Different

perceptions

of

the

burden

of

upper

GI

endoscopy

an

empirical

study

in

three

patient

groups

Background

Few

studies

have

evaluated

patients

perceived

burden

of

cancer

surveillance

tests

Cancer

screening

and

surveillance

however

require

a

large

number

of

patients

to

undergo

potentially

burdensome

tests

with

only

some

experiencing

health

gains

from

it

We

investigated

the

determinants

of

patients

reported

burden

of

upper

gastrointestinal

-LRB-

GI

-RRB-

endoscopy

by

comparing

data

from

three

patient

groups

Introduction

Opportunities

for

screening

and

surveillance

of

premalignant

conditions

have

increased

and

will

increase

in

the

future

However

such

interventions

can

be

burdensome

and

as

in

any

screening

situation

the

number

of

subjects

exposed

to

this

burden

is

often

much

higher

than

the

number

of

subjects

experiencing

the

beneficial

health

effects

of

the

screening

-LSB-

-RSB-

Upper

gastrointestinal

-LRB-

GI

-RRB-

endoscopy

is

commonly

used

to

diagnose

and

treat

patients

with

a

range

of

conditions

and

symptoms

Complications

related

to

upper

GI

endoscopy

are

rare

and

it

is

considered

to

be

a

safe

procedure

-LSB-

-RSB-

Patients

with

Barrett

esophagus

-LRB-

BE

-RRB-

a

premalignant

condition

mostly

without

physical

symptoms

but

associated

with

an

increased

risk

of

developing

esophageal

adenocarcinoma

of

per

year

are

recommended

to

undergo

regular

biennial

endoscopic

surveillance

for

early

detection

of

esophageal

cancer

-LSB-

-RSB-

All

patients

participating

in

surveillance

experience

the

pain

and

discomfort

of

biennial

upper

GI

endoscopy

whereas

progression

to

adenocarcinoma

occurs

only

in

a

minority

of

BE

patients

-LSB-

-RSB-

and

undisputable

evidence

that

surveillance

prolongs

survival

is

still

lacking

-LSB-

-RSB-

Hence

the

patients

perceived

burden

of

upper

GI

endoscopy

testing

needs

to

be

taken

in

to

account

in

evaluating

the

health

benefits

of

surveillance

of

subjects

with

BE

In

some

situations

there

is

a

trade-off

between

the

effectiveness

of

screening

-LRB-

or

surveillance

-RRB-

and

the

test

uptake

For

example

colorectal

cancer

screening

using

sigmoidoscopy

is

more

effective

than

faecal

occult

blood

testing

-LSB-

-RSB-

At

present

this

trade-off

is

not

relevant

for

surveillance

of

BE

because

a

less

burdensome

test

than

upper

GI

endoscopy

is

not

available

but

the

recognition

that

upper

GI

endoscopy

is

burdensome

may

prompt

a

reconsideration

of

the

frequency

of

surveillance

Ongoing

studies

aim

to

identify

groups

of

BE

patients

at

lower

risk

of

developing

esophageal

cancer

than

others

so

that

offering

less

frequent

surveillance

may

be

warranted

-LSB-

-RSB-

At

the

patient

level

empirical

data

on

perceived

burden

of

upper

GI

endoscopy

can

be

used

in

the

process

of

informing

subjects

with

BE

who

consider

participation

to

a

surveillance

programme

In

a

general

sense

empirical

data

of

the

patients

perceived

burden

of

testing

may

contribute

to

subjects

informed

decision-making

on

participation

-LRB-

or

non-participation

-RRB-

to

screening

or

surveillance

and

hence

to

quality

of

health

care

-LSB-

-RSB-

Studying

the

determinants

of

patients

perceived

burden

of

upper

GI

endoscopy

e.g.

by

comparing

data

from

different

patient

groups

may

allow

for

the

identification

of

patient

groups

who

are

likely

to

experience

more

pain

or

discomfort

than

others

This

information

can

be

used

in

practice

guidelines

e.g.

on

provision

of

sedation

to

prevent

pain

and

discomfort

or

other

types

of

patient

support

Studying

determinants

of

patients

perceived

burden

is

of

additional

interest

from

the

perspective

of

evaluation

research

If

patients

perception

of

the

burden

of

endoscopy

differs

by

the

context

of

e.g.

surveillance

or

diagnostic

work-up

the

generalisability

of

data

from

one

context

to

another

is

limited

Our

previous

work

-LSB-

-RSB-

has

shown

that

BE

patients

under

regular

surveillance

perceive

upper

GI

endoscopy

as

burdensome

They

experienced

anxiety

and

discomfort

but

hardly

reported

pain

or

symptoms

We

analysed

potential

determinants

of

the

perceived

burden

of

upper

GI

endoscopy

by

comparing

BE

patients

with

two

additional

patient

groups

i.e.

patients

with

non-specific

upper

GI

symptoms

-LRB-

NS

-RRB-

and

patients

with

a

recent

diagnosis

of

cancer

of

the

upper

GI

tract

-LRB-

CA

-RRB-

Methods

Ethics

approval

The

Medical

Ethical

Review

Board

of

Erasmus

MC

University

Medical

Center

Rotterdam

The

Netherlands

approved

of

the

study

-LRB-

MEC

October

-RRB-

Patients

Patients

undergoing

upper

GI

endoscopy

for

surveillance

of

BE

were

participants

of

an

ongoing

trial

-LRB-

CYBAR

-RRB-

whose

endoscopic

burden

was

previously

reported

-LSB-

-RSB-

Inclusion

criteria

were

BE

segment

of

cm

or

more

confirmed

by

a

histological

diagnosis

of

intestinal

metaplasia

absence

of

high-grade

dysplasia

and

carcinoma

willingness

to

adhere

to

endoscopic

surveillance

ability

to

read

the

Dutch

language

and

informed

consent

Patients

with

non-specific

upper

GI

symptoms

-LRB-

NS

-RRB-

were

referred

for

endoscopy

by

their

respective

GPs

because

of

non-specific

upper

GI

symptoms

They

needed

to

be

able

to

read

the

Dutch

language

provide

informed

consent

not

to

have

alarm

symptoms

such

as

hematemesis

melena

or

dysphagia

and

not

be

diagnosed

with

BE

previously

Patients

with

a

recent

diagnosis

of

upper

GI

cancer

-LRB-

CA

-RRB-

were

referred

for

upper

GI

endoscopy

plus

ultrasonography

-LRB-

EUS

-RRB-

to

determine

therapeutic

options

Ability

to

read

the

Dutch

language

and

to

give

informed

consent

was

also

required

in

these

patients

Patients

were

recruited

from

one

academic

and

two

regional

hospitals

for

BE

two

regional

hospitals

for

NS

and

in

one

academic

hospital

for

CA

Endoscopic

procedure

BE

and

NS

patients

underwent

endoscopy

with

adult

endoscopes

-LRB-

Olympus

Zoeterwoude

The

Netherlands

-RRB-

In

the

group

of

cancer

patients

a

combined

endoscopy

and

EUS

was

performed

with

a

Olympus

More

than

of

patients

received

oral

anaesthetics

-LRB-

Xylocain

spray

Astra

Zeneca

Zoetermeer

The

Netherlands

-RRB-

preceding

the

introduction

of

the

endoscope

Additional

sedation

with

mg

midazolam

-LRB-

Roche

Woerden

The

Netherlands

-RRB-

intravenously

was

offered

as

a

standard

procedure

to

all

cancer

patients

but

was

only

administered

with

explicit

patient

consent

In

BE

and

NS

patients

this

was

not

standard

but

it

was

administered

on

a

patient

's

request

Practice

variations

between

and

within

countries

in

the

use

of

sedation

for

upper

GI

endoscopy

are

common

-LSB-

-RSB-

Hypotheses

Perceived

burden

of

endoscopy

was

operationalised

as

pain

and

discomfort

during

the

procedure

symptoms

afterwards

and

psychological

distress

over

time

We

hypothesized

that

subjects

who

had

previous

endoscopies

may

get

used

to

it

to

some

extent

and

hence

report

less

burden

Demographic

characteristics

-LRB-

age

sex

educational

level

employment

status

etc

-RRB-

were

considered

as

potential

confounders

We

expected

that

BE

patients

may

get

used

to

regular

endoscopy

to

some

extent

and

that

they

adhere

to

surveillance

expecting

that

the

test

result

will

be

reassuring

Therefore

we

expected

BE

patients

to

report

less

discomfort

and

burden

than

the

patients

with

non-specific

GI

symptoms

who

had

less

endoscopy

experience

We

also

expected

the

BE

group

to

report

less

burden

from

the

endoscopy

than

the

cancer

patients

due

to

the

endoscopy

itself

-LRB-

combined

with

EUS

in

the

cancer

patients

-RRB-

and

the

fact

that

cancer

patients

were

aware

of

their

generally

bad

prognosis

Table

shows

the

potential

determinants

of

perceived

burden

of

endoscopy

between

patient

groups

Table

determinants

of

perceived

burden

of

endoscopy

for

three

patient

groupsDeterminantBENSCA

Indication

for

endoscopyRegular

endoscopic

surveillance

for

early

detection

of

cancerTo

find

out

if

symptoms

can

be

explained

by

e.g.

a

hiatal

hernia

or

duodenal

ulcer

a

life-threatening

diagnosis

is

not

expected.To

determine

whether

intentionally

curative

therapy

is

possible

or

notEndoscopy

experienceYes

under

endoscopic

surveillance

Limited

ranging

from

to

some

Yes

-LRB-

by

definition

at

least

one

previous

endoscopy

needed

to

diagnose

the

cancer

-RRB-

Generic

health

statusGenerally

healthy

Mild

impairment

-LRB-

aspecific

gastrointestinal

symptoms

-RRB-

Seriously

impaired

-LRB-

cancer

diagnosis

-RRB-

AgeIn-betweenYoungestOlderSexMore

males

than

females

Equal

sex

distributionPredominantly

maleEndoscopy

procedureNormal

endoscopy

procedure

sedation

only

on

patient

requestNormal

endoscopy

procedure

sedation

only

on

patient

requestEndoscopy

combined

with

ultrasonography

sedation

routinely

offered

Questionnaires

and

measurements

Patients

were

asked

to

complete

questionnaires

at

different

time

points

i.e.

one

week

before

the

endoscopy

-LRB-

baseline

-RRB-

at

the

day

of

endoscopy

-LRB-

just

before

undergoing

it

-RRB-

one

week

and

one

month

after

endoscopy

-LSB-

-RSB-

In

order

to

minimize

the

questionnaire

load

for

CA

patients

they

received

only

two

questionnaires

the

first

on

the

day

of

endoscopy

and

the

other

one

week

afterwards

Some

baseline

items

had

to

be

included

in

the

endoscopy

day

questionnaire

in

the

CA

group

The

content

of

the

questionnaires

is

described

below

Pain

and

discomfort

Separate

items

in

the

questionnaire

one

week

after

endoscopy

were

used

to

assess

pain

and

discomfort

respectively

as

experienced

during

the

procedure

for

four

steps

of

the

procedure

the

introduction

of

the

endoscope

the

endoscopy

itself

the

removal

of

the

endoscope

and

the

period

directly

after

endoscopy

Subjects

were

offered

three

response

options

-LRB-

no

quite

and

very

painful

or

discomforting

respectively

-RRB-

Additionally

patients

rated

the

overall

burden

of

undergoing

the

endoscopy

-LRB-

very

somewhat

not

burdensome

-RRB-

-LSB-

-RSB-

Symptoms

We

compared

the

prevalence

of

symptoms

experienced

in

the

week

after

endoscopy

with

the

prevalence

at

baseline

For

CA

patients

the

baseline

questions

were

asked

at

the

day

of

endoscopy

Presence

of

throat

ache

heartburn

regurgitation

flatulence

or

feeling

bloated

vomiting

hematemesis

dysphagia

for

solid

foods

or

for

of

liquids

diarrhea

and

constipation

was

assessed

using

four

response

options

-LRB-

not

at

all

one

day

days

or

more

days

-RRB-

-LSB-

-RSB-

Psychological

distress

-LRB-

BE

and

NS

patients

-RRB-

We

assessed

general

distress

using

the

Hospital

Anxiety

and

Depression

scale

-LRB-

HAD

-RRB-

at

all

time

points

-LSB-

-RSB-

Anxiety

and

depression

scores

of

this

scale

range

from

with

scores

of

or

over

indicating

clinical

and

scores

between

and

indicating

borderline

anxiety

or

depression

-LSB-

-RSB-

We

analysed

the

pattern

of

scores

across

measurements

assuming

scores

to

return

to

normal

after

endoscopy

Scores

from

a

Dutch

general

population

sample

-LRB-

n

mean

age

year

female

-RRB-

were

available

for

comparison

-LSB-

-RSB-

At

baseline

and

at

one

week

we

also

measured

specific

distress

with

the

Impact

of

Event

Scale

-LRB-

IES

-RRB-

-LSB-

-RSB-

At

baseline

we

assessed

intrusive

and

avoiding

thoughts

regarding

the

endoscopy

itself

and

at

one

week

regarding

the

communication

of

the

final

test

result

The

total

scale

ranges

between

and

with

scores

of

or

over

indicating

a

high

risk

of

developing

a

stress

disorder

-LSB-

-RSB-

Psychological

distress

-LRB-

CA

patients

-RRB-

For

CA

patients

we

omitted

the

HAD

and

the

IES

measures

regarding

the

endoscopy

itself

because

we

expected

that

distress

in

these

patients

was

already

at

the

top

of

the

scale

making

any

additional

distress

caused

by

the

procedure

itself

indiscernible

The

IES

to

assess

specific

distress

regarding

the

endoscopy

result

was

included

in

the

questionnaire

at

the

day

of

endoscopy

because

these

patients

received

the

endoscopy

results

earlier

than

the

next

questionnaire

Demographics

and

other

data

Demographic

data

were

collected

at

baseline

-LRB-

at

the

endoscopy

day

for

CA

patients

-RRB-

The

EQ

self-classifier

results

in

a

patient

's

classification

of

own

health

on

five

domains

mobility

self-care

usual

activities

pain

and

anxiety

and

depression

-LRB-

response

options

no

some

severe

complete

limitations

-RRB-

and

a

summary

score

-LSB-

-RSB-

We

asked

BE

and

NS

patients

whether

this

was

their

first

second

or

a

later

endoscopy

Whether

sedation

was

used

during

endoscopy

was

recorded

separately

Analyses

Differences

in

demographic

and

treatment

characteristics

between

patient

groups

were

analysed

by

Chi-square

tests

for

categorical

variables

or

one-way

analysis

of

variance

-LRB-

ANOVA

-RRB-

for

continuous

variables

The

items

for

pain

and

discomfort

were

combined

into

summary

scores

to

enable

adjustment

for

confounders

and

analysis

of

determinants

by

adding

up

the

item

responses

-LRB-

respectively

-RRB-

of

the

items

-LRB-

range

of

pain

and

discomfort

summary

scores

-LRB-

no

pain

or

discomfort

-RRB-

to

-RRB-

-LSB-

-RSB-

The

response

to

the

single

item

rating

of

overall

burden

was

also

treated

as

a

summary

score

with

a

range

from

-LRB-

no

burden

-RRB-

to

two

-LSB-

-RSB-

Because

these

summary

scores

had

a

limited

number

of

possible

values

and

because

the

data

were

not

distributed

normally

we

chose

to

analyse

them

with

proportional

odds

models

-LSB-

-RSB-

These

models

produce

odds-ratios

-LRB-

ORs

-RRB-

for

cumulative

probabilities

of

the

outcome

variables

Proportional

odds

models

are

a

variant

of

simple

logistic

regressions

but

now

ORs

for

dichotomies

at

all

possible

cut-off

levels

are

estimated

E.g.

for

a

variable

with

three

possible

outcomes

and

ORs

are

estimated

for

-LRB-

-RRB-

vs.

and

for

vs.

-LRB-

-RRB-

The

OR

presented

represents

an

overall

OR

that

is

assumed

to

be

similar

across

cut-off

levels

Because

some

of

the

outcome

variables

and

determinants

had

missing

data

and

there

were

no

reasons

for

selective

missing

data

we

used

multiple

imputation

-LRB-

function

AregImpute

in

Splus

-RRB-

-LSB-

-RSB-

so

that

all

available

information

in

our

dataset

was

used

In

multivariate

analysis

of

the

determinants

of

patients

perceived

burden

with

the

proportional

odds

model

we

first

adjusted

for

confounders

-LRB-

age

sex

and

employment

status

-RRB-

Subsequently

we

evaluated

the

potential

effects

of

the

following

determinants

on

discomfort

pain

and

overall

burden

respectively

patient

group

-LRB-

BE

NS

or

CA

-RRB-

This

variable

combines

the

differences

in

the

endoscopy

procedure

-LRB-

with

or

without

EUS

sedation

-RRB-

and

the

indication

to

undergo

the

endoscopy

For

BE

and

NS

patients

this

analysis

was

refined

by

additional

separate

analysis

of

the

effect

of

the

number

of

previous

endoscopies

-LRB-

continuous

truncated

at

-RRB-

baseline

generic

health

status

-LRB-

EQ

summary

score

-RRB-

whether

sedation

was

administrated

or

not.baseline

HAD

anxiety

score

-LRB-

not

available

for

the

CA

patients

-RRB-

The

prevalence

of

symptoms

before

and

after

endoscopy

was

compared

using

a

method

analogous

to

the

Wilcoxon

test

Responses

were

ranked

and

ANOVA

was

applied

to

the

differences

in

these

ranks

-LSB-

-RSB-

The

continuous

HAD

and

IES

scores

were

compared

over

time

in

SAS

version

with

repeated-measures

ANOVA

using

Proc

Mixed

with

REML

and

a

compound

symmetry

covariance

structure

Models

comprised

main

effects

of

time

-LRB-

the

measurements

-RRB-

confounders

determinants

and

interactions

between

determinants

and

time

Proportional

odds

models

were

estimated

with

Splus

All

other

analyses

were

conducted

in

SPSS

version

Results

Patients

and

response

In

total

patients

were

eligible

for

inclusion

BE

NS

and

CA

patients

The

overall

response

rate

was

with

patients

completed

at

least

one

questionnaire

The

response

differed

by

patient

group

it

was

-LRB-

-RRB-

in

BE

patients

-LRB-

-RRB-

in

NS

patients

and

-LRB-

-RRB-

in

CA

patients

Most

BE

patient

had

no

dysplasia

-LRB-

-RRB-

had

low-grade

dysplasia

-LSB-

-RSB-

NS

patients

were

diagnosed

with

hiatal

hernia

-LRB-

-RRB-

non-specific

gastritis

-LRB-

-RRB-

reflux

esophagitis

-LRB-

-RRB-

and

some

other

diagnoses

-LRB-

e.g.

ulcer

polyps

-RRB-

CA

patients

underwent

endoscopy

and

EUS

for

staging

of

esophageal

carcinoma

-LRB-

-RRB-

gastric

cancer

-LRB-

-RRB-

or

lymphoma

-LRB-

-RRB-

Differences

between

groups

in

mean

age

sex

and

employment

status

were

statistically

significant

-LRB-

P

-RRB-

-LRB-

Table

-RRB-

We

therefore

considered

these

variables

as

confounders

and

controlled

for

them

in

further

analyses

Table

Mean

age

-LRB-

sd

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Sex

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

EmploymentPaid

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Civil

status

Married

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Never

married

tog

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

HospitalAcademic

center

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

N.A.

hospital

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Endoscopy

-LRB-

-RRB-

-LRB-

-RRB-

Unknown

-LRB-

-RRB-

-LRB-

-RRB-

Third

or

-LRB-

-RRB-

-LRB-

-RRB-

EQ

summary

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

N.A.

Not

assessedaData

for

the

BE

group

were

published

previously

-LSB-

-RSB-

bχ

test

-LRB-

categorical

variables

-RRB-

or

F-test

-LRB-

continuous

-RRB-

for

differences

between

patient-groups

About

of

the

BE

patients

had

had

two

or

more

previous

endoscopies

-LSB-

-RSB-

compared

with

of

the

NS

patients

-LRB-

P

-RRB-

Seventy-seven

per

cent

of

the

CA

patients

received

sedation

during

endoscopy

compared

with

of

the

BE

and

of

the

NS

patients

-LRB-

P

-RRB-

The

differences

in

the

mean

EQ

summary

score

were

in

the

expected

direction

-LRB-

P

-RRB-

-LRB-

Table

-RRB-

Pain

and

discomfort

Tables

show

that

the

patient

groups

differed

significantly

in

reported

discomfort

pain

and

overall

burden

of

endoscopy

The

p-values

shown

for

the

summary

scores

relate

to

univariate

analysis

of

differences

between

the

patient

groups

before

adjustment

for

confounders

Table

during

upper

GI

endoscopy

as

reported

by

patientsaDiscomfortNotQuiteVerynDifferbIntroducing

the

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

the

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

immediately

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

summary

score

-LRB-

range

-RRB-

Mean

-LRB-

sd

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

for

the

BE

group

were

published

previously

-LSB-

-RSB-

bSignificance

of

differences

between

three

groups

as

determined

by

Chi-square

test

-LRB-

categorical

variables

-RRB-

or

proportional

odds

models

for

ordinal

response

data

-LRB-

summary

score

-RRB-

No

correction

for

confoundersTable

during

upper

GI

endoscopy

as

reported

by

patientsaPainNotQuiteVerynDifferbIntroducing

the

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

the

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Period

immediately

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

summary

score

-LRB-

range

-RRB-

Mean

-LRB-

sd

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

for

the

BE

group

were

published

previously

-LSB-

-RSB-

bSignificance

of

differences

between

three

groups

as

determined

by

Chi-square

test

-LRB-

categorical

variables

-RRB-

or

proportional

odds

models

for

ordinal

response

data

-LRB-

summary

score

-RRB-

No

correction

for

confoundersTable

burden

of

upper

GI

endoscopy

as

reported

by

patientsaOverall

burdenNotQuiteVerynDifferbEndoscopy

in

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

burden

summary

score

-LRB-

range

-RRB-

Mean

-LRB-

sd

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

for

the

BE

group

were

published

previously

-LSB-

-RSB-

bSignificance

of

differences

between

three

groups

as

determined

by

Chi-square

test

-LRB-

categorical

variable

-RRB-

or

proportional

odds

models

for

ordinal

response

data

-LRB-

summary

score

-RRB-

No

correction

for

confounders

Table

shows

these

adjusted

differences

in

summary

scores

for

pair

wise

comparisons

between

the

groups

and

how

these

are

affected

by

the

determinants

NS

patients

reported

significantly

more

discomfort

than

BE

patients

as

demonstrated

by

the

significant

OR

of

After

adjusting

for

differences

in

the

number

of

previous

endoscopies

the

difference

in

reported

discomfort

between

NS

and

BE

patients

was

no

longer

significant

Similarly

the

difference

in

reported

discomfort

between

NS

and

BE

patients

could

also

be

explained

by

differences

regarding

the

administration

of

sedation

The

differences

between

the

NS

and

BE

groups

in

the

baseline

EQ

summary

score

and

in

baseline

anxiety

scores

did

not

explain

the

differences

in

reported

discomfort

the

ORs

remained

significant

Reported

pain

during

upper

GI

endoscopy

did

not

differ

between

NS

and

BE

groups

The

difference

in

reported

overall

burden

was

significant

-LRB-

OR

P

-RRB-

This

difference

became

also

insignificant

after

adjustment

for

the

number

of

previous

endoscopies

and

for

sedation

Table

in

discomfort

summary

score

pain

summary

score

and

overall

burden

score

pair

wise

between

patient

groups

-LRB-

after

correction

for

age

sex

and

employment

status

as

confounders

-RRB-

and

effects

of

other

determinants

than

patient

group

on

these

differencesDeterminantDiscomfort

scorePain

scoreOverall

CIbP-valueNS

compared

to

BE

-LRB-

BE

reference

group

-RRB-

Patient

group

NS

versus

Number

of

previous

Baseline

EQ

Baseline

CA

compared

to

BE

-LRB-

BE

reference

group

-RRB-

cPatient

group

CA

versus

Baseline

EQ

aOdds

ratios

were

calculated

by

proportional

odds

models

for

ordinal

response

data

They

show

the

differences

between

the

patient

groups

corrected

for

confounders

and

the

determinant

confidence

intervalcNumbers

of

previous

endoscopies

and

baseline

anxiety

were

not

available

for

CA

patients

CA

patients

reported

significantly

more

pain

-LRB-

OR

P

-RRB-

and

overall

burden

than

BE

patients

-LRB-

OR

P

Table

-RRB-

The

differences

in

reported

pain

could

not

be

explained

by

differences

in

baseline

EQ

summary

scores

or

whether

sedation

had

been

administrated

or

not

-LRB-

all

ORs

remained

significant

Table

-RRB-

CA

and

BE

patients

did

not

differ

in

reported

discomfort

-LRB-

OR

P

-RRB-

but

after

taking

differences

in

the

provision

of

sedation

into

account

the

difference

in

reported

discomfort

became

significant

-LRB-

OR

P

-RRB-

Symptoms

After

endoscopy

throat

ache

was

the

only

symptom

that

was

reported

more

often

than

before

the

procedure

-LRB-

vs.

P

-RRB-

Other

symptoms

did

not

increase

in

frequency

Compared

to

BE

patients

the

increase

in

throat

ache

was

smaller

for

NS

patients

and

larger

for

CA

patients

-LRB-

P

-RRB-

of

NS

patients

reported

throat

ache

before

and

afterwards

compared

and

of

BE

patients

and

and

of

CA

patients

respectively

Psychological

distress

Figure

shows

unadjusted

mean

anxiety

and

depression

scores

-LRB-

HAD

not

available

for

CA

patients

-RRB-

by

patient

group

over

time

Fig.

between

BE

and

NS

groups

in

Hospital

Anxiety

and

Depression

-LRB-

HAD

-RRB-

scale

scores

for

general

distress

before

and

after

upper

GI

endoscopy

-LRB-

mean

scores

no

adjustment

for

confounders

-RRB-

After

adjusting

for

confounders

-LRB-

repeated

measures

ANOVA

-RRB-

anxiety

levels

were

similar

between

the

BE

and

NS

groups

across

measurements

but

the

pattern

differed

significantly

between

them

-LRB-

interaction

effect

of

group

with

time

P

-RRB-

BE

patients

reported

lower

anxiety

levels

at

the

start

and

slightly

higher

at

the

end

Determinants

-LRB-

number

of

previous

endoscopies

baseline

EQ

summary

score

sedation

-RRB-

did

not

influence

this

pattern

of

anxiety

over

time

-LRB-

no

significant

interaction

effects

with

time

-RRB-

Anxiety

scores

of

both

NS

and

BE

patients

were

significantly

higher

at

all

time

points

than

reported

by

a

general

population

sample

-LRB-

score

P

for

each

group

at

each

measurement

-RRB-

-LSB-

-RSB-

At

all

measurements

depression

scores

were

lower

in

BE

than

in

NS

patients

-LRB-

P

-RRB-

This

difference

was

significantly

larger

before

than

after

endoscopy

-LRB-

interaction

effect

of

group

with

time

P

-RRB-

The

number

of

previous

endoscopies

affected

the

pattern

of

depression

over

time

-LRB-

interaction

effect

of

number

of

previous

endoscopies

with

time

P

-RRB-

making

the

pattern

of

the

two

groups

more

similar

Depression

scores

differed

from

those

reported

by

the

general

population

sample

BE

patients

reported

significantly

lower

levels

at

all

measurements

while

baseline

NS

scores

were

significantly

higher

-LRB-

norm

score

P

for

each

comparison

-RRB-

Specific

distress

-LRB-

IES

-RRB-

scores

regarding

the

endoscopy

itself

and

its

outcome

were

lower

in

BE

patients

than

in

NS

patients

-LRB-

mean

scores

at

baseline

measurement

and

week

measurements

are

BE

-LRB-

sd

-RRB-

NS

-LRB-

sd

-RRB-

and

BE

-LRB-

sd

-RRB-

NS

-LRB-

sd

-RRB-

respectively

P

-RRB-

The

determinants

did

not

affect

this

difference

In

both

BE

and

NS

patients

specific

distress

regarding

the

endoscopy

-LRB-

IES

baseline

measurement

-RRB-

was

higher

than

regarding

the

test

result

-LRB-

IES

one

week

measurement

-RRB-

-LRB-

P

-RRB-

High

IES-distress

scores

regarding

the

endoscopy

were

seen

in

patients

-LRB-

-RRB-

CA

patients

-LRB-

mean

IES

score

-LRB-

sd

-RRB-

-RRB-

had

significantly

higher

distress

levels

-LRB-

IES

-RRB-

regarding

the

test-result

than

the

other

patient

groups

-LRB-

P

-RRB-

Discussion

This

study

is

the

first

to

investigate

determinants

of

patients

perceived

burden

of

upper

GI

endoscopy

Patients

undergoing

endoscopy

for

different

reasons

reported

a

different

burden

from

the

procedure

BE

patients

who

underwent

endoscopy

as

part

of

regular

surveillance

reported

the

lowest

discomfort

pain

and

overall

burden

confirming

our

hypotheses

in

this

respect

Patients

with

non-specific

GI

complaints

reported

more

discomfort

from

the

procedure

while

those

diagnosed

with

cancer

experienced

more

pain

and

both

groups

reported

more

overall

burden

than

patients

under

surveillance

for

BE

These

differences

remained

significant

after

adjustment

for

confounders

-LRB-

age

sex

employment

status

-RRB-

Differences

in

baseline

anxiety

scores

or

in

baseline

general

health

-LRB-

EQ

-RRB-

did

not

explain

the

differences

in

reported

discomfort

or

pain

Differences

in

the

number

of

previous

endoscopies

and

in

whether

sedation

was

provided

during

endoscopy

or

not

explained

part

of

the

differences

in

reported

discomfort

between

NS

and

BE

patients

Whether

sedation

was

provided

or

not

did

not

explain

the

differences

in

reported

pain

and

overall

burden

between

BE

and

CA

patients

The

study

also

confirms

that

that

upper

GI

endoscopy

is

burdensome

for

all

groups

of

patients

two-thirds

of

the

total

group

of

patients

reported

discomfort

and

overall

burden

from

the

procedure

and

patients

were

distressed

beforehand

These

results

may

however

underestimate

the

actual

burden

because

this

empirical

study

was

limited

to

patients

who

actually

underwent

upper

GI

endoscopy

hence

excluding

patients

who

refrained

from

undergoing

endoscopy

because

of

past

or

anticipated

adverse

experiences

Another

potential

limitation

of

our

study

results

from

the

differences

in

response

rates

between

the

groups

Differences

between

patient

groups

were

also

found

for

symptoms

resulting

from

the

endoscopy

Of

all

symptoms

explored

only

throat

ache

increased

after

upper

GI

endoscopy

CA

patients

reported

a

higher

increase

in

throat

ache

than

BE

patients

and

NS

patients

As

upper

GI

endoscopy

hardly

caused

any

symptoms

we

considered

an

investigation

into

determinants

of

these

differences

to

be

less

interesting

and

therefore

omitted

those

analyses

Furthermore

BE

and

NS

patients

differed

in

the

levels

of

generic

-LRB-

HAD

-RRB-

and

specific

-LRB-

IES

-RRB-

distress

they

reported

Specific

distress

-LRB-

IES

-RRB-

was

significantly

higher

in

NS

patients

than

in

BE

patients

both

regarding

the

endoscopy

itself

and

its

result

General

distress

-LRB-

HAD

-RRB-

also

differed

between

groups

BE

patients

reported

less

depression

across

all

measurements

and

the

pattern

of

anxiety

and

depression

across

measurements

was

different

However

general

distress

is

not

necessarily

related

to

the

endoscopy

The

persistent

higher

depression

scores

across

different

time

points

suggest

that

NS

patients

have

more

depressive

symptoms

in

general

but

that

this

was

not

related

to

the

endoscopy

The

different

pattern

of

anxiety

levels

before

and

after

endoscopy

however

suggests

that

the

patient

groups

also

differed

in

endoscopy-related

distress

The

pattern

corroborated

the

findings

of

the

specific

-LRB-

IES

-RRB-

distress

scores

NS

patients

were

more

distressed

than

BE

patients

before

the

endoscopy

The

investigated

determinants

did

not

explain

the

differences

between

groups

in

specific

distress

or

general

distress

pattern

except

for

the

number

of

previous

endoscopies

explaining

part

of

the

difference

in

the

depression

scores

BE

patients

thus

reported

less

distress

and

also

less

pain

or

discomfort

than

other

patient

groups

This

was

not

caused

by

differences

in

patient

characteristics

-LRB-

age

sex

employment

status

baseline

anxiety

baseline

general

health

-RRB-

There

are

several

potential

reasons

why

the

reported

burden

differs

Firstly

BE

patients

are

under

regular

surveillance

and

may

get

used

to

or

adapt

to

the

procedure

decreasing

its

burden

As

the

number

of

previous

endoscopies

explained

the

lower

distress

discomfort

and

overall

burden

reported

in

the

BE

group

we

conclude

that

getting

used

or

adapting

to

endoscopy

plays

a

role

Secondly

patients

who

perceive

a

greater

benefit

of

the

test

may

weigh

its

burden

differently

and

consequently

report

less

burden

BE

patients

potentially

have

more

to

gain

from

early

discovery

of

adenocarcinoma

than

NS

patients

who

are

usually

referred

for

endoscopy

to

detect

potential

explanations

for

their

symptoms

and

also

more

than

CA

patients

for

whom

endoscopy

and

ultrasonography

are

only

part

of

the

procedure

to

determine

their

treatment

options

and

prognosis

As

we

did

not

measure

perceived

expected

benefit

of

the

endoscopy

we

are

not

able

to

determine

whether

this

mechanism

is

part

of

the

explanation

Thirdly

the

endoscopic

procedure

was

slightly

different

for

the

different

patient

groups

CA

patients

received

sedation

more

often

Adjusting

for

this

difference

into

the

analysis

did

not

explain

the

differences

in

pain

and

overall

burden

whereas

the

difference

in

reported

discomfort

became

significant

after

adjustment

for

sedation

These

results

suggest

that

differences

in

the

proportions

of

patients

receiving

sedation

during

endoscopy

did

not

explain

the

differences

between

the

groups

and

that

sedation

was

provided

to

those

patients

who

really

needed

it

The

procedure

for

CA

patients

also

differed

they

underwent

upper

GI

endoscopy

combined

with

ultrasonography

and

for

the

combined

procedure

an

endoscope

with

a

slightly

larger

diameter

is

used

Our

data

did

not

allow

us

to

test

separately

whether

this

affected

perceived

pain

and

overall

burden

Finally

most

CA

patients

had

esophageal

carcinoma

and

this

disease

may

make

passing

the

endoscope

through

the

esophagus

more

difficult

and

therefore

more

painful

We

measured

general

psychological

distress

-LRB-

HAD

-RRB-

at

different

time

points

assuming

that

a

pattern

of

higher

distress

levels

before

compared

to

after

endoscopy

indicates

that

the

procedure

causes

distress

As

discussed

in

a

previous

paper

-LSB-

-RSB-

this

may

be

debated

for

the

reason

that

lower

distress

levels

afterwards

may

also

result

from

a

reassurance

effect

of

patients

receiving

a

negative

test

result

-LRB-

no

serious

disease

present

-RRB-

Nevertheless

the

fact

that

the

specific

distress

-LRB-

IES

-RRB-

score

relating

to

the

endoscopy

was

higher

than

the

IES

score

relating

to

the

test

outcome

led

us

to

conclude

that

the

prospect

of

undergoing

upper

GI

endoscopy

does

indeed

increase

distress

levels

Even

if

upper

GI

endoscopy

causes

HAD

anxiety

and

depression

scores

to

be

increased

before

the

endoscopy

the

relevance

of

these

increased

distress

levels

can

be

questioned

Anxiety

may

be

a

relevant

problem

with

of

patients

having

scores

indicating

clinical

anxiety

levels

at

baseline

while

the

depression

scores

are

less

worrisome

-LRB-

-RRB-

Endoscopy-specific

distress

-LRB-

IES

-RRB-

was

high

in

of

patients

and

higher

than

the

distress

related

to

the

outcome

Anxiety

scores

in

our

study

were

increased

compared

to

general

population

scores

at

all

time

points

Especially

the

fact

that

NS

patients

remained

at

increased

levels

one

month

after

endoscopy

makes

the

comparability

of

our

scores

with

the

population

scores

questionable

-LSB-

-RSB-

General

population

scores

are

not

available

for

procedure

specific-distress

-LRB-

IES

-RRB-

as

this

can

only

be

measured

in

patients

Considering

the

cut-off

values

for

clinical

scores

the

prospect

of

endoscopy

causes

moderate

distress

The

observation

that

patients

under

regular

endoscopic

surveillance

may

adapt

to

this

invasive

procedure

should

not

result

in

an

underestimation

of

the

burden

of

regular

endoscopic

surveillance

The

search

for

less

invasive

surveillance

tests

should

continue

and

frequency

of

surveillance

should

preferably

be

established

by

evidence-based

individualized

estimates

of

risk

of

progression

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O 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endoscopic surveillance
barrett esophagus
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upper gastrointestinal endoscopy
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Sonographic findings in bacterial meningitis in neonates and young infants Cranial sonography plays an important role in the initial evaluation of infants with suspected bacterial meningitis and in monitoring for complications of the disease . Echogenic widening of the brain sulci , meningeal thickening and hyperemia suggest the diagnosis in an at-risk population . Sonography can identify the presence of extra-axial fluid collections , and color Doppler sonography can be very helpful in differentiating benign enlargement of subarachnoid spaces from subdural effusions . Intraventricular debris and stranding , and an irregular and echogenic ependyma are highly suggestive findings associated with ventriculitis . Sonography can play an important role in the detection of postinfectious hydrocephalus , in the determination of the level of obstruction , and in the evaluation of intracranial compliance . Focal or diffuse parenchymal involvement can represent parenchymal involvement by cerebritis , infarction , secondary hemorrhage or early abscess . Introduction Bacterial meningitis is an uncommon but serious condition in the newborn and infant child . The incidence of bacterial meningitis has shown a dramatic decline in the last 25 years in the United States -LSB- 1 -RSB- . But despite a number of recent advances in neonatal intensive care , rapid bacteriological assays , and potent antibiotics , neonatal bacterial meningitis remains an important cause of neurological disability worldwide -LSB- 2 -- 4 -RSB- . Early diagnosis of the primary disease and its complications is essential for the prevention of neurodevelopmental sequelae . Cranial sonography is often the first imaging modality used in the evaluation of critically ill infants with suspected meningitis . Thus , familiarity with the pathophysiology and sonographic appearance of bacterial meningitis is important for the radiologist and neonatologist taking care of these patients . In this article we review and update the US features of bacterial meningitis and its complications with emphasis on the relationship between imaging findings and underlying pathological changes . Pathophysiology of meningitis Bacterial meningitis usually occurs as a result of bacteremia and sepsis , with initial seeding of the central nervous system via the choroid plexus . The infection then spreads into the cerebrospinal fluid -LRB- CSF -RRB- and can cause inflammation of the ventricular system -LRB- ventriculitis -RRB- . Inflammation of the meninges typically follows -LSB- 2 , 5 -RSB- . A key feature of arachnoiditis is the presence of vasculitis , predominantly in small and medium-size veins that traverse the subarachnoid space -LSB- 5 -RSB- . Meningeal inflammation extends to the walls of the bridging and cortical veins to cause thrombophlebitis and vascular occlusion , which is associated with cortical infarcts -LSB- 5 , 6 -RSB- . A number of bacterial virulence factors and inflammatory cytokines contribute to the inflammatory process , resulting in diffuse cerebral edema , increased intracranial pressure , and alterations of cerebral blood flow -LSB- 7 -- 9 -RSB- . Lipopolysaccharides found in the bacterial cell wall can lead to a disruption in the blood -- brain barrier and invasion of microorganisms into deeper cerebral structures -LSB- 10 , 11 -RSB- . Arachnoiditis and ventriculitis might also contribute to a more generalized encephalopathy characterized by neuronal loss , gliosis and periventricular leukomalacia -LSB- 2 -RSB- . Later pathological findings include diffuse cerebral cortical and white matter atrophy , hydrocephalus , which can also be seen in the early phase , multicystic encephalomalacia , porencephaly and ventricular septations -LSB- 2 , 3 , 5 , 12 , 13 -RSB- . In the acute phase of meningitis , marked vasodilatation of cortical vessels is often present as the result of potent vasogenic effects of bacterial toxins . In later stages of the disease , there is a global reduction in cerebral blood flow attributed to impairment of cerebral autoregulation and brain edema -LSB- 14 -RSB- . In the newborn infant , streptococcus group B , Escherichia coli , and Listeria monocytogenes are the most commonly isolated organisms in CSF . Although other gram-negative enteric organisms such as Klebsiella species and Citrobacter species are less common , they can have far more devastating consequences -LSB- 15 -RSB- . Sonographic features of meningitis Sonographic abnormalities are present in approximately 65 % of infants with acute bacterial meningitis -LSB- 3 , 16 -- 22 -RSB- . However , the frequency of imaging abnormalities in patients with a clinical presentation complicated by persistent seizures , abnormal neurological findings and a deterioration of CSF examination within the first 48 h can be as high as 100 % -LSB- 17 -RSB- . The high incidence of positive sonograms in infants with suspected complications resulted in the recommendation by some authors to use sonography only when there is a clinical suspicion of a complication -LSB- 3 -RSB- . Han et al. -LSB- 3 -RSB- found that no infant without a clinical indication of complications of meningitis had clinically significant findings on sonography . However , other authors suggest a sonographic examination should be used on every infant with or without evidence of complications on the basis of reports of a high incidence of positive findings in infants without any clinical indication of complications -LSB- 17 , 23 , 24 -RSB- . Rosenberg et al. -LSB- 23 -RSB- suggest an initial examination at the time of diagnosis of bacterial meningitis and a follow-up study within 1 week if the initial study demonstrates any parenchymal or ventricular abnormality . We recommend cranial sonography as a baseline study in every infant who has an adequate size fontanel if the diagnosis of bacterial meningitis is suspected clinically . Because the major advantage of sonography is its ability to be safely repeated , a second study should be performed if any clinical deterioration occurs , such as increasing head circumference , occurrence of new neurological findings , and lack of response to therapy . However , in patients with complicated bacterial meningitis whose clinical situation is sufficiently stable to leave the nursery , MRI should be the next study of choice . In children , MRI is widely accepted for its safety and high soft-tissue resolution . It is superior to sonography in showing the existence and extension of the complications , especially in the posterior fossa . It has the further advantage of not using ionizing radiation . It is essential to use state-of-the-art equipment with optimized settings including linear , curved and vector probes with variable megahertz in order to perform a complete evaluation of the meninges because of the often subtle sonographic changes of bacterial meningitis -LSB- 25 , 26 -RSB- . Meningeal and extra-axial findings In healthy individuals , the pia-arachnoidal membrane is seen as an echogenic line on the surface of the brain . Normal thickness of the membrane measured from the surface of a frontal gyrus -LRB- single layer -RRB- and within a sulcus -LRB- double layer -RRB- should not exceed 1.3 mm and 2 mm , respectively -LSB- 27 -RSB- . Echogenic widening of brain sulci , or meningeal thickening , is the most common and earliest sonographic sign of meningitis , seen in 26 -- 83 % of affected patients -LRB- Fig. 1 -RRB- -LSB- 3 , 16 -- 20 , 28 -RSB- . Prominent cortical vessels can be seen within the pia-arachnoid on color Doppler sonography -LRB- Fig. 2 -RRB- . These findings reflect the intense inflammatory exudate that accumulates in the depths of the fissures and sulci , especially around the pial and subarachnoid vessels -LSB- 5 -RSB- . Despite their common occurrence , signs of meningeal inflammation are temporary and unrelated to any significant clinical or neurological outcome -LSB- 3 , 16 , 20 -RSB- . Fig. 1Thickened meninges . a Coronal sonogram through frontal lobes in an 11-week-old infant with group streptococcus group B meningitis demonstrates diffuse echogenic thickening of the leptomeninges -LRB- arrows -RRB- and prominent extra-axial fluid spaces -LRB- asterisk -RRB- . b , c Coronal sonogram on a different infant with group streptococcus group B meningitis -LRB- b -RRB- shows marked thickening of the suprasellar cisterns -LRB- arrows -RRB- , compared to a normal infant -LRB- c -RRB- Fig. 2Vasodilatation of pial vessels . Angled sagittal midline color Doppler sonogram in a 3-week-old infant with streptococcus group B meningitis shows prominent vascularity along the surface of the brain parenchyma and a patent superior sagittal sinus -LRB- arrowheads -RRB- Accumulation of extra-axial fluid might be present in 8 -- 33 % of infants with bacterial meningitis . Most commonly , these represent sterile , reactive subdural effusions that have no prognostic significance -LSB- 3 , 16 , 19 , 20 , 28 -RSB- . On sonography , they appear as hypoechoic concave fluid spaces , sometimes containing mobile echogenic debris -LRB- Fig. 3 -RRB- . Empyema is a very rare complication of meningitis , present in up to 1 % of affected patients -LSB- 3 , 5 , 17 , 24 -RSB- . Although it is often difficult to differentiate a sterile effusion from an early empyema -LSB- 28 -RSB- , an enlarging complex extra-axial fluid space is a concerning finding . Such spaces can become quite large and cause a mass effect on the adjacent brain parenchyma -LSB- 29 -RSB- -LRB- Fig. 4 -RRB- . Clinical findings including persistent fever , new focal neurological signs or seizures are not sufficient for suspicion of subdural empyema because they are not specific for the diagnosis of empyema -LSB- 30 -RSB- . Hence , a combination of imaging modalities and clinical evaluation is necessary for the early diagnosis of subdural empyema . The final diagnosis is based on the analysis of the subdural effusion -LSB- 31 -RSB- . Fig. 3Subdural effusion . a Coronal midline sonogram in a 3-week-old infant with streptococcus group B meningitis shows echogenic debris within subdural fluid . b Axial diffusion-weighted MR image shows markedly hyperintense signal in the extra-axial fluid consistent with restricted diffusion caused by meningeal edema or pusFig . 4Subdural empyema . a Angled sagittal sonogram in a 1-week-old infant with E. coli meningitis shows thickened septations in the subdural space -LRB- arrows -RRB- . b Repeated sonogram at 2 weeks of age shows a complex heterogeneous collection consistent with focal empyema -LRB- arrows -RRB- . Needle aspiration confirmed the presence of pus The distinction between subarachnoid and subdural location of extra-axial fluid is important in the management of infants with meningitis . Isolated subarachnoid fluid spaces up to 3.3 mm are considered incidental findings of no clinical importance in meningitic infants , whereas neurosurgical evacuation is the therapy of choice for infected subdural effusions -LRB- empyema -RRB- -LSB- 25 , 32 -RSB- . Early detection with frequent sonographic monitoring of subdural effusions might lessen the neurological sequelae in infantile and neonatal purulent meningitis -LSB- 33 -RSB- . Color Doppler sonography can be very helpful in differentiating benign enlargement of subarachnoid spaces from subdural effusions -LSB- 34 , 35 -RSB- . When subarachnoid fluid is present cortical vessels on the brain surface are surrounded by fluid , whereas fluid in the subdural space compresses the cortical vessels along the surface of the brain -LRB- Fig. 5 -RRB- . Fig. 5Subdural fluid . Midline coronal color Doppler sonogram in an 11-week-old infant with group streptococcus group B meningitis shows cortical vessels along the surface of the left hemisphere -LRB- blue vessels -RRB- . Vasculature is located in the pia-arachnoid space and is not surrounded by fluid . This finding strongly suggests that fluid is in the subdural space . Note the superior sagittal sinus -LRB- asterisk -RRB- Intraventricular findings The most common sonographic signs of ventriculitis include an irregular and echogenic ependyma , the presence of intraventricular debris and stranding , often associated with ventricular dilatation . Debris in the ventricles can be caused by any infecting organism ; however , it is most frequently seen with E. coli meningitis -LSB- 3 , 36 -RSB- . The amount and coarseness of intraventricular debris can vary considerably -LRB- Fig. 6 -RRB- and reflects the extent of ventriculitis . Sonographic resolution of intraventricular debris reflects the efficacy of antibiotic treatment -LSB- 37 -RSB- . Inflammation within the ventricles can cause intraventricular adhesions and formation of septae as a more chronic complication of meningitis in about 10 % of patients -LSB- 21 , 28 , 38 -RSB- . These adhesions can cause compartmentalization in the ventricles , leading to intraventricular cyst formation -LRB- Fig. 7 -RRB- . The identification of the ventricular septations is very important in planning for appropriate shunt placement . Sonography is the study of choice for the demonstration of these septations , often demonstrating them better than CT -LSB- 38 -RSB- . Fig. 6Ventriculitis . a -- c Coronal -LRB- a -RRB- , left sagittal -LRB- b -RRB- , and mastoid sonograms -LRB- c -RRB- obtained in a 12-day-old premature infant with E. coli meningitis show extensive septations and echogenic debris clots filling the lateral , third and fourth ventricles . Note the echogenic thickening of edematous ependyma -LRB- arrows -RRB- . d Repeat coronal sonogram at 19 days of age shows a decrease in size and heterogeneity of the intraventricular debris . Note progression of ventricular dilatationFig . 7Cyst formation . Coronal image obtained in a 5-week-old infant with E. coli meningitis shows a midline cyst displacing the third ventricle -LRB- arrow -RRB- superiorly and to the right Although histopathological studies have shown exudative inflammation of the choroid plexus -LRB- plexitis -RRB- and of the ependymal lining -LRB- ventriculitis -RRB- in up to 93 % of those autopsied -LSB- 5 , 13 -RSB- , only those with more severe involvement exhibit abnormal findings on cranial sonography -LSB- 3 , 16 , 20 , 28 -RSB- . By US examination , the choroid plexus can appear more echogenic and its contours irregular and poorly defined -LSB- 16 , 28 , 38 , 39 -RSB- . The ependyma can have a thick , irregular and echogenic appearance , as well -LSB- 20 , 28 , 37 -- 39 -RSB- . Parenchymal findings Abnormal parenchymal echogenicity Areas of abnormal brain echogenicity have been reported in 12 % to 65 % of infants with bacterial meningitis -LSB- 3 , 20 , 28 -RSB- . Lesions can be focal or diffuse and can represent parenchymal involvement by cerebritis , infarction , secondary hemorrhage or early abscess -LSB- 3 , 17 , 40 -RSB- . The presence and size of parenchymal lesions are associated with significant neurological sequelae and are indicators of a poor prognosis -LSB- 3 -RSB- . One of the most devastating complications of bacterial meningitis is abscess formation . It has been reported with a frequency of between 1 % and 18 % in newborns with meningitis -LSB- 2 , 3 , 16 , 21 , 28 -RSB- . Mortality rates are significant -LRB- 15 -- 75 % -RRB- , and up to 66 % of survivors develop neurological sequelae -LSB- 41 , 42 -RSB- . Most cerebral abscesses are caused by a member of the Enterobacteriaceae family -LRB- Citrobacter and Enterobacter species -RRB- -LSB- 43 , 44 -RSB- . Citrobacter koseri -LRB- formerly C. diversus -RRB- is the main causative agent leading to abscess formation in the brain -LSB- 43 , 45 -RSB- . Up to 77 % of infected patients develop an intracerebral abscess . The major pathological feature of Citrobacter meningitis is vasculitis followed by infarction , with necrosis and liquefaction of large portions of the white matter of the hemispheres -LSB- 45 , 46 -RSB- . Hemorrhagic necrosis and liquefaction can also occur -LSB- 43 , 46 -RSB- . Surgical drainage of these lesions is not recommended to avoid further damage to surrounding brain parenchyma -LSB- 46 -RSB- . The sonographic appearance of abscess varies with the stage of the infection . During the initial stage of cerebritis , sonography might only show a poorly marginated area of increased echogenicity with increased vascularity using color or power Doppler -LSB- 2 -RSB- -LRB- Fig. 8 -RRB- . As the abscess matures the lesion becomes a well-circumscribed , complex solid mass with highly echogenic walls -LSB- 3 , 21 -RSB- . After progression with/or without antibiotic therapy the lesions progress to cavitation with marked peripheral hyperemia -LSB- 16 , 21 , 47 , 48 -RSB- . Sonographic differentiation between hemorrhagic necrosis and abscess is not always possible , and percutaneous sampling of the intracavitary fluid might be necessary . Sonographic guidance can be useful for puncture , aspiration , and irrigation of the abscess cavity -LSB- 49 , 50 -RSB- . Fig. 8Liquefactive cerebritis . a , b Coronal -LRB- a -RRB- and sagittal right -LRB- b -RRB- sonograms through the frontal lobes in a full-term infant with Citrobacter meningitis show extensive echogenic cerebritis involving the right frontal lobe and basal ganglia . c Repeated sonogram 5 days later shows early liquefaction of the frontal lobe -LRB- arrow -RRB- . d , e Coronal sonogram obtained after 7 days -LRB- d -RRB- demonstrates complete liquefaction of involved brain and surrounding hyperemia on color Doppler sonography -LRB- e -RRB- . Needle aspiration revealed necrotic tissue with no organism Brain edema In the acute stage of meningitis , both intra - and extracellular edema can occur . As a result , the lateral ventricles as well as the other cisternal structures can be compressed or obliterated -LSB- 5 -RSB- . The range of ventricular size is quite wide , from mild compression to complete sonographic obliteration , the latter being a poor prognostic factor -LSB- 28 , 51 -RSB- . On sonography , there might be a diffuse or heterogeneous increase in the echogenicity of the brain with effacement of the sulci and gyri -LSB- 20 , 23 , 28 , 50 , 52 -RSB- -LRB- Fig. 9 -RRB- . Increased intracranial pressure is associated with increased pulsatility of arterial flow , reflected in elevated resistive index -LRB- RI -RRB- values on pulsed Doppler sonography . Other causes of elevated pulsatility of flow include venous thrombosis -LRB- Fig. 10 -RRB- , large extra-axial fluid collections , and postinfectious hydrocephalus . Retrograde blood flow during diastole is an indication of markedly altered intracranial compliance -LSB- 53 -- 57 -RSB- . When equivalent antegrade and retrograde blood flow is present during numerous cardiac cycles , this might be an indication of nonviable brain blood flow -LSB- 35 , 58 -RSB- . Fig. 9Brain edema . Coronal sonogram in a 7-day-old infant with group B streptococcus meningitis shows generalized edema with compression of lateral ventricles and sulci and diffuse increased heterogeneity of the cerebral hemispheresFig . 10Sagittal sinus thrombosis , nonviable blood flow . a Coronal color Doppler image an 18-day-old infant with group B streptococcus meningitis shows flow limited to internal carotid arteries at the base of the brain . b On the magnified coronal color Doppler image no flow is identified in the superficial sagittal sinus -LRB- arrows -RRB- , and the thrombosis of the sinus was also confirmed on sagittal scans using high-sensitivity Doppler settings -LRB- not shown -RRB- . c Duplex Doppler waveform of the anterior cerebral artery without fontanel compression shows reversal of flow during the entire diastolic phase Diffuse cerebral atrophy , multicystic encephalopathy , and porencephaly might be seen as the end-stage of complications of bacterial meningitis . Hydrocephalus Ventricular dilatation is present in 14 -- 65 % of infants with bacterial meningitis and can occur in either the acute or the chronic phase of the disease -LSB- 16 -- 21 , 28 -RSB- . The level of obstruction to CSF flow is usually outside the ventricular system but can occur within the narrowest portions of the ventricles as a result of ependymitis and secondary adhesion . Common locations for intraventricular obstruction include the aqueduct of Sylvius and the exit foramina of the fourth ventricle -LSB- 16 -RSB- . Sonography can play an important role in the detection of hydrocephalus , in the determination of the level of obstruction , and in the evaluation of intracranial compliance . In aqueduct stenosis the lateral and third ventricles are disproportionately dilated , the aqueduct is thickened and echogenic and the fourth ventricle is of normal size -LRB- Fig. 11 -RRB- . Detection of CSF flow through the aqueduct of Sylvius is possible by imaging the aqueduct using the mastoid fontanel view . Using power Doppler sonography , the anterior fontanel is compressed and quickly released . Particulate debris within the CSF allows power Doppler signal to be detected when CSF flows in a retrograde fashion through a patent aqueduct into the third ventricle -LSB- 59 -RSB- . Fig. 11Postinfectious hydrocephalus . a Midline sagittal sonogram in an infant with aqueductal stenosis following group B streptococcus meningitis shows dilatation of the lateral and third ventricles ; the fourth ventricle is normal . b Mastoid fontanel view of another infant with group B streptococcus meningitis shows markedly dilated lateral , third , and fourth ventricles secondary to obstruction of the fourth ventricle outlet foramina . Note the echogenic particle in the third ventricle , which could be debris or a clot Pulsed Doppler interrogation of the anterior cerebral artery before and after compression of the anterior fontanel can be a useful adjunct in the serial monitoring of infants with postinfectious hydrocephalus -LSB- 53 , 54 , 57 -RSB- . Increasing response to fontanel compression as manifested by increasing changes in arterial RI can be an indication for shunt placement in infants with rapidly progressive hydrocephalus . Sonographic evaluation of the thoracolumbar spine in infants with meningitis might reveal the presence of echogenic debris within the spinal subarachnoid space . This finding has been associated with a higher risk of progressive hydrocephalus -LSB- 60 -RSB- . Conclusion Cranial sonography continues to be an excellent front-line imaging modality in the initial diagnosis and monitoring of infants with acute bacterial meningitis and its potential complications . Its utility is enhanced by the use of alternative scanning approaches and Doppler techniques for identification of ventriculitis , extra-axial fluid collections , and hemodynamic alterations . Spinal sonography might also play a role in assessing the risk of progressive hydrocephalus .

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O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

ultrasonography
bacterial infections
central nervous system infections