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[
1
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L
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C
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1
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s
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L
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p
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[
2
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[
3
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.
R
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[
4
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.
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1
9
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[
5
]
.
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p
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[
6
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No
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-
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I
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321
312
ac
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[
7
]
.
L
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[
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.
Mo
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Par
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ical
an
d
m
en
tal
h
ea
lth
asp
ec
ts
o
f
L
C
to
r
ec
eiv
e
e
q
u
al
atten
ti
o
n
an
d
im
p
o
r
tan
ce
[
1
0
]
.
I
n
th
e
co
n
tex
t
o
f
th
e
C
OVI
D
-
1
9
p
an
d
e
m
ic,
th
e
s
ig
n
if
ican
ce
o
f
th
is
c
o
n
ce
p
t
i
n
cr
ea
s
es
ev
en
f
u
r
th
er
.
As
in
it
ial
atten
tio
n
s
h
if
te
d
to
wa
r
d
s
d
iag
n
o
s
in
g
,
tr
ea
tin
g
,
an
d
p
r
ev
e
n
tin
g
th
e
v
ir
u
s
,
th
e
lo
n
g
-
ter
m
ef
f
ec
ts
o
f
C
OVI
D
-
1
9
,
k
n
o
wn
co
llectiv
ely
as
L
C
,
wer
e
s
o
m
ewh
at
o
v
er
s
h
ad
o
we
d
.
R
ec
o
g
n
izin
g
t
h
at
L
C
is
n
o
t
o
n
ly
a
p
h
y
s
ical
d
is
o
r
d
er
b
u
t
also
o
n
e
th
at
s
ig
n
if
ican
tly
af
f
ec
ts
th
e
m
en
tal
an
d
em
o
tio
n
a
l
h
ea
lth
o
f
in
d
iv
id
u
als,
Par
ity
o
f
E
s
teem
ac
k
n
o
wled
g
es
th
e
n
ee
d
to
a
d
d
r
ess
b
o
th
asp
ec
ts
o
f
L
C
eq
u
ally
.
I
n
d
iv
id
u
als
with
a
ch
r
o
n
ic
co
n
d
itio
n
s
u
ch
as
L
C
r
eq
u
ir
e
a
co
m
p
r
eh
en
s
iv
e
ap
p
r
o
ac
h
to
h
ea
lth
ca
r
e
th
at
ad
d
r
ess
es a
ll a
s
p
ec
ts
o
f
th
eir
h
ea
lth
.
T
o
em
p
h
asize
th
e
im
p
o
r
tan
ce
o
f
L
C
,
it
is
cr
u
cial
to
p
r
o
v
i
d
e
em
p
ir
ical
ev
id
e
n
ce
,
m
ai
n
ly
th
r
o
u
g
h
m
eta
-
an
aly
s
is
.
T
h
is
em
p
ir
ical
d
ata
will
p
r
o
v
id
e
a
co
m
p
r
eh
en
s
iv
e
o
v
er
v
iew
o
f
L
C
'
s
im
p
ac
t
an
d
p
r
ev
alen
ce
,
p
r
o
v
id
i
n
g
co
m
p
ellin
g
e
v
id
en
ce
f
o
r
r
e
f
o
cu
s
in
g
atten
tio
n
o
n
th
is
p
er
s
is
t
en
t
h
ea
lth
co
n
ce
r
n
.
T
h
r
o
u
g
h
th
e
p
r
esen
tatio
n
o
f
r
o
b
u
s
t
em
p
ir
i
ca
l
d
ata,
s
p
ec
if
ic
d
em
o
g
r
ap
h
ic
f
ac
to
r
s
s
u
ch
as
g
en
d
er
,
s
m
o
k
in
g
h
a
b
its
,
an
d
co
m
o
r
b
i
d
ities
ca
n
b
e
id
en
tifie
d
s
o
th
at
th
e
Ph
ilip
p
in
e
h
e
alth
ca
r
e
co
m
m
u
n
ity
ca
n
ad
v
o
ca
te
f
o
r
Par
ity
o
f
E
s
teem
,
en
s
u
r
in
g
th
at
p
o
licy
m
ak
er
s
will
b
e
ab
le
to
f
o
r
m
u
late
an
d
im
p
lem
e
n
t
s
tr
ateg
ies
an
d
in
ter
v
en
tio
n
s
t
h
at
ca
n
lead
to
m
o
r
e
ef
f
ec
tiv
e
m
a
n
ag
em
en
t a
n
d
im
p
r
o
v
e
d
q
u
alit
y
o
f
L
if
e
f
o
r
th
o
s
e
b
attlin
g
L
C
.
2.
M
E
T
H
O
D
T
h
e
m
eta
-
an
aly
s
is
o
f
g
e
n
er
al,
m
u
s
cu
lo
s
k
eleta
l,
n
e
u
r
o
lo
g
ical,
p
s
y
ch
o
lo
g
ical,
r
esp
ir
ato
r
y
,
ca
r
d
io
v
ascu
lar
,
ea
r
,
n
o
s
e
,
a
n
d
th
r
o
at
(
E
NT
)
,
g
astro
in
test
in
al,
an
d
d
er
m
ato
lo
g
ical
L
C
s
y
m
p
to
m
s
was
d
o
n
e
f
o
llo
win
g
th
e
Pre
f
er
r
e
d
R
ep
o
r
tin
g
I
tem
s
f
o
r
Sy
s
tem
atic
R
ev
iews
an
d
Me
ta
-
An
aly
s
es
(
PR
I
SMA)
,
2
0
0
9
[
1
1
]
.
T
h
e
R
s
o
f
twar
e
ap
p
licatio
n
wa
s
u
tili
ze
d
[
1
2
]
.
2
.
1
.
Study
s
elec
t
io
n a
nd
elig
ibi
lit
y
cr
it
er
ia
T
h
e
p
r
ev
ale
n
ce
o
f
l
o
n
g
-
te
r
m
C
OVI
D
-
1
9
s
y
m
p
to
m
s
b
etwe
en
J
an
u
ar
y
1
,
2
0
2
1
a
n
d
Ap
r
il
3
0
,
2
0
2
3
was
r
esear
ch
ed
u
s
in
g
o
p
e
n
–
ac
ce
s
s
d
atab
ases
s
u
ch
as
Pu
b
Me
d
,
Scien
ce
Dir
ec
t,
an
d
Go
o
g
le
Sch
o
lar
,
u
tili
zin
g
a
B
o
o
lean
s
ea
r
ch
co
m
p
r
is
ed
o
f
k
ey
wo
r
d
s
ass
o
ciate
d
with
th
e
v
ar
io
u
s
ca
teg
o
r
ies
o
f
L
C
s
y
m
p
to
m
s
.
T
h
e
titl
es
an
d
ab
s
tr
ac
ts
o
f
s
elec
ted
s
tu
d
i
es
wer
e
s
u
b
jecte
d
to
p
r
elim
in
ar
y
s
cr
ee
n
in
g
.
T
h
e
f
o
llo
win
g
cr
iter
ia
d
eter
m
in
e
d
th
e
elig
ib
ilit
y
o
f
s
tu
d
ie
s
:
i
)
S
tu
d
y
d
esig
n
:
c
o
h
o
r
t
an
d
cr
o
s
s
-
s
ec
tio
n
al
s
tu
d
ies
ii
)
T
h
e
s
u
b
je
cts
ar
e
s
elf
–
r
ep
o
r
ted
an
d
p
o
ly
m
e
r
ase
ch
ain
r
ea
ctio
n
(
PC
R
)
-
v
er
if
ied
C
OVI
D
-
1
9
s
u
r
v
iv
o
r
s
iii
)
Sam
p
le
s
ize:
3
0
>p
atien
ts
,
iv
)
Fo
llo
w
-
u
p
tim
e:
>4
wee
k
s
,
v
)
Dem
o
g
r
ap
h
ic
in
f
o
r
m
atio
n
,
an
d
vi
)
T
est
p
ar
am
eter
s
in
clu
d
in
g
s
u
r
v
ey
q
u
esti
o
n
n
air
es,
m
ed
ical
r
ec
o
r
d
s
,
an
d
d
iag
n
o
s
ti
c
test
s
.
2
.
2
.
Da
t
a
ex
t
r
a
ct
io
n a
nd
a
na
ly
s
is
T
h
e
f
o
llo
win
g
ch
a
r
ac
ter
is
tics
o
f
th
e
s
tu
d
y
wer
e
ex
tr
ac
ted
: a
u
th
o
r
,
co
u
n
tr
y
,
s
tu
d
y
d
esig
n
,
s
am
p
le
s
ize,
lo
n
g
est
f
o
llo
w
-
u
p
p
e
r
io
d
,
g
e
n
d
er
,
ag
e,
C
OVI
D
-
1
9
d
iag
n
o
s
is
,
co
m
o
r
b
id
ities
,
h
o
s
p
italizatio
n
s
tatu
s
,
an
d
n
u
m
b
er
o
f
s
m
o
k
er
s
.
T
h
e
esti
m
ated
co
m
b
in
ed
p
r
e
v
alen
ce
o
f
L
C
s
y
m
p
to
m
s
with
a
f
r
e
q
u
en
cy
o
f
>5
was
d
eter
m
in
ed
b
y
u
tili
zin
g
th
e
"I
n
v
er
s
e"
p
r
o
ce
d
u
r
e
in
R
[
1
3
]
.
T
h
e
o
u
tco
m
es
wer
e
p
r
es
en
ted
as
p
r
o
p
o
r
ti
o
n
esti
m
ates,
I
2
an
d
Q
s
tatis
tics
,
an
d
h
eter
o
g
en
eity
p
-
v
al
u
es (
if
s
ig
n
if
ican
t: 0
.
0
5
)
.
Su
b
g
r
o
u
p
a
n
aly
s
es
f
o
r
d
em
o
g
r
ap
h
ic
r
is
k
f
ac
to
r
s
wer
e
in
d
e
p
en
d
en
tly
c
o
n
d
u
cted
i
n
R
s
o
f
t
war
e
u
s
in
g
a
r
an
d
o
m
ef
f
ec
ts
m
o
d
el
b
ased
o
n
th
e
u
n
iv
a
r
iate
r
eg
r
ess
io
n
o
u
tco
m
e
o
f
s
tu
d
ies
r
ep
o
r
tin
g
ag
e,
g
en
d
er
,
s
m
o
k
in
g
s
tatu
s
,
p
r
esen
ce
o
f
c
o
m
o
r
b
id
it
ies,
p
r
esen
ce
o
f
co
m
o
r
b
id
ities
(
h
y
p
er
ten
s
io
n
a
n
d
d
iab
etes)
,
an
d
in
ten
s
iv
e
ca
r
e
u
n
it
(
I
C
U
)
ad
m
is
s
io
n
.
Fo
r
est
p
lo
ts
wer
e
u
s
ed
to
illu
s
tr
ate
th
e
r
esu
lts
.
Pro
s
p
ec
tiv
e
p
u
b
licatio
n
b
ias
was
v
is
u
ali
ze
d
u
s
in
g
a
f
u
n
n
el
p
lo
t,
an
d
th
e
lik
elih
o
o
d
o
f
p
u
b
li
ca
tio
n
b
ias
was
q
u
an
titativ
el
y
ass
ess
ed
u
s
in
g
a
lin
ea
r
r
eg
r
ess
io
n
test
.
2
.
3
.
Q
ua
lity
a
s
s
ess
m
ent
o
f
inclu
d
ed
s
t
ud
ie
s
T
h
e
q
u
ality
o
f
th
e
in
clu
d
e
d
s
tu
d
ies
was
a
s
s
es
s
ed
u
s
in
g
th
e
New
ca
s
tle
–
Ottawa
Scal
e
(
NOS)
,
co
n
s
is
tin
g
o
f
eig
h
t
item
s
d
is
tr
ib
u
ted
ac
r
o
s
s
th
r
ee
d
o
m
ain
s
:
s
elec
tio
n
,
co
m
p
ar
ab
ilit
y
,
a
n
d
o
u
tco
m
e.
T
h
e
f
o
llo
win
g
m
etr
ics we
r
e
u
s
ed
to
ass
ig
n
s
tar
s
to
ea
ch
d
o
m
ai
n
t
o
d
eter
m
in
e
t
h
e
s
tu
d
y
'
s
q
u
ality
:
-
Go
o
d
q
u
ality
:
3
o
r
4
s
tar
s
in
th
e
s
elec
t
io
n
d
o
m
ain
,
1
o
r
2
s
tar
s
in
th
e
co
m
p
ar
a
b
ilit
y
d
o
m
ain
,
an
d
2
o
r
3
s
tar
s
in
th
e
o
u
tco
m
e/ex
p
o
s
u
r
e
d
o
m
ain
.
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
A
meta
-
a
n
a
lysi
s
o
f lo
n
g
–
term C
OV
I
D
–
1
9
s
ymp
to
ms (
S
h
i D
.
P
r
a
n
till
a
)
313
-
Fair
q
u
ality
:
2
s
tar
s
in
th
e
s
el
ec
tio
n
d
o
m
ain
,
1
o
r
2
s
tar
s
in
th
e
co
m
p
ar
ab
ilit
y
d
o
m
ain
,
an
d
2
o
r
3
s
tar
s
in
th
e
o
u
tco
m
e/e
x
p
o
s
u
r
e
d
o
m
ai
n
.
-
Po
o
r
q
u
ality
:
0
o
r
1
s
tar
in
th
e
s
elec
tio
n
d
o
m
ain
OR
0
s
tar
s
in
th
e
co
m
p
ar
ab
ilit
y
d
o
m
ain
O
R
0
o
r
1
s
tar
in
th
e
o
u
tco
m
e/e
x
p
o
s
u
r
e
d
o
m
ai
n
.
3.
RE
SU
L
T
S AN
D
D
I
SCU
SS
I
O
N
T
h
e
h
eig
h
ten
ed
i
n
ter
est
in
elu
cid
atin
g
th
e
ca
u
s
es,
ef
f
ec
ts
,
a
n
d
m
an
ag
em
en
t
o
f
l
o
n
g
-
ter
m
C
OVI
D
-
19
(
L
C
)
is
r
ef
lecte
d
in
th
e
lar
g
e
n
u
m
b
er
o
f
s
tu
d
ies
u
n
co
v
er
ed
b
y
e
x
h
au
s
tiv
e
liter
atu
r
e
s
ea
r
c
h
es,
as
d
e
p
icted
b
y
th
e
PR
I
SMA
d
iag
r
am
as sh
o
wn
in
F
ig
u
r
e
1.
Fig
u
r
e
1
.
PR
I
SMA
f
lo
w
d
iag
r
am
3
.
1
.
Study
cha
ra
ct
er
is
t
ics
T
ab
le
1
d
is
p
lay
s
th
e
ch
ar
ac
te
r
is
tics
o
f
th
e
3
4
i
n
clu
d
e
d
p
u
b
licatio
n
s
[
1
4
]
–
[
4
7
]
,
wh
ich
r
ep
o
r
t
a
to
tal
p
o
p
u
latio
n
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p
r
o
m
in
e
n
ce
in
i
n
v
esti
g
atin
g
lu
n
g
an
d
ca
r
d
iac
ab
n
o
r
m
alities
,
with
ap
p
r
o
x
im
ately
o
n
e
–
t
h
ir
d
o
f
th
e
in
clu
d
ed
s
tu
d
ies
em
p
lo
y
in
g
th
ese
tech
n
iq
u
es
[
5
3
]
.
C
o
m
o
r
b
id
ities
id
en
tifie
d
in
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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2252
-
8
8
0
6
A
meta
-
a
n
a
lysi
s
o
f lo
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g
–
term C
OV
I
D
–
1
9
s
ymp
to
ms (
S
h
i D
.
P
r
a
n
till
a
)
315
3
4
p
u
b
licatio
n
s
,
in
clu
d
in
g
h
y
p
er
ten
s
io
n
,
d
iab
etes,
C
OPD,
p
r
e
-
ex
is
tin
g
p
u
lm
o
n
ar
y
d
is
ea
s
es,
an
d
o
b
esit
y
,
ar
e
also
co
n
s
is
ten
tly
cited
as
p
r
o
s
p
ec
tiv
e
r
is
k
f
ac
t
o
r
s
f
o
r
r
esp
ir
ato
r
y
a
n
d
ca
r
d
io
v
ascu
l
ar
L
C
[
5
4
]
,
[
5
6
]
.
R
em
ar
k
ab
ly
,
L
C
m
a
n
if
ests
d
iv
er
s
e
n
eu
r
o
p
s
y
ch
o
lo
g
ical
a
n
d
E
NT
s
y
m
p
to
m
s
,
as
o
b
s
er
v
e
d
i
n
th
e
h
ea
lth
ef
f
ec
ts
o
f
C
OVI
D
-
1
9
o
n
t
h
e
n
er
v
o
u
s
s
y
s
tem
[
5
7
]
.
T
h
e
p
er
s
is
ten
ce
an
d
in
v
asio
n
o
f
SAR
S
-
C
OV
-
2
i
n
th
e
ce
n
tr
al
a
n
d
p
er
ip
h
er
al
n
er
v
o
u
s
s
y
s
tem
s
an
d
p
er
s
is
ten
t
in
f
lam
m
ati
o
n
,
im
m
u
n
e
d
y
s
f
u
n
ctio
n
,
b
lo
o
d
c
o
ag
u
latio
n
ab
n
o
r
m
alities
,
an
d
en
d
o
th
eli
u
m
d
y
s
f
u
n
ctio
n
ar
e
am
o
n
g
th
e
p
o
ten
tial
m
ec
h
an
is
m
s
u
n
d
er
ly
i
n
g
th
ese
m
an
if
estatio
n
s
[
5
8
]
–
[
6
0
]
.
T
h
e
h
ig
h
p
r
ev
alen
ce
o
f
m
u
s
cu
lo
s
k
eleta
l,
g
astro
in
test
in
al,
an
d
d
er
m
ato
lo
g
ical
L
C
s
y
m
p
to
m
s
ex
em
p
lifie
s
th
e
ex
ten
s
iv
e
s
p
ec
tr
u
m
o
f
s
y
m
p
to
m
p
r
ev
alen
ce
ac
r
o
s
s
m
u
ltip
le
o
r
g
an
s
y
s
tem
s
.
T
h
is
m
ay
b
e
attr
ib
u
tab
le
to
m
u
lti
-
o
r
g
an
im
p
air
m
en
t
th
at
p
er
s
is
ts
f
r
o
m
th
e
ac
u
te
p
h
ase
o
f
C
OVI
D
-
1
9
in
f
e
ctio
n
s
to
th
e
L
C
p
h
ase
[
5
8
]
,
[
6
1
]
,
[
6
2
]
.
T
h
e
s
u
b
s
tan
tial
h
eter
o
g
en
eit
y
o
f
f
r
eq
u
en
tly
r
ep
o
r
te
d
s
y
m
p
to
m
s
d
em
o
n
s
tr
ates
th
e
co
m
p
lex
ity
o
f
L
C
,
p
ar
ti
cu
lar
ly
in
ter
m
s
o
f
th
e
v
ar
ia
tio
n
s
in
clin
ical
m
an
if
estatio
n
s
ac
r
o
s
s
d
if
f
er
en
t
p
o
p
u
latio
n
s
.
I
t
also
d
escr
ib
es
th
e
d
i
f
f
icu
lties
ass
o
ciate
d
with
s
u
b
jectiv
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ess
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en
ts
,
s
u
ch
as
s
elf
-
r
ep
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tin
g
an
d
r
ec
all
b
ias,
wh
ich
m
ay
h
a
v
e
im
p
ac
ted
th
e
r
ep
o
r
tin
g
o
f
L
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s
y
m
p
to
m
s
in
th
e
in
cl
u
d
ed
s
tu
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ies.
Acc
o
r
d
i
n
g
to
r
esear
ch
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th
e
p
s
y
ch
o
lo
g
ic
al
an
d
s
o
cial
co
n
s
eq
u
en
ce
s
o
f
g
e
n
er
al,
m
u
s
cu
lo
s
k
eleta
l,
ca
r
d
io
r
esp
ir
at
o
r
y
,
g
astro
in
test
in
al,
an
d
d
er
m
ato
l
o
g
ical
L
C
s
y
m
p
to
m
s
ar
e
cir
c
u
m
s
cr
ib
ed
b
y
th
e
p
h
y
s
ical
lim
itatio
n
s
ass
o
ciate
d
with
th
ese
s
y
m
p
to
m
ca
teg
o
r
i
es
[
6
3
]
–
[
6
7
]
.
I
n
th
e
p
u
r
s
u
it
o
f
co
m
p
r
eh
e
n
s
iv
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u
n
d
er
s
tan
d
in
g
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th
ese
f
in
d
in
g
s
p
r
o
v
id
e
a
co
m
p
elli
n
g
im
p
etu
s
to
in
teg
r
ate
th
e
Par
ity
o
f
E
s
teem
f
u
r
th
er
to
illu
m
in
ate
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p
ath
to
war
d
a
m
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b
alan
ce
d
an
d
h
o
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tic
h
ea
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p
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f
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ab
le
2
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3
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2
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Su
b
–
g
ro
up
a
na
ly
s
is
T
h
e
d
is
p
ar
ities
in
ag
e
a
n
d
g
en
d
er
ass
o
ciate
d
with
L
C
ar
e
a
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r
itical
asp
ec
t
o
f
t
h
e
d
is
ea
s
e
as
s
h
o
wn
i
n
F
ig
u
r
e
2
.
T
h
e
s
ig
n
if
ica
n
t
ass
o
ciatio
n
o
f
ag
e
o
v
er
5
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an
d
th
e
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k
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tically
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ig
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if
ican
t
ass
o
ciatio
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o
f
f
em
ale
g
en
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er
with
th
e
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e
lo
p
m
en
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L
C
in
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icate
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th
at
th
ese
p
o
p
u
latio
n
s
ap
p
ea
r
to
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e
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r
e
p
r
o
n
e
to
Evaluation Warning : The document was created with Spire.PDF for Python.
I
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I
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316
d
ev
elo
p
in
g
L
C
.
On
th
e
o
t
h
er
h
a
n
d
,
d
ata
f
o
r
th
e
r
em
ai
n
in
g
r
is
k
f
ac
to
r
s
wer
e
in
s
u
f
f
icien
t
to
estab
lis
h
s
tatis
t
ically
s
ig
n
if
ican
t
ass
o
ciatio
n
s
with
th
e
p
r
e
v
alen
ce
o
f
L
C
s
y
m
p
to
m
s
.
T
h
e
i
n
ter
p
lay
b
etwe
en
th
e
m
u
lti
-
s
y
s
tem
ic
n
atu
r
e
o
f
L
C
,
th
e
ass
o
ciate
d
r
is
k
f
ac
to
r
s
,
a
n
d
p
r
o
lo
n
g
ed
d
u
r
atio
n
o
f
L
C
s
y
m
p
to
m
s
(
6
-
1
2
m
o
n
t
h
s
)
h
ig
h
lig
h
ts
th
e
n
ee
d
f
o
r
in
teg
r
ativ
e
an
d
h
o
lis
tic
ap
p
r
o
ac
h
e
s
to
m
itig
ate
th
e
h
ea
lth
e
f
f
e
cts
o
f
L
C
o
n
th
e
p
o
p
u
latio
n
.
T
h
is
ac
co
r
d
s
with
ev
id
en
ce
-
b
ased
r
ec
o
m
m
en
d
atio
n
s
f
o
r
r
eh
a
b
ilit
atio
n
a
n
d
em
er
g
i
n
g
p
h
ar
m
ac
o
l
o
g
ical
th
er
a
p
ies
co
n
ce
r
n
in
g
L
C
[
6
8
]
,
[
6
9
]
.
T
h
e
e
v
id
en
t
p
r
o
tectiv
e
ef
f
ec
t
o
f
v
ac
cin
atio
n
ag
ain
s
t
th
e
o
n
s
et
o
f
L
C
s
y
m
p
to
m
s
is
co
n
s
is
ten
t
with
p
r
io
r
r
esear
ch
[
7
0
]
,
[
7
1
]
.
Ho
we
v
er
,
ad
d
itio
n
al
v
al
id
atio
n
is
r
eq
u
ir
ed
f
o
r
th
e
i
n
clu
s
io
n
o
f
C
OVI
D
-
19
v
ac
cin
atio
n
s
in
t
h
e
r
ec
o
m
m
e
n
d
ed
s
tr
ateg
ies an
d
p
o
licies f
o
r
L
C
m
an
ag
em
en
t.
Fig
u
r
e
2
.
Su
b
–
g
r
o
u
p
an
aly
s
is
f
o
r
p
o
ten
tial L
C
r
is
k
f
ac
to
r
s
: >
5
0
y
ea
r
s
,
g
en
d
e
r
,
s
m
o
k
in
g
s
tatu
s
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p
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esen
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o
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d
ities
,
co
m
o
r
b
i
d
ities
(
h
y
p
er
ten
s
io
n
an
d
d
iab
etes)
,
an
d
I
C
U
ad
m
is
s
io
n
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I
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2252
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8
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A
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3
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3
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3
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P
ub
lica
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io
n bia
s
T
h
e
ac
k
n
o
wled
g
m
en
t
o
f
p
u
b
licatio
n
b
ias
r
ev
ea
ls
an
u
n
eq
u
al
d
is
tr
ib
u
tio
n
o
f
s
tu
d
ies
with
in
th
e
m
eta
-
an
aly
s
is
as
s
h
o
wn
i
n
F
ig
u
r
e
3
.
T
h
is
d
is
p
ar
ity
m
a
y
r
esu
lt
f
r
o
m
a
p
r
ef
er
en
ce
f
o
r
p
u
b
li
s
h
in
g
s
tu
d
ies
with
p
o
s
itiv
e
o
r
s
tatis
tically
s
ig
n
i
f
ican
t
r
esu
lts
,
th
er
eb
y
m
a
r
g
i
n
alizin
g
th
o
s
e
with
less
co
n
clu
s
iv
e
r
esu
lts
an
d
in
tr
o
d
u
cin
g
b
ias
[
7
2
]
.
T
h
e
m
ajo
r
ity
o
f
s
tu
d
ies
ar
e
d
is
p
er
s
e
d
in
th
e
to
p
m
o
s
t
p
o
r
tio
n
o
f
t
h
e
p
lo
t.
As
a
r
esu
lt,
in
s
u
f
f
icien
t
s
tu
d
ies
ar
e
d
is
tr
ib
u
ted
th
r
o
u
g
h
o
u
t
th
e
g
r
ap
h
'
s
lo
wer
p
o
r
tio
n
to
ac
co
u
n
t
f
o
r
s
y
m
m
etr
y
.
E
g
g
er
'
s
tes
t
was p
er
f
o
r
m
ed
to
q
u
an
tify
t
h
e
asy
m
m
etr
y
in
q
u
esti
o
n
f
u
r
th
e
r
.
T
ab
le
3
s
h
o
ws
th
at
th
e
es
ti
m
ated
b
ias
(
1
,
3
6
0
2
)
co
r
r
esp
o
n
d
s
to
th
e
d
eg
r
ee
o
f
p
r
o
s
p
ec
tiv
e
b
ias
d
ep
icted
in
Fig
u
r
e
3
.
T
h
e
o
b
s
er
v
ed
b
ias
is
a
co
m
p
ellin
g
i
n
d
icato
r
o
f
r
esear
ch
d
ef
icien
cies
in
th
e
cu
r
r
en
t
lan
d
s
ca
p
e.
T
h
e
o
v
er
r
e
p
r
esen
t
atio
n
o
f
s
tu
d
ies
with
s
p
ec
if
ic
o
u
tco
m
es
f
o
r
L
C
,
e.
g
.
,
s
y
m
p
to
m
ca
teg
o
r
y
,
ag
e
,
g
en
d
er
,
a
n
d
r
eg
io
n
,
m
ay
ca
s
t
a
s
h
ad
o
w
o
n
o
th
er
n
ec
ess
ar
y
r
esear
ch
with
d
iv
er
s
e
L
C
f
in
d
in
g
s
[
7
2
]
.
T
h
is
s
ce
n
ar
io
ca
n
r
esu
lt
in
a
n
in
co
m
p
lete
o
r
d
is
to
r
ted
u
n
d
er
s
tan
d
in
g
o
f
L
C
.
T
h
e
m
u
ltifa
ce
ted
n
atu
r
e
o
f
th
is
b
ias
m
ay
also
b
e
attr
ib
u
tab
le
t
o
th
e
v
ar
iatio
n
s
in
h
o
w
th
e
in
c
lu
d
ed
s
tu
d
ies
wer
e
co
n
d
u
cte
d
an
d
th
eir
r
esu
lts
r
ep
o
r
ted
,
wh
ich
a
d
d
ed
c
o
m
p
l
ex
ity
wh
en
c
o
m
b
in
in
g
an
d
co
m
p
ar
in
g
t
h
e
s
tu
d
ies
with
in
th
e
m
eta
–
an
aly
s
is
.
I
n
co
n
tr
ast,
th
e
T
s
tatis
tic
is
m
o
d
est
(
0
.
8
7
)
,
in
d
icatin
g
th
at
th
e
p
r
e
v
io
u
s
ly
m
en
tio
n
e
d
ev
i
d
e
n
ce
f
o
r
th
e
b
ias
is
m
ea
g
er
.
T
h
e
p
-
v
alu
e
p
r
o
v
id
e
s
f
u
r
th
er
ev
id
en
c
e
th
at
t
h
e
as
y
m
m
etr
y
o
f
t
h
e
f
u
n
n
el
p
lo
t
i
s
n
o
t
s
u
p
p
o
r
ted
b
y
s
tatis
t
ically
s
ig
n
if
ican
t e
v
id
en
ce
.
T
h
e
q
u
an
titativ
e
d
ata
ex
p
o
s
e
s
a
v
ar
iety
o
f
h
ea
lth
r
ep
er
cu
s
s
io
n
s
,
ca
s
tin
g
lig
h
t
o
n
th
e
s
ig
n
if
ican
t
b
u
r
d
e
n
L
C
p
lace
s
o
n
g
l
o
b
al
h
ea
lth
ca
r
e
s
y
s
tem
s
an
d
th
e
s
ig
n
if
ican
ce
o
f
th
e
Par
ity
o
f
E
s
t
ee
m
.
T
h
is
n
ec
ess
itates
in
cr
ea
s
ed
p
u
b
lic
awa
r
en
ess
an
d
th
e
av
ailab
ilit
y
o
f
m
ed
ical
f
ac
ilit
ies
eq
u
ip
p
ed
to
tr
ea
t
L
C
p
atien
ts
[
7
3
]
,
[
7
4
]
.
No
n
eth
eless
,
it
is
e
s
s
en
tial
to
r
ec
o
g
n
ize
s
ev
er
al
lim
itatio
n
s
th
at
m
ay
af
f
ec
t
th
e
in
ter
p
r
etab
ilit
y
an
d
r
eliab
ilit
y
o
f
th
e
s
tu
d
y
'
s
f
in
d
in
g
s
.
D
u
e
to
in
co
n
s
is
ten
cies
in
d
e
f
in
in
g
an
d
r
ep
o
r
tin
g
L
C
,
it
was
d
if
f
icu
lt
to
d
ir
ec
tly
co
m
p
ar
e
p
r
ev
alen
ce
esti
m
ates
ac
r
o
s
s
s
tu
d
ies.
C
o
n
s
eq
u
en
tly
,
u
s
in
g
th
e
"in
v
er
s
e"
m
et
h
o
d
,
th
e
esti
m
ated
ag
g
r
eg
ated
p
r
e
v
alen
ce
f
o
r
ea
c
h
L
C
s
y
m
p
to
m
was
ca
lcu
lated
.
Ad
d
itio
n
ally
,
th
e
v
ar
y
in
g
f
o
llo
w
-
u
p
d
u
r
atio
n
s
h
am
p
er
ed
th
e
ass
ess
m
en
t
o
f
th
e
p
r
o
g
r
ess
io
n
o
f
L
C
s
y
m
p
t
o
m
s
.
I
n
ad
d
itio
n
,
th
e
s
m
all
n
u
m
b
er
o
f
s
tu
d
ies
in
clu
d
ed
i
n
th
e
s
u
b
g
r
o
u
p
an
a
ly
s
is
an
d
th
e
u
n
d
e
r
r
ep
r
esen
tat
io
n
o
f
r
e
p
r
esen
tativ
e
p
o
p
u
lati
o
n
s
m
ay
in
f
lu
e
n
ce
th
e
g
en
er
aliza
tio
n
s
o
f
th
e
s
tu
d
y
.
Fig
u
r
e
3
.
Fu
n
n
el
p
lo
t
f
o
r
p
u
b
li
ca
tio
n
b
ias s
h
o
win
g
asy
m
m
et
r
y
T
ab
le
3
.
L
in
ea
r
r
eg
r
ess
io
n
test
f
o
r
f
u
n
n
el
p
lo
t a
s
y
m
m
etr
y
Te
st
re
su
l
t
V
a
l
u
e
Est
i
m
a
t
e
d
b
i
a
s
1
.
3
6
0
2
t
-
st
a
t
i
s
t
i
c
0
.
8
7
p
-
v
a
l
u
e
0
.
3
9
2
6
4.
CO
NCLU
SI
O
N
T
h
e
m
eta
-
an
al
y
s
is
o
f
av
ailab
l
e
r
esear
ch
o
n
lo
n
g
-
ter
m
C
OVI
D
d
em
o
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8
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9
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