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C
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D
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Dep
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[
1
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T
h
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with
a
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d
a
h
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ate
[
2
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‒
[
4
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.
De
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6
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R
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Ma
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I
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20
26
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p
to
m
s
o
f
a
d
u
lts
with
d
ep
r
ess
io
n
.
Fo
r
ex
am
p
le,
R
u
b
io
-
Vale
r
a
et
a
l.
[
2
1
]
f
o
u
n
d
th
at
p
h
ar
m
ac
is
t
in
ter
v
en
tio
n
s
b
r
o
u
g
h
t
s
ig
n
if
ican
t
im
p
r
o
v
em
e
n
t
to
ad
h
e
r
en
ce
t
o
an
tid
ep
r
ess
an
ts
.
A
s
tu
d
y
b
y
Alju
m
ah
an
d
Qu
r
esh
i
[
1
0
]
also
s
h
o
wed
th
at
p
h
ar
m
ac
is
t
in
ter
v
en
tio
n
s
im
p
r
o
v
ed
t
h
e
ad
h
e
r
en
ce
o
f
d
e
p
r
ess
ed
p
atien
ts
f
r
o
m
1
5
to
2
7
%.
T
h
e
p
h
ar
m
ac
is
t
in
ter
v
en
tio
n
s
r
esp
o
n
s
ib
le
f
o
r
t
h
ese
im
p
r
o
v
em
en
ts
wer
e
in
th
e
f
o
r
m
o
f
p
atien
t
ad
v
is
in
g
an
d
s
u
p
er
v
is
io
n
[
1
0
]
.
Ho
wev
er
,
th
e
r
e
ar
e
m
an
y
o
t
h
e
r
f
o
r
m
s
o
f
in
ter
v
e
n
tio
n
s
to
im
p
r
o
v
e
ad
h
e
r
en
ce
,
in
clu
d
in
g
m
o
n
ito
r
in
g
th
e
ef
f
ec
ts
o
f
d
r
u
g
s
,
h
elp
i
n
g
p
a
tien
ts
ac
ce
s
s
o
th
er
tr
ea
tm
en
ts
,
an
d
r
em
in
d
in
g
th
em
o
f
th
ei
r
tr
ea
tm
en
t
g
o
als.
Ho
wev
er
,
litt
le
r
esear
ch
h
as
b
ee
n
c
o
n
d
u
cted
o
n
t
h
e
m
et
h
o
d
s
u
s
ed
b
y
p
h
a
r
m
ac
is
ts
in
ass
is
tin
g
ad
h
er
en
ce
p
r
o
g
r
am
s
.
Me
a
n
wh
ile,
r
esear
ch
-
b
ased
i
n
f
o
r
m
atio
n
o
n
v
ar
io
u
s
p
h
ar
m
ac
is
t
-
led
in
t
er
v
en
tio
n
m
eth
o
d
s
ca
n
h
elp
d
esig
n
m
o
r
e
e
f
f
ec
tiv
e
p
r
o
g
r
am
s
t
o
im
p
r
o
v
e
ad
h
er
en
ce
.
T
h
is
m
a
y
b
e
r
elate
d
to
th
e
in
f
o
r
m
atio
n
s
o
u
r
ce
s
,
th
e
co
m
m
u
n
icatio
n
ch
an
n
el,
t
h
e
o
p
tim
al
s
ettin
g
,
th
e
co
s
t
o
f
p
er
f
o
r
m
in
g
th
e
in
ter
v
e
n
tio
n
s
,
an
d
its
v
iab
ilit
y
in
th
e
lo
n
g
r
u
n
.
T
h
i
s
n
ec
ess
itate
s
co
m
p
ar
in
g
th
e
e
f
f
ec
tiv
en
es
s
o
f
d
if
f
er
en
t
m
eth
o
d
s
to
d
esig
n
m
o
r
e
e
f
f
ec
tiv
e
p
r
o
g
r
a
m
s
.
T
h
is
s
tu
d
y
aim
ed
to
r
ev
iew
th
e
r
esu
lts
o
f
r
esear
c
h
o
n
th
e
ef
f
ec
tiv
en
ess
o
f
d
if
f
e
r
en
t
p
h
ar
m
ac
is
t
-
led
in
ter
v
en
tio
n
m
eth
o
d
s
o
n
th
e
a
d
h
er
en
ce
a
n
d
clin
ical
s
y
m
p
to
m
s
o
f
ad
u
lts
with
d
ep
r
ess
io
n
.
2.
M
E
T
H
O
D
2
.
1
.
Str
a
t
eg
y
o
f
s
ea
rc
hin
g
a
nd
info
rm
a
t
io
n so
urce
s
An
ex
ten
s
iv
e
liter
atu
r
e
s
ea
r
ch
was
co
n
d
u
cted
in
Pu
b
Me
d
,
Sco
p
u
s
,
an
d
Scien
ce
Dir
ec
t
f
o
r
p
u
b
licatio
n
s
p
u
b
lis
h
ed
f
r
o
m
2
0
0
3
to
2
0
2
3
.
I
n
ad
d
itio
n
,
we
s
ea
r
ch
e
d
Go
o
g
le
Sch
o
l
ar
d
ata
b
ases
an
d
ex
a
m
in
ed
th
e
citatio
n
s
o
f
th
e
in
clu
d
ed
s
tu
d
ies.
T
h
e
s
e
ar
ch
ap
p
r
o
ac
h
co
n
s
is
ted
o
f
co
m
b
in
in
g
p
h
r
ases
r
elate
d
t
o
m
e
d
icatio
n
ad
h
er
en
ce
in
in
d
iv
id
u
als
with
d
ep
r
ess
i
o
n
an
d
p
h
ar
m
ac
ies.
T
h
e
k
e
y
wo
r
d
s
u
s
ed
in
th
e
s
tu
d
y
in
clu
d
ed
:
p
h
ar
m
ac
is
t
in
ter
v
en
t
io
n
,
p
h
a
r
m
ac
is
t
ed
u
c
atio
n
,
m
ed
icatio
n
ad
h
er
en
ce
,
d
ep
r
ess
io
n
,
an
d
m
e
d
icatio
n
c
o
m
p
lian
ce
.
W
e
also
u
s
ed
th
e
ter
m
s
"OR,"
"AN
D,
"
an
d
"NO
T
"
to
co
m
b
in
e
th
em
.
ME
SH
was
u
s
ed
f
o
r
th
e
s
ea
r
c
h
q
u
er
y
in
Pu
b
Me
d
.
Du
e
to
th
e
v
ar
y
in
g
lim
itatio
n
s
an
d
tech
n
ical
d
if
f
er
e
n
ce
s
in
th
e
d
atab
ases
,
th
e
s
ea
r
c
h
m
e
th
o
d
s
in
b
o
th
wer
e
m
o
d
if
ied
an
d
a
d
ap
ted
.
W
e
als
o
lo
o
k
ed
f
o
r
r
ef
er
e
n
ce
s
f
r
o
m
th
e
in
clu
d
ed
ar
ticles
an
d
Go
o
g
l
e
Sch
o
lar
to
id
en
tify
o
th
er
s
tu
d
ies th
at
wer
e
n
o
t in
c
lu
d
ed
in
t
h
e
s
y
s
tem
atic
s
ea
r
ch
.
2
.
2
.
Study
s
elec
t
io
n
T
h
e
s
ea
r
ch
r
esu
lts
wer
e
im
p
o
r
t
ed
an
d
o
r
g
an
ize
d
u
s
in
g
th
e
Me
n
d
eley
1
.
1
9
.
8
p
r
o
g
r
am
.
R
ep
eti
tio
n
s
wer
e
elim
in
ated
,
an
d
a
s
in
g
le
au
th
o
r
(
YF)
f
o
u
n
d
p
u
b
licatio
n
s
t
h
at
m
ay
b
e
r
elev
a
n
t
b
y
r
e
v
iewin
g
th
eir
titl
es
an
d
ab
s
tr
ac
ts
.
Su
b
s
eq
u
en
tly
,
co
m
p
lete
tex
ts
o
f
ar
ticles
th
at
m
ay
b
e
p
er
tin
en
t
wer
e
o
b
tain
ed
,
if
th
ey
wer
e
ac
ce
s
s
ib
le.
A
s
in
g
le
au
th
o
r
(
YF)
ass
ess
e
d
th
e
co
m
p
lete
tex
ts
to
d
eter
m
in
e
th
eir
s
u
itab
ilit
y
.
W
h
en
u
n
ce
r
tain
ties
wer
e
d
etec
ted
,
two
wr
iter
s
(
I
PS
an
d
AW
W
)
s
ep
ar
ately
ex
am
in
ed
th
e
wh
o
le
tex
ts
to
s
ee
if
th
e
y
m
et
th
e
cr
iter
ia
f
o
r
in
clu
s
io
n
.
I
n
ca
s
es
wh
er
e
ag
r
e
em
en
t
co
u
ld
n
o
t
b
e
ac
h
iev
ed
,
an
ad
d
itio
n
al
a
u
th
o
r
(
DS
an
d
SAK)
was
en
g
ag
ed
,
an
d
a
n
y
d
if
f
er
e
n
ce
s
wer
e
ad
d
r
ess
ed
th
r
o
u
g
h
d
is
cu
s
s
io
n
.
R
elev
an
t
s
tu
d
ies
wer
e
d
ef
in
e
d
as
th
o
s
e
th
at
m
et
t
h
e
f
o
llo
win
g
c
r
iter
ia:
b
ein
g
p
u
b
lis
h
ed
in
th
e
E
n
g
lis
h
la
n
g
u
a
g
e,
co
n
s
is
tin
g
o
f
f
u
ll
-
tex
t
p
u
b
licat
io
n
s
th
at
ex
am
i
n
ed
p
atien
ts
with
d
ep
r
ess
io
n
,
an
d
f
o
cu
s
in
g
o
n
th
e
m
ain
o
u
tco
m
e
o
f
ad
h
e
r
en
ce
to
a
n
tid
ep
r
ess
an
t
d
r
u
g
s
.
Stu
d
ies
wer
e
o
m
itted
if
th
e
p
h
ar
m
ac
is
t
d
id
n
o
t
p
ar
ticip
ate
in
th
e
in
ter
v
e
n
tio
n
o
r
s
er
v
ice
o
f
f
e
r
ed
to
p
atien
ts
.
W
e
o
m
itted
m
an
y
s
o
u
r
ce
s
o
f
i
n
f
o
r
m
atio
n
,
in
clu
d
in
g
clin
ical
d
r
u
g
tr
ials
,
co
n
f
er
en
ce
ab
s
tr
ac
ts
,
co
n
f
er
e
n
ce
r
ep
o
r
ts
,
s
y
s
tem
atic
r
ev
iews,
an
d
m
eta
-
a
n
aly
s
es.
Fig
u
r
e
1
d
is
p
lay
s
th
e
PR
I
SMA
f
lo
w
ch
ar
t illu
s
tr
atin
g
th
e
p
r
o
c
ed
u
r
e.
2
.
3
.
Q
ua
lit
y
a
s
s
ess
m
ent
T
h
e
s
tu
d
ies
in
clu
d
ed
in
th
e
an
aly
s
is
wer
e
ca
teg
o
r
ized
b
ased
o
n
th
eir
d
esig
n
to
f
ac
ilit
ate
th
e
ev
alu
atio
n
o
f
th
eir
q
u
ality
.
T
h
e
J
o
an
n
a
B
r
ig
g
s
I
n
s
titu
te
(
J
B
I
)
cr
itica
l
as
s
ess
m
en
t
tech
n
iq
u
es
[
2
2
]
‒
[
2
4
]
wer
e
u
tili
ze
d
f
o
r
all
s
tu
d
y
d
esig
n
s
,
in
clu
d
in
g
r
an
d
o
m
ized
co
n
tr
o
lled
tr
ials
(
R
C
T
s
)
,
q
u
asi
-
ex
p
e
r
im
en
tal,
an
d
co
h
o
r
t
d
esig
n
s
,
as
s
h
o
wn
in
T
a
b
le
1
[
2
5
]
‒
[
3
8
]
.
E
ac
h
q
u
esti
o
n
in
t
h
e
J
B
I
ch
e
ck
lis
ts
was
r
esp
o
n
d
ed
to
with
eith
er
a
p
o
s
itiv
e
af
f
ir
m
atio
n
(
y
es),
a
n
e
g
ativ
e
r
esp
o
n
s
e
(
n
o
)
,
a
n
am
b
ig
u
o
u
s
a
n
s
wer
(
u
n
clea
r
o
r
NC
)
,
o
r
a
s
tatem
en
t
in
d
icatin
g
th
at
th
e
item
was
n
o
t
r
elev
an
t
(
NA)
.
T
h
e
n
u
m
b
er
o
f
p
o
s
itiv
e
ev
alu
atio
n
s
o
f
th
e
c
h
ec
k
lis
ts
f
o
r
t
h
e
ass
ess
m
en
t
to
o
ls
was u
s
ed
to
h
elp
d
eter
m
in
e
th
e
q
u
ality
o
f
th
e
s
tu
d
ies f
ea
tu
r
ed
in
th
e
an
aly
s
is
.
T
h
e
r
an
k
in
g
f
o
r
ea
ch
s
tu
d
y
was a
s
s
ig
n
ed
to
a
lo
w
(
less
th
an
3
3
%),
m
e
d
iu
m
(
3
3
-
6
6
%),
o
r
h
ig
h
q
u
ality
(
o
v
er
6
6
%)
[
39
].
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
E
ffective
n
ess
o
f d
elive
r
y
mo
d
e
o
f p
h
a
r
ma
cist
in
terven
tio
n
to
imp
r
o
ve
med
ica
tio
n
…
(
Yo
s
i F
eb
r
ia
n
ti
)
101
Fig
u
r
e
1
.
Flo
w
d
ia
g
r
am
o
f
th
e
s
elec
tio
n
p
r
o
ce
s
s
o
f
th
e
s
tu
d
ie
s
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
N
3
.
1
.
I
nclud
ed
s
t
ud
ies a
nd
s
t
ud
y
cha
ra
ct
er
is
t
ics
A
to
tal
o
f
7
9
1
p
u
b
licatio
n
s
w
er
e
d
is
co
v
er
e
d
th
r
o
u
g
h
th
e
lit
er
atu
r
e
s
ea
r
ch
,
o
u
t
o
f
wh
ich
1
4
p
a
p
er
s
f
u
lf
illed
th
e
in
clu
s
io
n
cr
iter
ia
in
Fig
u
r
e
1
.
T
h
e
s
tu
d
y
d
esi
g
n
s
wer
e
d
iv
er
s
e,
c
o
n
s
is
tin
g
o
f
1
0
r
an
d
o
m
ized
co
n
tr
o
lled
tr
ials
[2
5
]
‒
[3
4
]
.
T
h
r
ee
r
esear
ch
e
r
s
u
tili
ze
d
a
n
ex
p
er
im
en
tal
b
ef
o
r
e
-
an
d
-
af
ter
d
esig
n
[3
5
]
‒
[3
7
]
,
wh
er
ea
s
o
n
e
s
tu
d
y
em
p
l
o
y
ed
a
co
h
o
r
t
ap
p
r
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ac
h
[3
8
]
.
T
h
e
m
ajo
r
ity
o
f
th
e
s
tu
d
ies
ev
alu
at
ed
wer
e
o
f
m
o
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er
ate
to
h
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h
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u
ality
.
E
x
ce
p
t
f
o
r
s
ix
,
th
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m
aj
o
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ity
o
f
t
h
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in
clu
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ed
R
C
T
s
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alu
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g
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q
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.
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t
o
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r
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asi
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ex
p
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in
v
esti
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two
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ated
as
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ig
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q
u
ality
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with
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co
r
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8
0
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.
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h
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h
o
r
t
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th
e
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th
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h
a
n
d
,
h
ad
a
q
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ality
ass
ess
m
en
t
s
co
r
e
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f
5
5
%,
in
d
icatin
g
a
m
e
d
iu
m
le
v
el
o
f
q
u
ality
.
T
h
e
s
tu
d
y
'
s
s
p
ec
if
ic
attr
ib
u
tes
ar
e
d
is
p
lay
ed
in
T
ab
le
1
.
T
h
e
in
cl
u
d
ed
s
tu
d
ies
wer
e
p
er
f
o
r
m
ed
i
n
v
ar
io
u
s
co
u
n
tr
ies,
s
u
c
h
a
s
t
h
e
U
n
i
t
e
d
S
t
a
t
es
o
f
Am
e
r
i
c
a
(
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SA
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(
n
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w
a
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t
(
n
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A
u
s
t
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a
l
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d
i
A
r
a
b
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a
(
n
=
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s
r
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el
(n
=
1
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,
N
i
g
e
r
i
a
(
n
=
1
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,
J
a
p
a
n
(
n
=
1
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a
n
d
N
e
p
a
l
(
n
=
1
)
.
T
h
e
y
w
e
r
e
c
o
n
d
u
c
t
e
d
f
r
o
m
2
0
0
4
t
o
2
0
2
3
a
n
d
w
e
r
e
p
u
b
lis
h
ed
in
E
n
g
lis
h
.
T
h
e
s
tu
d
ies
wer
e
co
n
d
u
cte
d
in
v
ar
io
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s
s
ettin
g
s
,
s
u
ch
as
p
r
im
ar
y
ca
r
e
(
n
=
2
)
,
co
m
m
u
n
it
y
(n
=
5
)
,
an
d
o
u
tp
atie
n
t (
n
=
4
)
.
T
h
e
r
esu
lts
an
d
m
et
h
o
d
s
o
f
th
e
in
clu
d
ed
s
tu
d
ies ar
e
p
r
esen
te
d
in
T
ab
le
1
.
3
.
2
.
Cha
ra
c
t
er
is
t
ics o
f
ph
a
rm
a
cist
inte
rv
ent
io
n
T
ab
le
2
(
s
ee
Ap
p
en
d
ix
)
d
escr
ib
es
th
e
p
h
a
r
m
ac
is
t'
s
in
ter
v
en
tio
n
ac
co
r
d
in
g
to
th
e
d
eliv
er
y
m
eth
o
d
.
T
h
is
r
ev
iew
an
aly
ze
d
th
e
v
ar
io
u
s
d
eliv
er
y
m
eth
o
d
s
u
s
ed
b
y
p
h
ar
m
ac
is
ts
in
th
eir
in
ter
v
e
n
tio
n
s
.
T
h
ese
in
clu
d
e
f
ac
e
-
to
-
f
ac
e
m
ee
tin
g
s
(
n
=
7
)
,
p
h
o
n
e
ca
lls
(
n
=
5
)
,
v
id
eo
i
n
f
o
r
m
atio
n
(
n
=
1
)
,
an
d
a
co
m
b
in
ati
o
n
o
f
t
h
ese
m
eth
o
d
s
(n
=
1
)
.
B
esid
es
th
e
s
tu
d
y
co
n
d
u
cted
b
y
B
r
o
o
k
et
al.
,
th
e
o
th
er
s
tu
d
ies
in
clu
d
ed
r
ef
er
en
ce
s
ab
o
u
t
th
e
d
u
r
atio
n
o
f
th
e
in
ter
v
en
tio
n
,
wh
ich
r
an
g
ed
f
r
o
m
2
to
1
8
m
o
n
th
s
.
Ou
t
o
f
th
e
to
tal
o
f
f
o
u
r
teen
s
tu
d
ies,
eig
h
t
o
f
th
e
s
tu
d
ies
wer
e
ab
le
to
s
h
o
w
f
a
v
o
r
a
b
le
r
esu
lts
wh
en
p
h
a
r
m
ac
is
ts
in
ter
v
en
ed
with
p
atien
ts
s
u
f
f
er
in
g
f
r
o
m
d
ep
r
ess
io
n
.
A
f
ac
e
-
to
-
f
ac
e
ap
p
r
o
ac
h
b
y
a
p
h
ar
m
ac
is
t is th
e
m
eth
o
d
th
at
m
o
s
t im
p
r
o
v
es m
ed
icatio
n
ad
h
er
en
ce
in
d
ep
r
ess
ed
p
atien
ts
.
A
telep
h
o
n
e
ca
ll
an
d
v
id
e
o
in
f
o
r
m
atio
n
we
r
e
n
o
t
ef
f
ec
tiv
e
at
im
p
r
o
v
in
g
th
e
ad
h
e
r
en
ce
o
f
p
a
tien
ts
with
d
ep
r
ess
io
n
to
th
eir
m
ed
icatio
n
.
On
e
s
tu
d
y
r
ep
o
r
te
d
th
at
th
e
t
elep
h
o
n
e
c
o
n
tact
with
th
e
p
atien
ts
im
p
r
o
v
e
d
th
ei
r
ad
h
er
en
ce
r
ate
[2
8
]
.
An
o
th
er
r
esear
ch
f
o
u
n
d
th
at
th
er
e
was
n
o
s
ig
n
if
ican
t
im
p
r
o
v
em
en
t
in
a
d
h
er
en
ce
[2
6
]
,
[
2
7
]
,
[
3
0
]
,
[
3
1
]
,
[
3
8
].
T
h
is
lack
o
f
c
h
an
g
e
was
lik
ely
b
ec
au
s
e
th
e
c
o
n
tr
o
l
g
r
o
u
p
h
a
d
a
h
ig
h
r
ate
o
f
ad
h
er
e
n
ce
,
an
d
th
e
s
am
p
le
s
ize
o
f
th
e
s
tu
d
y
was
to
o
s
m
all
(
n
=
6
0
)
.
Nev
e
r
th
eless
,
th
e
u
tili
za
tio
n
o
f
tele
p
h
o
n
e
an
d
v
id
eo
in
f
o
r
m
atio
n
ass
is
tan
ce
in
clin
ical
p
r
ac
tic
e
is
co
n
s
tr
ain
ed
d
u
e
to
t
h
e
co
n
s
tr
ain
ts
o
f
tim
e
an
d
ex
p
en
s
e.
Als
o
,
p
atien
ts
'
lev
el
o
f
u
n
d
er
s
tan
d
i
n
g
m
ig
h
t b
e
af
f
ec
t
ed
b
y
t
h
e
p
r
esen
ce
o
f
telep
h
o
n
e
co
n
tact.
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
.
1
,
M
ar
ch
20
26
:
99
-
1
09
102
T
h
e
s
tu
d
ies en
co
m
p
ass
a
v
ar
iety
o
f
p
h
ar
m
ac
is
t in
ter
v
en
tio
n
s
.
On
e
o
f
th
e
m
o
s
t c
o
m
m
o
n
in
ter
v
en
tio
n
s
th
at
p
h
a
r
m
ac
is
ts
p
r
o
v
i
d
e
is
ed
u
ca
tio
n
a
n
d
co
u
n
s
ellin
g
to
h
elp
p
atien
ts
ad
h
er
e
t
o
th
eir
p
r
escr
ib
e
d
an
tid
ep
r
ess
an
ts
.
Oth
er
th
an
th
i
s
,
s
tu
d
ies
also
lo
o
k
ed
in
to
th
e
e
f
f
ec
ts
o
f
m
ed
icatio
n
r
e
v
iew
[2
5
]
‒
[2
7
]
,
[
3
6
]
.
So
m
e
s
tu
d
ies
also
ad
d
ed
in
f
o
r
m
atio
n
leaf
lets
ab
o
u
t
d
ep
r
ess
io
n
tr
ea
t
m
en
t
[
29
]
‒
[3
4
]
.
Oth
e
r
s
p
r
o
v
i
d
ed
v
id
eo
e
d
u
ca
tio
n
[2
8
]
,
[
3
1
]
p
h
o
n
e
s
u
p
p
o
r
t
[2
6
]
‒
[2
8
]
,
[
3
1
]
,
[
3
8
]
,
a
n
d
a
c
o
g
n
itiv
e
b
eh
av
i
o
r
th
e
r
ap
y
(
C
B
T
)
p
r
o
g
r
am
[3
7
]
.
C
o
u
n
s
ellin
g
an
d
ed
u
ca
tio
n
p
r
o
v
id
ed
to
p
atien
ts
s
ig
n
if
ican
tly
im
p
r
o
v
ed
th
eir
m
ed
icatio
n
ad
h
er
en
ce
.
Me
r
ely
em
p
lo
y
in
g
a
n
o
n
-
f
ac
e
-
to
-
f
ac
e
m
eth
o
d
t
o
o
f
f
er
co
u
n
s
ellin
g
an
d
ed
u
ca
tio
n
to
p
atien
ts
is
in
s
u
f
f
icien
t
f
o
r
en
h
an
cin
g
m
ed
icatio
n
ad
h
e
r
en
ce
in
in
d
iv
id
u
als with
d
ep
r
ess
io
n
.
T
ab
le
1
.
C
h
ar
ac
ter
is
tics
o
f
th
e
in
clu
d
ed
ar
ticles
A
u
t
h
o
r
,
y
e
a
r
,
a
n
d
c
o
u
n
t
r
y
S
t
u
d
y
a
im
S
t
u
d
y
d
e
si
g
n
S
a
mp
l
e
s
i
z
e
,
s
e
t
t
i
n
g
JB
I
q
u
a
l
i
t
y
p
e
r
c
e
n
t
a
g
e
(
c
a
t
e
g
o
r
y
)
A
d
l
e
r
e
t
a
l
.
,
2
0
0
4
,
U
S
A
[
2
5
]
To
e
x
a
mi
n
e
t
h
e
e
f
f
e
c
t
o
f
p
h
a
r
ma
c
i
s
t
i
n
t
e
r
v
e
n
t
i
o
n
s
o
n
t
h
e
me
n
t
a
l
h
e
a
l
t
h
o
f
p
a
t
i
e
n
t
s
w
i
t
h
d
e
p
r
e
ss
i
o
n
i
n
p
r
i
mar
y
c
a
r
e
RCT
5
3
3
,
p
r
i
mar
y
c
a
r
e
p
h
a
r
mac
y
7
7
%
(
H
i
g
h
)
C
a
p
o
c
c
i
a
e
t
a
l
.
,
2
0
0
4
,
U
S
A
[
2
6
]
To
e
x
a
mi
n
e
t
h
e
e
f
f
e
c
t
o
f
p
h
a
r
ma
c
i
s
t
i
n
v
o
l
v
e
me
n
t
i
n
c
o
l
l
a
b
o
r
a
t
i
v
e
c
a
r
e
o
n
i
m
p
r
o
v
i
n
g
t
h
e
q
u
a
l
i
t
y
a
n
d
o
u
t
c
o
me
o
f
t
r
e
a
t
m
e
n
t
f
o
r
p
a
t
i
e
n
t
s
w
i
t
h
d
e
p
r
e
ss
i
o
n
.
RCT
7
4
,
p
r
i
mar
y
c
a
r
e
p
h
a
r
mac
y
4
6
%
(
M
e
d
i
u
m
)
R
i
c
k
l
e
s
e
t
a
l
.
,
2
0
0
5
,
U
S
A
[2
7
]
To
e
x
a
mi
n
e
t
h
e
e
f
f
e
c
t
o
f
p
h
o
n
e
-
b
a
se
d
mo
n
i
t
o
r
i
n
g
a
n
d
e
d
u
c
a
t
i
o
n
i
n
c
o
l
l
a
b
o
r
a
t
i
v
e
c
a
r
e
b
e
t
w
e
e
n
p
h
a
r
mac
i
st
s a
n
d
p
a
t
i
e
n
t
s
o
n
t
h
e
p
a
t
i
e
n
t
s’
c
l
i
n
i
c
a
l
o
u
t
c
o
mes
RCT
6
3
,
c
o
mm
u
n
i
t
y
p
h
a
r
mac
y
6
2
%
(
M
e
d
i
u
m
)
B
r
o
o
k
e
t
a
l
.
,
2
0
0
5
,
U
S
A
[2
8
]
To
e
x
a
mi
n
e
t
h
e
e
f
f
e
c
t
o
f
t
e
l
e
p
h
o
n
e
f
o
l
l
o
w
-
u
p
o
n
p
a
t
i
e
n
t
s’
w
i
l
l
i
n
g
n
e
ss
t
o
p
r
o
v
i
d
e
f
e
e
d
b
a
c
k
t
o
p
h
a
r
mac
i
st
s a
n
d
t
h
e
e
f
f
e
c
t
o
f
s
u
c
h
f
e
e
d
b
a
c
k
o
n
su
b
s
e
q
u
e
n
t
o
u
t
c
o
me
s.
RCT
6
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r
ep
o
r
ted
th
e
m
ed
ian
o
r
m
ea
n
s
co
r
es
o
f
th
e
q
u
esti
o
n
n
air
es,
o
t
h
er
s
n
o
ted
th
e
p
e
r
ce
n
tag
e
o
f
s
u
b
jects
ex
p
er
ien
cin
g
a
s
ig
n
if
ican
t
im
p
r
o
v
em
e
n
t
in
t
h
eir
s
y
m
p
to
m
s
.
Dep
r
ess
io
n
s
y
m
p
to
m
s
wer
e
ass
ess
ed
in
ten
s
tu
d
ies,
an
d
o
u
t
o
f
th
em
,
eig
h
t
s
tu
d
ies
f
o
u
n
d
n
o
s
ig
n
if
ican
t
d
is
p
ar
ity
in
th
e
im
p
r
o
v
em
e
n
t
o
f
d
ep
r
ess
io
n
s
y
m
p
to
m
s
b
etwe
en
th
e
g
r
o
u
p
th
at
r
ec
eiv
e
d
p
h
a
r
m
ac
is
t
in
ter
v
en
tio
n
a
n
d
th
e
c
o
n
tr
o
l
g
r
o
u
p
.
On
ly
two
s
tu
d
ies
wer
e
ab
le
to
im
p
r
o
v
e
th
e
s
y
m
p
to
m
s
o
f
d
e
p
r
ess
io
n
u
s
in
g
v
ar
io
u
s
m
ea
s
u
r
es
[3
3
]
,
[
3
7
]
.
On
e
s
tu
d
y
n
o
ted
th
at
p
atien
ts
'
s
at
is
f
ac
tio
n
with
th
eir
tr
ea
tm
en
t im
p
r
o
v
e
d
[3
2
]
,
wh
e
r
ea
s
th
r
ee
s
tu
d
ies s
aw
an
al
ter
atio
n
in
p
atien
ts
'
m
ed
icatio
n
k
n
o
wled
g
e
f
o
llo
win
g
p
h
ar
m
ac
is
t
in
t
er
ac
tio
n
[2
7
]
,
[
29
]
,
[
3
1
]
.
Ad
d
itio
n
ally
,
t
h
r
ee
s
tu
d
ies
f
o
u
n
d
n
o
in
cr
ea
s
e
in
t
h
e
q
u
ality
o
f
life
f
o
r
p
atien
ts
with
d
ep
r
ess
io
n
[3
2
]
,
[
3
4
]
,
[
3
5
]
.
Mu
ltip
le
s
elf
-
r
ep
o
r
t
s
y
m
p
to
m
ch
ec
k
lis
ts
wer
e
u
tili
ze
d
in
th
e
s
tu
d
ies
to
ass
ess
d
ep
r
ess
io
n
s
y
m
p
to
m
s
.
Sp
ec
if
ically
,
th
e
b
ec
k
d
ep
r
ess
io
n
in
v
en
to
r
y
(
B
DI
)
was
em
p
lo
y
ed
in
s
ev
er
a
l
s
tu
d
ies
[2
5
]
,
[
2
7
]
,
[
3
1
]
,
[
3
3
]
,
th
e
p
s
y
ch
o
lo
g
ical
h
ea
lth
q
u
es
tio
n
n
air
e
(
PHQ
-
9
)
was
u
s
ed
i
n
two
s
tu
d
ies
[3
4
]
,
[3
7
]
,
th
e
H
o
p
k
in
s
s
y
m
p
to
m
ch
ec
k
lis
t
(
SC
L
-
1
3
)
was
u
s
ed
i
n
o
n
e
s
tu
d
y
[
2
6
]
,
t
h
e
m
o
n
tg
o
m
er
y
ea
s
b
er
g
d
e
p
r
ess
io
n
r
atin
g
s
ca
le
(
MA
DR
S)
wa
s
u
s
ed
in
o
n
e
s
tu
d
y
[3
2
]
,
a
n
d
th
e
K
ess
ler
p
s
y
ch
o
lo
g
ical
d
is
tr
ess
s
ca
le
(
K1
0
)
was
u
s
ed
in
an
o
th
er
s
tu
d
y
[
3
0
]
.
T
h
ese
s
tu
d
ies'
r
esu
lt
s
an
d
th
e
m
ea
s
u
r
em
en
t
o
f
th
e
co
n
d
itio
n
'
s
s
ev
er
it
y
ar
e
s
u
m
m
ar
ized
in
T
ab
le
2
(
s
ee
Ap
p
e
n
d
ix
)
.
3
.
5
.
Dis
cus
s
io
n
T
h
e
r
esu
lts
o
f
o
u
r
s
tu
d
y
in
d
ic
ate
th
at
p
h
ar
m
ac
is
t
-
b
ased
in
te
r
v
en
tio
n
s
ca
n
im
p
r
o
v
e
th
e
a
d
h
er
en
ce
o
f
p
atien
ts
with
an
tid
ep
r
ess
an
t
m
ed
icatio
n
.
C
o
m
p
a
r
ed
to
u
s
u
al
ca
r
e,
th
e
in
ter
v
en
tio
n
s
wer
e
ass
o
ciate
d
with
a
h
ig
h
er
lik
elih
o
o
d
o
f
p
atien
ts
ad
h
er
in
g
t
o
th
eir
p
r
escr
ip
tio
n
s
.
T
h
e
f
in
d
in
g
s
alig
n
with
th
e
s
tu
d
ies
co
n
d
u
cte
d
b
y
R
u
b
io
-
Vale
r
a
et
a
l.
[
2
1
]
,
Alju
m
ah
an
d
Hass
ali
[
3
2
]
,
a
n
d
R
ea
d
d
ea
n
et
a
l
.
[
2
0
]
,
wh
ich
also
s
h
o
wn
a
f
av
o
r
ab
le
im
p
ac
t o
f
p
h
a
r
m
ac
y
-
b
ased
in
t
er
v
en
tio
n
s
o
n
a
d
h
er
e
n
ce
to
an
t
id
ep
r
ess
an
t m
ed
icatio
n
[
2
0
]
,
[
2
1
]
,
[
2
3
]
.
A
to
tal
o
f
f
o
u
r
s
tu
d
ies
[3
3
]
,
[
3
5
]
,
[
3
7
]
,
[
3
8
]
wer
e
n
o
t
i
n
clu
d
ed
i
n
th
e
an
a
ly
s
is
o
f
th
e
s
tu
d
y
co
n
d
u
cted
b
y
th
e
th
r
ee
p
r
i
n
cip
al
in
v
esti
g
ato
r
s
:
R
u
b
io
-
Vale
r
a
et
a
l.
[
2
1
]
,
Alju
m
a
h
an
d
Hass
ali
[
3
2
]
,
an
d
R
ea
d
d
ea
n
et
a
l.
[
2
0
]
.
T
h
e
e
v
id
en
ce
s
h
o
ws
t
h
at
t
h
e
f
a
ce
-
to
-
f
a
ce
m
o
d
e
is
a
n
e
f
f
ec
t
i
v
e
p
h
a
r
m
ac
is
t
d
el
iv
er
y
m
et
h
o
d
i
n
im
p
r
o
v
i
n
g
ad
h
e
r
e
n
ce
i
n
p
atie
n
ts
w
it
h
d
e
p
r
ess
i
o
n
.
Fi
v
e
s
t
u
d
ies
[
2
5
]
,
[
29
]
,
[
3
4
]
,
[
3
6
]
,
[
4
0
]
w
e
r
e
s
u
cc
ess
f
u
l
i
n
im
p
r
o
v
i
n
g
m
e
d
ic
ati
o
n
ad
h
e
r
en
ce
in
a
n
ti
d
ep
r
ess
an
t
t
r
e
at
m
e
n
t
.
O
n
t
h
e
o
t
h
e
r
h
a
n
d
,
t
h
e
r
es
u
lts
o
f
th
e
p
h
o
n
e
ca
l
l
i
n
te
r
v
e
n
t
io
n
an
d
v
i
d
eo
e
d
u
c
ati
o
n
w
er
e
n
o
t
s
u
c
ce
s
s
f
u
l
.
O
n
l
y
a
m
i
n
o
r
i
ty
we
r
e
e
f
f
ec
ti
v
e
.
T
h
is
s
t
u
d
y
'
s
r
esu
lts
d
i
f
f
er
f
r
o
m
p
r
e
v
i
o
u
s
r
es
ea
r
c
h
,
wh
ic
h
f
o
u
n
d
t
h
at
c
o
u
n
s
ell
in
g
o
r
e
d
u
ca
t
i
o
n
t
h
r
o
u
g
h
ei
th
er
o
f
f
li
n
e
o
r
f
ac
e
-
to
-
f
a
ce
m
et
h
o
d
s
w
as
as
ef
f
e
cti
v
e
as
o
n
li
n
e
o
r
te
le
p
h
o
n
e
i
n
te
r
a
cti
o
n
s
.
Va
r
i
o
u
s
f
o
r
m
s
o
f
te
ch
n
o
l
o
g
y
ca
n
b
e
u
t
ili
ze
d
t
o
h
el
p
i
m
p
r
o
v
e
th
e
ad
h
e
r
e
n
ce
o
f
p
ati
en
ts
t
o
t
h
ei
r
m
e
d
ic
ati
o
n
.
So
m
e
o
f
t
h
es
e
i
n
cl
u
d
e
w
eb
-
b
as
ed
e
-
m
a
ils
,
t
el
e
p
h
o
n
e
-
b
ase
d
ass
is
ta
n
c
e,
an
d
co
m
p
u
te
r
s
u
p
p
o
r
t
s
y
s
t
em
s
[
4
1
]
,
[
4
2
]
.
Ot
h
e
r
s
t
u
d
i
es
a
ls
o
n
o
te
d
t
h
at
o
n
l
in
e
-
b
ase
d
m
et
h
o
d
s
we
r
e
m
o
r
e
ef
f
e
cti
v
e
at
im
p
r
o
v
in
g
m
e
d
ic
ati
o
n
a
d
h
e
r
en
ce
t
h
a
n
f
a
ce
-
to
-
f
a
ce
o
n
es
[
4
3
]
.
A
s
t
u
d
y
c
o
n
d
u
ct
e
d
b
y
W
a
g
n
e
r
et
a
l
.
[
4
4
]
f
o
u
n
d
th
a
t
o
n
l
in
e
-
b
ase
d
in
te
r
v
e
n
ti
o
n
s
f
o
r
d
e
p
r
ess
i
o
n
w
er
e
j
u
s
t
as
ef
f
e
cti
v
e
as
r
e
g
u
l
ar
f
a
ce
-
to
-
f
a
ce
t
h
e
r
a
p
y
.
B
u
t
t
h
e
lo
n
g
-
t
e
r
m
e
f
f
ic
ac
y
o
f
th
ese
m
e
th
o
d
s
w
as
o
n
l
y
f
o
u
n
d
i
n
t
h
e
o
n
lin
e
g
r
o
u
p
[
4
4
]
.
Nev
er
th
eless
,
th
is
s
tu
d
y
d
eter
m
in
ed
th
at
b
o
th
th
e
f
ac
e
-
to
-
f
a
ce
ap
p
r
o
ac
h
an
d
th
e
telep
h
o
n
e
tech
n
iq
u
e
d
id
n
o
t
h
a
v
e
a
s
u
b
s
tan
tial
ef
f
e
ct
in
en
h
an
cin
g
d
e
p
r
ess
io
n
s
y
m
p
to
m
s
.
Mo
s
t
s
tu
d
ies d
is
co
v
e
r
ed
s
im
ilar
lev
els o
f
clin
ical
im
p
r
o
v
em
en
t
in
b
o
t
h
th
e
in
ter
v
en
tio
n
an
d
u
s
u
al
ca
r
e
co
h
o
r
ts
.
On
ly
th
r
ee
s
tu
d
ies
em
p
lo
y
in
g
th
e
f
ac
e
-
to
-
f
ac
e
tech
n
iq
u
e
d
em
o
n
s
tr
ated
a
s
tatis
tically
s
ig
n
if
ican
t
d
is
p
ar
ity
b
etwe
en
th
e
two
g
r
o
u
p
s
th
r
o
u
g
h
o
u
t
th
e
s
ix
to
eig
h
teen
-
m
o
n
th
f
o
llo
w
-
u
p
p
er
io
d
.
T
h
is
s
u
g
g
ests
th
at
th
e
p
h
ar
m
ac
o
lo
g
ical
th
e
r
ap
y
was
s
u
cc
ess
f
u
l,
b
u
t
th
e
p
h
ar
m
ac
is
t'
s
in
ter
v
en
tio
n
s
d
id
n
o
t
r
esu
lt
in
s
ig
n
if
ican
t
im
p
r
o
v
em
en
ts
in
d
ep
r
ess
io
n
s
y
m
p
t
o
m
s
.
Ho
wev
er
,
o
th
er
s
tu
d
ies
d
id
r
ev
ea
l
an
im
p
r
o
v
e
m
en
t
in
p
atien
t
k
n
o
wled
g
e
a
n
d
s
atis
f
ac
tio
n
with
d
ep
r
ess
io
n
th
er
ap
y
.
A
s
tu
d
y
r
ev
ea
led
th
at
in
-
p
er
s
o
n
th
e
r
a
p
y
an
d
o
n
lin
e
c
o
g
n
itiv
e
b
eh
a
v
io
u
r
al
th
er
a
p
y
(
e
-
C
B
T
)
wer
e
m
o
r
e
ef
f
ec
tiv
e
at
im
p
r
o
v
in
g
th
e
q
u
ality
o
f
life
f
o
r
p
ar
ticip
a
n
ts
with
d
ep
r
ess
io
n
.
C
o
m
p
ar
ed
to
th
e
e
-
C
B
T
g
r
o
u
p
,
th
o
s
e
wh
o
to
o
k
in
-
p
er
s
o
n
t
h
er
ap
y
h
ad
h
ig
h
er
s
y
m
p
to
m
ato
lo
g
y
s
co
r
es.
B
o
th
m
eth
o
d
s
wer
e
ab
le
t
o
im
p
r
o
v
e
th
e
q
u
ality
o
f
life
f
o
r
th
e
p
ar
ticip
an
ts
,
with
e
-
CB
T
r
ep
o
r
te
d
ly
h
a
v
in
g
a
h
ig
h
e
r
r
ate
o
f
p
ar
ticip
a
n
t c
o
m
p
lian
ce
[
4
5
]
.
Var
io
u
s
f
o
r
m
s
o
f
th
e
r
ap
y
ca
n
b
e
u
tili
ze
d
t
o
s
u
p
p
o
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t
in
d
iv
i
d
u
als
d
ea
lin
g
with
m
en
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is
s
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tu
al
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ap
y
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as
g
ain
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p
o
p
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lar
ity
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u
e
to
th
e
r
is
e
o
f
th
e
C
OVI
D
-
1
9
p
an
d
em
ic.
I
t
p
r
o
v
id
es
p
eo
p
le
with
a
co
n
v
en
ie
n
t
an
d
co
m
f
o
r
tab
le
w
ay
to
co
n
n
ec
t
with
a
th
er
ap
is
t.
On
th
e
o
th
er
h
an
d
,
a
th
er
ap
is
t'
s
o
f
f
ice
allo
ws
th
em
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
.
1
,
M
ar
ch
20
26
:
99
-
1
09
104
to
f
o
cu
s
o
n
th
eir
g
o
als an
d
tak
e
a
b
r
ea
k
f
r
o
m
th
eir
d
aily
liv
e
s
.
T
h
er
e
ar
e
m
an
y
ad
v
an
tag
es
to
b
o
th
f
ac
e
-
to
-
f
ac
e
an
d
v
ir
tu
al
th
e
r
a
p
y
,
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d
it
s
e
em
s
th
at
th
ese
will
co
n
tin
u
e
to
b
e
p
o
p
u
lar
.
No
n
-
v
e
r
b
al
cu
es
ca
n
b
e
u
s
ed
b
y
th
er
ap
is
ts
to
h
elp
p
eo
p
le
u
n
d
e
r
s
tan
d
th
eir
co
n
d
itio
n
.
I
n
-
p
er
s
o
n
s
ess
io
n
s
ca
n
p
r
o
v
id
e
a
d
ee
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er
u
n
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er
s
tan
d
in
g
o
f
th
e
p
atien
t'
s
n
ee
d
s
b
y
allo
win
g
th
em
to
r
ea
d
cu
es
th
at
a
r
e
n
o
t
v
er
b
al.
Ne
v
er
th
eless
,
th
e
ex
p
en
s
es,
av
ailab
ilit
y
,
an
d
s
ch
ed
u
lin
g
p
o
s
e
as o
b
s
tacle
s
f
o
r
f
ac
e
-
to
-
f
ac
e
th
e
r
ap
y
[
4
6
]
,
[
4
7
]
.
Vir
tu
al
m
eth
o
d
s
,
lik
e
c
h
attin
g
o
r
s
en
d
in
g
an
em
ail,
allo
w
y
o
u
to
k
ee
p
in
to
u
ch
with
a
th
e
r
ap
is
t
f
r
o
m
an
y
wh
er
e.
T
h
ese
s
er
v
ices m
ak
e
it e
asy
to
ac
ce
s
s
th
er
ap
eu
tic
ass
is
tan
ce
,
an
d
th
ey
ca
n
b
e
h
elp
f
u
l f
o
r
th
o
s
e
wh
o
h
av
e
d
if
f
icu
lty
tr
a
v
elin
g
to
in
-
p
er
s
o
n
s
ess
io
n
s
.
Vir
tu
al
in
ter
ac
tio
n
s
ca
n
h
elp
lo
wer
s
o
cial
an
x
iety
wh
en
it
co
m
es
to
s
h
ar
in
g
a
p
h
y
s
ical
s
p
ac
e
with
o
th
er
s
.
On
lin
e
th
er
ap
y
n
etw
o
r
k
s
allo
w
in
d
i
v
id
u
als
to
r
em
a
in
an
o
n
y
m
o
u
s
an
d
av
o
id
b
ein
g
s
ee
n
en
ter
i
n
g
t
h
er
ap
y
s
ess
io
n
s
.
So
m
e
m
e
n
tal
h
e
alth
co
n
d
itio
n
s
r
eq
u
ir
e
in
-
p
er
s
o
n
s
ess
io
n
s
,
an
d
th
is
ca
n
b
e
a
lim
itatio
n
o
f
o
n
lin
e
t
h
er
ap
y
s
er
v
ices.
Als
o
,
in
d
iv
i
d
u
als
wh
o
s
u
p
p
le
m
en
t
th
eir
in
c
o
m
e
th
r
o
u
g
h
th
ese
n
etwo
r
k
s
m
ay
en
d
u
p
b
u
r
n
in
g
o
u
t,
r
esu
ltin
g
in
in
f
er
io
r
ca
r
e.
I
n
ad
d
itio
n
,
th
e
lack
o
f
co
m
m
u
n
icatio
n
b
etwe
en
p
atien
ts
an
d
th
eir
th
e
r
ap
is
ts
ca
n
lim
it th
eir
u
n
d
er
s
tan
d
in
g
[
4
6
]
‒
[
5
0
]
.
4.
CO
NCLU
SI
O
N
T
h
is
ar
ticle
h
ig
h
lig
h
ts
th
e
f
a
ct
th
at
p
h
ar
m
ac
is
ts
ca
n
h
av
e
b
r
o
ad
er
r
esp
o
n
s
ib
ilit
ies
in
p
atien
t
ca
r
e
th
r
o
u
g
h
v
ar
io
u
s
m
eth
o
d
s
o
f
ad
m
in
is
ter
in
g
m
e
d
icatio
n
s
,
esp
e
cially
co
n
ce
r
n
in
g
th
e
m
an
a
g
e
m
en
t
an
d
m
e
d
icatio
n
ad
h
er
en
ce
o
f
ad
u
lts
with
d
ep
r
ess
io
n
.
T
h
is
a
r
ticle
s
h
o
ws
p
h
ar
m
ac
is
ts
p
er
f
o
r
m
in
g
p
atien
t
e
d
u
ca
tio
n
,
m
ed
icatio
n
r
e
v
iew,
an
d
c
o
u
n
s
ellin
g
th
r
o
u
g
h
f
ac
e
-
to
-
f
ac
e
in
t
er
ac
tio
n
s
co
u
ld
e
f
f
ec
tiv
ely
im
p
r
o
v
e
a
n
tid
ep
r
ess
an
t
ad
h
er
en
ce
.
T
h
e
r
ef
o
r
e
,
th
is
ar
ticle
p
r
o
v
id
es
s
u
p
p
o
r
t
f
o
r
th
e
in
c
r
ea
s
in
g
ly
s
ig
n
if
ica
n
t
in
v
o
lv
e
m
en
t
t
h
at
|
p
h
ar
m
ac
is
ts
m
ay
h
a
v
e
in
b
o
t
h
th
e
m
an
a
g
em
en
t
o
f
p
atien
ts
with
d
e
p
r
ess
io
n
a
n
d
th
e
e
f
f
o
r
t
to
im
p
r
o
v
e
t
h
eir
ad
h
er
en
ce
t
o
th
er
a
p
y
.
T
h
e
s
tu
d
y
h
as
a
lim
itatio
n
th
at
is
r
elate
d
to
m
eth
o
d
o
lo
g
ical
is
s
u
es.
I
t
was
q
u
ite
d
if
f
icu
lt
to
ass
es
s
th
e
f
in
d
in
g
s
d
u
e
to
th
e
v
a
r
y
in
g
ap
p
r
o
ac
h
es
u
s
ed
in
th
e
an
aly
s
is
.
Alth
o
u
g
h
th
e
s
y
s
tem
ati
c
r
ev
iew
id
en
tifie
d
im
p
r
o
v
e
d
m
ed
icatio
n
ad
h
e
r
en
ce
,
it
is
am
b
ig
u
o
u
s
wh
eth
er
t
h
e
in
ter
v
en
tio
n
s
co
u
l
d
also
im
p
r
o
v
e
d
e
p
r
ess
io
n
s
y
m
p
to
m
s
.
B
esid
es,
th
e
in
clu
d
ed
s
tu
d
ies
em
p
lo
y
e
d
v
ar
io
u
s
m
eth
o
d
s
to
m
ea
s
u
r
e
m
e
d
icatio
n
ad
h
er
e
n
ce
;
th
is
s
h
o
ws
a
lack
o
f
s
tan
d
ar
d
s
to
m
ea
s
u
r
e
th
is
p
h
en
o
m
en
o
n
.
T
h
ese
s
tu
d
ies
also
u
s
ed
a
lim
ited
s
am
p
le
s
ize;
th
u
s
,
a
q
u
esti
o
n
ar
is
es
wh
eth
er
o
r
n
o
t
th
e
f
in
d
i
n
g
s
ca
n
b
e
g
en
er
ali
ze
d
to
o
th
er
p
o
p
u
latio
n
s
.
I
t
is
r
ec
o
m
m
e
n
d
ed
th
at
f
u
tu
r
e
r
esear
c
h
u
s
e
lar
g
er
s
am
p
le
s
izes,
ex
am
in
e
th
e
ef
f
ec
tiv
en
ess
o
f
v
ir
tu
al
th
er
a
p
y
m
eth
o
d
s
,
co
m
p
ar
e
t
h
em
to
co
n
v
en
tio
n
al
f
ac
e
-
to
-
f
ac
e
in
ter
v
en
tio
n
s
,
an
d
f
o
cu
s
o
n
w
h
eth
er
o
r
n
o
t
th
e
in
ter
v
en
ti
o
n
s
co
u
ld
en
h
a
n
ce
d
ep
r
ess
io
n
s
y
m
p
to
m
s
.
Ho
wev
er
,
to
th
e
b
est
o
f
o
u
r
k
n
o
wled
g
e,
th
e
f
in
d
in
g
s
o
f
th
is
s
tu
d
y
s
till
o
f
f
er
th
e
f
ir
s
t
co
m
p
r
eh
e
n
s
iv
e
an
aly
s
is
o
f
th
e
ef
f
ec
ts
o
f
p
h
ar
m
ac
is
t
-
led
in
te
r
v
en
tio
n
m
eth
o
d
s
o
n
th
e
s
u
cc
e
s
s
o
f
th
e
tr
ea
tm
en
t
o
f
ad
u
lts
with
d
e
p
r
ess
io
n
.
F
UNDING
I
NF
O
R
M
A
T
I
O
N
Au
th
o
r
s
s
tate
n
o
f
u
n
d
in
g
in
v
o
lv
ed
.
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
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E
Vi
Su
P
Fu
Yo
s
i
Feb
r
ian
ti
✓
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I
k
a
Pu
s
p
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Sar
i
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An
n
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ti
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Dian
a
Setiy
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ti
✓
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C
:
C
o
n
c
e
p
t
u
a
l
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t
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M
:
M
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:
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t
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Fo
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Fu
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n
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c
q
u
i
si
t
i
o
n
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
E
ffective
n
ess
o
f d
elive
r
y
mo
d
e
o
f p
h
a
r
ma
cist
in
terven
tio
n
to
imp
r
o
ve
med
ica
tio
n
…
(
Yo
s
i F
eb
r
ia
n
ti
)
105
CO
NF
L
I
C
T
O
F
I
N
T
E
R
E
S
T
ST
A
T
E
M
E
NT
Au
th
o
r
s
s
tate
n
o
co
n
f
lict o
f
in
t
er
est.
DATA AV
AI
L
AB
I
L
I
T
Y
T
h
e
d
ata
t
h
at
s
u
p
p
o
r
t
th
e
f
in
d
in
g
s
o
f
t
h
is
s
tu
d
y
ar
e
av
ailab
l
e
f
r
o
m
th
e
c
o
r
r
esp
o
n
d
in
g
au
t
h
o
r
,
[
I
PS
]
,
u
p
o
n
r
ea
s
o
n
ab
le
r
eq
u
est.
RE
F
E
R
E
NC
E
S
[
1
]
W
H
O
,
“
D
e
p
r
e
ss
i
v
e
d
i
s
o
r
d
e
r
(
d
e
p
r
e
ss
i
o
n
)
,
”
2
0
2
3
.
[
O
n
l
i
n
e
]
.
A
v
a
i
l
a
b
l
e
:
h
t
t
p
s
:
/
/
w
w
w
.
w
h
o
.
i
n
t
/
n
e
w
s
-
r
o
o
m
/
f
a
c
t
-
sh
e
e
t
s
/
d
e
t
a
i
l
/
d
e
p
r
e
ssi
o
n
.
[
2
]
H
.
Y
u
s
u
f
,
J.
D
.
O
h
i
e
k
u
,
W
.
C
.
H
a
r
u
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5
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[3
8
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[
39
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L.
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7
]
P
h
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c
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M
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c
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3
F
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9
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D
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p
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2
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0
5
[
2
8
]
P
h
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c
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3
c
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M
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to
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on
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0
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t
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mo
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c
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(
1
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.
3
4
v
s.
2
1
.
4
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,
P
=
0
.
0
3
3
)
.
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