Intestinal

Perforations

in

Behçet

's

Disease

Behçet

's

disease

accompanied

by

intestinal

involvement

is

called

intestinal

Behçet

's

disease

The

intestinal

ulcers

of

Behçet

's

disease

are

usually

multiple

and

scattered

and

tend

to

perforate

easily

so

that

many

patients

require

emergency

operation

The

aim

of

this

study

is

to

determine

the

extent

of

surgical

resection

necessary

to

prevent

reperforation

and

to

point

out

the

findings

of

concurrent

oral

and

genital

ulcers

and

multiple

intestinal

perforations

in

all

patients

of

our

series

During

a

study

period

information

of

Behçet

's

disease

cases

was

gathered

Among

the

patients

who

were

diagnosed

with

intestinal

Behçet

's

disease

cases

had

intestinal

perforations

needing

emergency

laparotomy

We

investigated

and

analyzed

these

cases

according

to

the

patients

demographic

characteristics

clinical

presentations

laboratory

data

and

surgical

outcome

There

were

men

and

women

ranging

from

to

years

of

age

Nine

cases

were

diagnosed

preoperatively

and

the

diagnoses

were

confirmed

in

all

cases

during

the

surgical

intervention

Surgical

resection

was

performed

in

every

patient

with

right

hemicolectomy

and

ileocecal

resection

in

cases

partial

ileum

resection

in

cases

with

two

reperforations

and

ileocecal

resection

in

cases

with

one

reperforation

Introduction

Behçet

's

syndrome

is

a

systemic

process

affecting

multiple

organ

Surgeons

need

to

be

aware

of

the

lethal

complication

of

Behçet

's

disease

with

intestinal

ulcers

which

tend

to

perforate

at

multiple

A

review

of

the

literature

reveals

that

involvement

of

the

gastrointestinal

tract

is

not

infrequent

Most

cases

reported

in

the

literature

are

in

the

eastern

Mediterranean

countries

and

We

report

here

a

series

of

cases

of

intestinal

Behçet

's

disease

with

multiple

perforations

treated

by

emergency

surgical

resections

Materials

and

Methods

During

the

years

from

July

to

June

patients

with

Behçet

's

disease

were

encountered

at

the

Cardinal

Tien

Hospital

and

Tri-Service

General

Hospital

Taipei

Taiwan

Eighty-two

patients

were

diagnosed

as

having

intestinal

Behçet

's

disease

which

was

based

on

the

Mason

Barnes

criteria

-LRB-

Table

-RRB-

Among

these

patients

had

intestinal

perforations

-LRB-

see

Table

for

the

details

of

these

cases

-RRB-

Table

Mason

Barnes

CriteriaMajor

SymptomsMinor

SymptomsBuccal

ulcerationsGastrointestinal

lesionsGenital

ulcerationsThrombophlebitisOcular

lesionsCardiovascular

lesionsSkin

lesionsArthritisNeurologic

lesionsFamily

historyThree

major

or

two

major

and

two

minor

criteria

are

required

to

establish

the

diagnosis

of

Behçet

's

diseaseTable

Perforation

in

Behçet

's

Disease

Encountered

at

CTH

and

TSGH

-LRB-

from

to

n

-RRB-

Case

No.Age

-LRB-

years

-RRB-

SexOral

UlcerGenital

UlcerGI

S

SOcular

SignsSkin

LesionPathergic

ReactionArthritis

or

M

F

F

M

F

M

F

Plus

signs

mean

that

the

feature

is

present

minus

signs

mean

that

the

feature

is

not

present.CTH

Cardinal

Tien

Hospital

TSGH

Tri-Service

General

Hospital

S

S

symptoms

and

signsaReperforations

at

ileum

after

partial

resection

of

ileumbReperforation

at

ileum

after

ileocecal

resection

In

of

these

cases

the

diagnosis

was

confirmed

at

surgical

resection

for

multiple

perforations

Nine

of

the

cases

had

Behçet

's

disease

with

intestinal

involvement

which

was

confirmed

preoperatively

six

were

confirmed

by

endoscopic

examination

two

by

radiological

examination

and

one

patient

had

gastrointestinal

symptoms

of

intermittent

abdominal

pain

diarrhea

and

nausea

Results

Patient

Characteristics

There

were

men

and

women

in

the

cases

investigated

The

ages

of

the

patients

with

perforated

intestinal

Behçet

's

disease

ranged

from

to

years

with

a

mean

age

of

years

The

age

at

onset

of

symptoms

of

Behçet

's

disease

varied

from

to

years

on

diagnosis

with

a

mean

age

of

years

In

Table

oral

ulcers

with

gastrointestinal

symptoms

and

signs

were

found

concurrently

in

all

cases

genital

ulcers

in

cases

ocular

lesions

in

cases

and

skin

lesions

in

cases

The

painful

oral

ulcers

-LRB-

Fig.

-RRB-

occurred

on

oral

mucosa

lips

and

in

the

larynx

They

varied

from

to

mm

in

size

and

invariably

healed

without

scarring

The

genital

ulcers

-LRB-

Fig.

-RRB-

resembled

the

oral

ulcers

in

appearance

and

course

except

that

vaginal

ulcers

were

painless

Four

patients

had

anterior

uveitis

and

eight

had

a

mild

relapsing

conjunctivitis

as

their

sole

ocular

lesion

The

nodular

cutaneous

lesions

resembled

those

of

erythema

nodosum

and

were

chronic

and

multiple

Most

lesions

occurred

on

the

chest

wall

back

-LRB-

Fig.

-RRB-

and

legs

Biopsy

of

dermal

subcutaneous

lesions

had

been

done

in

cases

In

each

of

them

a

nonspecific

vasculitis

of

subcutaneous

capillaries

and

venules

was

present

-LRB-

Fig.

-RRB-

Pathergic

reaction

was

found

positive

in

of

patients

Figure

ulcer.Figure

ulcer.Figure

cutaneous

lesion

on

the

back.Figure

characterized

by

lymphocytic

and

plasmacytic

infiltration

of

perivascular

tissue

-LRB-

hematoxylin

and

eosin

-RRB-

There

were

no

specific

immunologic

abnormalities

in

any

of

the

patients

tested

-LRB-

Table

-RRB-

The

levels

of

immunoglobulin

were

variable

IgG

was

increased

in

of

patients

IgA

in

patients

and

IgM

in

patients

There

was

a

significant

decrease

of

IgG

in

two

patients

and

of

IgA

in

one

patient

The

total

hemolytic

complement

was

normal

in

all

serum

samples

globulin

was

increased

in

of

patients

and

gamma

globulin

was

increased

in

seven

patients

Table

DataCase

No.Immunoglobulins

-LRB-

mg/dl

-RRB-

Serum

Complement

-LRB-

mg/dl

-RRB-

Globulin

-LRB-

-RRB-

IgGIgAIgMC

411,9763752501453813.823.821,726245174924012.010.842,1504002401104514.224.651,500590300382510.518.07

.814.381,18019514059326.612.292,2704642621274614.016.2111,8503802501905012.523.512

,30032023588399.615.0142,3504902951804813.325.01668098561503513.021.817

,65047528076349.412.5181,8002901501054513.823.2192,4185812091664014.428.0211,8803302501803510.520.0221,9853862281683813.824.2

Normal

aReperforations

at

ileum

after

partial

resection

of

ileumbReperforation

at

ileum

after

ileocecal

resection

Multiple

concurrent

penetrating

ulcers

-LRB-

Fig.

-RRB-

were

found

in

all

cases

with

multiple

perforation

sites

identified

from

terminal

ileum

to

the

ascending

colon

-LRB-

Table

-RRB-

The

size

and

number

of

perforated

ulcers

were

variable

ranging

from

to

cm

in

size

and

to

in

number

The

perforations

were

found

at

the

ileocecal

region

and

ascending

colon

in

cases

at

the

terminal

ileum

in

cases

and

at

the

cecum

and

ascending

colon

in

cases

Figure

specimen

of

ileocecal

region

showing

multiple

penetrating

ulcers.Table

Findings

and

Operation

Performed

in

Perforated

Intestinal

Behçet

's

Disease

PatientsCase

No.Location

of

Perforated

UlcersNo

of

PerforationsOral/genital

UlcerOperation

Partial

resection

of

the

Partial

resection

of

the

region

and

ascending

Right

hemicolectomy

and

ileocecal

region

and

ascending

Right

hemicolectomy

and

ileocecal

and

ascending

Ileocecal

Partial

resection

of

the

Partial

resection

of

the

and

ascending

Right

hemicolectomy

and

ilececal

Partial

resection

of

the

region

and

ascending

Right

hemicolectomy

and

ileocecal

region

and

ascending

Right

hemicolectomy

and

ileocecal

Partial

resection

of

the

Partial

resection

of

the

region

and

ascending

Right

hemicolectomy

and

ileocecal

region

and

ascending

Right

hemicolectomy

and

ileocecal

region

and

ascending

Right

hemicolectomy

and

ileocecal

and

ascending

Ileocecal

region

and

ascending

Right

hemicolectomy

and

ileocecal

region

and

ascending

Right

hemicolectomy

and

ileocecal

and

ascending

Ileocecal

Partial

resection

of

the

region

and

ascending

Right

hemicolectomy

and

ileocecal

resectionaReperforations

at

ileum

after

partial

resection

of

ileumbReperforation

at

ileum

after

ileocecal

resection

Operative

Treatment

and

Outcome

All

perforated

intestinal

Behçet

's

disease

cases

were

confirmed

at

operation

with

nine

of

them

correctly

diagnosed

preoperatively

Surgical

resection

of

the

perforated

intestinal

ulcers

was

done

in

all

cases

with

right

hemicolectomy

and

ileocecal

resection

in

cases

partial

ileum

resection

in

cases

and

ileocecal

resection

in

cases

No

reperforation

occurred

in

the

group

of

patients

who

underwent

right

hemicolectomy

and

ileocecal

resection

However

two

reperforations

ocurred

in

patients

who

underwent

partial

ileum

resection

alone

and

one

in

the

ileocecal

resection

group

The

pathologic

study

of

the

resected

specimens

showed

nonspecific

inflammatory

reactions

with

the

infiltration

of

lymphocytes

and

plasma

cells

as

the

predominant

finding

-LRB-

Fig.

-RRB-

Histological

sections

from

the

ulcer

walls

showed

changes

consistent

with

a

nonspecific

ulcerative

inflammatory

process

and

infiltration

containing

both

plasma

cells

and

chronic

inflammatory

cells

Figure

inflammatory

response

and

perivascular

infiltration

-LRB-

hematoxylin

and

eosin

-RRB-

After

operation

on

these

patients

with

Behçet

's

disease

and

intestinal

perforation

four

patients

died

during

the

postoperative

course

due

to

septic

shock

which

was

present

prior

to

the

surgical

intervention

three

died

from

complications

of

hypertension

and

diabetes

mellitus

and

three

were

lost

to

follow-up

Thus

only

patients

are

still

under

observation

without

evidence

of

gastrointestinal

complications

up

to

this

date

The

remaining

cases

of

intestinal

Behçet

's

disease

without

perforations

are

still

under

surveillance

Discussion

In

Behçet

described

a

chronic

relapsing

triple-symptom

complex

of

oral

ulceration

genital

ulceration

and

ocular

Over

the

years

it

has

become

apparent

that

the

process

is

a

systemic

recurrent

inflammatory

disease

affecting

a

number

of

organs

In

Bechgaard

first

described

intestinal

involvement

in

Behçet

's

disease

Tsukada

et

al.

proposed

the

term

intestinal

Behçet

's

disease

in

Baba

et

al.

agreed

to

this

proposal

and

cited

cases

of

the

disease

treated

from

Since

then

the

number

of

operations

reported

has

increased

but

perforated

intestinal

Behçet

's

disease

is

still

rarely

reported

In

a

large

review

series

Oshima

and

colleagues

reported

that

of

patients

with

Behçet

's

disease

had

gastrointestinal

complaints

such

as

nausea

vomiting

and

abdominal

The

age

at

onset

of

these

symptoms

ranges

from

to

years

and

the

male-to-female

ratio

ranges

from

to

Our

cases

were

in

accordance

with

this

reported

age

range

and

sex

ratio

The

third

decade

is

the

most

commonly

reported

age

of

onset

for

Behçet

's

and

the

fourth

decade

for

intestinal

Behçet

's

In

our

study

intestinal

Behçet

's

disease

occurred

at

a

mean

age

of

years

However

Behçet

's

disease

and

intestinal

involvement

were

diagnosed

simultaneously

in

some

of

these

patients

most

of

whom

had

already

experienced

systemic

manifestations

The

exact

cause

of

this

disease

still

remains

an

enigma

Current

hypotheses

include

allergic

vasculitis

of

small

vessels

autoimmune

disease

and

immunologic

The

deposition

of

immune

complexes

in

the

walls

of

small

blood

vessels

was

found

by

the

laboratory

results

of

three

of

our

cases

and

this

process

has

been

proposed

as

one

of

the

underlying

pathologic

mechanisms

in

intestinal

Behçet

's

Since

no

clinicopathologic

findings

are

pathognomonic

in

this

disease

the

diagnosis

is

made

on

the

basis

of

combinations

of

various

clinical

symptoms

and

Mason

and

Barnes

constructed

an

elaborate

set

of

major

and

minor

criteria

for

They

suggested

the

triad

of

buccal

ulceration

genital

ulceration

and

eye

lesion

and

skin

lesion

as

major

symptoms

The

minor

symptoms

included

gastrointestinal

lesions

arthritis

thrombophlebitis

cardiovascular

lesions

neurologic

lesions

and

family

history

Three

major

criteria

or

two

major

criteria

and

two

minor

criteria

are

necessary

for

diagnosis

These

various

symptoms

are

not

usually

present

at

the

same

time

If

we

hold

the

original

triple-symptom

complex

as

a

prerequisite

for

the

diagnosis

cases

may

be

missed

In

the

International

Study

Group

for

Behçet

's

introduced

a

diagnostic

criteria

requiring

the

presence

of

oral

ulcerations

plus

any

two

of

the

following

genital

ulcerations

typical

eye

lesions

typical

skin

lesions

or

positive

results

to

a

pathergy

test

However

some

reports

have

shown

that

almost

of

patients

with

Behçet

's

disease

presented

without

oral

lesions

Furthermore

of

patients

did

not

show

any

oral

lesions

at

In

our

series

all

patients

had

manifestations

of

concurrent

oral

ulceration

All

perforated

cases

present

oral

or

genital

ulcerations

at

the

same

time

Because

we

warned

that

patients

of

intestinal

Behçet

's

disease

may

have

abdominal

pain

and

oral

or

genital

ulcerations

concurrently

intestinal

perforations

should

always

be

kept

in

mind

A

phenomenon

of

pathergy

was

first

described

by

Blobner

in

and

was

further

elaborated

by

Katzenellenbogen

in

It

consists

of

an

itradermal

test

applied

to

Behçet

's

disease

patients

with

a

sharp

needle

prick

causing

skin

hypersensitivity

which

is

characterized

by

the

formation

of

a

sterile

pustule

to

h

after

the

trauma

Biopsy

at

the

intradermal

puncture

site

is

taken

h

after

for

histopathologic

evaluation

In

a

study

conducted

by

Tuzum

et

al.

this

reaction

was

found

to

be

positive

in

of

patients

with

the

disease

as

compared

to

of

healthy

A

positive

pathergic

reaction

should

make

us

aware

of

the

possibility

of

the

disease

in

the

presence

of

any

of

the

accepted

symptoms

of

this

process

However

the

recent

results

and

interpretations

of

pathergy

tests

have

varied

widely

according

to

the

technical

aspects

of

the

and

ethnic

differences

of

the

patients

The

histological

lesions

in

Behçet

's

disease

are

rather

uncharacteristic

Nonspecific

perivascular

infiltrations

of

plasma

cells

and

lymphocytes

are

usually

found

in

the

cutaneous

and

mucosal

The

intestinal

ulcers

in

Behçet

's

disease

are

characterized

not

only

by

the

absence

of

the

granulomatous

formation

of

Crohn

's

disease

but

also

by

deeper

penetration

of

the

ulcers

to

areas

nearer

to

serosa

membrane

than

the

ulcers

of

ulcerative

The

ulcers

tend

to

be

undermined

and

the

submucosal

connective

tissues

are

usually

destroyed

The

bases

of

the

ulcers

are

avascular

with

edema-like

swelling

and

crater-shaped

formation

around

the

ulcer

margin

These

ulcers

are

usually

found

in

the

terminal

ileum

and

the

cecum

but

they

may

be

present

at

any

site

throughout

the

digestive

system

and

tend

to

perforate

at

multiple

The

gross

pathologic

characteristics

of

our

intestinal

Behçet

's

disease

included

perforations

at

multiple

sites

concurrently

in

variable

sizes

and

configurations

extending

from

the

ileocecal

region

to

ascending

colon

in

accordance

with

the

reported

The

medical

treatment

of

the

intestinal

Behçet

's

disease

remains

unsettled

The

beneficial

effect

of

steroid

therapy

has

not

been

convincing

in

most

It

may

control

the

disease

initially

but

recurrences

are

common

Topical

application

of

corticosteroids

decreases

the

ocular

inflammation

and

is

also

useful

in

relieving

the

pain

of

oral

ulcers

Haim

and

Sherf

reported

a

favorable

response

to

fresh

blood

and

plasma

in

cases

of

Behçet

's

disease

but

the

nature

of

the

useful

component

in

hematotherapy

is

In

our

two

patients

with

perforations

steroid

therapy

was

given

for

weeks

after

surgery

with

favorable

outcomes

Resection

of

the

ileocecal

region

or

the

right

half

of

the

colon

is

the

usual

operation

in

the

treatment

of

gastrointestinal

In

our

series

perforations

at

multiple

sites

were

found

in

all

cases

right

hemicolectomy

and

ileocecal

resection

were

performed

in

cases

without

reperforation

ileocecal

resection

in

cases

with

one

reperforation

and

partial

resection

of

the

ileum

in

cases

with

two

reperforations

Conclusion

Because

concurrent

oral

and

genital

ulcers

were

found

in

all

patients

in

our

series

the

presentation

of

this

seemingly

innocuous

clinical

manifestation

along

with

gastroinstestinal

symptoms

should

raise

the

level

of

suspicion

that

intestinal

involvement

and

complications

of

perforations

may

have

already

happened

The

other

constant

finding

among

our

patients

is

that

all

the

intestinal

perforations

were

located

between

the

terminal

ileum

and

the

ascending

colon

Therefore

to

prevent

reperforations

wide

excision

of

the

terminal

ileum

with

right

hemicolectomy

is

recommended

for

perforated

intestinal

Behçet

's

disease

We

found

out

that

the

specimens

of

the

resected

bowel

of

the

nonreperforated

patients

all

had

more

than

cm

of

terminal

ileum

but

those

of

the

three

reperforated

cases

had

less

than

cm

Furthermore

the

perforation

sites

were

all

at

to

cm

proximal

to

the

anastomosis

This

is

the

main

reason

we

recommend

the

resection

of

up

to

cm

of

ileum

from

the

ileocecal

valve

at

the

time

of

right

B I 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 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 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 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 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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

intestinal ulcers
intestinal perforations


Societal

Burden

of

Clinically

Anxious

Youth

Referred

for

Treatment

A

Cost-of-illness

Study

A

prevalence-based

cost-of-illness

study

using

a

societal

perspective

was

conducted

to

investigate

the

cost-of-illness

in

clinically

anxious

youth

aged

in

The

Netherlands

Discriminant

validity

of

the

cost

diary

used

was

obtained

by

comparing

costs

of

families

with

an

anxious

child

-LRB-

n

-RRB-

to

costs

of

families

from

the

general

population

-LRB-

n

-RRB-

To

examine

the

convergent

validity

bottom-up

acquired

costs

derived

from

cost

diaries

were

compared

to

top-down

acquired

costs

obtained

from

national

registrations

Bottom-up

acquired

costs

measured

by

means

of

cost

diaries

amounted

to

per

family

of

a

clinically

referred

anxious

child

per

annum

Societal

costs

of

families

with

clinically

anxious

children

were

almost

times

as

high

compared

to

families

from

the

general

population

With

respect

to

convergent

validity

total

health

care

costs

using

the

bottom-up

approach

from

clinically

anxious

children

were

quite

comparable

to

those

of

top-down

data

of

anxious

children

although

costs

within

the

subcategories

differed

considerably

Clinical

anxiety

disorders

in

childhood

cost

the

Dutch

society

more

than

million

euros

a

year

Based

on

results

of

discriminate

and

convergent

validity

the

cost

diary

seems

a

valid

method

in

establishing

cost-of-illness

in

childhood

anxiety

disorders

Anxiety

disorders

are

among

the

most

common

childhood

mental

disorders

Prevalence

rates

for

children

with

anxiety

disorders

vary

considerably

in

the

international

literature

from

-LRB-

Anderson

et

al.

-RRB-

to

-LRB-

Kessler

et

al.

-RRB-

In

The

Netherlands

a

prevalence

rate

of

for

anxiety

disorders

was

found

in

to

adolescents

When

impairment

in

daily

functioning

is

taken

into

consideration

Klein

and

Pine

-LRB-

-RRB-

estimated

the

prevalence

rate

to

be

between

and

A

Dutch

study

revealed

that

the

prevalence

rate

of

severely

interfering

child

anxiety

disorders

is

-LRB-

Verhulst

et

al.

-RRB-

The

yearly

prevalence

rate

of

children

with

a

mental

disorder

seeking

treatment

in

mental

health

care

ranges

from

-LRB-

Sytema

and

Koopmans

-RRB-

to

-LRB-

Leaf

et

al.

-RRB-

In

The

Netherlands

merely

of

to

children

with

a

mental

disorder

had

been

referred

yearly

to

mental

health

care

for

treatment

-LRB-

Verhulst

and

van

der

Ende

-RRB-

This

latter

percentage

resembles

the

of

Dutch

people

with

anxiety

disorders

who

are

referred

for

further

treatment

by

their

general

practitioner

-LRB-

van

Wieren

et

al.

-RRB-

With

respect

to

costs

the

total

costs

for

anxiety

disorders

in

adults

were

highest

of

all

mental

illnesses

namely

billion

dollars

accounting

for

of

total

expenditures

for

mental

health

in

in

the

USA

-LRB-

Dupont

et

al.

-RRB-

Greenberg

and

colleagues

-LRB-

-RRB-

estimated

the

annual

costs

of

anxiety

disorders

in

adults

to

be

billion

dollars

in

the

USA

in

by

extrapolating

the

costs

of

Besides

direct

costs

of

treating

anxiety

disorders

indirect

costs

due

to

impaired

social

functioning

such

as

financial

dependence

and

unemployment

also

are

found

in

adults

with

anxiety

disorders

-LRB-

Leon

et

al.

-RRB-

In

The

Netherlands

health

care

costs

of

anxiety

disorders

across

all

ages

were

million

euro

in

accounting

for

of

the

health

care

budget

More

specifically

health

care

costs

due

to

anxiety

disorders

in

to

children

and

young

adults

amounted

to

million

euros

-LRB-

Polder

et

al.

-RRB-

An

analysis

to

measure

the

magnitude

of

costs

related

to

illness

is

called

a

cost-of-illness

study

and

involves

an

estimation

of

the

total

economic

burden

which

an

illness

imposes

on

society

The

main

objective

of

a

cost-of-illness

study

is

to

translate

the

burden

on

society

into

monetary

costs

Typically

in

a

cost-of-illness

study

all

costs

associated

with

a

particular

illness

are

identified

and

measured

including

health

care

costs

patient

and

family

costs

and

costs

occurring

in

other

sectors

The

results

of

a

cost-of-illness

study

can

be

used

to

gain

insight

in

how

much

society

is

spending

on

a

disease

and

how

much

potentially

can

be

saved

if

effective

treatment

is

offered

Also

it

identifies

the

different

cost

categories

and

the

size

of

the

contribution

of

each

sector

in

society

The

information

coming

from

cost-of-illness

studies

can

be

helpful

in

setting

priorities

for

health

care

efficiency

research

-LRB-

Ament

and

Evers

Polder

et

al.

Rice

and

Miller

-RRB-

Essentially

there

are

two

approaches

to

establish

the

cost-of-illness

namely

the

bottom-up

and

the

top-down

approach

The

bottom-up

approach

acquires

data

on

the

patient

level

by

means

of

registrations

or

self-report

measures

Self-report

measures

contain

retrospective

cost

questionnaires

retrospective

cost

interviews

or

prospective

cost

diaries

-LRB-

Bruijnzeels

et

al.

Sleed

et

al.

-RRB-

The

bottom-up

approach

enables

one

to

capture

resource

use

that

is

likely

to

vary

from

patient

to

patient

and

may

not

be

easily

extracted

from

existing

data

sources

Multiplying

the

costs

per

patient

by

the

national

prevalence

rate

results

in

the

total

cost-of-illness

for

a

particular

patient

group

An

advantage

of

the

bottom-up

approach

is

that

detailed

data

can

be

obtained

regarding

costs

outside

the

health

care

sector

such

as

costs

due

to

productivity

losses

out-of-pocket

costs

costs

of

informal

care

and

costs

due

to

absence

from

school

A

disadvantage

of

this

method

may

be

that

the

sample

of

patients

used

for

the

cost-of-illness

calculations

is

not

representative

of

the

entire

patient

group

for

example

due

to

strict

inclusion

and

exclusion

criteria

-LRB-

Oostenbrink

et

al.

Polder

et

al.

-RRB-

The

top-down

approach

involves

gathering

data

from

existing

-LRB-

national

-RRB-

registrations

on

total

costs

of

a

service

category

such

as

hospital

care

and

dividing

these

costs

by

an

appropriate

unit

such

as

a

patient

group

using

the

service

category

mostly

per

year

if

appropriate

While

there

are

benefits

using

this

approach

such

as

being

less

resource

intensive

this

calculation

may

also

prove

to

be

less

accurate

-LRB-

Byford

et

al.

-RRB-

Furthermore

when

using

a

top-down

approach

it

is

difficult

if

not

impossible

to

obtain

costs

outside

the

health

care

sector

-LRB-

Oostenbrink

et

al.

Polder

et

al.

-RRB-

Another

important

distinction

in

cost-of-illness

studies

is

that

costs

can

be

determined

from

a

prevalence-based

or

incidence-based

perspective

In

a

prevalence-based

approach

the

costs

of

a

disorder

are

determined

for

a

fixed

period

of

time

as

a

result

of

the

prevalence

of

the

disorder

-LRB-

number

of

cases

of

a

disorder

at

a

specific

time

-RRB-

This

period

is

called

the

base

period

and

most

often

studies

investigate

the

annual

economic

burden

thus

based

on

a

year

-LRB-

Ament

and

Evers

Rice

and

Miller

-RRB-

A

disadvantage

of

the

prevalence-based

approach

is

that

it

may

be

difficult

to

isolate

potential

differences

in

costs

by

stage

or

duration

of

the

disorder

-LRB-

Greenberg

et

al.

-RRB-

The

incidence

based

approach

estimates

the

lifetime

costs

of

an

illness

from

its

onset

thus

costs

are

assigned

to

the

year

in

which

the

illness

begins

-LRB-

Ament

and

Evers

Rice

and

Miller

-RRB-

Incidence

based

studies

can

isolate

the

differences

in

costs

by

stage

or

duration

of

the

disease

However

a

disadvantage

of

using

this

approach

is

that

follow

up

research

is

required

In

this

article

a

prevalence-based

cost-of-illness

analysis

was

performed

in

to

children

and

adolescents

with

anxiety

disorders

who

were

referred

to

treatment

The

primary

aim

of

this

study

was

to

establish

the

societal

costs

of

illness

in

families

with

a

clinically

anxious

child

using

the

bottom-up

approach

by

means

of

a

prospective

cost

diary

A

secondary

aim

of

this

study

was

to

investigate

the

discriminative

validity

of

the

prospective

cost

diary

by

comparing

the

costs

related

to

anxiety

psychological

physical

and

other

problems

in

families

with

a

clinically

anxious

child

to

the

same

costs

in

families

from

the

general

population

The

third

aim

of

this

study

was

to

establish

convergent

validity

by

comparing

bottom-up

acquired

health

care

costs

obtained

with

the

cost

diaries

of

the

clinically

anxious

children

with

top-down

acquired

health

care

costs

of

children

with

a

primary

diagnosis

of

anxiety

disorder

Materials

and

Methods

Participants

For

the

cost-of-illness

study

and

the

discriminative

validity

study

participants

were

clinically

anxious

children

and

adolescents

from

the

general

population

respectively

The

clinically

anxious

group

consisted

of

families

with

a

child

referred

for

community

mental

health

treatment

because

of

anxiety

and

participated

in

a

multi-centre

randomized

clinical

trial

comparing

family

Cognitive

Behavioural

Therapy

-LRB-

CBT

-RRB-

with

individual

CBT

-LRB-

Bodden

et

al.

submitted

for

publication

-RRB-

This

study

was

conducted

from

March

to

November

inclusion

ended

in

March

Inclusion

criteria

were

-LRB-

-RRB-

age

-LRB-

-RRB-

a

primary

anxiety

disorder

-LRB-

except

for

obsessive-compulsive

and

post-traumatic

stress

disorder

-RRB-

-LRB-

-RRB-

IQ

and

-LRB-

-RRB-

at

least

one

parent

willing

to

participate

Children

were

excluded

if

suffering

from

-LRB-

-RRB-

substance

abuse

-LRB-

-RRB-

current

suicide

attempts

-LRB-

-RRB-

psychoses

-LRB-

-RRB-

autism-spectrum

disorders

or

-LRB-

-RRB-

untreated

Attention

Deficit

Hyperactivity

Disorder

-LRB-

ADHD

-RRB-

Children

using

medication

for

their

anxiety

were

only

included

if

dosage

was

kept

constant

during

treatment

and

follow-up

There

were

girls

-LRB-

-RRB-

and

boys

-LRB-

-RRB-

range

years

-LRB-

M

SD

-RRB-

Most

were

Caucasian

-LRB-

n

-RRB-

and

-LRB-

-RRB-

attended

primary

education

The

remaining

-LRB-

-RRB-

attended

secondary

education

According

to

the

compound

diagnosis

on

the

Anxiety

Disorders

Interview

Schedule

-LRB-

ADIS

Silverman

and

Albano

-RRB-

the

mean

number

of

diagnosis

per

child

was

-LRB-

SD

-RRB-

whereas

the

mean

severity

level

of

the

primary

diagnosis

was

-LRB-

SD

-RRB-

Furthermore

primary

anxiety

diagnoses

consisted

of

social

phobia

-LRB-

n

-RRB-

separation

anxiety

-LRB-

n

-RRB-

generalized

anxiety

disorder

-LRB-

n

-RRB-

specific

phobia

-LRB-

n

-RRB-

and

panic

disorder

with

or

without

agoraphobia

-LRB-

n

-RRB-

Of

the

children

-LRB-

-RRB-

had

one

or

more

comorbid

anxiety

disorder

-LRB-

s

-RRB-

separation

anxiety

disorder

-LRB-

n

-RRB-

social

phobia

-LRB-

n

-RRB-

specific

phobia

-LRB-

n

-RRB-

panic

disorder

-LRB-

n

-RRB-

generalized

anxiety

disorder

-LRB-

n

-RRB-

obsessive-compulsive

disorder

-LRB-

n

-RRB-

and

post-traumatic

stress

disorder

-LRB-

n

-RRB-

Moreover

-LRB-

-RRB-

had

comorbid

dysthymic

disorder

or

depression

-LRB-

-RRB-

ADHD

-LRB-

-RRB-

conduct

disorder

and

-LRB-

-RRB-

oppositional

defiant

disorder

The

sample

from

the

general

population

consisted

of

a

group

of

families

who

were

recruited

via

advertisements

Children

of

these

families

were

comparable

to

children

from

the

clinically

anxious

group

based

on

gender

χ2

-LRB-

-RRB-

p

age

F

-LRB-

-RRB-

p

and

educational

level

F

-LRB-

-RRB-

p

There

were

girls

-LRB-

-RRB-

and

boys

-LRB-

-RRB-

range

years

-LRB-

M

SD

-RRB-

Most

were

Caucasian

-LRB-

n

-RRB-

and

-LRB-

-RRB-

attended

primary

school

The

remaining

-LRB-

-RRB-

attended

secondary

education

According

to

the

compound

diagnosis

on

the

ADIS

the

prevalence

of

anxiety

disorders

in

this

sample

was

-LRB-

n

-RRB-

and

-LRB-

n

-RRB-

for

ADHD

closely

resembling

Dutch

prevalence

of

anxiety

disorders

and

ADHD

respectively

and

-LRB-

Verhulst

et

al.

-RRB-

The

primary

anxiety

diagnoses

consisted

of

social

phobia

-LRB-

n

-RRB-

and

specific

phobia

-LRB-

n

-RRB-

with

a

mean

severity

level

of

-LRB-

SD

-RRB-

The

overrepresentation

of

simple

phobia

and

the

relatively

low

severity

rates

of

the

anxiety

disorders

in

the

control

group

also

support

the

normality

of

the

control

children

All

children

and

parents

received

and

signed

a

written

informed

consent

after

receiving

oral

and

written

information

on

the

study

Clinically

anxious

children

their

siblings

and

parents

were

assessed

before

treatment

and

families

from

the

general

population

were

only

measured

once

Furthermore

all

family

members

had

to

fill

in

a

battery

of

questionnaires

including

a

prospective

cost

diary

Anxiety

Disorders

Interview

Schedule

Children

's

diagnostic

status

was

assessed

using

the

Dutch

ADIS-C/P

-LRB-

Siebelink

and

Treffers

-RRB-

which

is

a

semi-structured

diagnostic

interview

measuring

anxiety

disorders

and

other

DSM-IV

childhood

psychopathology

The

severity

score

consists

of

impairment

in

daily

functioning

per

diagnosis

and

ranges

from

to

indicating

a

clinical

diagnosis

Based

on

criteria

child

and

parents

ratings

are

combined

in

a

compound

summary

The

ADIS-C/P

possesses

good

psychometric

properties

-LRB-

Silverman

et

al.

-RRB-

In

our

study

the

total

inter-rater

agreement

for

all

ADIS

diagnoses

-LRB-

kappa

-RRB-

was

averaged

and

was

for

the

ADIS-C

and

for

the

ADIS-P

The

mean

inter-rater

agreement

for

the

severity

score

was

calculated

with

correlations

and

was

for

the

ADIS-C

and

for

the

ADIS-P

Prospective

Cost

Diary

A

cost

diary

was

used

to

determine

the

resources

used

-LRB-

Freer

Goossens

et

al.

-RRB-

in

both

the

cost-of-illness

study

as

well

as

in

the

discriminative

validity

study

Cost

dairies

were

completed

prospectively

by

one

of

the

parents

and

covered

a

period

of

weeks

Families

of

clinically

anxious

children

received

the

cost

diary

weeks

before

treatment

and

the

sample

of

families

from

the

general

population

received

the

same

cost

diary

during

their

one

time

assessment

Each

cost

diary

was

presented

in

a

booklet

form

with

instructions

and

an

example

diary

The

cost

diary

was

designed

such

that

all

costs

which

are

potentially

relevant

to

society

were

captured

including

health

care

costs

patient

and

family

costs

and

costs

in

other

sectors

Parents

recorded

the

following

resource

use

visits

to

psychologist

or

psychotherapist

visits

to

the

general

practitioner

outpatient

consultations

at

the

hospital

medication

day

treatment

costs

of

paid

house

help

children

's

day

care

after

school

care

informal

care

productivity

losses

due

to

absence

of

work

by

the

parents

loss

of

household

activities

or

voluntary

work

loss

of

leisure

time

absence

from

school

of

the

child

and

out-of-pocket

costs

Informal

care

means

that

persons

near

the

family

such

as

relatives

friends

or

neighbors

take

care

of

the

family

and

possibly

take

over

some

domestic

tasks

Out-of-pocket

costs

are

actual

expenses

made

by

the

family

-LRB-

and

are

therefore

paid

out

of

the

pocket

-RRB-

and

include

for

example

transportation

costs

parking

costs

over-the-counter

medication

and

own

monetary

contributions

for

health

care

services

which

are

not

fully

reimbursed

by

health

insurance

companies

Also

parents

recorded

the

name

of

the

family

member

for

whom

the

resource

use

was

applicable

-LRB-

child

sibling

mother

or

father

-RRB-

as

well

as

the

reason

for

the

resource

use

by

that

family

member

For

analysis

the

reported

reasons

were

grouped

into

-LRB-

-RRB-

due

to

anxiety

-LRB-

-RRB-

due

to

psychological

problems

-LRB-

-RRB-

due

to

physical

problems

and

-LRB-

-RRB-

due

to

other

reasons

Unit

Prices

Costs

were

calculated

by

multiplying

the

resources

used

obtained

with

the

prospective

cost

diaries

by

the

unit

price

of

each

resource

Costs

were

calculated

at

euros

-LRB-

July

-RRB-

It

should

be

noted

that

whenever

possible

unit

prices

and

not

transfer

payments

such

as

charges

reimbursements

or

patient

bills

were

used

to

value

health

care

resource

use

Money

transfers

may

bear

little

relation

to

actual

resource

consumption

as

a

result

of

-LRB-

local

-RRB-

budgeting

agreements

and

political

negotiations

-LRB-

Finkler

-RRB-

For

example

in

The

Netherlands

hospitals

receive

an

annual

budget

As

a

consequence

the

reimbursement

of

a

day

of

hospitalization

-LRB-

which

is

the

amount

a

hospital

charges

to

a

health

care

insurance

company

-RRB-

may

vary

from

year

to

year

as

it

is

used

as

a

balancing

item

for

a

budget

overdrawing

The

key

point

is

that

the

amount

that

exchanges

hands

between

providers

third-party

payers

and

patients

are

not

necessarily

a

good

measure

of

resources

used

Therefore

for

the

valuation

of

resource

consumption

in

health

care

mostly

actual

unit

prices

are

used

which

are

obtained

by

performing

unit

price

calculations

Unit

prices

consist

of

personnel

material

and

capacity

costs

as

well

as

costs

of

housing

and

overhead

Almost

all

unit

prices

were

obtained

by

using

published

Dutch

guideline

prices

-LRB-

Oostenbrink

et

al.

-RRB-

However

medication

prices

were

obtained

from

the

Medication

and

Aid

Information

Project

database

on

the

Internet

-LRB-

Board

of

Health

Insurances

-RRB-

and

were

based

on

the

Daily

Defined

Dosage

-LRB-

DDD

-RRB-

which

indicates

the

mean

medication

usage

per

person

a

day

with

claw

back

and

value

added

tax

-LRB-

VAT

-RRB-

-LRB-

-RRB-

An

average

unit

price

was

calculated

for

medication

for

anxiety

problems

and

medication

for

psychological

problems

As

actual

unit

prices

for

day

treatment

and

institutionalization

were

not

available

the

prices

were

derived

from

the

average

of

actual

reimbursements

-LRB-

Board

Tariff

Rates

Health

Care

and

Care

Authority

-RRB-

It

should

be

noted

that

the

unit

price

of

informal

care

loss

of

leisure

time

voluntary

work

and

domestic

activities

was

based

on

a

shadow

price

as

stated

in

the

Dutch

guideline

-LRB-

Oostenbrink

et

al.

-RRB-

A

key

characteristic

of

informal

care

leisure

time

voluntary

work

and

domestic

activities

is

that

it

is

unpaid

So

these

activities

by

definition

do

not

have

an

official

unit

price

since

no

actual

payments

take

place

If

an

official

unit

price

is

not

available

resource

use

should

be

valued

against

a

shadow

price

This

means

that

informal

care

loss

of

leisure

time

voluntary

work

and

domestic

activities

were

valued

against

the

wage

rate

per

hour

of

a

housekeeper

To

determine

the

costs

associated

with

absence

from

school

actual

annual

tuition

which

consists

of

a

contribution

by

parents

and

a

state-subsidy

per

child

-LRB-

National

Institute

of

Budget

information

-RRB-

was

divided

by

the

total

annual

hours

at

school

according

to

the

standard

resulting

in

a

price

per

hour

of

school

attendance

As

the

larger

part

of

school

costs

is

fixed

such

as

the

costs

of

housing

-LRB-

teaching

-RRB-

personnel

and

school

materials

a

child

missing

school

does

not

result

in

actual

savings

Therefore

the

actual

costs

per

hour

of

school

attendance

were

used

to

value

an

hour

of

school

absence

Productivity

costs

of

the

parents

due

to

absence

from

paid

work

were

calculated

by

means

of

the

friction

cost

method

based

on

a

mean

added

value

of

the

Dutch

working

population

-LRB-

Oostenbrink

et

al.

-RRB-

This

method

only

takes

into

account

production

losses

confined

to

the

period

needed

-LRB-

usually

days

-RRB-

to

replace

a

sick

employee

Cost-of-illness

The

primary

aim

of

this

study

was

to

calculate

the

societal

burden

of

illness

of

families

of

clinically

anxious

youth

in

The

Netherlands

The

cost-of-illness

study

was

performed

from

a

societal

perspective

and

included

direct

health

care

costs

direct

non-health

care

costs

indirect

costs

and

out-of-pocket

costs

The

costs

per

family

over

a

period

of

weeks

were

extrapolated

to

a

period

of

year

-LRB-

i.e.

multiplied

by

-RRB-

under

the

assumption

that

data

obtained

with

the

cost

diaries

were

representative

for

that

period

-LRB-

Goossens

et

al.

-RRB-

Subsequently

the

annual

costs

per

family

were

multiplied

by

the

Dutch

prevalence

figure

for

anxiety

disorders

which

is

-LRB-

Verhulst

et

al.

-RRB-

and

the

percentage

of

referred

children

of

-LRB-

Verhulst

and

van

der

Ende

-RRB-

which

results

in

a

multiplication

factor

of

to

calculate

the

total

annual

societal

cost-of-illness

of

families

of

clinically

anxious

children

referred

for

treatment

It

was

assumed

that

the

percentage

of

referred

children

with

a

mental

disorder

-LRB-

-RRB-

could

be

attributed

to

anxiety

disorders

as

well

Furthermore

a

low

and

high

estimation

of

the

cost-of-illness

was

calculated

The

low

multiplication

factor

of

was

derived

by

multiplying

the

low

prevalence

rate

of

children

with

a

mental

disorder

seeking

treatment

in

mental

health

care

of

with

the

low

prevalence

rate

of

impairment

in

functioning

of

-LRB-

i.e.

-RRB-

The

high

multiplication

factor

of

was

derived

by

taking

the

high

prevalence

rate

of

children

with

a

mental

disorder

seeking

treatment

in

mental

health

care

of

and

multiply

this

with

the

high

prevalence

rate

with

impairment

in

functioning

of

-LRB-

i.e.

-RRB-

Discriminative

Validity

To

determine

the

discriminative

validity

of

the

prospective

cost

diary

the

societal

costs

of

the

families

of

anxious

children

were

compared

to

the

societal

costs

of

families

from

the

general

population

For

this

purpose

all

costs

related

to

the

child

irrespective

of

reason

were

taken

into

account

-LRB-

i.e.

psychological

physical

or

other

-RRB-

For

both

groups

the

costs

per

family

over

a

period

of

weeks

were

extrapolated

to

a

period

of

year

to

obtain

the

annual

costs

per

child

for

both

groups

It

was

hypothesized

that

costs

for

anxiety

problems

were

higher

in

the

clinically

anxious

group

compared

to

the

general

population

but

comparable

between

the

two

groups

for

psychological

physical

and

other

problems

Convergent

Validity

To

establish

convergent

validity

health

care

costs

per

child

per

year

obtained

with

the

prospective

cost

diaries

of

clinically

anxious

children

were

compared

with

the

health

care

costs

of

children

with

a

primary

diagnosis

of

anxiety

disorder

according

to

top-down

registrations

For

this

comparison

only

health-care

costs

due

to

anxiety

of

the

child

were

considered

because

the

costs

obtained

with

the

top-down

registration

applied

to

children

with

a

primary

diagnosis

of

anxiety

disorder

and

only

consisted

of

costs

related

to

the

health

care

sector

The

top-down

data

were

obtained

from

a

generic

cost

study

based

on

national

registrations

-LRB-

Polder

et

al.

-RRB-

In

this

study

the

total

costs

of

health

care

in

were

assigned

to

diagnosis

groups

based

on

actual

delivered

care

according

to

distribution

codes

which

are

chosen

in

such

a

way

that

they

represent

equal

units

of

care

These

distribution

codes

are

adjusted

to

the

best

available

data

about

the

care

usage

-LRB-

for

more

details

see

Polder

et

al.

-RRB-

This

was

done

for

each

of

the

health

care

sectors

including

the

mental

health

care

sector

Diagnosis

groups

were

based

on

the

International

Statistical

Classification

of

Diseases

injuries

and

causes

of

death

-LRB-

World

Health

Organization

-RRB-

The

is

divided

into

chapters

including

chapter

V

mental

and

behavioural

disorders

Furthermore

a

more

intricate

classification

is

used

by

itemizing

the

chapters

into

specific

diagnosis

groups

including

anxiety

disorders

All

anxiety

disorders

are

taken

into

account

-LRB-

and

-RRB-

-LRB-

World

Health

Organization

-RRB-

The

top-down

data

could

not

be

compared

directly

to

the

group

of

year

old

children

included

in

the

bottom-up

cost-of-illness

analysis

because

costs

were

presented

for

the

age

groups

to

to

and

to

Therefore

the

assumption

was

made

that

costs

were

equally

distributed

within

the

age

groups

so

the

corresponding

ages

-LRB-

-RRB-

could

be

filtered

out

by

averaging

the

costs

and

multiplying

them

by

each

age

year

-LRB-

Polder

et

al.

-RRB-

Since

top-down

data

were

based

on

costs

in

for

comparison

with

the

bottom-up

cost-of-illness

approach

costs

were

actualized

to

euros

by

using

the

Consumer

Price

Index

-LRB-

CPI

Statistics

Netherlands

-RRB-

Statistical

Analysis

Statistical

analysis

could

only

be

performed

on

the

cost-of-illness

study

and

on

the

discriminative

validity

study

since

top-down

data

were

not

available

on

child

level

Missing

items

in

the

cost

diaries

were

handled

with

the

Missing

Value

Analysis

of

SPSS

based

on

the

regression

models

using

available

data

of

the

group

mean

the

available

data

of

the

individual

and

the

pattern

of

change

of

the

group

To

investigate

whether

data

were

normally

distributed

a

Kolmogorov

Smirnov

test

was

performed

Due

to

highly

skewed

cost

distributions

bootstrap

simulations

were

conducted

in

order

to

get

insight

in

significant

differences

on

subtotal

and

total

costs

between

families

of

clinically

anxious

children

and

families

from

the

general

population

and

the

uncertainty

surrounding

these

costs

The

bootstrap

method

estimates

the

sampling

distribution

of

a

statistic

through

simulations

based

on

sampling

with

replacement

from

the

original

data

-LRB-

Briggs

Wonderling

and

Mooney

-RRB-

Bootstrap

methods

are

increasingly

being

used

for

analysis

of

cost

data

as

traditional

parametric

and

nonparametric

statistical

methods

to

analyse

the

difference

in

mean

costs

between

groups

may

be

inappropriate

when

data

are

skewed

-LRB-

Barber

and

Thompson

Desgagné

et

al.

-RRB-

Results

Cost-of-illness

All

resources

used

and

costs

made

related

to

the

anxiety

of

the

child

by

families

with

a

clinically

anxious

child

were

summed

and

averaged

for

weeks

and

year

-LRB-

Table

-RRB-

The

mean

costs

per

family

over

weeks

were

extrapolated

to

a

year

and

amounted

to

per

family

with

a

clinically

anxious

child

Costs

were

not

normally

distributed

Kolmogorov

Smirnov

Z

p

and

skewed

to

the

left

indicating

that

a

minority

of

families

-LRB-

n

-RRB-

reported

costs

related

to

the

anxiety

of

the

child

A

logistic

regression

was

performed

using

families

with

and

without

costs

as

the

dependent

variable

and

age

gender

severity

and

number

of

diagnoses

as

covariates

within

an

enter

method

When

comparing

families

who

reported

costs

to

families

who

reported

no

costs

binary

logistic

regression

revealed

only

one

main

effect

for

age

corrected

for

gender

severity

and

number

of

diagnoses

Wald

-LRB-

-RRB-

p

O.R.

No

main

effect

was

found

for

gender

severity

or

number

of

diagnoses

Wald

-LRB-

-RRB-

s

ps

This

indicates

that

in

families

who

reported

costs

related

to

the

child

's

anxiety

the

child

was

older

compared

to

families

who

reported

no

costs

irrespective

of

gender

severity

and

number

of

diagnoses

The

main

contributor

to

costs

were

costs

related

to

institutionalized

treatment

-LRB-

of

total

costs

-RRB-

day

treatment

-LRB-

of

total

costs

-RRB-

productivity

loss

of

the

parents

-LRB-

of

total

costs

-RRB-

and

school

absence

-LRB-

of

total

costs

-RRB-

Table

total

resource

use

subtotal

and

total

societal

costs

due

to

anxiety

reasons

using

a

bottom-up

approach

-LRB-

n

-RRB-

Costs

per

unitTotal

resource

use

-LRB-

weeks

-RRB-

Total

costs

-LRB-

weeks

-RRB-

Total

costs

per

child

-LRB-

weeks

-RRB-

Total

costs

per

child

a

year

SumSumM

-LRB-

SD

-RRB-

M

-LRB-

SD

-RRB-

Direct

health

care

G.P

-LRB-

-RRB-

-LRB-

-RRB-

G.P.

-LRB-

-RRB-

-LRB-

-RRB-

Anxiety

-LRB-

-RRB-

-LRB-

-RRB-

Pharmacists

med

-LRB-

-RRB-

-LRB-

-RRB-

Institutionalized

-LRB-

-RRB-

-LRB-

-RRB-

Day

-LRB-

-RRB-

-LRB-

-RRB-

Subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Bootstrapped

subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Direct

non-health

care

costsPaid

house

-LRB-

-RRB-

-LRB-

-RRB-

Informal

-LRB-

-RRB-

-LRB-

-RRB-

Subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Bootstrapped

subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Indirect

costsPaid

-LRB-

-RRB-

-LRB-

-RRB-

Unpaid

-LRB-

-RRB-

-LRB-

-RRB-

Loss

of

leisure

-LRB-

-RRB-

-LRB-

-RRB-

Household

-LRB-

-RRB-

-LRB-

-RRB-

School

-LRB-

-RRB-

-LRB-

-RRB-

Subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Bootstrapped

subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Out-of-pocket

-LRB-

-RRB-

-LRB-

-RRB-

Own

contribution

alternative

treatment

-LRB-

-RRB-

-LRB-

-RRB-

Own

contribution

medication

not

prescribed

-LRB-

-RRB-

-LRB-

-RRB-

Subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Bootstrapped

subtotal

-LRB-

-RRB-

-LRB-

-RRB-

Total

costs

-LRB-

-RRB-

-LRB-

-RRB-

Bootstrapped

total

costs

-LRB-

-RRB-

-LRB-

-RRB-

of

volume

price

Oostenbrink

et

al.

databank

diary

costs

The

total

number

of

Dutch

children

aged

in

was

computed

using

data

of

the

Statistics

Netherlands

-LRB-

-RRB-

and

resulted

in

children

Multiplying

this

figure

by

resulted

in

Dutch

children

with

an

anxiety

disorder

that

interferes

with

daily

functioning

and

who

are

referred

to

treatment

Hence

the

annual

societal

cost-of-illness

accumulated

to

for

families

of

clinically

anxious

children

referred

for

treatment

in

the

Netherlands

The

same

calculation

was

performed

using

the

low

and

high

multiplication

factors

This

resulted

in

a

low

estimate

of

the

cost-of-illness

of

and

a

high

estimate

of

Discriminative

Validity

The

mean

total

annual

societal

costs

related

to

anxiety

psychological

physical

and

other

reasons

for

families

with

a

clinically

anxious

child

and

families

from

the

general

population

are

presented

in

Table

In

the

clinically

anxious

group

costs

due

to

anxiety

reasons

were

highest

-LRB-

of

total

costs

-RRB-

followed

by

costs

due

to

physical

reasons

-LRB-

of

total

costs

-RRB-

costs

due

to

other

reasons

-LRB-

of

total

costs

-RRB-

and

psychological

reasons

-LRB-

of

total

costs

-RRB-

The

total

annual

costs

of

families

with

clinically

anxious

children

due

to

anxiety

problems

psychological

problems

physical

problems

and

other

amounted

to

a

mean

of

-LRB-

SD

-RRB-

per

child

Table

and

total

costs

for

clinically

anxious

children

and

children

from

the

general

population

per

year

using

a

bottom-up

approach

-LRB-

n

-RRB-

Anxiety

reasonPsychological

reasonPhysical

reasonOther

reasonTotal

a

year

Cl

anx.Gen.Cl

anx.Gen.Cl

anx.Gen.Cl

anx.Gen.Cl

anx.Gen.Direct

health

care

G.P

.350.004.450.0013.350.000.000.0028.860.00

G.P.

Hospital

.000.000.000.0034.3798.8017.190.0051.4898.80

Emergence

visit

.000.000.000.0030.630.000.000.0030.680.00

.260.002.290.006.804.680.220.0011.704.68

Pharmacist

.250.0018.480.0029.8420.541.420.0069.9420.54

Day

Institutionalized

,3960.0027.440.0011912418.830.001,559124

Bootstrapped

subtotal

Direct

non-health

care

costsHouse

.610.000.000.000.000.008.410.0014.040.00

Informal

.230.000.000.000.000.0014.810.0074.100.00

.830.000.000.000.000.0023.210.0088.050.00

Bootstrapped

subtotal

Indirect

costsPaid

Unpaid

Leisure

time

.590.000.000.000.000.000.000.0079.560.00

Household

.030.000.000.000.000.000.000.0011.960.00

School

,1920.0051.010.0048.600.0023.550.001,3150.00

Bootstrapped

subtotal

.000.000.000.000.000.0011.130.2911.180.29

Own

.070.000.007.291.3816.490.000.0092.5623.66

.520.000.767.295.5516.4920.160.2912223.92

Bootstrapped

subtotal

Total

,7480.0079.217.2917414185.750.293,084148

Bootstrapped

,7900.0078.447.2317314286.990.323,070147

Incremental

costs

-LRB-

CI

-RRB-

-LRB-

to

-RRB-

-LRB-

to

-RRB-

-LRB-

to

-RRB-

-LRB-

to

-RRB-

-LRB-

to

-RRB-

Costs

of

families

from

the

general

population

were

highest

for

physical

reasons

-LRB-

of

total

costs

-RRB-

A

small

proportion

of

costs

was

assigned

to

psychological

reasons

-LRB-

of

total

costs

-RRB-

and

other

reasons

-LRB-

of

total

costs

-RRB-

Despite

the

fact

that

five

children

in

the

control

group

met

criteria

for

an

anxiety

disorder

families

reported

no

costs

for

anxiety

reasons

The

total

annual

costs

obtained

from

families

of

the

general

population

amounted

to

a

mean

of

-LRB-

SD

-RRB-

per

family

Costs

in

both

groups

were

not

normally

distributed

-LRB-

Kolmogorov

Smirnov

Z

p

-RRB-

The

bootstrapped

results

indicated

that

total

societal

costs

were

significantly

higher

in

families

with

clinically

anxious

children

compared

to

families

from

the

general

population

Subdividing

the

costs

into

reason

showed

significant

higher

costs

related

to

anxiety

and

other

reasons

in

families

with

a

clinically

anxious

child

compared

to

families

from

the

general

population

Costs

related

to

psychological

reasons

were

borderline

significantly

higher

for

the

families

with

a

clinically

anxious

child

-LRB-

see

Table

-RRB-

Convergent

Validity

The

total

health

care

costs

of

to

children

with

a

primary

diagnosis

of

anxiety

disorder

amounted

to

in

using

the

top-down

approach

which

augmented

to

in

when

corrected

with

CPI

The

total

number

of

anxious

to

children

referred

for

treatment

in

was

-LRB-

i.e.

-RRB-

Dividing

the

total

health

care

costs

due

to

anxiety

in

children

by

this

number

resulted

in

per

anxious

child

that

was

referred

-LRB-

see

Table

-RRB-

Table

health

care

costs

anxiety

based

per

child

a

year

based

on

the

Bottom-up

and

top-down

approach

Bottom-up

costsTop-down

costsA

day

of

Day

Polyclinic

Categorical

Subtotal

hospital

General

Paramedical

Subtotal

Primary

Pharmaceutical

Mental

health

Management

and

care

Total

Direct

health

care

costs

derived

from

the

bottom-up

method

were

used

to

compare

with

the

top-down

approach

and

amounted

to

per

referred

anxious

child

-LRB-

see

Table

-RRB-

Total

health

care

costs

for

clinically

anxious

children

resulted

in

with

a

low

estimate

of

and

a

high

estimate

of

Although

the

overall

difference

in

total

health

care

costs

between

the

bottom-up

and

top-down

approach

per

anxious

child

per

year

were

about

-LRB-

top-down

lower

than

bottom-up

-RRB-

the

differences

in

costs

per

health

care

sector

were

considerably

higher

For

instance

costs

of

medical

hospital

care

were

higher

using

the

top-down

approach

-LRB-

of

total

costs

-RRB-

compared

to

costs

obtained

with

the

bottom-up

approach

-LRB-

of

total

costs

-RRB-

On

the

other

hand

mental

health

care

costs

were

higher

-LRB-

top-down

lower

than

bottom-up

-RRB-

using

the

bottom-up

approach

-LRB-

of

total

costs

-RRB-

compared

to

the

costs

obtained

with

the

top-down

approach

-LRB-

of

total

costs

-RRB-

Discussion

To

the

authors

knowledge

this

is

the

first

cost-of-illness

study

in

clinically

anxious

children

referred

for

treatment

The

aim

of

this

study

was

threefold

The

first

aim

was

to

measure

the

societal

costs

of

illness

in

clinically

anxious

children

and

their

families

using

a

bottom-up

approach

by

means

of

a

prospective

cost

diary

The

second

aim

was

to

investigate

the

discriminative

validity

of

the

prospective

cost

diary

by

comparing

the

costs

of

families

with

a

clinically

anxious

child

to

the

costs

of

families

from

the

general

population

The

third

aim

of

the

study

was

to

establish

convergent

validity

by

comparing

bottom-up

acquired

health

care

costs

of

the

clinically

anxious

children

with

top-down

acquired

health

care

costs

of

children

with

a

primary

diagnosis

of

anxiety

With

respect

to

results

regarding

cost-of-illness

bottom-up

acquired

total

societal

costs

for

families

of

clinically

anxious

children

referred

for

treatment

amounted

to

more

than

million

per

year

in

the

Netherlands

with

a

low

estimation

of

and

a

high

estimation

of

million

euros

which

is

a

quite

broad

range

Costs

amounted

to

per

family

with

a

clinically

anxious

child

per

year

These

costs

seem

relatively

low

compared

to

costs

of

other

childhood

psychopathology

Knapp

et

al.

-LRB-

-RRB-

conducted

a

pilot

study

on

ten

children

aged

with

conduct

disorders

Cost

amounted

to

per

family

per

year

which

is

about

eight

times

as

high

as

the

costs

per

family

with

a

clinically

anxious

child

in

our

study

However

a

more

elaborate

study

-LRB-

n

-RRB-

on

to

children

with

anti-social

behaviour

-LRB-

Romeo

et

al.

-RRB-

reported

lower

mean

annual

total

costs

namely

per

child

still

times

higher

than

those

of

anxious

children

In

another

study

on

children

with

autism

spectrum

disorders

societal

costs

were

per

child

per

year

-LRB-

Järbrink

et

al.

-RRB-

which

is

times

higher

than

the

costs

per

anxious

child

It

should

be

noted

that

the

prevalence

rate

for

anxiety

is

almost

four

times

as

high

as

conduct

disorder

-LRB-

Verhulst

et

al.

-RRB-

and

to

times

higher

than

the

prevalence

rate

for

autism

spectrum

disorders

-LRB-

van

der

Gaag

et

al.

-RRB-

Consequently

the

relative

costs

for

society

of

childhood

anxiety

disorders

combining

absolute

costs

with

prevalence

are

similar

to

conduct

disorders

and

higher

than

those

of

autism

spectrum

disorders

In

line

with

Knapp

et

al.

-LRB-

-RRB-

Romeo

et

al.

-LRB-

-RRB-

and

Järbrink

et

al.

-LRB-

-RRB-

a

large

part

of

the

costs

in

our

study

can

be

attributed

to

the

parents

productivity

loss

due

to

anxiety

disorders

of

the

child

-LRB-

of

total

costs

-RRB-

Knapp

et

al.

-LRB-

-RRB-

found

that

per

family

with

a

child

with

conduct

disorder

the

annual

costs

due

to

lost

employment

were

-LRB-

of

the

total

costs

-RRB-

Costs

to

the

family

related

to

extra

time

spend

on

household

tasks

the

need

for

repairs

and

time

off

work

due

to

the

anti-social

behaviour

of

the

child

were

which

is

of

the

total

costs

Järbrink

et

al.

-LRB-

-RRB-

showed

that

more

than

of

the

total

costs

of

children

with

an

autism

spectrum

disorder

were

attributable

to

parents

and

costs

related

to

income

loss

were

-LRB-

of

total

costs

-RRB-

Our

study

also

found

high

costs

due

to

school

absenteeism

-LRB-

of

total

costs

-RRB-

School

absence

can

have

long-term

economic

consequences

such

as

decreased

job

opportunities

or

even

unemployment

Taken

together

both

productivity

costs

of

parents

and

school

absence

costs

of

children

seem

very

important

and

should

be

considered

in

future

costing

studies

Furthermore

logistic

regression

analysis

revealed

that

in

families

with

costs

related

to

the

child

's

anxiety

the

child

was

older

compared

to

families

with

no

costs

irrespective

of

gender

severity

and

number

of

diagnoses

This

is

in

line

with

the

finding

that

top-down

health

care

costs

related

to

anxiety

disorders

and

health

care

costs

in

general

increase

with

age

-LRB-

Polder

et

al.

-RRB-

Perhaps

older

children

are

more

prone

to

react

against

their

parents

and

are

more

independent

thereby

reducing

the

influence

of

parents

-LRB-

Hudson

et

al.

-RRB-

It

can

be

speculated

that

less

influence

from

the

parents

may

lead

to

more

school

absenteeism

among

older

children

Indeed

of

the

children

aged

reported

school

absenteeism

in

the

last

months

compared

to

of

the

children

aged

-LRB-

Statistics

Netherlands

-RRB-

Also

the

older

child

may

be

more

aware

of

the

anxiety

complaints

possibly

increasing

the

costs

of

mental

health

care

Future

research

should

investigate

this

issue

more

profoundly

An

additional

finding

of

this

study

concerns

the

difference

in

measuring

costs

in

children

with

anxiety

disorders

compared

to

cost-of-illness

studies

in

adults

with

anxiety

disorders

The

main

difference

of

measuring

costs

in

children

with

anxiety

disorders

as

other

mental

disorders

in

children

is

that

anxiety

in

the

child

does

not

only

affect

the

child

but

also

the

child

's

family

Therefore

the

costs

concerning

the

child

's

anxiety

should

also

be

measured

at

the

family

level

Although

many

would

argue

that

the

costs

of

illness

for

adults

spill

over

to

the

family

as

well

studies

on

costs

of

anxiety

disorders

in

adults

usually

do

not

include

family

members

especially

not

their

children

So

in

future

research

it

may

be

interesting

to

assess

the

costs

of

adult

anxiety

disorders

on

a

family

level

as

well

For

example

they

might

be

more

protective

of

their

children

and

therefore

increase

their

children

's

health

care

consumption

or

more

often

let

their

child

miss

a

day

from

school

Moreover

in

adult

cost-of-illness

studies

productivity

losses

due

to

absence

of

paid

work

are

measured

In

children

these

kind

of

productivity

losses

do

not

occur

However

alternatives

such

as

costs

due

to

absence

from

school

should

be

taken

into

account

since

school

participation

can

be

regarded

as

a

productive

activity

and

-LRB-

regular

-RRB-

absence

from

school

may

serve

as

a

proxy

for

future

productivity

losses

With

respect

to

the

results

regarding

discriminative

validity

total

costs

of

families

with

clinically

anxious

children

using

a

bottom-up

approach

were

almost

times

higher

than

costs

of

families

from

the

general

population

In

line

with

the

hypothesis

the

difference

in

costs

between

families

of

clinically

anxious

children

and

families

from

the

general

population

can

largely

be

subscribed

to

the

significant

difference

in

anxiety-related

costs

showing

good

discriminative

validity

of

the

cost

diary

on

anxiety

related

costs

However

significant

differences

were

also

found

on

costs

due

to

other

reasons

In

the

prospective

cost

diary

the

reasons

for

resource

use

were

recorded

based

on

subjective

judgments

by

the

parents

However

since

anxiety

is

an

internalizing

disorder

parents

may

not

always

have

been

able

to

interpret

children

's

symptoms

correctly

Therefore

they

may

have

attributed

costs

mistakenly

to

non-anxiety

reasons

For

example

parents

regularly

reported

a

baby-sitter

for

a

child

old

enough

to

stay

on

its

own

if

the

child

would

not

have

been

anxious

Another

item

that

was

reported

as

not

being

related

to

anxiety

was

extra

travel

expenses

for

the

separation

anxious

child

who

otherwise

could

have

stayed

at

home

With

respect

to

convergent

validity

total

direct

health

care

costs

related

to

anxiety

were

lower

using

a

top-down

approach

than

using

a

bottom-up

approach

which

seems

quite

comparable

However

subdividing

the

costs

into

several

cost

categories

showed

that

costs

were

distributed

differently

among

the

cost

categories

For

example

bottom-up

acquired

mental

health

care

costs

were

higher

than

top-down

acquired

mental

health

care

costs

Furthermore

of

the

total

costs

using

a

top-down

approach

were

attributed

to

hospital

care

whereas

no

hospital

care

costs

were

found

using

the

bottom-up

approach

Hence

convergent

validity

on

total

direct

health

care

costs

were

quite

comparable

while

the

specific

cost

categories

differed

between

bottom-up

and

the

top-down

approach

These

findings

suggest

that

children

who

are

not

yet

referred

for

mental

health

care

might

consume

more

medical

hospital

care

compared

to

children

who

are

referred

for

mental

health

care

Therefore

from

a

cost-of-illness

perspective

it

would

also

be

interesting

to

investigate

costs

of

families

with

children

with

anxiety

disorders

who

are

not

referred

for

mental

health

treatment

using

the

cost

dairy

developed

for

this

study

It

might

well

be

that

these

families

have

more

medical

health

care

costs

as

the

comparison

with

top-down

acquired

data

suggests

This

study

has

some

limitations

which

should

be

addressed

The

first

limitation

is

that

the

low

and

high

multiplication

factor

used

in

this

study

caused

a

broad

range

of

the

societal

costs

of

illness

This

can

be

explained

by

the

broad

range

of

internationally

reported

prevalence

rates

and

percentages

of

children

seeking

treatment

due

to

differences

in

measurements

populations

and

criteria

that

need

to

be

fulfilled

As

a

Dutch

population

was

investigated

the

most

appropriate

prevalence

rate

is

-LRB-

Verhulst

et

al.

-RRB-

which

was

obtained

through

the

use

of

a

reliable

structured

diagnostic

interview

The

same

is

true

for

the

of

children

with

mental

disorders

seeking

treatment

-LRB-

Verhulst

and

van

der

Ende

-RRB-

Besides

of

the

Dutch

people

with

anxiety

disorders

are

referred

for

further

treatment

by

their

general

practitioner

-LRB-

van

Wieren

et

al.

-RRB-

Therefore

the

prevalence

and

referral

rates

used

in

this

study

seem

reliable

The

second

limitation

of

the

current

study

is

that

it

can

be

argued

that

cost

diaries

filled

in

by

parents

are

not

representative

enough

to

reliably

assess

bottom-up

costs

due

to

the

limited

time

period

However

Goossens

et

al.

-LRB-

-RRB-

have

found

that

keeping

a

diary

in

a

limited

period

namely

week

every

month

weeks

every

months

or

an

entire

year

resulted

in

similar

outcomes

in

fibromyalgia

and

pain

patients

Another

study

of

Bruijnzeels

et

al.

-LRB-

-RRB-

found

that

there

was

a

substantial

agreement

between

a

cost

diary

filled

in

by

parents

and

medical

records

concerning

general

practitioner

visits

of

children

Moreover

the

inclusion

period

of

this

study

lasted

years

in

which

the

cost

diaries

were

filled

out

therefore

possible

seasonal

influences

are

ruled

out

However

it

is

likely

that

service

use

patterns

may

vary

over

the

year

and

do

not

follow

a

stable

trajectory

So

for

some

families

the

period

for

collecting

costs

may

have

led

to

an

underestimation

of

the

total

annual

costs

whereas

for

other

families

this

may

have

led

to

an

overestimation

of

the

total

annual

costs

Nevertheless

as

the

mean

annual

costs

are

based

on

cost

data

from

each

of

these

families

it

is

expected

that

possible

over

and

underestimations

of

annual

costs

are

balanced

The

third

and

most

serious

limitation

of

this

study

is

that

although

total

health

care

costs

obtained

with

the

top-down

and

bottom-up

method

seemed

quite

comparable

the

sample

of

children

with

a

primary

diagnosis

of

anxiety

disorder

used

in

the

top-down

study

by

Polder

et

al.

-LRB-

-RRB-

might

not

be

fully

comparable

to

the

clinically

anxious

children

from

our

bottom-up

approach

in

at

least

three

respects

First

the

children

in

the

bottom-up

sample

were

clinically

anxious

children

with

severe

anxiety

disorders

The

mean

number

of

anxiety

disorders

was

and

the

mean

severity

level

indicating

severe

interference

with

daily

functioning

The

children

with

a

primary

diagnosis

of

anxiety

disorder

in

the

top-down

sample

might

suffer

from

different

levels

of

anxiety

disorders

some

may

have

minor

anxiety

problems

while

others

may

have

severe

anxiety

problems

This

kind

of

information

was

not

available

using

the

top-down

data

Second

while

the

clinically

anxious

children

in

the

bottom-up

sample

were

awaiting

CBT

in

a

community

mental

health

care

setting

the

anxious

children

in

the

top-down

sample

might

be

in

different

types

and/or

phases

of

treatment

Again

this

kind

of

information

was

not

available

using

the

top-down

data

Third

the

clinically

anxious

children

in

the

bottom-up

sample

were

diagnosed

using

a

universally

used

semi-structured

interview

the

ADIS

which

is

based

on

DSM-IV

criteria

-LRB-

American

Psychiatric

Association

-RRB-

In

the

top-down

sample

children

were

diagnosed

by

the

doctor

in

attendance

who

attributed

the

anxiety

diagnosis

to

the

patient

based

on

the

code

without

a

structured

interview

Due

to

the

classification

method

the

top-down

estimation

is

possibly

less

reliable

than

the

bottom-up

cost

estimation

Therefore

results

of

the

comparison

between

top-down

and

bottom-up

costs

should

be

interpreted

with

caution

In

conclusion

this

cost-of-illness

study

shows

that

the

societal

costs

of

families

with

a

clinically

anxious

child

who

seek

treatment

amount

to

more

than

million

euros

a

year

in

the

Dutch

population

and

were

times

higher

than

in

families

of

the

general

population

An

effective

treatment

could

decrease

these

costs

on

the

long

term

A

recent

cost-effectiveness

study

on

family

CBT

versus

individual

CBT

showed

that

societal

costs

in

families

with

a

clinically

anxious

child

increased

during

treatment

-LRB-

due

to

total

costs

of

sessions

CBT

a

-RRB-

but

decreased

directly

after

treatment

to

baseline

level

Even

more

during

the

follow-up

societal

costs

dropped

below

the

costs

at

baseline

-LRB-

Bodden

et

al.

submitted

for

publication

-RRB-

Since

anxiety

disorders

tend

to

last

into

adulthood

-LRB-

Newman

et

al.

-RRB-

societal

costs

are

likely

to

be

higher

at

the

long

term

This

results

in

anxiety

disorders

accounting

for

the

highest

costs

of

all

mental

illnesses

in

adulthood

in

the

USA

-LRB-

Dupont

et

al.

-RRB-

Hence

societal

costs

in

adults

with

anxiety

disorders

may

be

saved

by

providing

effective

treatments

to

children

with

clinical

anxiety

disorders

O O O O O O O O O O O O O O O O O O O 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 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 B O O O O O O O O O O B 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 B I O O O O O O O O O B I O B I O O O O O O O O O O O O B 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 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 B I 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 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 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 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 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