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[
5
]
.
Ho
wev
er
,
m
ap
p
in
g
h
o
w
v
ar
io
u
s
d
im
e
n
s
io
n
s
o
f
ad
h
e
r
en
ce
in
f
l
u
en
c
e
s
p
ec
if
ic
s
o
m
atic
p
er
ce
p
tio
n
s
u
b
s
ca
les
r
em
a
in
s
lim
ited
.
T
h
er
ef
o
r
e,
a
s
co
p
in
g
r
ev
iew
is
n
ee
d
ed
t
o
m
ap
th
e
ex
is
tin
g
s
cien
tific
ev
id
en
ce
to
u
n
d
e
r
s
tan
d
th
e
in
t
er
ac
tio
n
b
etwe
en
a
d
h
er
e
n
ce
b
eh
av
io
r
a
n
d
p
atien
t'
s
p
h
y
s
ical
p
er
ce
p
tio
n
[
3
]
,
[
4
]
.
T
h
is
s
co
p
in
g
r
e
v
iew
aim
s
to
m
ap
s
cien
tific
ev
id
e
n
ce
r
e
g
ar
d
in
g
th
e
r
elatio
n
s
h
i
p
b
etwe
en
th
e
lev
el
o
f
th
e
r
ap
y
co
m
p
lian
ce
(
m
ed
icatio
n
,
d
iet,
an
d
f
lu
id
s
)
a
n
d
s
o
m
atic
p
er
ce
p
tio
n
in
h
ea
r
t
f
ailu
r
e
p
atien
ts
,
an
d
t
o
id
en
tif
y
f
ac
to
r
s
th
at
in
f
lu
e
n
ce
th
e
ac
cu
r
ac
y
o
f
th
is
p
er
ce
p
tio
n
.
2.
M
E
T
H
O
D
T
h
is
s
co
p
in
g
r
ev
iew
f
o
llo
we
d
th
e
m
eth
o
d
o
lo
g
ical
f
r
am
ew
o
r
k
o
f
th
e
J
o
an
n
a
B
r
ig
g
s
I
n
s
titu
te
(
J
B
I
)
2
0
2
0
an
d
was r
ep
o
r
ted
ac
co
r
d
in
g
to
th
e
PR
I
SMA
E
x
ten
s
io
n
f
o
r
Sco
p
in
g
R
ev
iews (
PR
I
SM
A
-
ScR
)
g
u
id
elin
es.
T
h
e
r
ev
iew
aim
ed
t
o
m
ap
e
x
i
s
tin
g
ev
id
en
ce
o
n
th
e
r
elatio
n
s
h
ip
b
etwe
en
th
er
ap
e
u
tic
ad
h
er
en
ce
a
n
d
s
o
m
atic
s
y
m
p
to
m
p
e
r
ce
p
tio
n
i
n
p
atien
t
s
with
h
ea
r
t f
ailu
r
e.
2
.
1
.
E
lig
ibi
lity
c
rit
er
ia
T
h
e
elig
ib
ilit
y
cr
iter
ia
wer
e
d
ef
in
ed
u
s
in
g
th
e
Po
p
u
latio
n
–
C
o
n
ce
p
t
–
C
o
n
tex
t
(
PC
C
)
f
r
am
ewo
r
k
.
T
h
e
p
o
p
u
latio
n
in
clu
d
e
d
ad
u
lts
(
≥
1
8
y
ea
r
s
)
d
iag
n
o
s
ed
with
h
ea
r
t f
ailu
r
e
b
a
s
ed
o
n
clin
ical
cr
iter
i
a
o
r
class
if
icatio
n
s
s
u
ch
as
New
Yo
r
k
Hea
r
t
Ass
o
ciatio
n
(
NYHA
)
o
r
AC
C
/AHA.
T
h
e
co
n
ce
p
t
f
o
cu
s
ed
o
n
th
er
ap
eu
tic
ad
h
er
en
ce
(
p
h
ar
m
ac
o
lo
g
ical
a
n
d
n
o
n
-
p
h
a
r
m
ac
o
lo
g
ical,
in
clu
d
i
n
g
m
ed
ic
atio
n
ad
h
er
en
ce
,
d
ietar
y
s
o
d
iu
m
r
estrictio
n
,
f
lu
id
m
an
ag
em
en
t,
an
d
p
h
y
s
ical
ac
tiv
ity
)
an
d
s
o
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
,
p
a
r
ticu
lar
ly
m
ea
s
u
r
ed
u
s
in
g
in
s
tr
u
m
en
ts
s
u
ch
as
th
e
Hea
r
t
Failu
r
e
So
m
atic
Per
ce
p
tio
n
Scale
(
HFSP
S)
o
r
s
im
ilar
v
alid
ated
to
o
ls
.
T
h
e
co
n
tex
t
in
clu
d
ed
h
o
s
p
ital
s
ett
in
g
s
,
o
u
tp
atien
t
clin
ics,
ca
r
d
iac
r
eh
ab
ilit
atio
n
p
r
o
g
r
am
s
,
o
r
co
m
m
u
n
ity
/h
o
m
e
-
b
ased
ca
r
e.
E
lig
ib
le
ar
ticles
wer
e
p
r
im
ar
y
o
r
s
ec
o
n
d
a
r
y
r
esear
ch
s
tu
d
ie
s
p
u
b
lis
h
ed
b
etwe
en
2
0
1
6
an
d
2
0
2
5
in
E
n
g
lis
h
o
r
I
n
d
o
n
esian
with
f
u
ll
-
tex
t
av
ailab
ilit
y
.
I
n
cl
u
d
ed
s
tu
d
y
d
esig
n
s
c
o
m
p
r
is
ed
o
b
s
er
v
atio
n
al
s
tu
d
ie
s
,
cr
o
s
s
-
s
ec
tio
n
al
s
tu
d
ies,
co
h
o
r
t
s
tu
d
ies,
r
an
d
o
m
ized
co
n
tr
o
l
led
tr
ials
(
R
C
T
s
)
,
an
d
r
ev
iew
s
tu
d
ies
ex
am
in
in
g
th
e
r
elatio
n
s
h
ip
b
etwe
en
ad
h
e
r
en
ce
an
d
s
o
m
atic
s
y
m
p
t
o
m
p
er
ce
p
tio
n
.
E
d
ito
r
ials
,
co
m
m
e
n
tar
ies,
co
n
f
er
en
ce
ab
s
tr
ac
ts
with
o
u
t
f
u
ll
tex
t,
n
o
n
–
p
ee
r
-
r
ev
i
ewe
d
p
u
b
licatio
n
s
,
d
u
p
licate
s
tu
d
ies,
an
d
s
tu
d
ies
th
at
ass
ess
ed
ad
h
er
en
ce
with
o
u
t e
v
alu
ati
n
g
s
y
m
p
to
m
p
e
r
ce
p
tio
n
wer
e
ex
c
lu
d
ed
.
2
.
2
.
Sea
rc
h
s
t
ra
t
eg
y
a
nd
s
t
ud
y
s
elec
t
io
n
A
s
y
s
tem
atic
s
ea
r
ch
was
co
n
d
u
cted
in
Pr
o
Qu
est,
Scien
ce
Dir
ec
t,
Sp
r
in
g
er
,
an
d
Go
o
g
le
Sch
o
lar
u
s
in
g
co
m
b
in
atio
n
s
o
f
k
e
y
wo
r
d
s
r
e
lated
to
h
ea
r
t
f
ailu
r
e,
th
er
ap
y
ad
h
e
r
en
ce
,
a
n
d
s
o
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
,
s
tr
u
ctu
r
ed
u
s
in
g
B
o
o
lea
n
o
p
e
r
ato
r
s
.
T
h
e
s
tu
d
y
s
elec
tio
n
p
r
o
ce
s
s
co
n
s
is
ted
o
f
th
r
ee
s
tag
es:
i
)
r
em
o
v
al
o
f
d
u
p
licate
r
ec
o
r
d
s
,
ii
)
titl
e
an
d
ab
s
tr
ac
t
s
cr
ee
n
in
g
,
an
d
iii
)
f
u
l
l
-
tex
t
r
ev
iew
ac
co
r
d
in
g
to
th
e
elig
ib
ilit
y
cr
iter
ia.
T
h
e
s
elec
tio
n
p
r
o
ce
s
s
was d
o
c
u
m
en
ted
u
s
in
g
th
e
PR
I
SMA
-
ScR
f
lo
w
d
iag
r
am
.
2
.
3
.
Da
t
a
e
x
t
ra
c
t
i
o
n a
nd
qu
a
lity
a
pp
ra
is
a
l
Data
wer
e
ex
tr
ac
te
d
u
s
in
g
a
s
tr
u
ctu
r
ed
d
ata
ch
ar
tin
g
f
o
r
m
a
d
ap
ted
f
r
o
m
th
e
J
B
I
SUMAR
I
tem
p
late.
E
x
tr
ac
ted
in
f
o
r
m
atio
n
in
clu
d
ed
au
th
o
r
,
y
ea
r
,
co
u
n
tr
y
,
s
tu
d
y
d
esig
n
,
p
ar
ticip
an
t
c
h
ar
ac
ter
is
tics
,
ad
h
er
en
ce
v
ar
iab
les,
in
s
tr
u
m
en
ts
u
s
e
d
t
o
ass
ess
s
o
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
,
a
n
d
k
ey
f
i
n
d
in
g
s
r
elev
an
t
to
th
e
s
tu
d
y
o
b
jectiv
e.
Me
th
o
d
o
lo
g
ical
q
u
ality
was
a
s
s
es
s
ed
u
s
in
g
th
e
J
B
I
C
r
itical
Ap
p
r
aisal
T
o
o
ls
ap
p
r
o
p
r
iate
to
ea
ch
s
tu
d
y
d
esig
n
.
T
h
e
ap
p
r
aisal
r
esu
lts
wer
e
u
s
ed
to
s
u
p
p
o
r
t
t
h
e
in
ter
p
r
etatio
n
o
f
th
e
ev
i
d
e
n
ce
r
ath
er
th
an
as
cr
iter
ia
f
o
r
e
x
clu
s
io
n
.
2
.
4
.
Da
t
a
s
y
nthesi
s
T
h
e
ex
tr
ac
ted
d
ata
wer
e
s
y
n
th
esized
u
s
in
g
th
em
atic
s
y
n
th
esis
.
T
h
e
s
y
n
th
esis
p
r
o
ce
s
s
in
v
o
lv
ed
f
o
u
r
s
tag
es:
i
)
r
ev
iewin
g
an
d
f
a
m
iliar
izin
g
with
ex
tr
ac
ted
s
t
u
d
y
f
i
n
d
in
g
s
,
ii
)
c
o
d
in
g
k
e
y
r
esu
lts
r
elate
d
to
ad
h
er
en
ce
b
e
h
av
io
r
s
an
d
s
o
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
,
iii
)
g
r
o
u
p
in
g
s
im
ilar
co
d
es
in
to
b
r
o
ad
er
th
em
atic
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
Th
era
p
eu
tic
a
d
h
eren
ce
a
n
d
s
o
ma
tic
s
ymp
to
m
p
ercep
tio
n
in
p
a
tien
ts
w
ith
h
ea
r
t fa
ilu
r
e:
… (
Tr
i A
n
d
a
ya
n
i
)
419
ca
teg
o
r
ies,
an
d
iv
)
in
te
g
r
atin
g
th
ese
th
em
es
to
id
en
tify
p
atter
n
s
,
r
elatio
n
s
h
ip
s
,
an
d
r
e
s
ea
r
ch
g
ap
s
ac
r
o
s
s
s
tu
d
ies.
T
h
is
ap
p
r
o
ac
h
e
n
ab
l
ed
th
e
d
ev
elo
p
m
en
t
o
f
a
n
i
n
teg
r
ativ
e
n
ar
r
ativ
e
ex
p
lain
in
g
h
o
w
th
er
ap
e
u
tic
ad
h
er
en
ce
in
f
lu
en
ce
s
s
y
m
p
to
m
p
er
ce
p
tio
n
,
s
elf
-
m
a
n
ag
em
e
n
t
b
eh
av
io
r
,
an
d
clin
ical
o
u
tc
o
m
es
am
o
n
g
p
atien
ts
with
h
ea
r
t f
ailu
r
e.
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
N
3
.
1
.
R
esu
lt
T
h
e
m
ajo
r
ity
o
f
s
tu
d
ies
(
n
=
4
)
u
s
ed
a
c
r
o
s
s
-
s
ec
tio
n
al
d
e
s
ig
n
,
an
d
(
n
=
3
)
a
q
u
asi
-
ex
p
er
im
en
tal
r
an
d
o
m
ize
d
co
n
tr
o
lled
tr
ial
(
R
C
T
)
.
T
h
e
m
o
s
t
f
r
eq
u
en
tly
u
s
ed
ad
h
er
en
ce
in
s
tr
u
m
en
t
was
th
e
Self
-
C
ar
e
o
f
Hea
r
t
Failu
r
e
I
n
d
ex
(
SC
HFI
)
,
wh
ile
s
o
m
atic
p
er
ce
p
tio
n
s
co
n
s
is
ten
tly
u
s
ed
th
e
1
8
-
item
HF
SP
S
.
B
ased
o
n
th
e
s
y
n
th
esis
o
f
eig
h
t
in
clu
d
ed
s
tu
d
ies
(
as
s
h
o
wn
in
T
ab
le
1
(
s
ee
Ap
p
en
d
ix
)
[
4
]
,
[
6
]
–
[
1
2
]
)
.
T
h
e
f
in
d
in
g
s
h
ig
h
lig
h
t
s
ev
er
al
th
em
atic
p
atter
n
s
ex
p
lain
in
g
th
e
r
elatio
n
s
h
ip
b
etwe
en
th
er
ap
eu
tic
ad
h
er
en
ce
a
n
d
s
o
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
i
n
p
atien
ts
with
h
ea
r
t f
ailu
r
e.
3
.
1
.
1
.
So
ma
t
ic
s
y
m
pt
o
m
perc
ept
io
n a
s
a
driv
er
o
f
s
elf
-
ca
r
e
a
nd
t
hera
peutic
a
dh
er
ence
Sev
er
al
s
tu
d
ies
in
d
icate
th
at
p
atien
ts
’
p
er
ce
p
tio
n
o
f
p
h
y
s
ical
s
y
m
p
to
m
s
p
lay
s
an
im
p
o
r
t
an
t
r
o
le
in
m
o
ti
v
at
in
g
s
e
lf
-
c
ar
e
b
e
h
a
v
i
o
r
s
a
n
d
a
d
h
e
r
e
n
c
e
t
o
tr
ea
tm
en
t.
Pat
ie
n
ts
w
h
o
e
x
p
e
r
ie
n
ce
m
o
r
e
n
o
ti
ce
ab
le
o
r
d
is
t
u
r
b
in
g
s
y
m
p
t
o
m
s
t
en
d
t
o
e
n
g
a
g
e
m
o
r
e
c
o
n
s
is
te
n
t
ly
i
n
s
e
lf
-
ca
r
e
a
cti
v
it
ies
.
A
l
o
n
g
it
u
d
i
n
al
s
t
u
d
y
b
y
Au
l
d
et
a
l
.
[
8
]
r
ep
o
r
ted
th
at
p
ati
en
ts
wh
o
p
er
ce
iv
ed
a
h
ig
h
er
b
u
r
d
en
o
f
s
y
m
p
to
m
s
d
em
o
n
s
tr
ated
m
o
r
e
c
o
n
s
i
s
t
e
n
t
s
e
l
f
-
ca
r
e
b
e
h
a
v
i
o
r
s
o
v
e
r
t
i
m
e
.
S
i
m
i
l
a
r
l
y
,
L
i
u
et
a
l
.
[
1
0
]
f
o
u
n
d
t
h
a
t
p
a
ti
e
n
ts
wi
t
h
s
e
v
e
r
e
p
h
y
s
ic
al
s
y
m
p
t
o
m
s
s
u
c
h
as
d
y
s
p
n
e
a
w
er
e
m
o
r
e
l
i
k
e
l
y
t
o
i
m
p
r
o
v
e
t
h
e
i
r
s
e
l
f
-
c
a
r
e
m
a
n
a
g
e
m
e
n
t
,
s
u
g
g
e
s
t
i
n
g
t
h
a
t
w
o
r
s
e
n
i
n
g
s
y
m
p
to
m
s
m
ay
ac
t
as
a
ca
ta
ly
s
t
f
o
r
ad
h
er
en
ce
b
e
h
av
io
r
s
.
T
h
ese
f
in
d
in
g
s
in
d
icate
th
at
s
o
m
atic
s
y
m
p
to
m
awa
r
en
ess
ca
n
s
tim
u
late
p
atien
t e
n
g
ag
e
m
en
t in
th
e
r
ap
eu
tic
a
d
h
er
en
ce
a
n
d
s
elf
-
m
a
n
ag
em
e
n
t p
r
ac
tices.
3
.
1
.
2
.
T
he
ro
le
o
f
s
y
m
pt
o
m
m
o
nito
ring
in im
pro
v
ing
s
elf
-
ca
re
re
s
po
ns
e
Sy
m
p
to
m
m
o
n
ito
r
in
g
is
an
ess
en
tial
co
m
p
o
n
e
n
t
o
f
e
f
f
ec
tiv
e
h
ea
r
t
f
ailu
r
e
m
a
n
ag
em
en
t
.
W
u
et
a
l
.
[
4
]
d
em
o
n
s
tr
ated
t
h
at
s
y
m
p
t
o
m
m
o
n
ito
r
in
g
m
e
d
iates
th
e
r
ela
tio
n
s
h
ip
b
etwe
en
h
ea
r
t
f
ailu
r
e
k
n
o
wled
g
e
a
n
d
p
atien
ts
’
ab
ilit
y
to
r
ec
o
g
n
ize
an
d
r
esp
o
n
d
to
s
y
m
p
to
m
s
.
Pa
tien
ts
wh
o
ac
tiv
ely
m
o
n
ito
r
t
h
eir
s
y
m
p
to
m
s
ar
e
m
o
r
e
ca
p
a
b
le
o
f
id
en
tif
y
in
g
e
ar
ly
s
ig
n
s
o
f
clin
ical
d
eter
io
r
a
tio
n
an
d
r
esp
o
n
d
in
g
ap
p
r
o
p
r
ia
tely
.
T
h
ese
f
in
d
in
g
s
s
u
p
p
o
r
t
p
r
ev
io
u
s
r
ec
o
m
m
e
n
d
a
tio
n
s
th
at
s
y
m
p
to
m
p
er
ce
p
tio
n
an
d
m
o
n
ito
r
in
g
ar
e
ce
n
tr
al
el
em
en
ts
o
f
s
elf
-
ca
r
e
in
h
ea
r
t
f
ailu
r
e
m
an
a
g
em
en
t
[
5
]
.
T
h
er
e
f
o
r
e,
im
p
r
o
v
in
g
p
atien
ts
’
s
k
ills
in
m
o
n
ito
r
in
g
an
d
in
ter
p
r
etin
g
s
y
m
p
to
m
s
m
ay
s
tr
en
g
t
h
en
a
d
h
er
en
ce
to
tr
ea
tm
e
n
t a
n
d
e
n
h
an
ce
s
elf
-
m
an
ag
em
en
t
o
u
tco
m
es.
3
.
1
.
3
.
I
nte
rv
ent
io
ns
t
o
im
pro
v
e
a
dh
er
ence
a
nd
s
y
m
pto
m
perc
ept
io
n
S
ev
er
al
s
tu
d
ies
ev
alu
ated
in
ter
v
en
tio
n
s
d
esig
n
e
d
to
en
h
a
n
ce
ad
h
er
e
n
ce
b
eh
a
v
io
r
s
an
d
s
y
m
p
to
m
p
er
ce
p
tio
n
.
A
r
an
d
o
m
ized
co
n
tr
o
lled
tr
ial
b
y
C
ag
g
ian
elli
et
a
l
.
[
6
]
d
em
o
n
s
tr
ated
th
at
m
o
tiv
atio
n
a
l
in
ter
v
iewin
g
(
MI
)
s
ig
n
if
ican
tly
r
ed
u
ce
d
th
e
b
u
r
d
en
o
f
p
h
y
s
ical
s
y
m
p
to
m
s
in
h
ea
r
t
f
ailu
r
e
p
atien
ts
,
p
ar
ticu
lar
ly
wh
en
ca
r
e
g
iv
er
s
wer
e
ac
tiv
ely
in
v
o
lv
ed
i
n
th
e
in
ter
v
en
tio
n
.
L
i
k
ewise,
th
e
SYMPE
R
HE
AR
T
in
ter
v
en
tio
n
p
r
o
p
o
s
ed
b
y
Sa
n
to
s
et
a
l
.
[
1
1
]
aim
ed
to
im
p
r
o
v
e
p
atien
ts
’
ab
ilit
y
to
p
e
r
ce
iv
e
an
d
in
ter
p
r
et
s
y
m
p
to
m
s
,
en
ab
lin
g
ea
r
lier
h
ea
lth
ca
r
e
s
ee
k
in
g
an
d
p
o
te
n
tially
r
ed
u
cin
g
r
eh
o
s
p
italiz
atio
n
r
ates.
T
h
ese
f
in
d
in
g
s
em
p
h
asize
th
at
b
eh
av
io
r
al
in
ter
v
e
n
tio
n
s
,
p
atien
t
ed
u
ca
tio
n
,
a
n
d
ca
r
eg
iv
e
r
in
v
o
l
v
e
m
en
t
ar
e
im
p
o
r
tan
t
s
tr
ateg
ies to
im
p
r
o
v
e
b
o
th
a
d
h
er
en
ce
an
d
s
y
m
p
to
m
m
an
ag
e
m
en
t in
h
ea
r
t
f
ailu
r
e
p
atien
ts
.
3
.
1
.
4
.
F
a
ct
o
rs
influencing
s
o
m
a
t
ic
s
y
m
pto
m per
ce
ptio
n
So
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
am
o
n
g
h
ea
r
t
f
ailu
r
e
p
atie
n
ts
is
in
f
lu
en
ce
d
b
y
m
u
ltip
le
f
ac
t
o
r
s
,
in
clu
d
in
g
clin
ical,
p
s
y
ch
o
lo
g
i
ca
l,
an
d
s
o
cio
-
d
em
o
g
r
ap
h
ic
ch
ar
ac
ter
is
tics
.
L
u
o
et
a
l
.
[
1
2
]
i
d
en
tifie
d
d
e
p
r
ess
io
n
lev
els,
NYHA
f
u
n
ctio
n
al
clas
s
,
lef
t
v
en
tr
icu
lar
ejec
tio
n
f
r
a
ctio
n
,
an
d
ed
u
ca
tio
n
al
b
ac
k
g
r
o
u
n
d
as
s
ig
n
if
ican
t
p
r
ed
icto
r
s
o
f
s
y
m
p
to
m
p
er
ce
p
tio
n
.
I
n
ad
d
itio
n
,
th
e
s
tu
d
y
in
[
7
]
r
e
p
o
r
ted
s
ig
n
if
ican
t
in
ter
n
atio
n
al
d
if
f
er
e
n
ce
s
in
s
y
m
p
to
m
b
u
r
d
en
a
m
o
n
g
h
e
ar
t
f
ailu
r
e
p
atien
ts
,
s
u
g
g
esti
n
g
th
at
cu
ltu
r
al
an
d
h
ea
lth
ca
r
e
s
y
s
tem
f
ac
to
r
s
m
ay
in
f
lu
en
ce
s
y
m
p
to
m
p
er
ce
p
tio
n
an
d
r
ep
o
r
tin
g
.
Sy
m
p
to
m
s
ev
e
r
ity
h
as
also
b
ee
n
ass
o
ciate
d
with
p
o
o
r
er
h
e
alth
-
r
elate
d
q
u
ality
o
f
life
am
o
n
g
h
ea
r
t
f
ailu
r
e
p
atien
ts
,
em
p
h
asizin
g
th
e
im
p
o
r
tan
ce
o
f
ef
f
ec
tiv
e
s
y
m
p
to
m
m
an
ag
em
en
t stra
teg
ies
[
9
]
.
3
.
2
.
Su
mm
a
ry
o
f
f
ind
ing
s
Ov
er
all,
th
e
ev
i
d
en
ce
s
u
g
g
ests
a
r
ec
ip
r
o
ca
l
r
elatio
n
s
h
ip
b
et
wee
n
th
er
ap
e
u
tic
ad
h
e
r
en
ce
a
n
d
s
o
m
atic
s
y
m
p
to
m
p
e
r
ce
p
tio
n
.
I
n
cr
ea
s
ed
s
y
m
p
to
m
awa
r
en
ess
ca
n
en
co
u
r
a
g
e
s
elf
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ca
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e
b
eh
av
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d
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h
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r
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to
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wh
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Fu
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tar
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Evaluation Warning : The document was created with Spire.PDF for Python.
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1
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420
ca
r
eg
iv
er
in
v
o
lv
em
e
n
t,
an
d
p
s
y
ch
o
lo
g
ical
s
u
p
p
o
r
t
ar
e
ess
en
tial
to
o
p
tim
ize
b
o
th
a
d
h
er
e
n
ce
an
d
s
y
m
p
t
o
m
p
er
ce
p
tio
n
i
n
h
ea
r
t
f
ailu
r
e
m
a
n
ag
em
en
t.
Sy
n
th
esized
r
esu
lts
f
r
o
m
v
ar
io
u
s
s
tu
d
ies
[
4
]
,
[
6
]
,
[
1
1
]
,
[
1
2
]
i
n
d
icate
th
at
h
ea
r
t
f
ailu
r
e
m
an
a
g
em
en
t
is
a
d
y
n
am
ic
p
r
o
ce
s
s
th
at
r
elies
h
ea
v
ily
o
n
th
e
p
atien
t'
s
co
g
n
itiv
e
an
d
b
eh
a
v
io
r
al
ab
ilit
ies
an
d
ca
r
eg
iv
er
s
u
p
p
o
r
t.
C
o
llectiv
e
ly
,
th
is
l
iter
atu
r
e
co
n
f
ir
m
s
th
at
k
n
o
wled
g
e
ab
o
u
t
th
e
d
is
ea
s
e
i
s
a
k
ey
f
o
u
n
d
atio
n
,
b
u
t
it
is
in
s
u
f
f
icien
t
with
o
u
t
a
k
ee
n
a
b
ilit
y
to
p
er
ce
iv
e
s
y
m
p
to
m
s
.
Mo
d
er
n
in
ter
v
en
tio
n
s
ar
e
s
h
if
tin
g
f
r
o
m
s
im
p
ly
p
r
o
v
id
i
n
g
m
ed
ical
in
f
o
r
m
atio
n
to
b
eh
av
i
o
r
al
ap
p
r
o
ac
h
es,
s
u
c
h
as
m
o
tiv
atio
n
al
in
ter
v
ie
win
g
an
d
in
f
o
r
m
al
ca
r
eg
iv
er
e
n
g
ag
e
m
en
t
(
as
in
t
h
e
SYMPE
R
HE
A
R
T
p
r
o
to
co
l
)
,
to
e
n
s
u
r
e
th
at
p
atien
ts
n
o
t
o
n
ly
k
n
o
w
wh
at
to
d
o
b
u
t
ar
e
also
m
o
tiv
ated
an
d
ab
le
to
d
etec
t
ev
e
n
th
e
s
m
allest
p
h
y
s
ical
ch
an
g
es
b
ef
o
r
e
t
h
ey
escalate
in
to
a
cli
n
ical
cr
is
is
[
1
3
]
.
Op
tim
al
th
er
ap
y
ad
h
er
e
n
ce
is
d
ir
ec
tly
p
r
o
p
o
r
tio
n
al
to
th
e
p
atien
t'
s
ab
ilit
y
to
m
an
ag
e
th
eir
s
o
m
atic
p
er
ce
p
tio
n
s
.
T
h
e
HFSP
S
h
as
b
ee
n
s
h
o
wn
to
b
e
an
ef
f
ec
tiv
e
s
cr
ee
n
in
g
to
o
l
f
o
r
n
u
r
s
es
to
d
etec
t
p
o
ten
tial
p
atien
t
n
o
n
a
d
h
er
e
n
ce
.
Su
cc
ess
f
u
l
h
ea
r
t
f
ailu
r
e
m
a
n
ag
em
e
n
t
r
ests
n
o
t
o
n
ly
o
n
th
e
ap
p
r
o
p
r
iaten
ess
o
f
m
ed
ical
th
er
ap
y
,
b
u
t
also
o
n
th
e
cr
itical
in
ter
ac
tio
n
b
etwe
en
k
n
o
wled
g
e,
ad
h
er
e
n
ce
b
eh
av
io
r
s
,
an
d
th
e
ac
u
ity
o
f
s
o
m
atic
p
er
ce
p
tio
n
s
.
T
h
er
e
is
a
clea
r
lin
ea
r
r
elatio
n
s
h
ip
w
h
er
e
ad
h
er
e
n
ce
b
eh
av
io
r
s
s
u
ch
as
r
eg
u
lar
s
elf
-
m
o
n
ito
r
in
g
ac
t
as
a
m
ea
n
s
f
o
r
p
atien
ts
to
cu
ltiv
ate
th
eir
b
o
d
y
awa
r
e
n
ess
.
W
h
en
p
atien
ts
ad
h
er
e
to
s
elf
-
m
o
n
ito
r
in
g
,
th
ey
g
r
a
d
u
ally
d
ev
elo
p
b
o
d
y
liter
ac
y
th
at
all
o
ws
th
em
to
r
ec
o
g
n
ize
ex
ac
er
b
atio
n
s
y
m
p
to
m
s
ea
r
lier
.
Ho
wev
er
,
th
is
p
e
r
ce
p
tio
n
is
o
f
ten
d
is
r
u
p
te
d
b
y
i
n
ter
n
al
b
ar
r
i
er
s
s
u
ch
as
h
ea
v
y
s
y
m
p
to
m
b
u
r
d
en
,
an
x
iety
,
a
n
d
c
o
g
n
itiv
e
d
ec
lin
e,
wh
ich
,
i
f
n
o
t
in
ter
v
e
n
ed
,
will
b
r
ea
k
th
e
cy
cle
o
f
s
elf
-
c
ar
e
an
d
wo
r
s
en
t
h
e
p
atien
t'
s
p
r
o
g
n
o
s
is
[
1
4
]
.
Sy
m
p
to
m
r
ec
o
g
n
itio
n
e
d
u
ca
t
io
n
is
cr
u
cial
f
o
r
h
ea
r
t
f
ailu
r
e
p
atien
ts
to
im
p
r
o
v
e
ad
h
e
r
en
ce
an
d
p
r
ev
en
t
r
e
h
o
s
p
italizatio
n
.
He
alth
ca
r
e
wo
r
k
er
s
,
p
a
r
ticu
lar
ly
n
u
r
s
es,
s
h
o
u
ld
f
o
cu
s
o
n
s
y
m
p
to
m
p
er
ce
p
tio
n
tr
ain
in
g
r
at
h
er
th
a
n
s
im
p
ly
p
r
o
v
id
in
g
p
ass
iv
e
ed
u
ca
tio
n
.
Pa
tien
ts
n
ee
d
to
b
e
ta
u
g
h
t
h
o
w
t
o
d
if
f
e
r
en
tiate
h
ea
r
t
f
ailu
r
e
s
y
m
p
to
m
s
f
r
o
m
o
th
e
r
co
m
o
r
b
i
d
ities
to
en
s
u
r
e
tar
g
eted
r
esp
o
n
s
es.
Fam
ily
I
n
v
o
lv
e
m
en
t,
as
o
u
tlin
ed
in
th
e
SYMPE
R
HE
A
R
T
p
r
o
to
co
l,
r
eq
u
i
r
es
d
y
ad
ic
in
te
r
v
en
ti
o
n
s
(
in
v
o
l
v
in
g
ca
r
eg
iv
er
s
)
.
F
am
ilies
s
h
o
u
ld
b
e
em
p
o
wer
ed
as
s
ec
o
n
d
o
b
s
er
v
er
s
to
ass
is
t
p
atien
t
s
with
p
er
ce
p
tu
al
o
r
c
o
g
n
itiv
e
lim
it
atio
n
s
in
d
etec
tin
g
war
n
in
g
s
ig
n
s
.
Ps
y
ch
o
lo
g
ical
a
p
p
r
o
ac
h
:
T
h
e
u
s
e
o
f
tech
n
i
q
u
es
s
u
ch
as
m
o
tiv
atio
n
al
in
ter
v
iewin
g
(
MI
)
is
h
ig
h
ly
r
ec
o
m
m
e
n
d
ed
t
o
im
p
r
o
v
e
a
d
h
er
en
ce
.
B
y
in
cr
ea
s
i
n
g
in
ter
n
al
m
o
tiv
atio
n
,
p
atie
n
ts
will
b
e
m
o
r
e
co
n
s
is
ten
t
in
th
eir
m
o
n
ito
r
in
g
b
e
h
av
io
r
,
u
ltima
tely
s
tr
en
g
th
en
in
g
th
e
q
u
ality
o
f
t
h
eir
s
o
m
atic
p
er
ce
p
tio
n
.
Hea
lth
ca
r
e
p
o
licies
r
eq
u
ir
e
a
co
n
tin
u
o
u
s
f
o
llo
w
-
u
p
s
y
s
t
em
to
m
o
n
ito
r
p
atie
n
t
s
y
m
p
to
m
p
atter
n
s
o
v
e
r
tim
e,
allo
win
g
in
ter
v
en
tio
n
s
to
b
e
d
y
n
a
m
ically
ad
ju
s
ted
to
d
y
n
am
ic
ch
a
n
g
es
in
t
h
e
p
atien
t'
s
p
h
y
s
ical
co
n
d
itio
n
[
1
1
]
,
[
1
5
]
,
[
1
6
]
.
3
.
3
.
D
is
cus
s
io
n
Patien
ts
with
h
ea
r
t
f
ailu
r
e
f
r
e
q
u
en
tly
r
ep
o
r
t
in
a
d
eq
u
ate
s
elf
-
ca
r
e
b
e
h
av
io
r
s
.
Ph
y
s
ical
s
y
m
p
to
m
s
ca
n
im
p
ac
t
a
p
atie
n
t'
s
ab
ilit
y
to
p
er
f
o
r
m
s
elf
-
ca
r
e
b
eh
a
v
io
r
s
.
Ho
wev
er
,
s
tu
d
ies
in
v
esti
g
atin
g
th
e
r
elatio
n
s
h
i
p
b
etwe
en
p
h
y
s
ical
s
y
m
p
to
m
s
an
d
s
elf
-
ca
r
e
b
e
h
av
io
r
s
in
h
ea
r
t
f
ailu
r
e
p
atien
ts
h
av
e
y
ield
ed
in
co
n
s
is
ten
t
f
in
d
in
g
s
,
lik
ely
d
u
e
to
v
ar
iatio
n
s
in
th
e
d
eter
m
in
a
n
ts
o
f
s
elf
-
ca
r
e
b
e
h
av
io
r
s
am
o
n
g
p
atien
ts
with
d
if
f
er
en
t
lev
els
o
f
s
elf
-
ca
r
e
ab
ilit
y
.
Un
d
er
s
tan
d
in
g
th
e
r
elatio
n
s
h
ip
b
etwe
en
p
h
y
s
ical
s
y
m
p
to
m
s
an
d
s
elf
-
ca
r
e
b
eh
av
io
r
s
in
h
ea
r
t
f
ailu
r
e
p
atien
ts
with
in
ad
e
q
u
ate
s
elf
-
ca
r
e
b
eh
av
io
r
s
m
ay
im
p
r
o
v
e
ca
r
e
f
o
r
th
is
s
u
b
p
o
p
u
latio
n
[
1
4
]
,
[
1
7
]
–
[
1
9
]
.
Hea
r
t
f
ailu
r
e
p
atien
ts
id
en
tifie
d
as
h
av
in
g
in
ad
eq
u
ate
s
elf
-
ca
r
e
b
eh
av
io
r
s
wer
e
s
tu
d
ied
,
with
th
e
aim
o
f
an
aly
zi
n
g
th
e
r
elatio
n
s
h
ip
b
etwe
en
th
eir
p
h
y
s
ical
s
y
m
p
to
m
s
an
d
t
h
eir
lev
el
o
f
ad
h
er
en
ce
to
s
elf
-
ca
r
e
b
eh
av
io
r
s
[
2
0
]
–
[
2
3
]
.
T
h
e
s
tu
d
y
r
ev
ea
led
th
at
m
o
r
e
s
ev
er
e
a
n
d
f
r
eq
u
en
t
p
h
y
s
ical
s
y
m
p
to
m
s
,
s
u
ch
as
s
h
o
r
tn
ess
o
f
b
r
ea
th
,
f
ati
g
u
e,
an
d
ed
em
a
wer
e
s
ig
n
if
ican
tly
ass
o
ciate
d
with
p
o
o
r
er
s
elf
-
ca
r
e
b
e
h
av
i
o
r
s
in
th
is
p
atien
t
g
r
o
u
p
.
T
h
ese
f
in
d
in
g
s
co
n
f
ir
m
th
a
t
h
ig
h
s
y
m
p
to
m
b
u
r
d
e
n
ca
n
b
e
a
s
ig
n
if
ican
t
b
a
r
r
i
er
f
o
r
p
atien
ts
to
im
p
lem
en
t
s
elf
-
ca
r
e
r
ec
o
m
m
en
d
atio
n
s
,
s
u
ch
as
m
o
n
ito
r
i
n
g
s
y
m
p
to
m
s
,
f
o
llo
win
g
a
lo
w
-
s
alt
d
iet,
an
d
en
g
ag
in
g
in
p
h
y
s
ical
ac
tiv
ity
as
d
ir
ec
ted
.
T
h
is
s
tu
d
y
h
ig
h
lig
h
ts
th
e
im
p
o
r
tan
ce
f
o
r
h
ea
lth
c
a
r
e
p
r
o
f
ess
io
n
als
to
ef
f
ec
tiv
ely
p
r
o
ac
tiv
ely
ass
ess
i
n
g
an
d
m
an
ag
i
n
g
th
e
p
h
y
s
ical
s
y
m
p
to
m
s
o
f
h
ea
r
t
f
ailu
r
e
p
at
ien
ts
as
an
in
teg
r
al
p
ar
t
o
f
a
s
tr
ateg
y
to
in
cr
ea
s
e
th
eir
en
g
a
g
em
en
t
an
d
ad
h
e
r
en
ce
to
s
elf
-
ca
r
e
p
r
ac
tices,
u
ltima
tely
aim
in
g
to
im
p
r
o
v
e
p
atien
ts
'
q
u
ality
o
f
lif
e
an
d
clin
ical
o
u
tco
m
es
[
1
0
]
,
[
2
4
]
.
T
h
e
n
ex
t
f
in
d
in
g
is
th
e
d
y
n
a
m
ic
an
d
co
m
p
lex
r
elatio
n
s
h
i
p
b
etwe
en
h
ea
r
t
f
ailu
r
e
s
y
m
p
to
m
p
atter
n
s
an
d
p
atien
ts
'
s
elf
-
ca
r
e
b
eh
av
io
r
s
.
T
h
is
s
tu
d
y
f
o
u
n
d
t
h
at
p
atien
ts
n
o
t
o
n
ly
r
esp
o
n
d
to
ac
u
te
s
y
m
p
to
m
s
b
u
t
also
d
ev
e
lo
p
an
d
ad
ju
s
t
th
eir
s
elf
-
ca
r
e
b
eh
av
io
r
s
b
ased
o
n
th
eir
s
y
m
p
to
m
p
atter
n
s
o
v
er
tim
e,
wh
eth
er
th
ey
ar
e
s
tab
le,
wo
r
s
en
in
g
,
o
r
f
lu
ct
u
atin
g
[
2
5
]
,
[
2
6
]
.
Sp
ec
if
ically
,
w
o
r
s
en
in
g
o
r
h
i
g
h
ly
f
l
u
ctu
atin
g
s
y
m
p
to
m
p
atter
n
s
ten
d
to
b
e
ass
o
ciate
d
with
m
o
r
e
in
ten
s
e
a
n
d
f
r
eq
u
e
n
t
s
elf
-
ca
r
e
ef
f
o
r
ts
,
b
u
t
d
o
n
o
t
n
ec
ess
ar
ily
g
u
ar
a
n
tee
m
o
r
e
ef
f
ec
tiv
e
b
e
h
av
io
r
s
.
T
h
ese
f
i
n
d
in
g
s
s
u
g
g
est
th
at
p
atien
ts
'
s
y
m
p
to
m
e
x
p
er
ien
ce
s
a
r
e
u
n
iq
u
e
an
d
ev
o
lv
i
n
g
,
an
d
th
at
s
elf
-
c
ar
e
ass
ess
m
en
ts
,
i
n
ter
v
en
tio
n
s
,
an
d
ad
h
er
e
n
ce
s
h
o
u
ld
n
o
t
b
e
s
tatic
b
u
t
s
h
o
u
ld
ad
ap
t
t
o
th
e
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
Th
era
p
eu
tic
a
d
h
eren
ce
a
n
d
s
o
ma
tic
s
ymp
to
m
p
ercep
tio
n
in
p
a
tien
ts
w
ith
h
ea
r
t fa
ilu
r
e:
… (
Tr
i A
n
d
a
ya
n
i
)
421
in
d
iv
id
u
al'
s
s
y
m
p
to
m
atic
c
o
u
r
s
e
o
v
er
tim
e.
C
o
n
tin
u
o
u
s
m
o
n
ito
r
in
g
an
d
a
p
er
s
o
n
alize
d
ap
p
r
o
ac
h
s
u
p
p
o
r
t
p
atien
ts
in
m
o
d
if
y
in
g
a
n
d
m
ai
n
tain
in
g
o
p
tim
al
s
elf
-
ca
r
e
b
e
h
av
io
r
s
as th
eir
s
y
m
p
to
m
s
c
h
an
g
e
[
4
]
,
[
8
]
.
A
m
o
tiv
atio
n
al
in
ter
v
iewin
g
(
MI
)
in
ter
v
en
tio
n
h
as
b
ee
n
s
h
o
wn
to
b
e
ef
f
ec
tiv
e
in
n
o
t
o
n
ly
im
p
r
o
v
in
g
s
elf
-
ca
r
e
b
eh
av
io
r
s
an
d
ad
h
er
en
ce
b
u
t
also
s
ig
n
if
ican
tly
r
e
d
u
cin
g
p
h
y
s
ical
s
y
m
p
to
m
b
u
r
d
en
in
h
ea
r
t
f
ailu
r
e
p
atien
ts
o
v
er
a
o
n
e
-
y
ea
r
p
er
i
o
d
.
A
r
elativ
ely
s
h
o
r
t
MI
p
r
o
g
r
am
co
n
s
is
tin
g
o
f
o
n
e
f
ac
e
-
to
-
f
ac
e
s
ess
io
n
an
d
th
r
ee
f
o
llo
w
-
u
p
p
h
o
n
e
ca
lls
ca
n
p
r
o
d
u
ce
clin
ically
m
ea
n
in
g
f
u
l im
p
r
o
v
em
e
n
ts
.
T
h
e
g
r
o
u
p
o
f
p
atien
ts
r
ec
eiv
in
g
MI
ex
p
er
ien
ce
d
a
r
ed
u
ctio
n
i
n
s
y
m
p
to
m
s
,
p
ar
ticu
lar
l
y
ch
e
s
t
d
is
co
m
f
o
r
t
an
d
s
h
o
r
t
n
ess
o
f
b
r
ea
th
(
d
y
s
p
n
ea
)
,
co
m
p
ar
ed
with
th
e
g
r
o
u
p
r
ec
e
iv
in
g
s
tan
d
ar
d
ca
r
e
alo
n
e
.
T
h
e
g
r
ea
test
an
d
m
o
s
t
co
n
s
is
ten
t
b
en
ef
its
wer
e
s
ee
n
wh
en
th
e
in
ter
v
e
n
tio
n
ac
tiv
ely
in
v
o
l
v
ed
p
atien
t
ca
r
e
g
iv
er
s
,
with
th
is
g
r
o
u
p
s
h
o
win
g
s
ig
n
if
ican
t
im
p
r
o
v
em
en
ts
in
o
v
er
all
to
tal
p
h
y
s
ical
s
y
m
p
to
m
b
u
r
d
e
n
s
co
r
es
[
2
7
]
,
[
2
8
]
.
T
h
ese
f
in
d
in
g
s
s
tr
en
g
th
en
th
e
ev
id
e
n
ce
th
at
co
llab
o
r
ativ
e
co
m
m
u
n
icatio
n
ap
p
r
o
ac
h
es
lik
e
MI
,
wh
ic
h
em
p
o
wer
p
atien
ts
an
d
en
g
ag
e
t
h
e
ir
s
u
p
p
o
r
t
s
y
s
tem
s
,
ar
e
p
r
ac
tical
an
d
im
p
ac
tf
u
l
i
n
ter
v
en
tio
n
s
tr
ateg
ies.
to
im
p
r
o
v
e
th
e
q
u
ality
o
f
life
o
f
p
atien
ts
b
y
r
ed
u
cin
g
d
eb
ilit
atin
g
s
y
m
p
to
m
s
[
6
]
,
[
7
]
.
A
p
r
ev
io
u
s
s
tu
d
y
we
d
is
cu
s
s
ed
[
8
]
also
s
h
o
wed
th
at
p
ati
en
ts
with
f
lu
ctu
atin
g
s
y
m
p
to
m
p
atter
n
s
ten
d
e
d
t
o
en
g
ag
e
m
o
r
e
in
te
n
s
iv
ely
in
s
elf
-
m
o
n
ito
r
i
n
g
,
wh
ich
m
ay
b
e
a
n
at
u
r
al
a
d
ap
tatio
n
[
2
9
]
,
[
3
0
]
.
Fu
r
th
er
m
o
r
e
,
in
ter
v
en
tio
n
s
lik
e
Mo
t
iv
atio
n
al
I
n
ter
v
iewin
g
t
h
at
s
u
cc
ess
f
u
lly
in
cr
ea
s
ed
p
ati
en
t
en
g
a
g
em
en
t
(
as
in
th
e
C
ag
g
ian
elli
et
a
l
.
[
6
]
)
li
k
ely
wo
r
k
b
y
s
tr
en
g
th
en
in
g
m
o
tiv
atio
n
f
o
r
co
n
s
is
ten
t sy
m
p
to
m
m
o
n
ito
r
in
g
[
4
]
.
E
v
id
en
ce
s
u
g
g
ests
th
at
th
e
r
ap
eu
tic
ad
h
e
r
en
ce
is
n
o
t
s
im
p
l
y
ab
o
u
t
m
ed
icatio
n
ad
h
e
r
en
ce
,
b
u
t
is
a
k
ey
f
ac
to
r
in
s
tab
ilizin
g
a
p
atien
t
'
s
h
em
o
d
y
n
am
ic
s
tatu
s
,
en
s
u
r
in
g
th
at
s
o
m
atic
p
e
r
ce
p
tio
n
r
em
ain
s
with
in
th
e
n
o
r
m
al
r
a
n
g
e
[
3
1
]
,
[
3
2
]
.
T
h
ese
r
esu
lts
ad
d
r
ess
th
e
r
ev
iew'
s
o
b
jectiv
e:
a
lin
ea
r
r
elatio
n
s
h
ip
ex
is
ts
b
etwe
en
s
elf
-
m
an
ag
em
en
t
b
eh
av
io
r
s
an
d
t
h
e
q
u
ality
o
f
p
h
y
s
ical
s
en
s
o
r
y
p
er
ce
p
tio
n
in
h
ea
r
t
f
ailu
r
e
p
at
ien
ts
.
A
lim
itatio
n
lies
in
th
e
u
s
e
o
f
s
elf
-
r
e
p
o
r
t
d
ata
f
o
r
ad
h
er
e
n
ce
d
ata,
wh
ich
is
s
u
s
ce
p
tib
le
to
r
ec
all
b
ias.
T
h
e
m
ain
f
in
d
i
n
g
s
f
r
o
m
th
ese
s
tu
d
ies
co
n
s
is
ten
tly
d
em
o
n
s
tr
ate
a
p
o
s
itiv
e
lin
ea
r
r
elatio
n
s
h
ip
b
etwe
en
a
d
h
er
e
n
ce
b
eh
av
i
o
r
s
(
s
u
ch
as
s
elf
-
ca
r
e)
an
d
th
e
q
u
ality
o
f
s
o
m
atic
p
er
ce
p
tio
n
in
h
ea
r
t
f
ailu
r
e
p
atien
ts
.
Patien
ts
wh
o
a
r
e
m
o
r
e
co
m
p
lian
t
with
d
aily
m
o
n
ito
r
in
g
,
s
u
ch
as
weig
h
in
g
an
d
ch
ec
k
i
n
g
f
o
r
e
d
em
a,
ten
d
to
h
av
e
a
h
ig
h
er
p
er
ce
p
tu
al
s
e
n
s
itiv
ity
to
ch
an
g
es
in
t
h
eir
b
o
d
y
co
n
d
itio
n
[
3
3
]
,
[
3
4
]
.
T
h
eo
r
etica
lly
,
ad
h
e
r
en
ce
to
s
elf
-
ca
r
e
b
eh
av
io
r
s
s
er
v
es
as
a
f
ee
d
b
ac
k
m
ec
h
a
n
is
m
;
th
e
m
o
r
e
r
o
u
tin
ely
p
atien
ts
m
o
n
ito
r
,
th
e
b
etter
th
ey
a
r
e
at
r
ec
o
g
n
izin
g
th
eir
u
n
i
q
u
e
s
y
m
p
to
m
p
atter
n
s
(
s
y
m
p
to
m
r
ec
o
g
n
itio
n
)
.
T
h
is
ad
d
r
ess
es
th
e
s
tu
d
y
'
s
o
b
jectiv
e:
in
cr
ea
s
ed
k
n
o
wled
g
e
an
d
b
eh
av
io
r
al
ad
h
er
en
ce
d
ir
ec
tly
s
tr
en
g
th
en
s
o
m
atic
p
er
ce
p
ti
o
n
a
b
ilit
ies,
wh
ich
in
tu
r
n
a
cc
eler
ate
d
ec
is
io
n
-
m
ak
in
g
to
s
ee
k
m
ed
ical
h
el
p
(
s
y
m
p
to
m
r
esp
o
n
s
e)
an
d
im
p
r
o
v
e
o
v
er
all
q
u
ality
o
f
life
[
1
3
]
,
[
3
5
]
,
[
3
6
]
.
Ho
wev
er
,
th
e
r
e
ar
e
s
ig
n
if
ica
n
t
b
ar
r
ier
s
a
n
d
lim
itatio
n
s
t
h
at
n
ee
d
to
b
e
ad
d
r
ess
ed
in
ac
h
iev
in
g
o
p
tim
al
o
u
tc
o
m
es.
T
h
e
m
ain
b
ar
r
ier
id
e
n
tifie
d
in
cr
o
s
s
-
s
ec
tio
n
al
s
tu
d
ies
,
s
u
ch
as
th
o
s
e
b
y
[
1
0
]
,
[
1
2
]
,
is
th
e
ex
ce
s
s
iv
e
b
u
r
d
en
o
f
p
h
y
s
ical
s
y
m
p
to
m
s
ca
n
ac
tu
ally
h
am
p
er
p
atien
ts
'
ab
ilit
y
to
p
er
f
o
r
m
s
elf
-
ca
r
e.
Fu
r
th
er
m
o
r
e
,
p
s
y
ch
o
lo
g
ical
f
a
cto
r
s
s
u
ch
as
d
ep
r
ess
io
n
an
d
an
x
iety
,
as
well
as
co
g
n
itiv
e
li
m
itatio
n
s
in
eld
er
ly
p
atien
ts
,
o
f
ten
h
in
d
er
ac
cu
r
ate
s
o
m
atic
p
er
ce
p
tio
n
.
Me
th
o
d
o
lo
g
ical
lim
itatio
n
s
in
th
e
cu
r
r
en
t
liter
atu
r
e
ar
e
also
ev
id
en
t
in
th
e
p
r
ed
o
m
in
a
n
ce
o
f
cr
o
s
s
-
s
ec
tio
n
al
s
tu
d
y
d
esig
n
s
,
wh
ich
ca
n
n
o
t
elu
cid
at
e
lo
n
g
-
te
r
m
ca
u
s
e
-
an
d
-
ef
f
ec
t
r
elatio
n
s
h
ip
s
.
Fu
r
th
er
m
o
r
e,
m
an
y
s
tu
d
ies
ar
e
lo
ca
l
in
n
atu
r
e
with
eth
n
ically
d
iv
er
s
e
s
am
p
les
,
th
u
s
lim
itin
g
th
e
g
en
er
aliza
b
ilit
y
o
f
th
e
r
esu
lts
to
g
l
o
b
al
p
o
p
u
latio
n
s
with
d
iv
e
r
s
e
s
o
cial
s
u
p
p
o
r
t
s
y
s
tem
s
.
T
h
er
ef
o
r
e,
th
e
in
v
o
l
v
em
en
t
o
f
in
f
o
r
m
al
ca
r
eg
iv
er
s
a
n
d
a
m
o
r
e
p
er
s
o
n
alize
d
p
s
y
ch
o
lo
g
ical
in
ter
v
e
n
tio
n
ap
p
r
o
ac
h
ar
e
k
ey
r
ec
o
m
m
en
d
a
tio
n
s
to
ad
d
r
ess
th
ese
b
ar
r
ie
r
s
[
1
2
]
,
[
1
3
]
.
T
h
is
s
co
p
in
g
r
ev
iew
m
a
p
p
e
d
cu
r
r
e
n
t
ev
id
en
ce
r
eg
ar
d
in
g
th
e
r
elatio
n
s
h
ip
b
etwe
en
th
er
ap
eu
tic
ad
h
er
en
ce
an
d
s
o
m
atic
s
y
m
p
to
m
p
er
ce
p
tio
n
in
p
atien
ts
with
h
ea
r
t f
ailu
r
e.
T
h
e
f
in
d
in
g
s
in
d
icate
th
at
th
ese
two
co
m
p
o
n
en
ts
ar
e
clo
s
ely
in
ter
co
n
n
ec
ted
an
d
p
lay
an
ess
en
t
ial
r
o
le
in
s
u
p
p
o
r
tin
g
e
f
f
ec
tiv
e
s
elf
-
m
an
ag
em
en
t
am
o
n
g
h
ea
r
t
f
ailu
r
e
p
atien
ts
.
T
h
e
r
esu
lts
also
h
ig
h
lig
h
t
th
a
t
s
y
m
p
to
m
p
er
ce
p
tio
n
n
o
t
o
n
ly
r
ef
lects
d
is
ea
s
e
s
ev
er
ity
b
u
t
also
f
u
n
ctio
n
s
as
an
im
p
o
r
tan
t
b
eh
a
v
io
r
a
l
tr
ig
g
er
in
f
lu
en
ci
n
g
ad
h
er
e
n
ce
to
th
er
ap
eu
tic
r
ec
o
m
m
en
d
atio
n
s
an
d
s
elf
-
ca
r
e
p
r
ac
tices.
T
h
e
r
elatio
n
s
h
ip
b
etwe
en
s
y
m
p
to
m
p
er
ce
p
ti
o
n
an
d
s
elf
-
c
ar
e
b
eh
av
io
r
s
ca
n
b
e
u
n
d
er
s
to
o
d
th
r
o
u
g
h
th
e
s
itu
atio
n
-
s
p
ec
if
ic
th
eo
r
y
o
f
h
ea
r
t
f
ailu
r
e
s
elf
-
ca
r
e
,
wh
ich
em
p
h
asizes
th
at
s
y
m
p
to
m
m
o
n
ito
r
in
g
,
s
y
m
p
to
m
r
ec
o
g
n
itio
n
,
an
d
s
y
m
p
to
m
r
esp
o
n
s
e
ar
e
ce
n
tr
al
p
r
o
ce
s
s
es
in
p
atien
t
s
elf
-
m
a
n
ag
em
en
t
[
5
]
.
Acc
o
r
d
in
g
to
th
is
th
eo
r
etica
l
f
r
a
m
ewo
r
k
,
p
atie
n
ts
wh
o
ca
n
ac
c
u
r
ately
p
er
ce
iv
e
an
d
in
te
r
p
r
et
th
ei
r
s
y
m
p
to
m
s
ar
e
m
o
r
e
lik
ely
t
o
tak
e
ap
p
r
o
p
r
iate
s
elf
-
ca
r
e
ac
ti
o
n
s
,
s
u
ch
as
ad
h
er
in
g
to
m
e
d
i
ca
tio
n
,
m
an
a
g
in
g
f
lu
id
i
n
tak
e,
an
d
s
ee
k
in
g
tim
ely
m
ed
ical
ass
is
tan
ce
.
T
h
e
f
in
d
in
g
s
o
f
th
is
r
e
v
iew
s
u
p
p
o
r
t
th
is
co
n
ce
p
t,
as
p
atien
ts
wh
o
r
e
p
o
r
ted
h
ig
h
e
r
s
y
m
p
to
m
awa
r
e
n
ess
ten
d
ed
to
d
e
m
o
n
s
tr
ate
b
etter
en
g
a
g
em
en
t
in
s
elf
-
ca
r
e
b
eh
av
io
r
s
an
d
th
e
r
ap
eu
ti
c
ad
h
er
en
ce
[
8
]
,
[
1
0
]
.
I
n
ad
d
itio
n
,
s
y
m
p
t
o
m
m
o
n
ito
r
in
g
p
lay
s
a
m
ed
iatin
g
r
o
le
b
etwe
en
p
atien
t
k
n
o
wled
g
e
an
d
s
y
m
p
to
m
m
an
ag
em
en
t.
Patien
ts
wh
o
ac
tiv
ely
m
o
n
ito
r
th
eir
s
y
m
p
to
m
s
ar
e
m
o
r
e
ca
p
ab
le
o
f
r
ec
o
g
n
i
zin
g
ea
r
ly
s
ig
n
s
o
f
clin
ical
d
eter
io
r
atio
n
an
d
r
esp
o
n
d
in
g
ap
p
r
o
p
r
iately
[
4
]
.
T
h
is
h
ig
h
lig
h
ts
th
at
k
n
o
wled
g
e
alo
n
e
m
ay
n
o
t
b
e
s
u
f
f
icien
t
to
im
p
r
o
v
e
s
elf
-
c
ar
e
b
eh
a
v
io
r
s
;
p
atien
ts
m
u
s
t
also
d
ev
elo
p
p
r
ac
tical
s
k
ills
in
s
y
m
p
to
m
m
o
n
ito
r
in
g
an
d
in
ter
p
r
etatio
n
.
T
h
e
r
ef
o
r
e
,
ed
u
ca
tio
n
al
in
ter
v
en
tio
n
s
f
o
r
h
ea
r
t
f
ailu
r
e
p
atien
ts
s
h
o
u
l
d
f
o
cu
s
n
o
t
o
n
ly
o
n
d
is
ea
s
e
k
n
o
wled
g
e
b
u
t a
ls
o
o
n
s
tr
en
g
th
en
in
g
s
y
m
p
to
m
r
ec
o
g
n
itio
n
an
d
d
ec
is
io
n
-
m
a
k
in
g
s
k
ills
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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Vo
l.
15
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No
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2
,
J
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n
e
20
26
:
4
1
7
-
4
2
7
422
An
o
th
er
im
p
o
r
ta
n
t
f
i
n
d
in
g
i
s
th
e
ef
f
ec
tiv
en
ess
o
f
b
e
h
a
v
io
r
al
a
n
d
s
u
p
p
o
r
tiv
e
i
n
ter
v
en
tio
n
s
in
im
p
r
o
v
in
g
b
o
th
s
y
m
p
to
m
p
e
r
ce
p
tio
n
a
n
d
a
d
h
er
e
n
ce
.
I
n
ter
v
en
tio
n
s
s
u
ch
as
m
o
tiv
atio
n
a
l
in
ter
v
iewin
g
an
d
ca
r
eg
iv
er
-
s
u
p
p
o
r
te
d
p
r
o
g
r
am
s
h
av
e
b
e
e
n
s
h
o
w
n
to
r
e
d
u
ce
s
y
m
p
to
m
b
u
r
d
en
an
d
im
p
r
o
v
e
p
atien
t
en
g
ag
em
en
t
in
s
elf
-
ca
r
e
b
eh
av
i
o
r
s
[
6
]
,
[
1
1
]
.
T
h
ese
f
in
d
in
g
s
alig
n
with
p
r
ev
i
o
u
s
s
tu
d
ies
em
p
h
asizin
g
th
e
r
o
le
o
f
s
o
cial
s
u
p
p
o
r
t
a
n
d
p
atien
t
–
ca
r
e
g
iv
er
co
llab
o
r
atio
n
in
im
p
r
o
v
in
g
a
d
h
er
en
ce
a
n
d
l
o
n
g
-
te
r
m
d
is
ea
s
e
m
an
ag
em
e
n
t
[
1
3
]
.
C
ar
eg
iv
er
in
v
o
l
v
em
en
t
m
a
y
en
h
an
ce
p
atien
ts
’
co
n
f
i
d
en
ce
in
in
ter
p
r
etin
g
s
y
m
p
t
o
m
s
a
n
d
f
ac
ilit
ate
tim
ely
h
ea
lth
ca
r
e
u
tili
za
tio
n
.
T
h
is
r
ev
iew
also
h
ig
h
lig
h
ts
th
at
s
o
m
atic
s
y
m
p
t
o
m
p
er
ce
p
tio
n
is
in
f
lu
e
n
ce
d
b
y
m
u
ltip
l
e
f
ac
to
r
s
,
in
clu
d
in
g
clin
ical
s
ev
e
r
ity
,
p
s
y
ch
o
lo
g
ical
co
n
d
itio
n
s
,
a
n
d
s
o
cio
-
d
em
o
g
r
ap
h
ic
ch
ar
ac
te
r
is
tics
.
Dep
r
ess
io
n
,
f
u
n
ctio
n
al
s
tatu
s
,
an
d
ed
u
ca
ti
o
n
al
lev
el
h
av
e
b
ee
n
id
e
n
tifie
d
as
s
ig
n
if
ican
t
p
r
ed
icto
r
s
o
f
s
y
m
p
to
m
p
er
ce
p
tio
n
am
o
n
g
h
ea
r
t
f
ailu
r
e
p
atien
t
s
[
1
2
]
.
T
h
ese
f
in
d
in
g
s
s
u
g
g
est
th
at
s
y
m
p
to
m
p
er
ce
p
ti
o
n
is
n
o
t
s
o
lely
a
p
h
y
s
io
lo
g
ical
p
h
en
o
m
e
n
o
n
b
u
t
is
also
s
h
ap
ed
b
y
p
s
y
ch
o
lo
g
ical
an
d
s
o
cial
co
n
te
x
ts
.
C
o
n
s
eq
u
en
tly
,
co
m
p
r
eh
e
n
s
iv
e
h
ea
r
t
f
ailu
r
e
m
an
ag
em
en
t
s
h
o
u
ld
in
co
r
p
o
r
ate
p
s
y
ch
o
s
o
cial
ass
ess
m
en
t
an
d
s
u
p
p
o
r
t
i
n
ad
d
itio
n
to
s
tan
d
ar
d
m
e
d
ical
tr
ea
tm
en
t.
Fro
m
a
h
ea
lth
p
o
licy
an
d
h
ea
lth
ca
r
e
s
y
s
tem
p
e
r
s
p
ec
tiv
e,
t
h
e
f
in
d
i
n
g
s
o
f
th
is
r
ev
iew
e
m
p
h
asize
th
e
im
p
o
r
tan
ce
o
f
i
n
teg
r
atin
g
s
y
m
p
to
m
m
o
n
ito
r
i
n
g
a
n
d
s
elf
-
c
ar
e
s
u
p
p
o
r
t
in
to
r
o
u
tin
e
h
ea
r
t
f
ailu
r
e
m
an
ag
em
e
n
t
p
r
o
g
r
a
m
s
.
Hea
lth
ca
r
e
s
y
s
tem
s
s
h
o
u
ld
p
r
io
r
itize
s
tr
u
ctu
r
ed
p
atien
t
ed
u
ca
tio
n
p
r
o
g
r
am
s
,
d
is
ch
ar
g
e
p
lan
n
in
g
,
an
d
c
o
m
m
u
n
ity
-
b
ased
f
o
llo
w
-
u
p
to
s
tr
en
g
th
e
n
p
atien
t
ad
h
er
en
ce
an
d
s
y
m
p
to
m
r
ec
o
g
n
itio
n
[
3
7
]
,
[
3
8
]
.
E
ar
ly
r
ec
o
g
n
itio
n
o
f
wo
r
s
en
in
g
s
y
m
p
to
m
s
m
ay
r
e
d
u
ce
p
r
ev
e
n
t
ab
le
h
o
s
p
ital
r
ea
d
m
is
s
io
n
s
a
n
d
im
p
r
o
v
e
p
atien
t
o
u
tco
m
es,
wh
ich
is
a
k
ey
g
o
al
in
h
ea
r
t f
ailu
r
e
m
an
a
g
em
en
t s
tr
ateg
ies wo
r
ld
wid
e
[
1
]
,
[
2
]
.
Fu
r
th
er
m
o
r
e
,
p
o
licy
m
a
k
er
s
s
h
o
u
ld
co
n
s
id
er
s
tr
en
g
th
en
in
g
co
m
m
u
n
ity
-
b
ased
h
e
ar
t
f
ailu
r
e
m
an
ag
em
en
t
p
r
o
g
r
am
s
th
at
i
n
v
o
lv
e
m
u
ltid
is
cip
lin
ar
y
tea
m
s
,
in
clu
d
in
g
n
u
r
s
es,
p
h
y
s
ician
s
,
an
d
ca
r
eg
iv
er
s
.
Nu
r
s
es,
in
p
ar
ticu
lar
,
p
lay
a
cr
itical
r
o
le
in
ed
u
ca
tin
g
p
atien
t
s
ab
o
u
t
s
y
m
p
to
m
m
o
n
ito
r
i
n
g
a
n
d
s
u
p
p
o
r
tin
g
s
elf
-
ca
r
e
b
eh
a
v
io
r
s
in
b
o
th
h
o
s
p
it
al
an
d
co
m
m
u
n
ity
s
ettin
g
s
.
Stre
n
g
th
en
i
n
g
th
ese
p
r
o
g
r
am
s
m
ay
h
elp
b
r
id
g
e
th
e
g
ap
b
etwe
en
clin
ical
tr
ea
tm
e
n
t
an
d
lo
n
g
-
ter
m
d
is
ea
s
e
m
an
ag
em
en
t a
t h
o
m
e
[
3
7
]
,
[
3
8
]
.
Ov
er
all,
th
e
f
in
d
in
g
s
o
f
th
is
r
ev
iew
s
u
g
g
est
th
at
th
er
ap
eu
tic
ad
h
er
en
ce
an
d
s
o
m
ati
c
s
y
m
p
to
m
p
er
ce
p
tio
n
a
r
e
in
ter
d
e
p
en
d
e
n
t
elem
en
ts
o
f
h
ea
r
t
f
ailu
r
e
s
el
f
-
m
an
ag
e
m
en
t.
Stre
n
g
th
en
in
g
p
atien
t
ed
u
ca
tio
n
,
b
eh
av
io
r
al
in
ter
v
en
tio
n
s
,
an
d
ca
r
eg
iv
er
in
v
o
l
v
em
en
t
m
ay
i
m
p
r
o
v
e
p
atien
ts
’
ab
ilit
y
to
r
ec
o
g
n
ize
s
y
m
p
to
m
s
an
d
ad
h
e
r
e
to
tr
ea
tm
en
t
r
ec
o
m
m
en
d
ati
o
n
s
.
I
n
teg
r
atin
g
th
e
s
e
s
tr
ateg
ies
in
to
h
ea
lth
ca
r
e
s
y
s
tem
s
an
d
p
o
licies
co
u
ld
co
n
tr
ib
u
te
to
im
p
r
o
v
ed
clin
ical
o
u
tco
m
es a
n
d
r
ed
u
ce
d
h
ea
lth
ca
r
e
b
u
r
d
e
n
ass
o
ciate
d
with
h
ea
r
t f
ailu
r
e.
3
.
4
.
Str
eng
t
hs
a
nd
wea
k
nes
s
es
A
k
ey
s
tr
en
g
th
o
f
th
is
co
llectio
n
o
f
s
tu
d
ies
is
th
e
u
n
if
o
r
m
ity
o
f
m
ea
s
u
r
em
en
t
co
n
s
tr
u
cts,
p
ar
ticu
lar
ly
th
e
co
n
s
is
ten
t
u
s
e
o
f
th
e
HFSP
S
to
ass
ess
s
o
m
atic
p
er
ce
p
ti
o
n
.
T
h
is
allo
ws
f
o
r
c
r
o
s
s
-
s
tu
d
y
co
m
p
ar
is
o
n
s
an
d
s
tr
en
g
th
en
s
th
e
v
alid
ity
o
f
th
e
f
in
d
in
g
s
.
Fu
r
th
er
m
o
r
e,
th
e
d
iv
er
s
ity
o
f
s
tu
d
y
d
esig
n
s
,
in
clu
d
in
g
R
C
T
s
,
cr
o
s
s
-
s
ec
tio
n
al
s
tu
d
ies,
an
d
q
u
asi
-
ex
p
er
im
en
tal
s
tu
d
ies,
p
r
o
v
id
es
a
co
m
p
r
e
h
en
s
iv
e
p
e
r
s
p
ec
tiv
e,
r
an
g
i
n
g
f
r
o
m
co
r
r
elatio
n
al
to
ca
u
s
al
in
ter
v
en
tio
n
s
.
T
h
ese
s
tu
d
ies
h
av
e
a
ls
o
id
en
tifie
d
cr
itical
m
ed
iati
n
g
an
d
m
o
d
er
atin
g
f
ac
to
r
s
,
s
u
ch
as
ca
r
eg
i
v
er
r
o
le,
d
ep
r
ess
io
n
lev
el,
a
n
d
s
y
m
p
to
m
p
atter
n
s
,
d
ee
p
e
n
in
g
u
n
d
er
s
tan
d
in
g
o
f
t
h
e
co
m
p
lex
r
elatio
n
s
h
ip
b
etwe
en
ad
h
er
e
n
ce
an
d
s
o
m
atic
p
er
ce
p
tio
n
.
Fin
d
in
g
s
r
e
g
ar
d
in
g
th
e
ef
f
ec
tiv
en
ess
o
f
b
eh
av
io
r
al
in
ter
v
en
tio
n
s
s
u
ch
as
m
o
tiv
atio
n
al
in
ter
v
iewin
g
(
MI
)
an
d
th
e
SYMPE
R
HE
AR
T
p
r
o
to
co
l
p
r
o
v
i
d
e
v
alu
ab
le
ap
p
licab
ilit
y
ev
id
en
c
e
f
o
r
clin
ical
p
r
ac
tic
e
[
1
7
]
,
[
2
4
]
.
A
f
u
n
d
am
en
tal
wea
k
n
ess
lies
in
t
h
e
p
r
ed
o
m
in
an
ce
o
f
cr
o
s
s
-
s
ec
tio
n
al
d
esig
n
s
in
m
o
s
t
s
tu
d
ies.
T
h
is
d
esig
n
ca
n
o
n
ly
d
escr
ib
e
r
el
atio
n
s
h
ip
s
o
r
co
r
r
elatio
n
s
at
a
s
in
g
le
p
o
in
t
in
tim
e,
m
ak
in
g
it
in
ca
p
ab
le
o
f
estab
lis
h
in
g
lo
n
g
-
ter
m
ca
u
s
ality
o
r
e
x
p
lain
in
g
th
e
d
y
n
am
ic
s
o
f
ch
an
g
e
o
v
er
tim
e.
A
d
h
er
en
ce
m
ea
s
u
r
em
en
t
m
eth
o
d
s
,
wh
ich
r
el
y
lar
g
ely
o
n
s
elf
-
r
ep
o
r
t,
ar
e
also
s
u
s
ce
p
tib
le
to
b
iases
,
s
u
ch
as
r
ec
all
b
ias
an
d
s
o
cial
d
esira
b
ilit
y
b
ias,
wh
ich
ca
n
r
e
d
u
ce
d
ata
ac
cu
r
ac
y
.
Fu
r
th
er
m
o
r
e,
lim
ited
g
en
e
r
aliza
b
ilit
y
is
a
s
ig
n
if
ican
t
is
s
u
e
b
ec
au
s
e
m
an
y
s
tu
d
ies
wer
e
co
n
d
u
cted
in
s
p
ec
if
ic
cu
ltu
r
al
an
d
h
ea
lth
s
y
s
tem
co
n
tex
ts
(
s
u
c
h
as
th
e
US,
C
h
in
a,
o
r
Au
s
tr
alia)
with
h
o
m
o
g
e
n
eo
u
s
s
am
p
les.
T
h
er
ef
o
r
e,
f
i
n
d
in
g
s
m
ay
n
o
t
b
e
f
u
lly
a
p
p
licab
le
to
g
l
o
b
al
p
o
p
u
latio
n
s
with
d
if
f
er
e
n
t so
cio
d
em
o
g
r
ap
h
ic
c
h
ar
ac
ter
is
tics
an
d
s
u
p
p
o
r
t sy
s
tem
s
[
1
7
]
,
[
2
4
]
.
4.
CO
NCLU
SI
O
N
T
h
is
s
co
p
in
g
r
ev
iew
d
em
o
n
s
tr
ates
th
at
th
er
a
p
eu
tic
a
d
h
er
e
n
ce
an
d
s
o
m
atic
s
y
m
p
to
m
p
er
c
ep
tio
n
a
r
e
clo
s
ely
in
ter
co
n
n
ec
te
d
in
th
e
s
elf
-
m
an
ag
em
e
n
t o
f
p
atien
ts
with
h
ea
r
t f
ailu
r
e
.
Patien
ts
wh
o
co
n
s
is
ten
tly
en
g
ag
e
in
ad
h
er
e
n
ce
b
e
h
av
io
r
s
,
p
ar
t
icu
lar
ly
s
y
m
p
to
m
m
o
n
ito
r
in
g
,
ten
d
to
d
ev
el
o
p
g
r
ea
ter
a
war
en
ess
o
f
b
o
d
ily
ch
an
g
es
an
d
r
ec
o
g
n
ize
ea
r
ly
s
ig
n
s
o
f
clin
ical
d
eter
io
r
atio
n
.
C
o
n
v
er
s
ely
,
p
o
o
r
ad
h
er
en
ce
an
d
h
ig
h
s
y
m
p
t
o
m
b
u
r
d
e
n
m
ay
im
p
air
s
y
m
p
t
o
m
r
ec
o
g
n
itio
n
a
n
d
d
elay
ap
p
r
o
p
r
i
ate
r
esp
o
n
s
es.
T
h
e
m
ain
co
n
tr
i
b
u
tio
n
o
f
th
is
r
ev
iew
is
th
e
s
y
n
t
h
esis
o
f
cu
r
r
en
t
ev
id
en
ce
s
h
o
wi
n
g
th
at
s
tr
e
n
g
th
en
in
g
s
y
m
p
to
m
p
e
r
ce
p
tio
n
s
h
o
u
l
d
b
e
co
n
s
id
er
ed
an
in
teg
r
al
c
o
m
p
o
n
en
t
o
f
ad
h
er
e
n
ce
-
b
ased
in
ter
v
en
tio
n
s
in
h
ea
r
t
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t J Pu
b
lic
Hea
lth
Sci
I
SS
N:
2252
-
8
8
0
6
Th
era
p
eu
tic
a
d
h
eren
ce
a
n
d
s
o
ma
tic
s
ymp
to
m
p
ercep
tio
n
in
p
a
tien
ts
w
ith
h
ea
r
t fa
ilu
r
e:
… (
Tr
i A
n
d
a
ya
n
i
)
423
f
ailu
r
e
m
an
a
g
em
en
t.
Fo
r
n
u
r
s
in
g
an
d
clin
ical
p
r
ac
tice,
th
e
f
in
d
in
g
s
h
i
g
h
lig
h
t
t
h
e
im
p
o
r
t
an
ce
o
f
in
teg
r
atin
g
s
y
m
p
to
m
m
o
n
ito
r
in
g
ed
u
ca
ti
o
n
,
p
atien
t e
n
g
ag
em
e
n
t stra
teg
ies,
an
d
ca
r
eg
iv
er
in
v
o
l
v
em
en
t
in
to
r
o
u
tin
e
ca
r
e
to
im
p
r
o
v
e
ea
r
ly
s
y
m
p
t
o
m
r
ec
o
g
n
itio
n
an
d
s
elf
-
ca
r
e
b
eh
av
io
r
s
.
Fu
tu
r
e
r
esear
ch
s
h
o
u
ld
f
o
cu
s
o
n
d
ev
elo
p
i
n
g
an
d
ev
alu
atin
g
in
teg
r
ated
in
ter
v
en
tio
n
s
th
at
s
im
u
ltan
eo
u
s
ly
ad
d
r
ess
ad
h
er
en
ce
an
d
s
y
m
p
to
m
p
er
ce
p
tio
n
ac
r
o
s
s
d
iv
er
s
e
h
ea
lth
ca
r
e
s
ettin
g
s
.
ACK
NO
WL
E
DG
M
E
N
T
S
T
h
e
r
esear
ch
er
wo
u
ld
lik
e
to
ex
p
r
ess
h
er
d
ee
p
est
g
r
atitu
d
e
to
B
r
awijay
a
Un
iv
er
s
ity
an
d
Saif
u
l
An
war
Ho
s
p
ital
f
o
r
p
r
o
v
id
i
n
g
s
u
p
p
o
r
t,
ac
a
d
em
ic
g
u
i
d
an
ce
,
a
n
d
f
ac
ilit
ies
th
at
en
ab
led
th
is
r
esear
ch
to
p
r
o
c
ee
d
s
m
o
o
th
ly
.
T
h
is
in
s
titu
tio
n
al
s
u
p
p
o
r
t w
as c
r
u
cial
to
th
e
s
u
cc
ess
o
f
th
e
en
tire
r
esear
ch
p
r
o
ce
s
s
.
F
UNDING
I
NF
O
R
M
A
T
I
O
N
T
h
is
r
esear
ch
was
c
o
n
d
u
cted
u
s
in
g
p
e
r
s
o
n
al
f
u
n
d
i
n
g
f
r
o
m
t
h
e
au
th
o
r
s
.
No
ex
ter
n
al
f
i
n
an
c
ial
s
u
p
p
o
r
t
o
r
g
r
an
t
was
r
ec
eiv
ed
f
r
o
m
a
n
y
f
u
n
d
in
g
ag
e
n
cy
,
in
s
titu
tio
n
,
o
r
o
r
g
a
n
izatio
n
f
o
r
th
e
im
p
lem
en
tatio
n
o
f
th
is
s
tu
d
y
,
d
ata
an
al
y
s
is
,
m
an
u
s
cr
ip
t p
r
ep
a
r
atio
n
,
o
r
p
u
b
lic
atio
n
p
r
o
ce
s
s
.
AUTHO
R
CO
NT
RI
B
UT
I
O
NS ST
A
T
E
M
E
N
T
T
h
is
jo
u
r
n
al
u
s
es
th
e
C
o
n
tr
ib
u
to
r
R
o
les
T
ax
o
n
o
m
y
(
C
R
ed
iT)
to
r
ec
o
g
n
ize
in
d
iv
id
u
al
au
th
o
r
co
n
tr
ib
u
tio
n
s
,
r
ed
u
ce
au
th
o
r
s
h
ip
d
is
p
u
tes,
an
d
f
ac
ilit
ate
co
llab
o
r
atio
n
.
Na
m
e
o
f
Aut
ho
r
C
M
So
Va
Fo
I
R
D
O
E
Vi
Su
P
Fu
T
r
i A
n
d
ay
a
n
i
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Ku
m
b
o
y
o
n
o
✓
✓
✓
✓
✓
✓
✓
L
ilik
Su
p
r
iati
✓
✓
✓
✓
✓
✓
✓
✓
C
:
C
o
n
c
e
p
t
u
a
l
i
z
a
t
i
o
n
M
:
M
e
t
h
o
d
o
l
o
g
y
So
:
So
f
t
w
a
r
e
Va
:
Va
l
i
d
a
t
i
o
n
Fo
:
Fo
r
mal
a
n
a
l
y
s
i
s
I
:
I
n
v
e
s
t
i
g
a
t
i
o
n
R
:
R
e
so
u
r
c
e
s
D
:
D
a
t
a
C
u
r
a
t
i
o
n
O
:
W
r
i
t
i
n
g
-
O
r
i
g
i
n
a
l
D
r
a
f
t
E
:
W
r
i
t
i
n
g
-
R
e
v
i
e
w
&
E
d
i
t
i
n
g
Vi
:
Vi
su
a
l
i
z
a
t
i
o
n
Su
:
Su
p
e
r
v
i
s
i
o
n
P
:
P
r
o
j
e
c
t
a
d
mi
n
i
st
r
a
t
i
o
n
Fu
:
Fu
n
d
i
n
g
a
c
q
u
i
si
t
i
o
n
CO
NF
L
I
C
T
O
F
I
N
T
E
R
E
S
T
ST
A
T
E
M
E
NT
T
h
e
au
th
o
r
s
d
ec
lar
e
th
at
th
er
e
ar
e
n
o
co
n
f
licts
o
f
in
ter
est
r
eg
ar
d
in
g
th
e
p
u
b
licatio
n
o
f
th
is
p
ap
er
.
T
h
e
r
esear
ch
was
co
n
d
u
cted
in
th
e
ab
s
en
ce
o
f
an
y
co
m
m
er
cial,
f
in
an
cial,
o
r
p
e
r
s
o
n
al
r
elatio
n
s
h
ip
s
th
at
co
u
ld
b
e
co
n
s
tr
u
ed
as a
p
o
ten
tial c
o
n
f
lict o
f
in
ter
est.
I
NF
O
RM
E
D
CO
NS
E
N
T
I
n
f
o
r
m
ed
co
n
s
en
t
was
o
b
tain
e
d
f
r
o
m
all
p
ar
ticip
a
n
ts
in
v
o
lv
ed
in
th
is
s
tu
d
y
p
r
io
r
to
d
ata
co
llectio
n
.
Par
ticip
an
ts
wer
e
in
f
o
r
m
ed
a
b
o
u
t
th
e
o
b
jectiv
es,
p
r
o
ce
d
u
r
es,
p
o
ten
tial
b
e
n
ef
its
,
an
d
co
n
f
id
en
tiality
o
f
th
e
r
esear
ch
,
an
d
th
eir
p
a
r
ticip
atio
n
was e
n
tire
ly
v
o
l
u
n
tar
y
.
E
T
H
I
CAL AP
P
RO
V
A
L
E
th
ical
ap
p
r
o
v
al
was
n
o
t
r
e
q
u
ir
ed
f
o
r
t
h
is
s
tu
d
y
b
ec
au
s
e
t
h
e
r
esear
ch
em
p
lo
y
ed
a
s
co
p
i
n
g
r
e
v
iew
m
eth
o
d
o
l
o
g
y
u
s
in
g
d
ata
o
b
t
ain
ed
f
r
o
m
p
r
ev
io
u
s
ly
p
u
b
li
s
h
ed
liter
atu
r
e
an
d
p
u
b
licly
ac
ce
s
s
ib
le
s
o
u
r
ce
s
.
T
h
er
ef
o
r
e,
n
o
d
ir
ec
t in
v
o
lv
em
en
t o
f
h
u
m
an
p
ar
ticip
an
ts
o
r
a
n
im
als wa
s
in
clu
d
ed
in
th
is
s
tu
d
y
.
DATA AV
AI
L
AB
I
L
I
T
Y
Data
av
ailab
ilit
y
is
n
o
t
ap
p
li
ca
b
le
to
th
is
s
tu
d
y
b
ec
au
s
e
th
e
r
esear
ch
em
p
lo
y
e
d
a
s
co
p
in
g
r
ev
iew
m
eth
o
d
o
l
o
g
y
u
s
in
g
p
r
e
v
io
u
s
ly
p
u
b
lis
h
ed
ar
ticles
an
d
p
u
b
licl
y
ac
ce
s
s
ib
le
s
o
u
r
ce
s
.
N
o
n
ew
p
r
im
ar
y
d
ata
we
r
e
cr
ea
ted
o
r
a
n
aly
ze
d
i
n
th
is
s
tu
d
y
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
SS
N
:
2
2
5
2
-
8
8
0
6
I
n
t J Pu
b
lic
Hea
lth
Sci
,
Vo
l.
15
,
No
.
2
,
J
u
n
e
20
26
:
4
1
7
-
4
2
7
424
RE
F
E
R
E
NC
E
S
[
1
]
2
0
2
3
P
ER
K
I
,
Pe
d
o
m
a
m
T
a
t
a
l
a
k
s
a
n
a
p
e
n
y
a
k
i
t
g
a
g
a
l
j
a
n
t
u
n
g
,
3
r
d
Ed
i
t
i
o
n
.
P
e
r
h
i
m
p
u
n
a
n
D
o
k
t
e
r
S
p
e
s
i
a
l
i
s
K
a
r
d
i
o
v
a
s
k
u
l
a
r
I
n
d
o
n
e
si
a
,
2
0
2
3
.
[
O
n
l
i
n
e
]
.
A
v
a
i
l
a
b
l
e
:
h
t
t
p
:
/
/
w
w
w
.
n
b
e
r
.
o
r
g
/
p
a
p
e
r
s
/
w
1
6
0
1
9
[
2
]
M
.
V
o
l
t
e
r
r
a
n
i
e
t
a
l
.
,
“
Q
u
a
l
i
t
y
o
f
l
i
f
e
i
n
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T.
S
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[
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