: An 8-Year Follow-up
Yu-Chun Chen, Jau-Ching Wu, Laura Liu, Tzeng-Ji Chen, Wen-Cheng Huang and
Henrich Cheng
Pediatrics 2011;128;e121; originally published online June 20, 2011;
DOI: 10.1542/peds.2010-3906
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