Low

back

pain

in

general

practice

cost-effectiveness

of

a

minimal

psychosocial

intervention

versus

usual

care

An

intervention

that

can

prevent

low

back

pain

-LRB-

LBP

-RRB-

becoming

chronic

may

not

only

prevent

great

discomfort

for

patients

but

also

save

substantial

costs

for

the

society

Psychosocial

factors

appear

to

be

of

importance

in

the

transition

of

acute

to

chronic

LBP

The

aim

of

this

study

was

to

compare

the

cost-effectiveness

of

an

intervention

aimed

at

psychosocial

factors

to

usual

care

in

patients

with

-LRB-

sub

-RRB-

acute

LBP

The

study

design

was

an

economic

evaluation

alongside

a

cluster-randomized

controlled

trial

conducted

from

a

societal

perspective

with

a

follow-up

of

year

Sixty

general

practitioners

in

general

practices

recruited

patients

with

non-specific

LBP

of

less

than

weeks

duration

General

practitioners

in

the

minimal

intervention

strategy

-LRB-

MIS

-RRB-

group

explored

and

discussed

psychosocial

prognostic

factors

Usual

care

-LRB-

UC

-RRB-

was

not

protocolized

Clinical

outcomes

were

functional

disability

-LRB-

Roland

Morris

Disability

Questionnaire

-RRB-

perceived

recovery

and

health-related

quality

of

life

-LRB-

EuroQol

-RRB-

Cost

data

consisted

of

direct

and

indirect

costs

and

were

measured

by

patient

cost

diaries

and

general

practitioner

registration

forms

Complete

cost

data

were

available

for

of

the

patients

Differences

in

clinical

outcomes

between

both

the

groups

were

small

and

not

statistically

significant

Differences

in

cost

data

were

in

favor

of

MIS

However

the

complete

case

analysis

and

the

sensitivity

analyses

with

imputed

cost

data

were

inconsistent

with

regard

to

the

statistical

significance

of

this

difference

in

cost

data

This

study

presents

conflicting

points

of

view

regarding

the

cost-effectiveness

of

MIS

We

conclude

that

-LRB-

Dutch

-RRB-

general

practitioners

as

yet

should

not

replace

their

usual

care

by

this

new

intervention

Introduction

Low

back

pain

-LRB-

LBP

-RRB-

affects

a

large

number

of

people

each

year

Lifetime

prevalence

rates

range

from

to

-LSB-

-RSB-

LBP

causes

not

only

great

discomfort

but

also

great

economic

loss

due

to

work

absenteeism

-LSB-

-RSB-

In

the

UK

LBP

is

one

of

the

most

expensive

conditions

for

which

an

economic

analysis

has

been

carried

out

-LSB-

-RSB-

Economic

evaluations

in

which

both

the

costs

and

clinical

outcomes

of

two

or

more

interventions

are

compared

are

becoming

increasingly

important

as

health

care

expenditures

rise

while

budgets

remain

limited

-LSB-

-RSB-

The

importance

of

economic

evaluations

is

illustrated

by

the

fact

that

some

authors

suggest

that

an

intervention

might

be

implemented

when

it

is

less

effective

but

saves

substantial

costs

-LSB-

-RSB-

As

especially

chronic

LBP

is

associated

with

substantial

costs

to

society

-LSB-

-RSB-

a

large

amount

of

costs

can

be

saved

by

interventions

that

prevent

acute

LBP

becoming

chronic

The

rationale

is

that

it

will

be

more

cost-effective

to

address

a

wider

target

population

early

with

simple

low-cost

interventions

than

to

expend

considerable

time

and

resources

on

rehabilitating

the

smaller

group

of

back

pain

patients

who

have

become

incapacitated

by

chronic

pain

As

psychosocial

factors

have

been

shown

to

play

an

important

role

in

the

transition

from

acute

to

chronic

back

pain

-LSB-

-RSB-

one

may

assume

that

early

interventions

focusing

on

these

factors

prevent

chronicity

We

tested

this

assumption

by

conducting

a

cluster-randomized

clinical

trial

in

general

practice

comparing

a

minimal

intervention

strategy

-LRB-

MIS

-RRB-

aimed

at

psychosocial

factors

for

patients

with

-LRB-

sub

-RRB-

acute

LBP

to

usual

care

-LRB-

UC

-RRB-

by

the

GP

which

was

not

standardized

Our

theory

on

the

working

mechanisms

of

MIS

was

that

identification

and

discussion

of

psychosocial

factors

would

lead

to

modification

of

these

factors

eventually

leading

to

better

functioning

Unfortunately

MIS

appeared

to

be

no

more

effective

than

UC

in

improving

the

following

clinical

outcomes

the

degree

of

functional

disability

the

recovery

rate

and

the

number

of

patients

on

sick-leave

due

to

LBP

-LSB-

-RSB-

These

findings

are

in

line

with

Linton

and

Andersson

-LSB-

-RSB-

who

showed

that

their

cognitive-behavioral

intervention

was

not

more

effective

than

usual

care

in

reducing

the

degree

of

back

pain

and

generic

function

status

However

their

intervention

was

effective

in

reducing

the

number

of

visits

to

a

physician

for

spinal

pain

and

number

of

days

of

sick-leave

implicating

time

savings

for

physicians

and

thus

substantial

cost

savings

for

society

These

results

may

indicate

an

increase

in

coping

or

self-care

with

the

pain

patients

who

received

the

psychosocial

intervention

less

often

visited

a

physician

and

had

less

days

of

work

while

they

had

the

same

degree

of

functional

disability

as

the

patients

who

received

usual

care

These

promising

results

in

combination

with

the

fact

that

self-care

with

the

pain

was

also

a

goal

in

our

MIS

the

recent

emphasis

on

health

care

budgets

and

the

call

for

more

high

quality

economic

evaluations

on

the

cost-effectiveness

of

treatments

for

LBP

-LSB-

-RSB-

stimulated

us

to

conduct

an

economic

evaluation

from

a

societal

perspective

with

a

follow-up

of

year

We

hypothesized

that

MIS

would

be

cost-effective

compared

to

UC

Materials

and

methods

Study

design

The

study

is

designed

as

a

full

economic

evaluation

alongside

a

cluster-randomized

controlled

trial

and

was

approved

by

the

Medical

Ethics

Committee

of

the

VU

University

Medical

Center

in

Amsterdam

the

Netherlands

Randomization

and

training

sessions

Randomization

took

place

at

the

level

of

the

general

practice

in

blocks

of

four

practices

according

to

a

random

numbers

table

prepared

before

recruitment

of

general

practitioners

General

practitioners

were

informed

about

their

allocation

after

they

had

given

final

consent

to

participation

Twenty

practices

-LRB-

GPs

-RRB-

were

randomized

to

the

MIS

group

and

practices

-LRB-

GPs

-RRB-

to

the

UC

group

The

GPs

randomized

to

the

MIS

group

received

two

training

sessions

of

h

each

which

were

given

by

a

GP

-LRB-

HvdH

-RRB-

with

extensive

expertise

in

development

and

training

of

psychosocial

interventions

The

training

consisted

of

theory

role-playing

and

feedback

on

the

practiced

skills

In

addition

a

treatment

manual

was

provided

The

contents

of

the

training

sessions

and

its

evaluation

by

GPs

have

been

described

in

more

detail

elsewhere

-LSB-

-RSB-

Patients

and

interventions

Participating

GPs

were

asked

to

select

ten

consecutive

patients

who

consulted

them

for

LBP

Inclusion

criteria

were

age

non-specific

LBP

of

less

than

weeks

duration

-LRB-

i.e.

-LRB-

sub

-RRB-

acute

LBP

-RRB-

or

an

exacerbation

of

mild

symptoms

and

sufficient

knowledge

of

the

Dutch

language

Exclusion

criteria

were

specific

LBP

-LRB-

i.e.

LBP

caused

by

specific

pathological

conditions

-RRB-

LBP

currently

treated

by

another

healthcare

professional

and

pregnancy

Patients

but

not

their

GPs

were

kept

unaware

that

two

different

interventions

were

studied

Patients

received

a

minimal

intervention

strategy

-LRB-

MIS

-RRB-

or

usual

care

-LRB-

UC

-RRB-

The

MIS

was

aimed

at

identification

and

discussion

of

psychosocial

prognostic

factors

The

MIS

consultation

lasted

about

min

and

consisted

of

three

phases

exploration

information

and

self

care

During

the

exploration

phase

the

GP

explored

the

presence

of

psychosocial

prognostic

factors

by

asking

standardized

questions

that

could

be

rephrased

to

fit

the

style

of

communication

of

the

doctor

and

the

patient

The

following

psychosocial

prognostic

factors

were

explored

the

patient

's

own

ideas

on

the

cause

of

their

LBP

fear

avoidance

beliefs

worries/distress

pain

catastrophising

pain

behaviors

and

reactions

from

the

social

environment

-LRB-

family

friends

work

-RRB-

In

the

information

phase

the

GP

provided

general

information

on

the

cause

course

and

-LRB-

im

-RRB-

possibilities

of

treatment

of

LBP

thereby

giving

specific

attention

to

psychosocial

factors

identified

in

the

exploration

phase

Finally

in

the

self

care

phase

the

GP

and

patient

set

specific

goals

on

resuming

activities

or

work

Follow-up

consultations

were

not

protocolized

but

we

advised

GPs

to

make

an

appointment

for

a

follow-up

visit

in

case

they

identified

obstacles

to

recovery

and

suspected

an

increased

risk

of

chronic

LBP

GPs

in

the

UC

group

provided

care

as

usual

We

did

not

protocolize

the

content

and

number

of

UC

consultations

and

assumed

that

GPs

would

generally

follow

the

guideline

for

LBP

of

the

Dutch

College

of

General

Practitioners

-LSB-

-RSB-

For

acute

LBP

-LRB-

weeks

duration

-RRB-

this

guideline

advises

a

wait

and

see

policy

For

subacute

LBP

-LRB-

weeks

duration

-RRB-

the

guideline

advises

referral

for

physical

therapy

in

the

case

of

persistent

functional

disability

Explicit

guidance

on

psychosocial

factors

is

lacking

The

contents

of

both

interventions

have

been

described

in

more

detail

elsewhere

-LSB-

-RSB-

Data

collection

Clinical

outcomes

Baseline

data

were

collected

during

a

home

visit

by

a

research

assistant

while

follow-up

data

after

months

were

collected

using

postal

questionnaires

Primary

clinical

outcome

measures

were

functional

disability

perceived

recovery

and

health

related

quality

of

life

Functional

disability

was

measured

at

baseline

and

after

months

by

the

Roland

Morris

disability

questionnaire

-LRB-

-RRB-

-LSB-

-RSB-

Perceived

recovery

was

scored

by

the

patient

on

a

Likert

scale

-LRB-

very

much/much/slightly

improved

no

change

slightly/much/very

much

worse

-RRB-

after

months

-LSB-

-RSB-

As

a

score

of

at

least

much

improved

has

been

denoted

a

minimal

clinically

important

change

-LSB-

-RSB-

patients

were

a

priori

defined

as

recovered

if

they

reported

at

least

much

improvement

Health

related

quality

of

life

was

measured

at

baseline

and

after

and

months

by

the

EuroQol

-LRB-

-RRB-

-LSB-

-RSB-

covering

five

domains

mobility

self-care

usual

activities

pain/discomfort

and

anxiety/depression

The

EuroQol

scores

were

transformed

into

utilities

using

a

representative

British

sample

and

time

trade-off

methods

The

utilities

were

then

multiplied

by

the

amount

of

time

a

patient

spent

in

this

particular

health

state

with

transitions

between

health

states

linearly

interpolated

-LSB-

-RSB-

This

results

in

quality

adjusted

life

years

-LRB-

QALYs

-RRB-

In

order

to

describe

the

study

population

characteristics

in

more

detail

and

to

compare

baseline

similarity

of

both

intervention

groups

five

other

outcome

measures

were

assessed

at

baseline

-LRB-

-RRB-

pain

severity

during

the

day

-LRB-

-RRB-

-LSB-

-RSB-

-LRB-

-RRB-

perceived

general

health

-LRB-

-RRB-

using

the

first

question

of

the

subscale

general

health

perceptions

of

the

short

form

health

survey

-LRB-

-RRB-

-LSB-

-RSB-

-LRB-

-RRB-

fear

avoidance

beliefs

using

the

physical

activity

subscale

of

the

fear

avoidance

beliefs

questionnaire

-LRB-

FABQ

-RRB-

-LSB-

-RSB-

-LRB-

-RRB-

catastrophising

thoughts

using

the

subscale

of

the

coping

strategies

questionnaire

-LRB-

CSQ

-RRB-

-LSB-

-RSB-

and

-LRB-

-RRB-

distress

measured

by

the

subscale

of

the

four-dimensional

symptom

questionnaire

-LRB-

-RRB-

-LSB-

-RSB-

Cost

data

The

economic

evaluation

was

conducted

from

a

societal

perspective

indicating

that

all

costs

and

consequences

of

the

competing

interventions

are

taken

into

account

regardless

of

who

pays

for

or

benefits

from

them

-LSB-

-RSB-

A

societal

perspective

incorporates

direct

health

care

costs

direct

non-health

care

costs

and

indirect

costs

due

to

LBP

All

cost

data

were

collected

by

prospective

cost

diaries

-LSB-

-RSB-

that

patients

completed

for

the

periods

baseline

to

months

months

months

and

months

In

addition

GPs

were

contacted

after

months

follow-up

to

provide

information

on

follow-up

consultations

due

to

LBP

in

the

last

year

-LRB-

date

referrals

medication

prescribed

by

physician

-RRB-

GPs

used

their

medical

records

to

complete

these

registration

forms

Table

summarizes

the

cost

categories

and

the

prices

and

sources

used

for

valuing

Medication

in

Table

includes

both

the

over-the-counter

medication

and

medication

prescribed

by

physicians

while

self-prescribed

alternative

interventions

are

included

in

complementary

care

Costs

of

absenteeism

from

paid

labor

due

to

LBP

were

calculated

according

to

the

friction

cost

approach

-LSB-

-RSB-

This

approach

is

based

on

a

mean

income

of

the

Dutch

population

according

to

age

and

gender

and

defines

a

friction

period

as

days

-LSB-

-RSB-

As

most

cost

data

were

collected

during

the

year

prices

were

adjusted

using

consumer

price

index

figures

Table

used

for

valuing

resources

-LRB-

year

-RRB-

ResourcesEuroDirect

health

care

Primary

care

costs

General

practitioner

-LRB-

consultation

-RRB-

MIS-consultation

including

intervention

costs

-LRB-

consultation

-RRB-

Physical

therapist

-LRB-

treatment

session

-RRB-

Manual

therapist

-LRB-

treatment

session

-RRB-

Exercise

therapist

-LRB-

treatment

session

-RRB-

Back

school

-LRB-

treatment

session

-RRB-

-LSB-

-RSB-

Chiropractor

-LRB-

treatment

session

-RRB-

Physiofitness

-LRB-

treatment

program

sessions

-RRB-

Professional

homecare

-LRB-

per

hour

-RRB-

Psychologist

-LRB-

treatment

session

-RRB-

Secondary

care

costs

Outpatient

Hospitalization

general

hospital

-LRB-

per

day

-RRB-

Surgery

-LRB-

per

hour

-RRB-

MedicationeDirect

non-health

care

Complementary

care

d

Informal

care

-LRB-

per

hour

-RRB-

Equipment

aidsfIndirect

costsAbsenteeism

from

paid

workgAbsenteeism

from

unpaid

MIS

Minimal

intervention

strategy

MRI

Magnetic

resonance

imagingaPrice

according

to

Dutch

guidelines

-LSB-

-RSB-

bCalculated

unit

costscPrice

according

Dutch

Central

Organisation

for

Health

Care

Charges

-LSB-

-RSB-

dPrice

according

to

professional

organisation

or

health

care

providerePrice

of

medication

prescribed

by

the

GP

according

to

Royal

Dutch

Society

for

Pharmacy

-LSB-

-RSB-

price

of

over-the-counter

medication

according

to

cost

diariesfPrice

according

to

cost

diariesgCosts

based

on

mean

income

of

Dutch

population

according

to

age

and

sex

-LSB-

-RSB-

Statistical

analysis

Firstly

baseline

similarity

was

studied

Secondly

we

compared

baseline

characteristics

of

patients

with

complete

cost

data

to

those

with

incomplete

cost

data

by

using

logistic

regression

analysis

Thirdly

clinical

outcomes

and

total

costs

were

compared

As

cost

data

are

characterized

by

large

variation

and

irregular

distributions

and

as

a

complete

cost

dataset

was

available

for

of

our

participants

-LRB-

-RRB-

we

decided

that

our

primary

analysis

would

be

a

complete

case

analysis

Differences

between

groups

-LRB-

MIS

minus

UC

-RRB-

were

calculated

for

the

clinical

outcomes

-LRB-

-RRB-

functional

disability

by

calculating

change

scores

between

baseline

and

months

follow-up

-LRB-

-RRB-

perceived

recovery

at

months

follow-up

and

-LRB-

-RRB-

health-related

quality

of

life

gained

over

months

-LRB-

i.e.

QALYs

-RRB-

Students

t

tests

were

used

to

analyze

the

change

scores

between

the

treatment

groups

for

functional

disability

and

quality

of

life

and

a

Chi-square

test

for

perceived

recovery

To

compare

costs

between

the

two

groups

confidence

intervals

-LRB-

CIs

-RRB-

for

the

mean

differences

in

costs

were

calculated

using

bias-corrected

and

accelerated

bootstrapping

-LRB-

replications

-RRB-

-LSB-

-RSB-

Bootstrapping

incorporates

drawing

samples

with

replacement

and

is

a

preferred

method

for

the

analysis

of

cost

data

as

it

uses

the

observed

distributions

of

the

data

without

making

assumptions

about

the

shape

of

the

distribution

-LSB-

-RSB-

Fourthly

cost-effectiveness

analyses

were

performed

Incremental

cost-effectiveness

ratios

were

calculated

in

which

the

mean

difference

in

total

costs

-LRB-

MIS

minus

UC

-RRB-

was

divided

by

the

mean

difference

in

improvement

on

the

clinical

outcomes

-LRB-

MIS

minus

UC

-RRB-

Uncertainty

around

the

ratios

was

calculated

using

the

bias-corrected

percentile

bootstrapping

method

-LRB-

replications

-RRB-

-LSB-

-RSB-

and

plotted

on

a

cost-effectiveness

plane

Sensitivity

analyses

A

complete

case

analysis

has

some

disadvantages

Due

to

the

missing

data

the

power

of

the

analysis

is

reduced

and

bias

may

be

introduced

due

to

selective

drop-out

Imputation

can

be

used

to

replace

missing

data

by

statistical

estimates

of

the

missing

values

To

explore

the

robustness

of

our

primary

analysis

we

performed

two

sensitivity

analyses

in

which

we

imputed

missing

data

in

one

analysis

we

imputed

all

missing

cost

data

and

in

the

other

we

imputed

only

missing

days

of

absenteeism

Imputation

was

done

using

the

Expectation

Maximization

algorithm

-LRB-

SPSS

-RRB-

Results

Between

September

and

April

patients

were

enrolled

in

our

study

in

the

MIS

group

and

in

the

UC

group

Table

shows

that

baseline

characteristics

of

GPs

and

patients

were

largely

similar

for

the

two

groups

Less

than

of

all

patients

withdrew

from

the

study

during

follow-up

Reasons

were

no

time

and

no

complaints

anymore

-LRB-

MIS

n

UC

n

-RRB-

burden

too

high

due

to

psychological

problems

-LRB-

UC

n

-RRB-

or

unknown

-LRB-

MIS

n

UC

n

-RRB-

The

flow

chart

of

this

study

including

information

on

refusals

exclusions

and

drop-outs

has

been

published

in

our

previous

paper

-LSB-

-RSB-

Table

characteristics

of

general

practitioners

and

patientsMIS

UC

GPsn

characteristics

Age

-LRB-

years

-RRB-

a

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Gender

of

included

patients

per

GP

0 1/285

5 10/28

characteristics

Age

-LRB-

years

-RRB-

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Gender

Nationality

Health

insurance

Educational

level

and

work

status

Education

levela

College

university

Paid

job

Sick

leave

because

of

LBPa

-LRB-

among

the

working

population

-RRB-

Characteristics

of

LBP

Duration

current

episode

-LRB-

days

-RRB-

median

-LRB-

IQR

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Frequency

of

LBP

episodes

last

year

or

or

more

episodes

Exacerbation

of

persisting

Pain

radiating

below

kneea

Clinical

outcomes

primary

measures

Functional

disability

-LRB-

RDQ

-RRB-

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Health

related

quality

of

life

-LRB-

EuroQol

-RRB-

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Clinical

outcomes

secondary

measures

Pain

severity

during

the

day

-LRB-

-RRB-

b

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Severity

of

the

main

complaint

-LRB-

-RRB-

a

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Perceived

general

health

-LRB-

-RRB-

a

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Clinical

outcomes

psychosocial

measures

Fear-avoidance

beliefs

-LRB-

FABQ

-RRB-

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Catastrophising

thoughts

-LRB-

CSQ

-RRB-

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Distress

-LRB-

-RRB-

b

mean

-LRB-

SD

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

GP

General

practitioner

MIS

Minimal

intervention

strategy

UC

Usual

care

n

number

SD

Standard

deviation

IQR

Inter

quartile

range

-LRB-

percentile

-RRB-

LBP

Low

back

pain

RDQ

Roland

Morris

disability

Questionnaire

Short-form

FABQ

Fear

avoidance

and

beliefs

questionnaire

CSQ

Coping

strategies

questionnaire

symptom

questionnaire

-LRB-

higher

scores

means

more

functional

disability

worse

health

more

fear-avoidance

more

catastrophising

or

more

distress

-RRB-

aTwo

missing

valuesbOne

missing

value

For

patients

-LRB-

-RRB-

in

the

MIS

group

and

patients

-LRB-

-RRB-

in

the

UC

group

complete

cost

data

were

available

Logistic

regression

analysis

comparing

baseline

characteristics

of

patients

with

complete

cost

data

to

those

with

incomplete

cost

data

showed

that

patients

with

incomplete

cost

data

on

average

were

younger

and

scored

higher

on

distress

at

baseline

Clinical

outcomes

After

year

follow-up

both

the

groups

showed

similar

improvements

in

clinical

outcomes

Sixty-nine

percent

of

the

patients

were

defined

as

recovered

after

year

The

difference

between

both

the

groups

in

mean

improvement

on

functional

disability

was

points

on

the

RDQ

-LRB-

CI

to

-RRB-

and

-LRB-

CI

to

-RRB-

on

recovery

rate

Over

the

follow-up

period

of

year

the

mean

difference

in

quality

of

life

was

QALYs

-LRB-

CI

to

-RRB-

All

differences

favored

UC

but

were

neither

clinically

relevant

nor

statistically

significant

-LRB-

Table

-RRB-

Cost

data

Table

lists

per

patient

the

mean

utilization

of

resources

-LRB-

i.e.

health

care

help

absenteeism

-RRB-

In

both

the

groups

resource

utilization

was

low

and

largely

similar

Only

two

statistically

significant

differences

were

found

In

the

year

following

randomization

patients

in

the

MIS

group

had

more

consultations

with

a

GP

-LRB-

MIS

vs.

UC

-RRB-

excluding

the

consultation

leading

to

recruitment

but

including

the

min

consultation

aimed

at

psychosocial

measures

as

specified

by

the

study

protocol

Patients

in

the

UC

group

reported

more

consultations

with

a

manual

therapist

-LRB-

MIS

vs.

UC

-RRB-

but

the

proportions

of

patients

who

received

such

a

treatment

-LRB-

MIS

vs.

UC

-RRB-

were

very

low

Table

resource

use

-LRB-

SD

-RRB-

per

patient

-LRB-

n

-RRB-

for

MIS

and

UC

during

months

follow-up

and

the

percentage

of

patients

who

made

use

of

that

specific

resourceResourcesMIS

-LRB-

n

-RRB-

UC

-LRB-

n

-RRB-

Direct

health

care

Primary

care

General

practitioner

-LRB-

consultations

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Physical

therapy

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Manual

therapy

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Exercise

therapy

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Back

school

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Chiropractor

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Physiofitness

-LRB-

treatment

programs

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Professional

home

care

-LRB-

hours

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Psychologist

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Secondary

care

Outpatient

visit

-LRB-

number

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Hospitalization

-LRB-

days

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

X-ray

-LRB-

number

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

MRI-scan

-LRB-

number

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Medication

-LRB-

yes

-RRB-

Direct

non-health

care

Complementary

care

Homeopathy

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Osteopathy

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Massage

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Acupuncture

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Magnetizer

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Orthomanual

therapy

-LRB-

treatment

sessions

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Podiatrist

-LRB-

-RRB-

-LRB-

-RRB-

Informal

care

-LRB-

hours

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Equipment

aids

-LRB-

yes

-RRB-

Indirect

costs

Absenteeism

paid

work

-LRB-

days

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Absenteeism

unpaid

work

-LRB-

hours

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Significant

difference

-LRB-

P

-RRB-

SD

Standard

deviation

n

number

MIS

Minimal

intervention

strategy

UC

Usual

care

Table

shows

the

mean

total

costs

in

both

the

treatment

groups

and

the

difference

in

costs

with

CI

Total

indirect

costs

especially

absenteeism

from

paid

work

were

the

largest

contributor

to

the

total

costs

The

difference

in

total

costs

amounted

to

-LRB-

CI

to

-RRB-

in

favor

of

the

MIS

group

-LRB-

MIS

UC

-RRB-

but

this

difference

was

not

statistically

significant

Table

costs

-LRB-

SD

-RRB-

in

Euros

per

patient

in

the

MIS

and

UC

group

and

differences

between

both

the

groups

during

follow-up

of

weeksMIS

-LRB-

n

-RRB-

UC

-LRB-

n

-RRB-

Mean

difference

-LRB-

CI

-RRB-

Direct

health

care

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Primary

care

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Secondary

care

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Medication

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Direct

non-health

care

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Complementary

care

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Informal

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Equipment

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Indirect

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Absenteeism

paid

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Absenteeism

unpaid

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Total

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

of

the

mean

differences

between

MIS

and

UC

are

statistically

significant

-LRB-

P

-RRB-

SD

Standard

deviation

MIS

Minimal

intervention

strategy

UC

Usual

care

n

Number

CI

confidence

interval

Cost-effectiveness

Table

shows

the

incremental

cost-effectiveness

ratios

-LRB-

ICERs

-RRB-

for

the

three

outcome

measures

MIS

resulted

in

less

improvement

than

UC

but

saved

money

The

ICER

for

functioning

was

indicating

that

per

point

less

improvement

on

the

RDQ

MIS

saved

while

per

percent

less

improvement

in

recovery

rate

MIS

saved

The

difference

in

QALY

's

gained

during

year

between

both

the

groups

was

very

small

resulting

in

a

large

ICER

of

The

large

majority

of

the

bootstrapped

ICERs

presented

on

the

cost-effectiveness

planes

are

located

in

the

southern

quadrants

-LRB-

Fig.

-RRB-

indicating

that

the

costs

of

MIS

were

lower

than

the

costs

of

UC

Table

cost-effectiveness

ratios

for

functional

disability

perceived

recovery

and

health-related

quality

of

lifeOutcome

measureMISUCMIS

versus

UCCostsEffectsaCostsEffectsaICERFunctional

disability

-LRB-

RDQ

-RRB-

Change

score

between

baseline

and

year

-LRB-

n

-RRB-

-LRB-

n

-RRB-

-LRB-

n

-RRB-

-LRB-

n

-RRB-

MIS

results

in

less

improvement

but

saves

per

RDQ

pointRecovery

rate

Score

at

year

follow-up

-LRB-

n

-RRB-

-LRB-

n

-RRB-

-LRB-

n

-RRB-

-LRB-

n

-RRB-

MIS

results

in

less

improvement

but

saves

per

Quality

of

life

-LRB-

EuroQol

QALY

-RRB-

Score

over

year

-LRB-

n

-RRB-

-LRB-

n

-RRB-

-LRB-

n

-RRB-

-LRB-

n

-RRB-

MIS

results

in

less

improvement

but

saves

per

QALY

MIS

Minimal

intervention

strategy

UC

Usual

care

ICER

Incremental

cost-effectiveness

ratio

n

Number

QALY

Quality

adjusted

life

yearaDifference

in

clinical

outcomes

between

baseline

and

months

follow-upFig

plane

for

functional

disability

-LRB-

RDQ

-RRB-

in

which

MIS

is

compared

to

UC

Sensitivity

analyses

Imputation

of

missing

cost

data

led

to

a

mean

difference

of

-LRB-

CI

to

-RRB-

in

total

costs

Imputation

of

missing

data

on

days

of

absenteeism

led

to

a

mean

difference

of

-LRB-

CI

to

-RRB-

in

total

costs

Both

differences

are

statistically

significant

and

in

favor

of

MIS

Discussion

The

results

of

our

primary

analysis

showed

no

statistically

significant

differences

in

total

costs

or

clinical

outcomes

between

our

psychosocial

intervention

and

UC

in

patients

with

-LRB-

sub

-RRB-

acute

LBP

in

general

practice

However

the

results

of

our

sensitivity

analyses

are

inconsistent

with

those

of

the

primary

analysis

In

this

discussion

section

we

will

focus

on

the

interpretation

of

our

cost

data

and

the

methodological

issues

involved

when

interpreting

cost

data

In

previous

papers

we

have

discussed

several

methodological

issues

involved

when

interpreting

the

clinical

outcomes

-LRB-

e.g.

the

quality

of

the

training

sessions

and

interventions

-RRB-

-LSB-

-RSB-

Comparison

to

the

literature

A

recent

review

on

the

cost-effectiveness

of

treatments

for

patients

with

LBP

reported

that

of

the

studies

concluded

that

the

intervention

of

interest

was

more

cost-effective

than

the

control

intervention

-LSB-

-RSB-

Unfortunately

no

definite

conclusions

for

the

cost-effectiveness

of

a

specific

intervention

could

be

given

as

the

number

of

economic

evaluations

per

type

of

intervention

was

limited

More

recently

the

cost-effectiveness

analyses

of

two

trials

on

psychosocial

primary

care

interventions

for

LBP

have

been

published

The

UK

BEAM

Trial

compared

spinal

manipulation

exercise

classes

incorporating

cognitive

behavioral

principles

spinal

manipulation

plus

exercise

classes

and

best

care

-LSB-

-RSB-

Although

the

authors

conclude

that

spinal

manipulation

is

a

cost-effective

addition

to

best

care

as

it

generates

more

QALYs

for

an

extra

-LSB-

-RSB-

others

question

this

conclusion

-LSB-

-RSB-

Another

study

in

primary

care

compared

advice

directed

towards

promoting

self-management

and

modifying

beliefs

and

behavior

and

routine

physiotherapy

treatment

with

advice

only

-LSB-

-RSB-

The

authors

conclude

that

advice

should

be

considered

as

the

first-line

treatment

as

out-of-pocket

expenses

of

patients

receiving

routine

physiotherapy

were

significantly

higher

-LRB-

-RRB-

while

differences

in

either

QALYs

-LRB-

-RRB-

or

National

Health

Service

costs

-LRB-

-RRB-

were

not

significantly

different

-LSB-

-RSB-

Both

the

above

mentioned

studies

found

lower

QALYs

and

higher

health

care

costs

over

months

than

we

found

in

our

study

The

shorter

duration

of

the

LBP

episode

at

baseline

of

our

patients

and

thus

their

more

favorable

prognosis

may

-LRB-

partly

-RRB-

explain

these

results

In

contrast

to

our

study

both

the

trials

did

not

include

indirect

costs

in

their

cost-effectiveness

analyses

even

though

it

is

generally

agreed

upon

that

indirect

costs

associated

with

work

absence

due

to

LBP

account

for

high

economic

costs

in

western

societies

-LSB-

-RSB-

Methodological

issues

and

secondary

analyses

In

our

study

we

used

the

British

sample

as

reference

population

for

the

utilities

as

until

recently

these

were

the

only

reference

data

available

in

the

Netherlands

Recently

a

EuroQol

transformation

has

been

introduced

based

on

a

Dutch

sample

-LSB-

-RSB-

We

decided

not

to

use

this

Dutch

transformation

as

-LRB-

-RRB-

it

has

only

been

internally

validated

through

bootstrapping

methods

but

not

yet

externally

validated

-LRB-

-RRB-

the

representativeness

of

the

rather

small

-LRB-

n

-RRB-

Dutch

sample

can

be

debated

-LSB-

-RSB-

and

finally

-LRB-

-RRB-

use

of

the

Dutch

transformation

would

complicate

comparison

across

international

studies

A

comparison

between

the

use

of

a

Dutch

or

UK

sample

showed

that

although

QALYs

based

on

the

Dutch

sample

were

slightly

higher

compared

to

the

British

sample

the

mean

differences

between

the

groups

in

this

case

two

primary

care

interventions

for

treatment

of

depression

were

largely

the

same

-LSB-

-RSB-

We

based

our

sample

size

calculations

on

demonstrating

a

clinically

relevant

difference

of

points

on

the

RDQ

instead

of

demonstrating

the

cost-effectiveness

-LSB-

-RSB-

Although

the

usefulness

of

sample

size

calculations

in

economic

evaluations

has

been

debated

-LSB-

-RSB-

the

required

sample

size

in

an

appropriately

powered

cost-effectiveness

study

is

expected

to

be

much

larger

than

in

a

clinical

effectiveness

trial

-LSB-

-RSB-

Work

absence

due

to

LBP

was

the

main

contributor

to

the

total

costs

associated

with

LBP

The

number

of

days

of

absenteeism

was

twice

as

high

in

the

UC

group

as

in

the

MIS

group

Although

not

statistically

significant

this

finding

induced

us

to

explore

whether

MIS

was

cost-effective

among

patients

having

a

paid

job

-LRB-

n

MIS

n

UC

-RRB-

This

post-hoc

subgroup

analysis

showed

that

the

difference

in

total

costs

amounted

to

-LRB-

CI

to

-RRB-

in

favor

of

MIS

which

was

not

statistically

significant

As

this

subgroup

analysis

was

clearly

insufficiently

powered

and

as

other

early

interventions

have

been

shown

to

reduce

sick-leave

in

workers

-LSB-

-RSB-

one

may

hypothesize

that

MIS

may

be

cost-effective

in

an

occupational

setting

The

sensitivity

analyses

with

imputed

data

were

less

underpowered

and

interestingly

showed

statistically

significant

differences

in

total

costs

between

groups

The

question

now

arises

which

analysis

we

should

value

most

Interpretation

of

the

conflicting

results

A

complete

case

analysis

has

the

advantage

over

an

imputed

analysis

that

no

assumptions

have

to

be

made

regarding

imputation

of

data

that

are

characterized

by

large

variation

and

irregular

distributions

However

a

complete

case

analysis

does

not

include

all

participating

patients

which

reduces

the

statistical

power

and

which

may

introduce

bias

Advocates

of

the

-LRB-

conclusions

of

our

-RRB-

complete

case

analysis

may

among

others

be

-LRB-

-RRB-

researchers

who

do

not

favor

imputation

techniques

when

data

are

available

for

of

the

cases

-LRB-

-RRB-

GPs

as

application

of

MIS

will

increase

their

workload

with

no

evidence

of

improvement

of

the

patients

functional

disability

recovery

rates

or

pain

intensity

Advocates

of

the

-LRB-

conclusions

of

our

-RRB-

sensitivity

analysis

may

among

others

be

-LRB-

-RRB-

researchers

who

favor

imputation

techniques

-LRB-

-RRB-

policy

makers

who

are

interested

in

all

relevant

costs

and

effects

regardless

of

who

will

pay

the

costs

and

who

may

benefit

or

-LRB-

-RRB-

managers

in

workplace

settings

as

they

may

be

especially

interested

in

the

reduction

of

costs

due

to

sick-leave

The

cost-effectiveness

planes

do

not

provide

a

solution

for

the

impasse

The

plane

for

functional

disability

showed

that

of

the

bootstrapped

cost-effect

pairs

although

very

close

to

the

origin

of

the

plane

were

located

in

the

southern

quadrants

Does

this

indicate

cost-effectiveness

of

MIS

The

answer

to

this

question

will

depend

on

the

way

one

defines

cost-effectiveness

Obviously

when

a

new

intervention

is

clinically

more

effective

and

less

costly

than

the

old

intervention

-LRB-

south

east

quadrant

-RRB-

there

will

be

no

debate

about

cost-effectiveness

and

implementation

of

the

new

intervention

When

a

new

intervention

is

clinically

more

effective

and

more

costly

-LRB-

north-east

quadrant

-RRB-

a

new

intervention

will

be

considered

cost-effective

when

costs

stay

below

a

certain

threshold

Dowie

-LRB-

-RRB-

-LSB-

-RSB-

however

questions

why

an

intervention

should

not

also

be

implemented

when

it

is

less

effective

but

does

save

substantial

costs

pleading

for

defining

a

threshold

that

extends

into

the

south-west

quadrant

This

threshold

can

be

a

straight

line

from

the

north-east

to

the

south-west

quadrant

or

kinked

at

the

origin

of

the

cost-effectiveness

plane

indicating

that

the

selling

price

for

an

unit

of

effect

is

greater

than

the

buying

price

of

an

additional

unit

of

effect

-LSB-

-RSB-

Although

there

are

various

points

of

view

we

conclude

that

-LRB-

Dutch

-RRB-

GPs

should

not

replace

their

UC

by

MIS

in

patients

with

-LRB-

sub

-RRB-

acute

LBP

This

conclusion

is

based

on

the

results

of

the

complete

case

analysis

because

this

was

our

pre-planned

analysis

The

second

reason

is

that

the

difference

in

costs

if

any

was

mainly

caused

by

a

small

proportion

of

the

population

who

reported

sick

leave

due

to

back

pain

We

can

not

rule

out

the

possibility

that

this

was

a

chance

finding

The

third

reason

is

that

MIS

is

a

new

approach

in

general

practice

Implementation

of

MIS

will

meet

many

difficulties

given

the

lack

of

evidence

for

clinical

effects

the

need

for

training

of

GPs

and

the

increase

of

GP

workload

The

final

and

maybe

most

important

reason

is

that

our

study

is

the

first

and

as

far

as

we

know

the

only

study

that

investigated

the

cost-effectiveness

of

a

psychosocial

intervention

in

patients

with

-LRB-

sub

-RRB-

acute

LBP

in

general

practice

Conclusions

Results

of

only

one

study

are

insufficient

to

establish

firm

evidence

on

the

cost-effectiveness

of

an

intervention

More

studies

on

the

cost-effectiveness

of

psychosocial

interventions

in

general

practice

are

needed

thereby

taking

into

account

some

of

the

factors

that

may

explain

why

our

intervention

was

not

more

successful

than

usual

GP

care

as

described

in

previous

papers

-LSB-

-RSB-

As

yet

we

conclude

that

-LRB-

Dutch

-RRB-

general

practitioners

should

not

replace

their

usual

care

by

our

new

intervention

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

low back pain
minimal intervention strategy
psychosocial factors
general practice