Reducing medication errors in hospitals through interventions

https://doi.org/10.1177/2042098620968309
https://doi.org/10.1177/2042098620968309
Ther Adv Drug Saf
2020, Vol. 11: 1–29
DOI: 10.1177/
2042098620968309
© The Author(s), 2020.
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Lay summary
Activities to reduce medication errors in adult medical and

surgical hospital areas
Introduction: Medication errors or mistakes may happen at any
time in hospital, and they
are a major reason for death and harm around the world.
Interventions to reduce medication errors
in adult medical and surgical settings: a
systematic review
Elizabeth Manias , Snezana Kusljic and Angela Wu
Abstract
Background and Aims: Medication errors occur at any point of
the medication management
process, and are a major cause of death and harm globally. The
objective of this review was to
compare the effectiveness of different interventions in reducing
prescribing, dispensing and
administration medication errors in acute medical and surgical
settings.
Methods: The protocol for this systematic review was registered
in PROSPERO
(CRD42019124587). The library databases, MEDLINE,
CINAHL, EMBASE, PsycINFO, Cochrane
Database of Systematic Reviews and the Cochrane Central
Register of Controlled Trials were
searched from inception to February 2019. Studies were
included if they involved testing of an
intervention aimed at reducing medication errors in adult, acute
medical or surgical settings.
Meta-analyses were performed to examine the effectiveness of
intervention types.
Results: A total of 34 articles were included with 12
intervention types identified. Meta-analysis
showed that prescribing errors were reduced by pharmacist-led
medication reconciliation,

computerised medication reconciliation, pharmacist partnership,
prescriber education,
medication reconciliation by trained mentors and computerised
physician order entry (CPOE)
as single interventions. Medication administration errors were
reduced by CPOE and the use
of an automated drug distribution system as single
interventions. Combined interventions
were also found to be effective in reducing prescribing or
administration medication errors.
No interventions were found to reduce dispensing error rates.
Most studies were conducted at
single-site hospitals, with chart review being the most common
method for collecting medication
error data. Clinical significance of interventions was examined
in 21 studies. Since many studies
were conducted in a pre–post format, future studies should
include a concurrent control group.
Conclusion: The systematic review identified a number of single
and combined intervention
types that were effective in reducing medication errors, which
clinicians and policymakers
could consider for implementation in medical and surgical
settings. New directions for future
research should examine interdisciplinary collaborative
approaches comprising physicians,
pharmacists and nurses.
Keywords: hospitals, medication errors, medical order entry
systems, medication reconciliation,
medication therapy management, nurses, patient safety,
pharmacists, physicians, systematic
review
Received: 27 May 2020; revised manuscript accepted: 23
September 2020.

Correspondence to:
Elizabeth Manias
School of Nursing and
Midwifery, Centre for
Quality and Patient Safety
Research, Institute for
Health Transformation,
Deakin University, 221
Burwood Highway,
Burwood, Victoria 3125,
Australia
Melbourne School of
Health Sciences, The
University of Melbourne,
Melbourne, Australia
Department of Medicine,
Royal Melbourne Hospital
[email protected];
[email protected]
Snezana Kusljic
Department of Nursing,
The University of
Melbourne, Melbourne,
Victoria, Australia
The Florey Institute of
Neuroscience and Mental
Health, Melbourne,
Australia
Angela Wu
Melbourne Medical
School, The University of

Melbourne, Melbourne,
Victoria, Australia
968309TAW0010.1177/2042098620968309Therapeutic
Advances in Drug SafetyE Manias, S Kusljic
research-article20202020
Systematic Review
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Therapeutic Advances in Drug Safety 11
Objective: To compare the effectiveness of different activities
in reducing medication
errors occurring with prescribing, giving and supplying
medications in adult medical and
surgical settings in hospital.
Methods: Six library databases were examined from the time
they were developed
to February 2019. Studies were included if they involved testing
of an activity aimed at
reducing medication errors in adult medical and surgical
settings in hospital. Statistical
analysis was used to look at the success of different types of
activities.
Results: A total of 34 studies were included with 12 activity

types identified. Statistical
analysis showed that prescribing errors were reduced by
pharmacists matching
medications, computers matching medications, partnerships
with pharmacists, prescriber
education, medication matching by trained physicians, and
computerised physician order
entry (CPOE). Medication-giving errors were reduced by the
use of CPOE and an automated
medication distribution system. The combination of different
activity types were also shown
to be successful in reducing prescribing or medication-giving
errors. No activities were
found to be successful in reducing errors relating to supplying
medications. Most studies
were conducted at one hospital with reviewing patient charts
being the most common way
for collecting information about medication errors. In 21 out of
34 articles, researchers
examined the effect of activity types on patient harm caused by
medication errors. Many
studies did not involve the use of a control group that does not
receive the activity.
Conclusion: A number of activity types were shown to be
successful in reducing prescribing
and medication-giving errors. New directions for future
research should examine activities
comprising health professionals working together.
Introduction
Medication errors occur at any point of the medi-
cation management process involving prescrib-
ing, transcribing, dispensing, administering and
monitoring,1,2 have been reported to account for
approximately one-quarter of all healthcare
errors.3 Medication errors are a major cause of

death and harm globally.4 According to the World
Health Organisation (WHO), medication errors
cost an estimated US$42 billion annually world-
wide, which is 0.7% of the total global health
expenditure.5
Systematic reviews examining interventions
aimed at reducing medication errors have largely
focused on specialty settings, such as patients sit-
uated in adult and paediatric intensive care units,
emergency departments, and neonatal intensive
care and paediatric units.6–10 Previous relevant
systematic reviews relating to testing interven-
tions for reducing medication errors in general
hospital settings have focused on administration
errors only,11,12 have involved adult and paediat-
ric settings or have tested interventions in spe-
cialty and general hospital settings with no
differentiation in results.11–13 This systematic
review aims to compare the effectiveness of differ-
ent interventions in reducing prescribing, dis-
pensing and administration medication errors in
acute medical and surgical settings. Information
obtained from this review can inform clinicians
and policymakers about the types of interventions
that have been shown to be effective, which can
guide the development of comprehensive guide-
lines for clinical practice and policy directives.
Methods
In conducting this systematic review, the authors
followed the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses
(PRISMA) guidelines.14 The review protocol was
registered with PROSPERO (CRD42019124587).

Search strategy
A search was conducted of the following library
databases, MEDLINE, CINAHL, EMBASE,
PsycINFO, Cochrane Database of Systematic
Reviews and the Cochrane Central Register of
Controlled Trials, from inception to February
2019.
A search strategy was devised following consulta-
tion with a university research librarian to yield
relevant studies. Keywords used in the search
comprised five categories: the setting, with key-
words ‘hospital’, ‘acute’, ‘medical’, ‘surgical’;
E Manias, S Kusljic et al.
perspective, with keywords ‘medication manage-
ment’, ‘medication process’, ‘medicines manage-
ment’, ‘prescribing’, ‘dispensing’,
‘administration’, ‘monitoring’; population, with
keyword ‘adult’; activity, with keywords ‘pro-
gram’ and ‘intervention’; and phenomenon of
interest, with keywords ‘medication errors’, ‘pre-
ventive adverse drug events’, and ‘medicine
errors’. Keywords in each category were searched
using the operator OR, and then combined
between categories using the operator AND.
Search histories for all databases are listed in
Supplemental file S1. Key article cross-checking
was performed using citation-linking databases,

Scopus and Web of Science in an attempt to iden-
tify further articles. Reference lists of relevant
articles were checked to identify additional
papers. Previous systematic reviews on a similar
topic were also examined to determine possible
papers for inclusion.11–13
Eligibility criteria
Studies were included if they involved testing an
intervention aimed at reducing medication errors
in adult acute medical or surgical settings. Adults
were defined as patients aged 18 years or over. If
patients received the intervention during hospitali-
sation and the effect on medication errors was
measured in the hospital setting, these studies were
included. Medication errors comprised any pre-
ventable events that may cause or lead to inappro-
priate medication use or patient harm during
prescribing, dispensing or administration.15 The
prevalence of medication errors must have been
identified as a primary or secondary outcome to be
included. Papers were considered for inclusion if
they were published before 2000, as this was the
year when the landmark publication, To Err is
Human: Building a Safer Health System was released
by the Institute of Medicine.16 This publication
drew attention of the need for health services to
develop tools and systems to address problems in
patient safety, such as medication errors.
Near misses were not included as medication
errors. Only papers published in English were
included. Case studies, commentaries, editorials,
reviews, epidemiological studies and conference
abstracts were excluded. If studies examined
medication-related problems as an outcome,

which often comprised a combination of medica-
tion errors, as well as problems with medication
knowledge, medication adherence and other
aspects of medication management, these studies
were not included. If the effect of the intervention
was measured outside the hospital setting, these
studies were excluded. Specialty wards such as
intensive care, emergency care, perioperative
care, neurological and cancer care were excluded.
Outpatient settings and subacute settings, such as
rehabilitation wards and geriatric evaluation and
management units were excluded.
Study selection
Rayyan (Qatar Computing Research Institute),
an online platform, was used for independent
screening of articles at the title and abstract level,
and subsequently at the full text level.17 Two
authors reviewed titles and abstracts indepen-
dently. The third author assessed discrepancies at
the title and abstract level. Any uncertainty or
disagreement about articles meeting the inclusion
criteria was resolved after discussion among all
authors. Full texts of papers were then examined
independently by two authors to determine if
studies were eligible for inclusion in the review.
Any discrepancies identified at the full-text level
were examined by the third author. Previous sys-
tematic reviews on similar topics were also exam-
ined to determine possible papers for inclusion.
Quality assessment
Quality assessment was undertaken using the
Equator reporting guidelines whereby ran-
domised controlled trials were assessed using the

CONSORT guidelines,18 non-randomised stud-
ies were assessed using the TREND guide-
lines,19 and quality improvement studies were
assessed using the SQUIRE guidelines.20 No
study was excluded on the basis of the score
obtained for quality assessment. Risk of bias
assessment was also undertaken using Review
Manager, version 5.3 (RevMan) (Cochrane
Collaboration) software.
Data extraction
Data were extracted from each paper to a stand-
ard form for study design, country and setting,
number of patients, intervention type, type of
medication error analysed and effect of the inter-
vention (Table 1). If the studies provided infor-
mation about the severity of medication errors
using their approach for measuring severity, these
data were also included in data extraction.
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ed
a
t
d
is
ch
ar
ge
C
on
tr
ol
:
2.
71
p
er
p
at
ie
n
t
26

8
U
D
s
in
9
9
p
at
ie
n
ts
In
te
rv
en
ti
on
:
0.
02
p
er
p

at
ie
n
t
2
U
D
s
in
9
1
p
at
ie
n
ts
N
o
p-
va
lu
e
re
p

or
te
d
U
n
p
la
n
n
ed
r
ea
d
m
is
si
on
a
t
3
m
on
th
s

C
on
tr
ol
3
7
(3
6.
6%
)
p
at
ie
n
ts
In
te
rv
en
ti
on
3
0
(3

1.
6%
)
p
at
ie
n
ts
L
en
gt
h
o
f
h
os
p
it
al
s
ta
y
C
on

tr
ol
:
10
9.
3
h
(
95
%
C
I 8
7.
0
to
1
37
.3
)
In
te
rv
en
ti

on
9
9.
6
(9
5%
C
I 7
6.
59
t
o
12
9.
63
)
(C
on
ti
nu
ed
)

R
ef
er
en
ce
(c
ou
n
tr
y)
S
tu
d
y
d
es
ig
n
S
et

ti
n
g
N
u
m
b
er
o
f
p
at
ie
n
ts
In
te
rv
en
ti
on
t
yp
e

Ty
p
e
of
m
ed
ic
at
io
n
e
rr
or
a
n
al
ys
ed
(
m
et
h
od
o

f
d
at
a
co
ll
ec
ti
on
f
or
m
ed
ic
at
io
n
e
rr
or
s)
,
ef
fe

ct
o
f
in
te
rv
en
ti
on
o
n
m
ed
ic
at
io
n
e
rr
or
r
at
e
T

on
g
et
a
l.2
6
(A
u
st
ra
li
a)
U
n
b
li
n
d
ed
, c
lu
st
er

ra
n
d
om
is
ed
,
co
n
tr
ol
le
d
s
tu
d
y
G
en
er
al
m
ed
ic

al
u
n
it
o
f
an
a
d
u
lt
m
aj
or
r
ef
er
ra
l
h
os
p

it
al
43
1
(c
on
tr
ol
),
4
01
(i
n
te
rv
en
ti
on
)
P
h
ar
m

ac
is
t-
le
d
m
ed
ic
at
io
n
re
co
n
ci
li
at
io
n
(P
L
-M

R
)
P
at
ie
n
ts
’ d
is
ch
ar
ge
s
u
m
m
ar
ie
s
w
it
h
a
t

le
as
t
on
e
m
ed
ic
at
io
n
e
rr
or
(
p
re
sc
ri
b
in
g
er
ro

rs
)
(d
is
ch
ar
ge
s
u
m
m
ar
y)
C
on
tr
ol
:
26
5/
43
1
p
at

ie
n
ts
(
61
.5
%
)
In
te
rv
en
ti
on
:
60
/4
01
p
at
ie
n
ts
(

15
%
),
p
<
0
.0
1
S
ev
er
it
y
of
e
rr
or
s
C
on
tr
ol
:
in

si
gn
if
ic
an
t
50
(
18
.9
%
),
l
ow
8
6
(3
2.
5%
),
m
od
er
at

e
81
(
30
.6
%
)
h
ig
h
3
6
(1
3.
6%
),
ex
tr
em
e
12
(
4.

5%
)
In
te
rv
en
ti
on
:
in
si
gn
if
ic
an
t
20
(
33
%
),
l
ow
2

2
(3
7%
),
m
od
er
at
e
12
(
20
%
),
h
ig
h
5
(
8%
),
ex
tr

em
e
1
(2
%
),
p
<
0
.0
1
IT
-M
R
A
ll
is
on
e
t
al
.2
7

(U
S
)
R
et
ro
sp
ec
ti
ve
m
ed
ic
al
c
h
ar
t
re
vi
ew
o
f

p
re
-p
os
t
in
te
rv
en
ti
on
M
ed
ic
al
s
et
ti
n
gs
o
f
a
te

rt
ia
ry
h
os
p
it
al
10
0
(p
re
-
in
te
rv
en
ti
on
),
1
00
(p

os
t-
in
te
rv
en
ti
on
)
E
le
ct
ro
n
ic
d
is
ch
ar
ge
m
ed

ic
at
io
n
re
co
n
ci
li
at
io
n
t
oo
l
(I
T
-M
R
)
P
at
ie

n
ts
w
it
h
a
t
le
as
t
on
e
d
is
ch
ar
ge
a
n
ti
b
io
ti
c

m
ed
ic
at
io
n
e
rr
or
(
p
re
sc
ri
b
in
g
er
ro
r)
(c
h
ar

t
re
vi
ew
)
P
re
-i
n
te
rv
en
ti
on
:
23
/1
00
p
at
ie
n
ts
P

os
t-
in
te
rv
en
ti
on
:
11
/1
00
p
at
ie
n
ts
N
o
p-
va
lu
e
re

p
or
te
d
T
ot
al
n
u
m
b
er
o
f
d
is
ch
ar
ge
m
ed
ic
at
io

n
e
rr
or
s
P
re
-i
n
te
rv
en
ti
on
:
30
/4
5
to
ta
l
n
u
m

b
er
o
f
er
ro
rs
P
os
t-
in
te
rv
en
ti
on
:
15
/4
5
to
ta
l
n

u
m
b
er
o
f
er
ro
rs
N
o
p-
va
lu
e
re
p
or
te
d
S
m
it
h

e
t
al
.2
8
(U
S
)
P
re
–p
os
t
q
u
as
i-
ex
p
er
im
en
ta
l

st
u
d
y
G
en
er
al
m
ed
ic
in
e,
ge
ri
at
ri
cs
,
ca
rd
io
lo

gy
in
p
at
ie
n
ts
31
7
(p
re
-
in
te
rv
en
ti
on
),
2
43
(p

os
t-
in
te
rv
en
ti
on
)
IT
-M
R
D
is
ch
ar
ge
m
ed
ic
at
io
n

e
rr
or
s
(p
re
sc
ri
b
in
g
er
ro
rs
)
(e
le
ct
ro
n
ic
m
ed
ic

al
r
ec
or
d
a
n
d
c
h
ar
t
re
vi
ew
)
P
re
-i
n
te
rv
en
ti

on
:
64
5
er
ro
rs
/3
49
0
m
ed
ic
at
io
n
v
ar
ia
n
ce
P
os
t-

in
te
rv
en
ti
on
:
35
9
er
ro
rs
/2
82
3
m
ed
ic
at
io
n
v
ar
ia

n
ce
, p
<
0
.0
01
C
li
n
ic
al
ly
im
p
or
ta
n
t
m
ed
ic
at
io

n
e
rr
or
s
(w
it
h
p
ot
en
ti
al
f
or
s
er
io
u
s
or
l
if
e-

th
re
at
en
in
g
h
ar
m
)
P
re
-i
n
te
rv
en
ti
on
:
9/
64
5
er

ro
rs
(
1.
4%
)
P
os
t-
in
te
rv
en
ti
on
:
11
/3
59
e
rr
or
s
(3

.1
%
),
p
=
0
.1
0
M
ed
ic
at
io
n
r
ec
on
ci
li
at
io
n
b
y

tr
ai
n
ed
m
en
to
rs
S
ch
n
ip
p
er
e
t
al
.2
9
(U
S
)
Q
u

al
it
y
im
p
ro
ve
m
en
t
st
u
d
y
M
ed
ic
al
o
r
su
rg
ic
al

u
n
it
s
ac
ro
ss
5
h
os
p
it
al
s,
n
o
co
n
tr
ol
u
n

it
s
at
h
os
p
it
al
s
it
es
4
a
n
d
5,
n
o
in
te
rv
en

ti
on
u
n
it
s
at
h
os
p
it
al
si
te
1
85
7
(c
on
tr
ol
),

7
91
(i
n
te
rv
en
ti
on
)
L
oc
al
im
p
le
m
en
ta
ti
on

of
m
ed
ic
at
io
n
re
co
n
ci
li
at
io
n
b
es
t
p
ra
ct
ic
es

P
ot
en
ti
al
ly
h
ar
m
fu
l
d
is
cr
ep
an
ci
es
in
a
d
m
is
si

on
a
n
d
d
is
ch
ar
ge
o
rd
er
s
p
er
p
at
ie
n
t
(c
h
ar
t

re
vi
ew
)
R
es
u
lt
s
re
p
or
te
d
a
s
m
ea
n
n
u
m
b
er

o
f
er
ro
rs
p
er
p
at
ie
n
t
S
it
e
1:
d
id
n
ot
im
p
le
m

en
t
th
e
in
te
rv
en
ti
on
.
S
it
e
2:
C
on
tr
ol
u
n
it
s
P

re
-i
m
p
le
m
en
ta
ti
on
:
0.
98
P
os
t-
im
p
le
m
en
ta
ti
on

:
1.
32
In
te
rv
en
ti
on
u
n
it
s
P
re
-i
m
p
le
m
en
ta
ti
on

:
1.
00
P
os
t-
im
p
le
m
en
ta
ti
on
:
0.
88
S
it
e
3
C
on
tr

ol
u
n
it
s
P
re
-i
m
p
le
m
en
ta
ti
on
:
0.
17
P
os
t-
im
p

le
m
en
ta
ti
on
:
0.
23
In
te
rv
en
ti
on
u
n
it
s
P
re
-i
m
p

le
m
en
ta
ti
on
:
0.
30
P
os
t-
im
p
le
m
en
ta
ti
on
:
0.
18
S

it
e
4
an
d
s
it
e
5:
d
id
n
ot
h
av
e
co
n
tr
ol
u
n
it
s

at
b
as
el
in
e.
N
o
p-
va
lu
e
re
p
or
te
d
Ta
b
le
1
. (
C

on
ti
n
u
ed
)
(C
on
ti
nu
ed
)
R
ef
er
en
ce
(c
ou

n
tr
y)
S
tu
d
y
d
es
ig
n
S
et
ti
n
g
N
u
m
b
er
o
f
p

at
ie
n
ts
In
te
rv
en
ti
on
t
yp
e
Ty
p
e
of
m
ed
ic
at
io
n
e

rr
or
a
n
al
ys
ed
(
m
et
h
od
o
f
d
at
a
co
ll
ec
ti
on
f
or

m
ed
ic
at
io
n
e
rr
or
s)
,
ef
fe
ct
o
f
in
te
rv
en
ti
on
o
n

m
ed
ic
at
io
n
e
rr
or
r
at
e
C
D
S
S
H
er
n
an
d
ez
e
t

al
.3
0
(F
ra
n
ce
)
B
ef
or
e
an
d
a
ft
er
ob
se
rv
at
io
n

al
s
tu
d
y
66
-b
ed
o
rt
h
op
ae
d
ic
su
rg
er
y
u
n
it
o

f
a
70
0-
b
ed
t
ea
ch
in
g
h
os
p
it
al
11
1
(p
re
-C
P
O
E

),
8
6
p
at
ie
n
ts
(
p
os
t-
C
P
O
E
)
C
P
O
E
w
it

h
a
le
rt
s
fo
r
d
ru
g-
al
le
rg
y
ch
ec
ki
n
g,
th
er
ap
eu

ti
c
d
u
p
li
ca
ti
on
s,
d
os
e-
ra
n
ge
a
n
d
a
ge
-
b
as

ed
c
h
ec
ki
n
g,
an
d
d
ru
g–
d
ru
g
in
te
ra
ct
io
n
s.
N

o
m
en
ti
on
o
f
C
D
S
S
P
re
sc
ri
b
in
g
er
ro
rs
(
d
ir

ec
t
d
is
gu
is
ed
o
b
se
rv
at
io
n
)
P
re
-i
n
te
rv
en
ti
on

:
47
9/
15
93
p
re
sc
ri
b
ed
d
ru
gs
(
30
.1
%
)
P
os
t-
in
te

rv
en
ti
on
:
33
/1
38
8
p
re
sc
ri
b
ed
d
ru
gs
(
2.
4%
),
p
<

0
.0
00
1
D
is
p
en
si
n
g
er
ro
rs
P
re
-i
n
te
rv
en
ti
on
:

43
0/
12
19
o
p
p
or
tu
n
it
ie
s
(3
5.
3%
)
P
os
t-
in
te
rv
en

ti
on
:
44
9/
14
07
o
p
p
or
tu
n
it
ie
s
(3
1.
9%
),
p
=
0
.0

7
A
d
m
in
is
tr
at
io
n
e
rr
or
s
P
re
-i
n
te
rv
en
ti
on
:

20
9/
12
22
o
p
p
or
tu
n
it
ie
s
(1
7.
1%
)
P
os
t-
in
te
rv
en

ti
on
:
20
0/
14
13
o
p
p
or
tu
n
it
ie
s
(1
4.
2%
),
p
<
0
.0

5
M
il
an
i e
t
al
.3
1
(U
S
)
P
ro
sp
ec
ti
ve
in
te
rv
en
ti

on
P
at
ie
n
ts
w
it
h
ch
ro
n
ic
k
id
n
ey
d
is
ea
se
a

d
m
it
te
d
w
it
h
a
cu
te
c
or
on
ar
y
sy
n
d
ro
m
e
to

m
ed
ic
al
w
ar
d
33
(
in
te
rv
en
ti
on
),
47
(
co
n
tr
ol

)
C
P
O
E
w
it
h
al
er
ts
a
n
d
C
D
S
S
fo
r
ch
oi

ce
o
f
m
ed
ic
at
io
n
, d
ru
g
d
os
in
g
b
as
ed
o
n
cl
in

ic
al
r
is
k,
p
at
ie
n
t
w
ei
gh
t,
c
al
cu
la
te
d
cr
ea
ti

n
in
e
cl
ea
ra
n
ce
a
n
d
co
n
se
n
su
s
gu
id
el
in
es

A
d
ve
rs
e
d
ru
g
ev
en
ts
(
C
h
ar
t
re
vi
ew
)
C
on
tr
ai

n
d
ic
at
ed
m
ed
ic
at
io
n
s
C
on
tr
ol
:
8/
47
p
at
ie
n
ts

(
17
%
)
In
te
rv
en
ti
on
:
0/
33
p
at
ie
n
ts
(
0%
),
p
=
0

.0
1
In
-h
os
p
it
al
b
le
ed
in
g
C
on
tr
ol
:
10
/4
7
p
at
ie

n
ts
In
te
rv
en
ti
on
:
3/
33
p
at
ie
n
ts
, p
=
0
.1
2
90
-d
ay

m
or
ta
li
ty
C
on
tr
ol
7
(
15
%
),
In
te
rv
en
ti
on
4
(
12
%

),
p
=
0
.5
0
L
en
gt
h
o
f
st
ay
C
on
tr
ol
m
ea
n
9
.1
, S

D
1
0.
2
In
te
rv
en
ti
on
m
ea
n
4
.8
, S
D
4
.0
, p
=
0
.0
1

P
et
ti
t
et
a
l.3
2
(U
S
)
R
et
ro
sp
ec
ti
ve
si
n
gl
e
ce

n
tr
e,
p
re
-
p
os
t
in
te
rv
en
ti
on
st
u
d
y
P
at
ie
n

ts
a
d
m
it
te
d
to
a
8
11
-b
ed
ac
ad
em
ic
m
ed
ic
al

c
en
tr
e
w
h
o
co
n
ti
n
u
ed
on
a
n
ti
re
tr
ov
ir
al

th
er
ap
y
16
7
(p
re
-
in
te
rv
en
ti
on
),
1
31
(p
os
t-
in
te

rv
en
ti
on
)
C
P
O
E
w
it
h
a
le
rt
s
to
d
ru
g-
in
te
ra

ct
io
n
s
an
d
in
fo
rm
at
io
n
on
m
ed
ic
at
io
n
gu
id
el

in
es
. N
o
m
en
ti
on
o
f
C
D
S
S
P
re
sc
ri
b
in
g
er
ro
rs

(
ch
ar
t
re
vi
ew
)
P
re
-i
n
te
rv
en
ti
on
:
84
/1
67
p
at
ie

n
ts
(
50
.2
%
)
P
os
t-
in
te
rv
en
ti
on
:
37
/1
31
p
at
ie
n

ts
(
28
.2
%
),
p
<
0
.0
1
S
h
aw
ah
n
a
et
a
l.3
3
(P
ak

is
ta
n
)
P
ro
sp
ec
ti
ve
r
ev
ie
w
st
u
d
y
V
ar
io
u
s

w
ar
d
s
of
h
os
p
it
al
, t
h
re
e
m
ed
ic
al
w
ar
d
s
in

o
n
e
te
ac
h
in
g
h
os
p
it
al
N
ot
a
va
il
ab
le
P
ap
er
b

as
ed
ve
rs
us
e
le
ct
ro
n
ic
p
re
sc
ri
b
in
g
w
it
h

n
o
al
er
ts
o
r
C
D
S
S
su
ch
a
s
ch
ec
ks
o
n
d
ru

g
in
te
ra
ct
io
n
s
or
a
ll
er
gi
es
P
re
sc
ri
b
in
g
er
ro
rs

(
ch
ar
t
re
vi
ew
)
(n
o
n
u
m
er
at
or
o
r
d
en
om
in
at
or

p
ro
vi
d
ed
f
or
m
ed
ic
al
w
ar
d
s)
P
re
sc
ri
p
ti
on
e

rr
or
s
in
m
ed
ic
al
w
ar
d
1
C
on
tr
ol
:
19
.6
%
(
95
%
C

I 1
1.
0–
29
.3
)
In
te
rv
en
ti
on
:
8.
3%
(
95
%
C
I 7
.2
–8
.9
),

p
<
0
.0
5
P
re
sc
ri
p
ti
on
e
rr
or
s
in
m
ed
ic
al
w
ar
d

2
C
on
tr
ol
:
19
.6
%
(
95
%
C
I 1
3.
2–
24
.5
)
In
te
rv
en
ti

on
:
6.
3%
(
95
%
C
I 5
.2
–7
.1
),
p
<
0
.0
5
P
re
sc
ri
p
ti

on
e
rr
or
s
in
m
ed
ic
al
w
ar
d
3
C
on
tr
ol
:
25
.0
%
(
95

%
C
I 1
7.
0–
29
.7
)
In
te
rv
en
ti
on
:
6.
0%
(
95
%
C
I 2
.0
–8

.0
),
p
<
0
.0
5
S
ev
er
it
y
of
p
re
sc
ri
p
ti
on
e
rr
or
s

–
n
o
b
re
ak
d
ow
n
a
cc
or
d
in
g
to
m
ed
ic
al
w
ar
d
s

P
re
sc
ri
p
ti
on
e
rr
or
s
m
ad
e
b
u
t
n
o
cl
in
ic
al
c

on
se
q
u
en
ce
s
C
on
tr
ol
:
51
0/
30
08
t
ot
al
in
p
at
ie
n

t
p
re
sc
ri
p
ti
on
e
rr
or
s
(1
7.
0%
)
In
te
rv
en
ti
on
:
31

5/
11
47
t
ot
al
in
p
at
ie
n
t
p
re
sc
ri
p
ti
on
e
rr
or
s
(2

7.
5%
),
p
<
0
.0
1
P
re
sc
ri
p
ti
on
e
rr
or
s
m
ad
e
th
at

c
au
se
p
at
ie
n
t
h
ar
m
C
on
tr
ol
:
41
5/
30
08
t
ot
al
in

p
at
ie
n
t
p
re
sc
ri
p
ti
on
e
rr
or
s
(1
3.
8%
)
In
te
rv
en

ti
on
:
21
5/
11
47
t
ot
al
in
p
at
ie
n
t
p
re
sc
ri
p
ti
on
e

rr
or
s
(1
8.
7%
),
p
<
0
.0
1
P
re
sc
ri
p
ti
on
e
rr
or
s
m

ad
e
th
at
c
ou
ld
p
ot
en
ti
al
ly
r
es
u
lt
p
at
ie
n
t
d
ea

th
C
on
tr
ol
:
23
0/
30
08
t
ot
al
in
p
at
ie
n
t
p
re
sc
ri
p

ti
on
e
rr
or
s
(7
.6
%
)
In
te
rv
en
ti
on
:
17
0/
11
47
t
ot
al

in
p
at
ie
n
t
p
re
sc
ri
p
ti
on
e
rr
or
s
(1
4.
8%
),
p
<
0

.0
5
Ta
b
le
1
. (
C
on
ti
n
u
ed
)
(C
on
ti
nu
ed
)

R
ef
er
en
ce
(c
ou
n
tr
y)
S
tu
d
y
d
es
ig
n
S
et
ti
n

g
N
u
m
b
er
o
f
p
at
ie
n
ts
In
te
rv
en
ti
on
t
yp
e
Ty
p

e
of
m
ed
ic
at
io
n
e
rr
or
a
n
al
ys
ed
(
m
et
h
od
o
f
d

at
a
co
ll
ec
ti
on
f
or
m
ed
ic
at
io
n
e
rr
or
s)
,
ef
fe
ct
o

f
in
te
rv
en
ti
on
o
n
m
ed
ic
at
io
n
e
rr
or
r
at
e
va
n
D

oo
rm
aa
l
et
a
l.3
4
(T
h
e
N
et
h
er
la
n
d
s)
In
te
rr
u
p

te
d
t
im
e-
se
ri
es
d
es
ig
n
T
w
o
m
ed
ic
al
w
ar
d
s
of

a
u
n
iv
er
si
ty
h
os
p
it
al
a
n
d
t
w
o
m
ed
ic
al
w

ar
d
s
of
a
te
ac
h
in
g
h
os
p
it
al
59
2
(b
as
el
in
e)
60

3
(p
os
t-
in
te
rv
en
ti
on
)
C
P
O
E
w
it
h
al
er
ts
f

or
d
ru
g
in
te
ra
ct
io
n
s,
ov
er
d
os
es
a
n
d
al
le
rg

ie
s,
n
o
C
D
S
S
P
re
sc
ri
b
in
g
er
ro
rs
(
ch
ar
t
re
vi

ew
)
B
as
el
in
e:
5
72
4/
90
39
p
re
sc
ri
p
ti
on
s
(6
3.
3%
)

In
te
rv
en
ti
on
:
13
55
/7
21
0
p
re
sc
ri
p
ti
on
s
(1
8.
8%
),

p
<
0
.0
5
S
ev
er
e
ad
ve
rs
e
d
ru
g
ev
en
ts
:
B
as
el
in

e:
1
02
/9
03
9
(1
.1
%
)
In
te
rv
en
ti
on
5
4/
72
10
(
0.
7%
),

p
<
0
.0
5
P
P
G
ar
ci
a-
M
ol
in
a
S
ae
z
et
a
l.3
5
(S
p

ai
n
)
Q
u
as
i-
ex
pe
ri
m
en
ta
l
in
te
rr
u
p
te
d
t
im
e-

se
ri
es
s
tu
d
y
C
ar
di
o-
pn
eu
m
ol
og
y
u
n
it
o
f
ge
n

er
al
h
os
p
it
al
3
p
h
as
es
:
to
ta
l
32
1
p
at
ie
n
ts

P
re
-i
n
te
rv
en
ti
on
al
:
11
9
In
te
rv
en
ti
on
al
:
10
5
P

os
t-
in
te
rv
en
ti
on
al
:
97
P
P
R
ec
on
ci
li
at
io
n
e
rr

or
s
(s
tr
u
ct
u
re
d
in
te
rv
ie
w
w
it
h
p
at
ie
n
ts
o
r

fa
m
il
y)
P
re
-i
n
te
rv
en
ti
on
(
p
er
io
d
1
):
5
18
/1
08

7
to
ta
l
re
co
n
ci
li
at
io
n
e
rr
or
s
(4
7.
7%
)
In
te
rv
en

ti
on
(
p
er
io
d
2
):
1
88
/1
08
7
to
ta
l
re
co
n
ci
li
at
io

n
e
rr
or
s
(1
7.
3%
)
P
os
t-
in
te
rv
en
ti
on
(
p
er
io
d
3

):
3
81
/1
08
7
to
ta
l
re
co
n
ci
li
at
io
n
e
rr
or
s
(3
5.
1%

)
p
<
0
.0
01
b
et
w
ee
n
p
er
io
d
1
–2
a
n
d
2
–3
p
=
0.

28
8
b
et
w
ee
n
p
er
io
d
1
–3
S
ev
er
it
y
E
rr
or
o
cc
u

rr
ed
b
u
t
d
id
n
ot
r
ea
ch
p
at
ie
n
t
P
re
-i
n
te
rv
en

ti
on
:
27
3/
51
8
er
ro
rs
(
52
.7
%
)
P
os
t-
in
te
rv
en
ti
on

:
20
1/
38
1
er
ro
rs
(
52
.8
%
)
E
rr
or
o
cc
u
rr
ed
b
u
t

d
id
n
ot
c
au
se
p
at
ie
n
t
h
ar
m
P
re
-i
n
te
rv
en
ti
on

:
67
/5
18
e
rr
or
s
(1
2.
9%
)
P
os
t-
in
te
rv
en
ti
on
:
39
/3

81
e
rr
or
s
(1
0.
2%
)
E
rr
or
o
cc
u
rr
ed
a
n
d
r
eq
u
ir

ed
m
on
it
or
in
g
P
re
-i
n
te
rv
en
ti
on
:
12
0/
51
8
er
ro
rs

(
23
.2
%
)
P
os
t-
in
te
rv
en
ti
on
:
11
8/
38
1
er
ro
rs
(
31

.0
%
)
E
rr
or
r
eq
u
ir
ed
in
te
rv
en
ti
on
P
re
-i
n
te
rv
en

ti
on
:
55
/5
18
e
rr
or
s
(1
0.
6%
)
P
os
t-
in
te
rv
en
ti
on
:

19
/3
81
e
rr
or
s
(5
.0
%
)
E
rr
or
r
eq
u
ir
ed
h
os
p
it
al

is
at
io
n
P
re
-i
n
te
rv
en
ti
on
:3
/5
18
e
rr
or
s
(0
.6
%
)

P
os
t-
in
te
rv
en
ti
on
:
4/
38
1
er
ro
rs
(
1.
0%
)
N
o
p-
va

lu
e
re
p
or
te
d
H
as
sa
n
e
t
al
.3
6
(M
al
ay
si
a)
P
re

in
te
rv
en
ti
on
an
d
p
os
t
in
te
rv
en
ti
on
s
tu
d
y
35
-b

ed
n
ep
h
ro
lo
gy
u
n
it
30
0
(i
n
te
rv
en
ti
on
),
30
0

(c
on
tr
ol
)
P
P
S
u
sp
ec
te
d
A
D
E
s
(c
h
ar
t
re
vi
ew

a
n
d
w
ar
d
r
ou
n
d
p
ar
ti
ci
p
at
io
n
)
C
on
tr
ol
:

73
e
ve
n
ts
, 6
4
p
at
ie
n
ts
/3
00
p
at
ie
n
ts
In
te
rv
en
ti

on
:
49
e
ve
n
ts
, 4
8
p
at
ie
n
ts
/3
00
p
at
ie
n
ts
, p
<
0

.0
5
In
ap
p
ro
p
ri
at
e
m
ed
ic
at
io
n
C
on
tr
ol
:
32
2/
28

14
t
ot
al
p
re
sc
ri
p
ti
on
s
(1
1.
4%
)
In
te
rv
en
ti
on
:
17

6/
29
81
t
ot
al
p
re
sc
ri
p
ti
on
s
(5
.9
%
),
p
<
0
.0
01
S

ev
er
it
y
of
A
D
E
s
S
er
io
u
s
C
on
tr
ol
:
20
e
ve
n
ts

/3
00
p
at
ie
n
ts
In
te
rv
en
ti
on
:
5
ev
en
ts
/3
00
p
at
ie
n

ts
S
ig
n
if
ic
an
t
C
on
tr
ol
:
42
e
ve
n
ts
/3
00
p
at
ie
n

ts
In
te
rv
en
ti
on
:
36
e
ve
n
ts
/3
00
p
at
ie
n
ts
In
si
gn
if

ic
an
t
C
on
tr
ol
:
11
e
ve
n
ts
/3
00
p
at
ie
n
ts
In
te
rv
en

ti
on
:
8
ev
en
ts
/3
00
p
at
ie
n
ts
N
o
p-
va
lu
e
re
p
or
te

d
Ta
b
le
1
. (
C
on
ti
n
u
ed
)
(C
on
ti
nu
ed
)
R

ef
er
en
ce
(c
ou
n
tr
y)
S
tu
d
y
d
es
ig
n
S
et
ti
n
g
N

u
m
b
er
o
f
p
at
ie
n
ts
In
te
rv
en
ti
on
t
yp
e
Ty
p
e
of

m
ed
ic
at
io
n
e
rr
or
a
n
al
ys
ed
(
m
et
h
od
o
f
d
at
a

co
ll
ec
ti
on
f
or
m
ed
ic
at
io
n
e
rr
or
s)
,
ef
fe
ct
o
f
in

te
rv
en
ti
on
o
n
m
ed
ic
at
io
n
e
rr
or
r
at
e
L
ie
d
tk

e
et
a
l.3
7
(U
S
)
R
et
ro
sp
ec
ti
ve
ob
se
rv
at
io
n
al
s

tu
d
y
H
IV
-s
er
op
os
it
iv
e
p
at
ie
n
ts
a
d
m
it
te
d

to
a
l
ar
ge
t
ea
ch
in
g
h
os
p
it
al
T
ot
al
3
30
p
at
ie
n

t
ad
m
is
si
on
s:
P
re
-i
n
te
rv
en
ti
on
:
15
3
p
at
ie
n
t

ad
m
is
si
on
s
(9
6
p
at
ie
n
ts
)
In
te
rv
en
ti
on
:
17
7
p

at
ie
n
t
ad
m
is
si
on
s
(1
14
p
at
ie
n
ts
)
P
P
T
ot
al
n

u
m
b
er
o
f
p
re
sc
ri
b
in
g
er
ro
rs
(
su
m
o
f
th
e
ab

ov
e
n
u
m
b
er
s)
(
ch
ar
t
re
vi
ew
)
P
re
-i
n
te
rv
en
ti

on
:
85
e
rr
or
s/
33
0
ad
m
is
si
on
s
In
te
rv
en
ti
on
:
24
e

rr
or
s/
33
0
ad
m
is
si
on
s,
p
<
0
.0
01
P
E
G
u
rs
an
sc
ky

e
t
al
.3
8
(A
u
st
ra
li
a)
C
lu
st
er
r
an
d
om
is
ed
tr
ia

l
in
vo
lv
in
g
p
re
sc
ri
b
er
s
F
ou
r
ge
n
er
al
m
ed

ic
al
u
n
it
s
of
a
te
rt
ia
ry
h
os
p
it
al
In
te
rv
en
ti
on

o
n
d
oc
to
rs
:
12
in
te
rn
s,
4
re
gi
st
ra
rs
P
E
E
d

u
ca
ti
on
:
P
re
sc
ri
b
in
g
fe
ed
b
ac
k
an
d
ta
rg
et
ed

e
d
u
ca
ti
on
;
e-
le
ar
n
in
g
on
s
af
e-
p
re
sc
ri
b
in
g

P
re
sc
ri
b
in
g
er
ro
rs
(
ch
ar
t
re
vi
ew
)
C
on
tr
ol
:
B

as
el
in
e:
1
17
1
to
ta
l
er
ro
rs
/2
38
9
to
ta
l
m
ed
ic
at
io

n
o
rd
er
s
P
os
t-
in
te
rv
en
ti
on
:
16
30
t
ot
al
e
rr
or
s/

27
71
t
ot
al
m
ed
ic
at
io
n
o
rd
er
s,
p
<
0
.0
01
P
h
ar
m

ac
is
t
ed
u
ca
ti
on
:
P
re
-i
n
te
rv
en
ti
on
:
62
1
to
ta
l

er
ro
rs
/1
07
4
to
ta
l
m
ed
ic
at
io
n
o
rd
er
s
(5
7.
8%
)
P

os
t-
in
te
rv
en
ti
on
:
49
3
to
ta
l
er
ro
rs
/1
33
3
to
ta
l
m

ed
ic
at
io
n
o
rd
er
s
(3
7.
0%
),
p
<
0
.0
01
E
-l
ea
rn
in
g:

P
re
-i
n
te
rv
en
ti
on
:
40
6
to
ta
l
er
ro
rs
/6
97
t
ot
al
m

ed
ic
at
io
n
o
rd
er
s
P
os
t-
in
te
rv
en
ti
on
:
88
2
to
ta
l

er
ro
rs
/1
39
3
to
ta
l
m
ed
ic
at
io
n
o
rd
er
s,
p
=
0
.0
25

R
at
es
o
f
cl
in
ic
al
ly
s
ig
n
if
ic
an
t
p
re
sc
ri
b
in
g

er
ro
rs
(
p
ot
en
ti
al
ly
l
et
h
al
, s
er
io
u
s,
s
ig
n
if
ic

an
t
er
ro
rs
)
C
on
tr
ol
:
B
as
el
in
e:
1
04
e
rr
or
s/
23
89

t
ot
al
m
ed
ic
at
io
n
o
rd
er
s
P
os
t-
in
te
rv
en
ti
on
:
16

6
er
ro
rs
/2
77
1
to
ta
l
m
ed
ic
at
io
n
o
rd
er
s,
p
<
0
.0

1
P
h
ar
m
ac
is
t
ed
u
ca
ti
on
:
B
as
el
in
e:
7
0
er
ro
rs

/1
07
4
to
ta
l
m
ed
ic
at
io
n
o
rd
er
s
(6
.5
2%
)
P
os
t-
in

te
rv
en
ti
on
:
64
e
rr
or
s/
13
33
t
ot
al
m
ed
ic
at
io
n
o
rd

er
s
(4
.8
0%
),
p
=
0
.0
68
E
-l
ea
rn
in
g:
B
as
el
in
e:
4
2

er
ro
rs
/6
97
t
ot
al
m
ed
ic
at
io
n
o
rd
er
s
P
os
t-
in
te
rv

en
ti
on
:
83
e
rr
or
s/
13
93
t
ot
al
m
ed
ic
at
io
n
o
rd
er
s,

p
=
0
.9
51
P
T
E
W
ei
n
ga
rt
e
t
al
.3
9
(U
S
)
P
ro
sp

ec
ti
ve
ra
n
d
om
is
ed
,
co
n
tr
ol
le
d
p
il
ot
tr
ia
l

40
-b
ed
g
en
er
al
m
ed
ic
in
e
u
n
it
o
f
a
B
os
to
n
t

ea
ch
in
g
h
os
p
it
al
10
7
(i
n
te
rv
en
ti
on
),
10
2
(c

on
tr
ol
)
P
T
E
A
D
E
s
(c
h
ar
t
re
vi
ew
)
C
on
tr
ol
:

3/
10
2
to
ta
l
n
u
m
b
er
o
f
p
at
ie
n
ts
(
2.
9%
)
In
te

rv
en
ti
on
:
8/
10
7
to
ta
l
n
u
m
b
er
o
f
p
at
ie
n
ts
(

7.
5%
),
p
=
0
.2
2
S
ev
er
it
y
L
if
e
th
re
at
en
in
g
C
on

tr
ol
:
0
ev
en
ts
/1
02
p
at
ie
n
ts
In
te
rv
en
ti
on
:
2
ev
en

ts
/1
07
p
at
ie
n
ts
S
er
io
u
s
C
on
tr
ol
:
0
ev
en
ts
/1
02

p
at
ie
n
ts
In
te
rv
en
ti
on
:
3
ev
en
ts
/1
07
p
at
ie
n
ts
S

ig
n
if
ic
an
t
C
on
tr
ol
:
3
ev
en
ts
/1
02
p
at
ie
n
ts
In
te

rv
en
ti
on
:
3
ev
en
ts
/1
07
p
at
ie
n
ts
L
it
tl
e
or
n
on
e

C
on
tr
ol
:
0
ev
en
ts
/1
02
p
at
ie
n
ts
In
te
rv
en
ti
on
:
0

ev
en
ts
/1
07
p
at
ie
n
ts
, p
=
0
.0
9
Ta
b
le
1
. (
C
on
ti
n

u
ed
)
(C
on
ti
nu
ed
)
R
ef
er
en
ce
(c
ou
n
tr

y)
S
tu
d
y
d
es
ig
n
S
et
ti
n
g
N
u
m
b
er
o
f
p
at
ie

n
ts
In
te
rv
en
ti
on
t
yp
e
Ty
p
e
of
m
ed
ic
at
io
n
e
rr
or

a
n
al
ys
ed
(
m
et
h
od
o
f
d
at
a
co
ll
ec
ti
on
f
or
m
ed

ic
at
io
n
e
rr
or
s)
,
ef
fe
ct
o
f
in
te
rv
en
ti
on
o
n
m
ed

ic
at
io
n
e
rr
or
r
at
e
T
M
E
B
aq
ir
e
t
al
.4
0
(U
K
)

Q
u
as
i-
ex
pe
ri
m
en
ta
l
st
u
d
y
O
n
e
ac
u
te
s
u
rg

ic
al
an
d
o
n
e
ac
u
te
m
ed
ic
al
w
ar
d
a
t
a
d
is

tr
ic
t
ge
n
er
al
h
os
p
it
al
18
1
(i
n
te
rv
en
ti
on
),

23
0
(i
n
tr
a-
w
ar
d
co
n
tr
ol
),
3
69
(
in
te
r-
w
ar
d

c
on
tr
ol
)
T
M
E
P
at
ie
n
t
w
it
h
a
t
le
as
t
on
e
u

n
ac
ce
p
ta
b
le
o
m
it
te
d
d
os
e
(a
d
m
in
is
tr
at
io
n

e
rr
or
s)
(
ch
ar
t
re
vi
ew
)
In
te
r-
w
ar
d
c
on
tr
ol
:
68

/3
69
p
at
ie
n
ts
(
18
.5
%
)
In
te
rv
en
ti
on
:
2/
18
1
p
at

ie
n
ts
(
1.
1%
),
p
<
0
.0
00
1
C
ri
ti
ca
l
u
n
ac
ce
p
ta

b
le
o
m
it
te
d
d
os
e
In
te
r-
w
ar
d
c
on
tr
ol
:
51
/3
69

(
13
.8
%
)
In
te
rv
en
ti
on
:
2/
18
1
(1
.1
%
),
p
=
0
.0
3

G
re
en
go
ld
e
t
al
.4
1
(U
S
)
R
an
d
om
is
ed
, d
ir
ec
t
ob

se
rv
at
io
n
s
tu
d
y
M
ed
ic
al
a
n
d
su
rg
ic
al
u
n
it

s
of
a
n
a
ca
d
em
ic
co
m
m
u
n
it
y
h
os
p
it
al
an

d
a
u
n
iv
er
si
ty
te
ac
h
in
g
h
os
p
it
al
T
ot
al
n

u
m
b
er
o
f
n
u
rs
es
:
M
ed
ic
at
io
n
n
u
rs
es
:
10 G
en

er
al
n
u
rs
es
:
18
T
M
E
M
ed
ic
at
io
n
a
d
m
in
is
tr
at

io
n
e
rr
or
s
(o
b
se
rv
at
io
n
)
C
on
tr
ol
:
54
5/
36
61
o

p
p
or
tu
n
it
ie
s
fo
r
er
ro
r
(1
4.
9%
)
In
te
rv
en
ti
on
:

91
2/
57
92
o
p
p
or
tu
n
it
ie
s
fo
r
er
ro
r
(1
5.
7%
),
p
<

0
.8
4
N
o
kn
ow
n
p
at
ie
n
t
h
ar
m
o
r
d
ea
th
d
u
ri

n
g
st
u
d
y
p
er
io
d
s
(d
at
a
w
er
e
n
ot
s
h
ow
n
)

N
gu
ye
n
e
t
al
.4
2
(U
S
)
P
ro
ce
ss
im
p
ro
ve
m
en
t

st
u
d
y
O
n
e
m
ed
ic
al
-
su
rg
ic
al
w
ar
d
in
ac
ad
em

ic
t
ea
ch
in
g
h
os
p
it
al
T
ot
al
n
u
m
b
er
o
f
n
u
rs

es
:
45
T
M
E
-
T
ea
ch
in
g
n
u
rs
es
to
u
n
d
er
ta
ke

m
ed
ic
at
io
n
p
as
s
ti
m
e
ou
t
M
ed
ic
at
io
n
a
d
m

in
is
tr
at
io
n
e
rr
or
s
(o
b
se
rv
at
io
n
)
P
re
-i
n
te
rv

en
ti
on
:
2
er
ro
rs
/1
00
a
d
m
in
is
te
re
d
m
ed
ic
at
io
n

s
P
os
t-
in
te
rv
en
ti
on
:
0
er
ro
rs
/1
00
a
d
m
in
is
te
re

d
m
ed
ic
at
io
n
s,
p
v
al
u
e
n
ot
s
ta
te
d
S
ch
n
ei
d

er
e
t
al
.4
3
(U
S
)
R
an
d
om
is
ed
,
co
n
tr
ol
le
d
, n
on

-
b
li
n
d
ed
s
tu
d
y
M
ed
ic
al
o
r
m
ed
ic
al
-s
u
rg
ic

al
u
n
it
s
of
t
h
re
e
u
n
iv
er
si
ty
h
os
p
it
al
s

T
ot
al
n
u
m
b
er
of
n
u
rs
es
:
30
,
as
si
gn
ed
t
o
ei

th
er
c
on
tr
ol
o
r
in
te
rv
en
ti
on
g
ro
u
p
.
T
M
E
–
C

D
-R
O
M
t
o
n
u
rs
es
M
ed
ic
at
io
n
a
d
m
in
is
tr
at
io

n
e
rr
or
r
at
e
(i
n
co
rr
ec
t
ti
m
e,
d
os
e
p
re
p
ar
at

io
n
a
n
d
t
ec
h
n
iq
u
e)
(o
b
se
rv
at
io
n
):
C
on
tr

ol
(
p
re
):
2
9/
26
6
(1
0.
9%
)
C
on
tr
ol
(
p
os
t)
:
25
/2

84
(
8.
8%
)
In
te
rv
en
ti
on
(
p
re
):
1
6/
30
1
(5
.3
%
)
In

te
rv
en
ti
on
(
p
os
t)
:
41
/2
85
(
14
.4
%
)
O
d
d
s
ra
ti

o:
1
.9
2
(9
5%
C
I 0
.8
1–
4.
58
),
p
=
0
.1
4
M
D
D
ea
n
a

n
d
B
ar
b
er
44
(U
K
)
P
ro
sp
ec
ti
ve
ob
se
rv
at
io
n

al
,
b
ef
or
e
an
d
a
ft
er
st
u
d
y
M
ed
ic
al
w
ar
d
a

n
d
su
rg
ic
al
w
ar
d
o
f
te
ac
h
in
g
h
os
p
it
al
23
p

at
ie
n
ts
(s
u
rg
ic
al
w
ar
d
)
21
p
at
ie
n
ts
(m
ed
ic

al
w
ar
d
)
P
at
ie
n
ts
b
ri
n
gi
n
g
in
o
w
n
m
ed
ic

at
io
n
s
ve
rs
us
t
ra
d
it
io
n
al
p
h
ar
m
ac
y
su
p
p

ly
A
d
m
in
is
tr
at
io
n
e
rr
or
s
(o
b
se
rv
at
io
n
):
S
u

rg
ic
al
w
ar
d
:
T
ra
d
it
io
n
al
:
66
e
rr
or
s/
15
10
o
p

p
or
tu
n
it
ie
s
(4
.4
%
)
In
te
rv
en
ti
on
:
64
e
rr
or
s/
12

79
o
p
p
or
tu
n
it
ie
s
(5
.0
%
)
M
ed
ic
al
w
ar
d
:
T
ra

d
it
io
n
al
:
86
e
rr
or
s/
20
66
o
p
p
or
tu
n
it
ie
s
(4
.2

%
)
In
te
rv
en
ti
on
:
41
e
rr
or
s/
12
12
o
p
p
or
tu
n
it
ie

s
(3
.4
%
)
O
ve
ra
ll
a
d
m
in
is
tr
at
io
n
e
rr
or
s:
T
ra

d
it
io
n
al
:
15
2
er
ro
rs
/3
57
6
op
p
or
tu
n
it
ie
s
4.
3%

In
te
rv
en
ti
on
:
10
5
er
ro
rs
/2
49
1
op
p
or
tu
n
it
ie
s
4.

2%
, p
=
0
.9
9
S
ev
er
it
y
sc
or
e
(0
–1
0,
<
3
m
in
or
, 3
–7

m
od
er
at
e,
>
7
se
ve
re
)
S
u
rg
ic
al
w
ar
d
s
C
on
tr
ol

:
M
ea
n
1
.8
(
S
D
1
.1
)
In
te
rv
en
ti
on
:
M
ea
n
1
.8

(
S
D
1
.1
),
M
ed
ic
al
w
ar
d
s
C
on
tr
ol
:
M
ea
n
1
.9

(
S
D
1
.1
)
In
te
rv
en
ti
on
:
M
ea
n
1
.9
(
1.
0)
, p
=
0

.4
1
Ta
b
le
1
. (
C
on
ti
n
u
ed
)
(C
on
ti
nu
ed
)

R
ef
er
en
ce
(c
ou
n
tr
y)
S
tu
d
y
d
es
ig
n
S
et
ti
n

f
in
te
rv
en
ti
on
o
n
m
ed
ic
at
io
n
e
rr
or
r
at
e
S
ch
im

m
el
e
t
al
.4
5
(T
h
e
N
et
h
er
la
n
d
s)
P
ro
sp
ec
ti
ve

ob
se
rv
at
io
n
al
b
ef
or
e
an
d
a
ft
er
st
u
d
y
30

-b
ed
o
rt
h
op
ae
d
ic
w
ar
d
in
a
u
n
iv
er
si
ty
m
ed

ic
al
c
en
tr
e
45
(
p
re
-
in
te
rv
en
ti
on
),
4
6
(p
os
t-
in

te
rv
en
ti
on
)
M
D
M
ed
ic
at
io
n
a
d
m
in
is
tr
at
io
n
e

rr
or
s
(o
b
se
rv
at
io
n
)
P
re
-i
n
te
rv
en
ti
on
:
11
4
er

ro
rs
/5
89
t
ot
al
o
b
se
rv
ed
m
ed
ic
at
io
n
a
d
m
in
is
tr

at
io
n
(
19
.4
%
)
P
os
t-
in
te
rv
en
ti
on
:
17
0
er
ro
rs
/7

40
t
ot
al
o
b
se
rv
ed
m
ed
ic
at
io
n
a
d
m
in
is
tr
at
io
n

(
23
.0
%
)
O
d
d
s
ra
ti
o:
1
.2
4
(9
5%
C
I 0
.9
5–
1.
62
),

p
>
0
.0
5
D
D
±
e
M
A
R
C
ou
se
in
e
t
al
.4
6
(F
ra

n
ce
)
B
ef
or
e–
af
te
r
ob
se
rv
at
io
n
al
s
tu
d
y
40
-b
ed

s
h
or
t
st
ay
ge
ri
at
ri
c
u
n
it
w
it
h
in
a
18
00
b

ed
g
en
er
al
h
os
p
it
al
14
8
(p
re
-
in
te
rv
en
ti
on
),
1

66
(p
os
t
in
te
rv
en
ti
on
)
B
as
el
in
e:
w
ar
d
st
oc
k

sy
st
em
D
D
L
in
ki
n
g
w
it
h
o
r
w
it
h
ou
t
eM
A
R
A

d
m
in
is
tr
at
io
n
e
rr
or
r
at
es
(
ob
se
rv
at
io
n
)
P
re

-i
n
te
rv
en
ti
on
:
74
/6
15
o
p
p
or
tu
n
it
ie
s
of
e
rr
or

s
(1
0.
6%
)
P
os
t-
in
te
rv
en
ti
on
:
41
/7
83
o
p
p
or
tu
n

it
ie
s
of
e
rr
or
s
(5
.0
%
)
W
it
h
ou
t
eM
A
R
:
25
/3
78

o
p
p
or
tu
n
it
ie
s
of
e
rr
or
s
(5
.8
%
)
p
=
0.
02
W
it

h
e
M
A
R
:
16
/4
05
o
p
p
or
tu
n
it
ie
s
of
e
rr
or
s
(4

.1
%
)
p
=
0.
00
1
S
ev
er
it
y
of
e
rr
or
s
N
o
h
ar
m
C

on
tr
ol
:
21
.1
%
In
te
rv
en
ti
on
:
23
.2
%
M
in
im
u
m
h
ar

m
C
on
tr
ol
:
31
.7
%
In
te
rv
en
ti
on
:
32
.7
%
M
on
it
or
in

g
C
on
tr
ol
:
35
.0
%
In
te
rv
en
ti
on
:
33
.3
%
N
ee
d
f
or

in
te
rv
en
ti
on
C
on
tr
ol
:
12
.2
%
In
te
rv
en
ti
on
:
10
.7
%

, p
<
0
.0
1
C
om
b
in
at
io
n
o
f
tw
o
ty
p
es
o
f
in
te
rv

en
ti
on
s
C
an
n
e
t
al
.4
7
(A
u
st
ra
li
a)
P
re
–p
os
t
te

st
d
es
ig
n
29
-b
ed
a
cu
te
su
rg
ic
al
w
ar
d
at
t
er

ti
ar
y-
le
ve
l
re
gi
on
al
h
os
p
it
al
11
15
(
p
re
-
in
te

rv
en
ti
on
),
1
06
9
(p
os
t-
in
te
rv
en
ti
on
)
P
E
, P
P
M
ed

ic
at
io
n
e
rr
or
s
(d
id
n
ot
s
p
ec
if
y
w
h
ic
h
t
yp
e)

(
on
li
n
e
cl
in
ic
al
in
ci
d
en
t
re
p
or
ti
n
g)
P
re
-i
n

te
rv
en
ti
on
:
12
.0
e
rr
or
s/
10
0,
00
0
p
at
ie
n
t
h
ou
rs

P
os
t-
in
te
rv
en
ti
on
:
10
.9
e
rr
or
s/
10
0,
00
0
p
at
ie
n

t
h
ou
rs
, p
=
0
.8
35
P
at
ie
n
t
fa
ll
s
P
re
-i
n
te
rv
en

ti
on
:
13
.9
/1
00
,0
00
p
at
ie
n
t
h
ou
rs
P
os
t-
in
te
rv
en

ti
on
:
10
.9
/1
00
,0
00
p
at
ie
n
t
h
ou
rs
, p
=
0
.5
0
D
an

ie
ls
e
t
al
.4
8
(U
S
)
P
ro
sp
ec
ti
ve
in
te
rv
en
ti
on
H

IV
-i
n
fe
ct
ed
p
at
ie
n
ts
a
d
m
it
te
d
to
a
8
03
-b

ed
ac
ad
em
ic
m
ed
ic
al
ce
n
tr
e
78
(
in
te
rv
en
ti
on
),

68
(
co
n
tr
ol
)
P
E
, C
P
O
E
T
yp
es
o
f
er
ro
rs
(
in

p
at
ie
n
t
p
h
ar
m
ac
y
m
ed
ic
at
io
n
s
ys
te
m
)
P
re

sc
ri
b
in
g
er
ro
rs
:
C
on
tr
ol
:
62
/1
19
t
ot
al
e
rr
or
s

(5
2%
)
In
te
rv
en
ti
on
:
12
/1
7
to
ta
l
er
ro
rs
(
70
%
)
D

is
p
en
si
n
g
er
ro
rs
:
C
on
tr
ol
:
39
/1
19
t
ot
al
e
rr
or

s
(3
3%
)
In
te
rv
en
ti
on
:
4/
17
t
ot
al
e
rr
or
s
(2
4%
)
N

o
p-
va
lu
e
re
p
or
te
d
P
ot
en
ti
al
t
o
ca
u
se
m
od
er
at

e
or
s
ev
er
e
d
is
co
m
fo
rt
o
r
cl
in
ic
al
d
et
er
io
ra
ti

on
C
on
tr
ol
:
In
it
ia
l
re
gi
m
en
3
8/
68
(
56
%
),
D
u
ri

n
g
h
os
p
it
al
is
at
io
n
4
4/
68
(
65
%
)
In
te
rv
en
ti
on

:
In
it
ia
l
re
gi
m
en
1
2/
78
(
15
%
),
D
u
ri
n
g
h
os
p

it
al
is
at
io
n
1
7/
78
(
22
%
),
p
<
0
.0
00
1
G
im
en
ez

-M
an
zo
rr
o
et
a
l.4
9
(S
p
ai
n
)
P
re
–p
os
t
in
te
rv
en
ti

on
s
tu
d
y
w
it
h
n
o
eq
u
iv
al
en
t
co
n
tr
ol
g
ro
u
p

G
en
er
al
s
u
rg
er
y
d
ep
ar
tm
en
t
10
7
(p
re
-
in
te
rv
en

ti
on
),
8
4
(p
os
t-
in
te
rv
en
ti
on
)
C
P
O
E
, I
T
-M
R
U

n
in
te
n
d
ed
d
is
cr
ep
an
ci
es
(
p
re
sc
ri
b
in
g
er
ro
rs

)
(p
at
ie
n
t
in
te
rv
ie
w
)
P
re
-i
n
te
rv
en
ti
on
:
10
2

u
n
in
te
n
d
ed
d
is
cr
ep
an
ci
es
/8
87
t
ot
al
n
u
m
b
er

o
f
d
is
cr
ep
an
ci
es
(1
0.
6%
)
P
os
t-
in
te
rv
en
ti
on
:

65
u
n
in
te
n
d
ed
d
is
cr
ep
an
ci
es
/7
91
t
ot
al
n
u
m
b

er
o
f
d
is
cr
ep
an
ci
es
(6
.6
%
),
p
=
0
.0
02
Ta
b
le
1

. (
C
on
ti
n
u
ed
)
(C
on
ti
nu
ed
)
R
ef
er
en
ce

(c
ou
n
tr
y)
S
tu
d
y
d
es
ig
n
S
et
ti
n
g
N
u
m
b
er

o
f
p
at
ie
n
ts
In
te
rv
en
ti
on
t
yp
e
Ty
p
e
of
m
ed
ic
at

io
n
e
rr
or
a
n
al
ys
ed
(
m
et
h
od
o
f
d
at
a
co
ll
ec
ti

on
f
or
m
ed
ic
at
io
n
e
rr
or
s)
,
ef
fe
ct
o
f
in
te
rv
en
ti

on
o
n
m
ed
ic
at
io
n
e
rr
or
r
at
e
G
ri
m
es
e
t
al
.5
0

(I
re
la
n
d
)
U
n
co
n
tr
ol
le
d
b
ef
or
e–
af
te
r
st
u

d
y
F
ou
r
ac
u
te
m
ed
ic
al
ca
re
w
ar
d
s
11
2
in
te
rv

en
ti
on
gr
ou
p
, 1
21
st
an
d
ar
d
P
L
-M
R
, P
P
E
rr
or

s
on
a
d
m
is
si
on
(
p
re
sc
ri
b
in
g
er
ro
rs
)
(p
re
-a
d

m
is
si
on
m
ed
ic
at
io
n
l
is
t,
c
h
ar
t
re
vi
ew
,
d
is
ch

ar
ge
m
ed
ic
at
io
n
l
is
t)
S
ta
n
d
ar
d
:
49
p
at
ie
n
ts

/1
21
t
ot
al
n
u
m
b
er
o
f
p
at
ie
n
ts
(
40
.5
%
)
In
te

rv
en
ti
on
:
10
p
at
ie
n
ts
/1
12
t
ot
al
n
u
m
b
er
o
f
p

at
ie
n
ts
(
9%
),
p
<
0
.0
00
1
E
rr
or
s
at
d
is
ch
ar
ge
(

p
re
sc
ri
b
in
g
er
ro
rs
)
S
ta
n
d
ar
d
:
66
p
at
ie
n
ts

/1
01
t
ot
al
n
u
m
b
er
o
f
p
at
ie
n
ts
(
65
.3
%
)
In
te

rv
en
ti
on
1
5
p
at
ie
n
ts
/1
08
t
ot
al
n
u
m
b
er
o
f
p

at
ie
n
ts
(
13
.9
%
),
p
<
0
.0
00
1
N
o
h
ar
m
S
ta
n
d

ar
d
:
35
(
34
.7
%
)
In
te
rv
en
ti
on
:
93
(
86
.1
%
)
M
in

or
h
ar
m
S
ta
n
d
ar
d
:
6
(5
.9
%
)
In
te
rv
en
ti
on
:
2

(1
.9
%
)
M
od
er
at
e
h
ar
m
S
ta
n
d
ar
d
:
54
(
53
.5
%

)
In
te
rv
en
ti
on
:
13
(
12
.0
%
)
S
ev
er
e
h
ar
m
S
ta
n

d
ar
d
:
6
(5
.9
%
)
In
te
rv
en
ti
on
:
0
(0
%
),
p
<
0
.0

01
Jh
ee
ta
e
t
al
.5
4
(U
K
)
In
te
rr
u
p
te
d
t
im
e
se
ri

es
, p
re
–p
os
t
in
te
rv
en
ti
on
s
tu
d
y
A
1
4-
b
ed
e
ld
er

ly
m
ed
ic
in
e
in
p
at
ie
n
t
w
ar
d
in
a
l
ar
ge
te
ac

h
in
g
h
os
p
it
al
86
(
p
re
-
in
te
rv
en
ti
on
),
8
6
(p
os

t-
in
te
rv
en
ti
on
)
C
P
O
E
+
e
le
ct
ro
n
ic
ad
m
in
s

ys
te
m
(
C
A
)
M
ed
ic
at
io
n
a
d
m
in
is
tr
at
io
n
e
rr

or
s
(o
b
se
rv
at
io
n
)
P
re
-i
n
te
rv
en
ti
on
:
18
/4
28
o

p
p
or
tu
n
it
ie
s
fo
r
er
ro
r
(4
.2
%
)
P
os
t-
in
te
rv
en

ti
on
:
18
/5
28
o
p
p
or
tu
n
it
ie
s
fo
r
er
ro
r
(3
.4
%
),

p
=
0
.6
4
D
oc
u
m
en
ta
ti
on
d
is
cr
ep
an
ci
es
P
re
-i
n

te
rv
en
ti
on
:
5/
46
0
ob
se
rv
ed
d
oc
u
m
en
ta
ti
on
s
(1
.1

%
)
P
os
t-
in
te
rv
en
ti
on
:
18
/5
57
o
b
se
rv
ed
d
oc
u
m

en
ta
ti
on
s
(3
.2
%
),
p
=
0
.0
4
M
ou
ra
e
t
al
.5
1
(B
ra

zi
l)
Q
u
as
i-
ex
pe
ri
m
en
ta
l
st
u
d
y
A
1
72
-b
ed
p

u
b
li
c
in
st
it
u
ti
on
p
ro
vi
d
in
g
p
ri
m
ar
y
an
d

t
er
ti
ar
y
ca
re
18
52
(
p
re
-
in
te
rv
en
ti
on
),
2
95

(i
n
te
rv
en
ti
on
)
C
P
O
E
, P
P
In
ci
d
en
ce
r
at
e
of
a

ll
d
ru
g-
d
ru
g
in
te
ra
ct
io
n
s
(c
h
ar
t
re
vi
ew
)
P
re

-i
n
te
rv
en
ti
on
:
27
.5
/1
00
0
p
at
ie
n
t
d
ay
s
In
te
rv

en
ti
on
:
13
.2
/1
00
0
p
at
ie
n
t
d
ay
s,
r
el
at
iv
e
ri
sk

=
0
.4
8
(0
.4
4–
0.
52
)
In
ci
d
en
ce
r
at
e
of
h
ig
h
-s
ev

er
it
y
d
ru
g-
d
ru
g
in
te
ra
ct
io
n
s:
P
re
-i
n
te
rv
en
ti

on
:
8.
20
/1
00
0
p
at
ie
n
t
d
ay
s
In
te
rv
en
ti
on
:
1.
36

/1
00
0
p
at
ie
n
t
d
ay
s,
r
el
at
iv
e
ri
sk
=
0
.1
7
(0
.1

3–
0.
21
)
S
h
ea
e
t
al
.5
2
(U
S
)
R
et
ro
sp
ec
ti
ve
co

m
p
ar
at
iv
e
co
h
or
t
st
u
d
y
H
IV
-i
n
fe
ct
ed
p
at

ie
n
ts
a
d
m
it
te
d
to
a
2
44
-b
ed
u
rb
an
ac
ad
em
ic

m
ed
ic
al
ce
n
tr
e
T
ot
al
2
34
p
at
ie
n
t
ad
m
is
si
on

s
P
re
-i
n
te
rv
en
ti
on
:
12
6
P
os
t-
in
te
rv
en
ti
on
:
10

8
P
E
, P
L
-M
R
P
at
ie
n
t
ad
m
is
si
on
s
w
it
h
p
re
sc

ri
b
in
g
er
ro
rs
(
ch
ar
t
re
vi
ew
)
S
u
m
o
f
in
co
rr
ec

t/
in
co
m
p
le
te
m
ed
ic
at
io
n
r
eg
im
en
, i
n
co
rr
ec
t
d

os
ag
e
re
gi
m
en
, i
n
co
rr
ec
t
re
n
al
d
os
e
ad
ju
st
m
en

t,
m
aj
or
d
ru
g
in
te
ra
ct
io
n
P
re
-i
n
te
rv
en
ti
on
:
73

/1
26
t
ot
al
a
d
m
is
si
on
P
os
t-
in
te
rv
en
ti
on
:
10
/1
08

t
ot
al
a
d
m
is
si
on
P
at
ie
n
t
ad
m
is
si
on
s
w
it
h
m

ed
ic
at
io
n
e
rr
or
t
yp
es
In
co
rr
ec
t/
in
co
m
p
le
te
m
ed

ic
at
io
n
r
eg
im
en
P
re
-i
n
te
rv
en
ti
on
:
15
/1
26
t
ot
al

a
d
m
is
si
on
(
11
.9
%
)
P
os
t-
in
te
rv
en
ti
on
:
0/
10
8

to
ta
l
ad
m
is
si
on
, p
<
0
.0
01
In
co
rr
ec
t
d
os
ag
e
re
gi

m
en
P
re
-i
n
te
rv
en
ti
on
:
13
/1
26
t
ot
al
a
d
m
is
si
on

(
10
.3
%
)
P
os
t-
in
te
rv
en
ti
on
:
0/
10
8
to
ta
l
ad
m
is

si
on
, p
<
0
.0
01
In
co
rr
ec
t
re
n
al
d
os
e
ad
ju
st
m
en
t

P
re
-i
n
te
rv
en
ti
on
:
9/
12
6
to
ta
l
ad
m
is
si
on
(
7.
1%

)
P
os
t-
in
te
rv
en
ti
on
:
0/
10
8
to
ta
l
ad
m
is
si
on
, p
=

0
.0
1
In
co
rr
ec
t
ad
m
in
is
tr
at
io
n
P
re
-i
n
te
rv
en
ti

on
:
56
/1
26
t
ot
al
a
d
m
is
si
on
(
44
.4
%
)
P
os
t-
in
te

rv
en
ti
on
:
3/
10
8
to
ta
l
ad
m
is
si
on
(
2.
8%
),
p
<
0
.0

01
M
aj
or
d
ru
g
in
te
ra
ct
io
n
P
re
-i
n
te
rv
en
ti
on
:
36

/1
26
t
ot
al
a
d
m
is
si
on
(
28
.6
%
)
P
os
t-
in
te
rv
en
ti

on
:
10
/1
08
t
ot
al
a
d
m
is
si
on
(
9.
3%
),
p
=
0
.0
01
Ta

b
le
1
. (
C
on
ti
n
u
ed
)
(C
on
ti
nu
ed
)
R
ef
er

en
ce
(c
ou
n
tr
y)
S
tu
d
y
d
es
ig
n
S
et
ti
n
g
N
u
m

b
er
o
f
p
at
ie
n
ts
In
te
rv
en
ti
on
t
yp
e
Ty
p
e
of
m
ed

ic
at
io
n
e
rr
or
a
n
al
ys
ed
(
m
et
h
od
o
f
d
at
a
co
ll

ec
ti
on
f
or
m
ed
ic
at
io
n
e
rr
or
s)
,
ef
fe
ct
o
f
in
te
rv

en
ti
on
o
n
m
ed
ic
at
io
n
e
rr
or
r
at
e
C
om
b
in
at
io

n
o
f
th
re
e
ty
p
es
o
f
in
te
rv
en
ti
on
s
S
an
d
er
s
et

a
l.5
3
(U
S
)
R
et
ro
sp
ec
ti
ve
b
ef
or
e–
af
te
r
st
u
d

y
H
IV
in
fe
ct
ed
p
at
ie
n
ts
a
d
m
it
te
d
to
a
l
ar

ge
a
ca
d
em
ic
m
ed
ic
al
c
en
tr
e
16
2
(p
re
-
in
te
rv
en

ti
on
),
1
10
(p
os
t-
in
te
rv
en
ti
on
)
C
P
O
E
, P
E
, I
C

A
n
ti
m
ic
ro
b
ia
l
st
ew
ar
d
sh
ip
p
ro
gr
am
:
u
p
d

at
es
of
e
le
ct
ro
n
ic
m
ed
ic
at
io
n
re
co
rd
s
w
it

h
in
C
P
O
E
, e
d
u
ca
ti
on
,
co
ll
ab
or
at
iv
e
st
ew
ar

d
sh
ip
ef
fo
rt
w
it
h
in
fe
ct
io
u
s
d
is
ea
se
s
d
ep

ar
tm
en
t
P
re
sc
ri
b
in
g
er
ro
rs
(
ch
ar
t
re
vi
ew
)
P
re

-i
n
te
rv
en
ti
on
:
12
4
to
ta
l
er
ro
rs
P
os
t-
in
te
rv
en
ti

on
:
43
t
ot
al
e
rr
or
s
N
o
d
en
om
in
at
or
g
iv
en
N
o
p-

va
lu
e
re
p
or
te
d
N
u
m
b
er
o
f
ad
m
is
si
on
s
w
it
h

a
m
ed
ic
at
io
n
e
rr
or
P
re
-i
n
te
rv
en
ti
on
:
81
/1
62
a

d
m
is
si
on
s
(5
0%
)
P
os
t-
in
te
rv
en
ti
on
:
37
/1
10
a
d

m
is
si
on
s
(3
4%
),
p
<
0
.0
01
A
D
E
, a
d
ve
rs
e
d
ru

g
ev
en
t;
C
A
, C
P
O
E
+
e
le
ct
ro
n
ic
a
d
m
in
is
tr
at

io
n
s
ys
te
m
;
C
D
S
S
, C
P
O
E
w
it
h
o
r
w
it
h
ou

t
cl
in
ic
al
d
ec
is
io
n
s
u
p
p
or
t
sy
st
em
;
C
P
O
E

, c
om
p
u
te
ri
se
d
p
h
ys
ic
ia
n
o
rd
er
e
n
tr
y;
D
D
, a

u
to
m
at
ed
d
ru
g
d
is
tr
ib
u
ti
on
s
ys
te
m
;
eM
A
R
, e

le
ct
ro
n
ic
m
ed
ic
at
io
n
a
d
m
in
is
tr
at
io
n
r
ec
or
d

;
H
IV
, h
u
m
an
im
m
u
n
od
ef
ic
ie
n
cy
v
ir
u
s;
IC
, i
n

te
rd
is
ci
p
li
n
ar
y
co
ll
ab
or
at
io
n
;
IT
-M
R
, c
om
p
u

te
ri
se
d
m
ed
ic
at
io
n
r
ec
on
ci
li
at
io
n
;
M
D
,
m
ed

ic
at
io
n
d
is
p
en
si
n
g;
P
E
, p
re
sc
ri
b
er
e
d
u
ca
ti

on
;
P
L
-M
R
, p
h
ar
m
ac
is
t-
le
d
m
ed
ic
at
io
n
r
ec
on

ci
li
at
io
n
;
P
P
, p
h
ar
m
ac
is
t
p
ar
tn
er
sh
ip
;
P
T

E
, p
at
ie
n
t
ed
u
ca
ti
on
;
T
M
E
, t
ra
in
ed
m
ed
ic
at
io

n
e
xp
er
ts
;
U
D
, u
n
in
te
n
ti
on
al
d
is
cr
ep
an
ci
es

;
U
K
, U
n
it
ed
K
in
gd
om
;
U
S
, U
n
it
ed
S
ta
te
s.
Ta
b

le
1
. (
C
on
ti
n
u
ed
)
Data synthesis
Data synthesis was undertaken qualitatively,
which involved grouping results into meaningful
clusters. These meaningful clusters comprised
categorising results in terms of dispensing errors,
prescribing errors, and administration errors, as
well as examining the types of interventions used.
Patterns of medication errors were examined
across and between studies.
For the calculation of meta-analysis, data were
entered into RevMan software according to inter-
vention types. The risk ratio was calculated for
categorical outcomes relating to dispensing, pre-
scribing and administration medication errors.
For medication error types expressed as continu-
ous outcomes, the standard mean difference was
calculated. Studies with incomplete data for
RevMan entry were excluded from the meta-anal-
ysis. Statistical heterogeneity was calculated and
reported in forest plots.

Results
The initial search identified 1980 studies. No
additional articles were identified after perform-
ing key article cross-checking on Web of Science
and Scopus. There were 135 articles selected for
full-text screening, of which 34 articles were
included for data extraction. A PRISMA flow
diagram is included in Figure 1. A total of 26
studies reported on prescribing errors, 11 studies
on administration errors and 2 studies on dis-
pensing errors (Table 1).
Study and patient characteristics
The sample size ranged from 33 to 1115 patients in
the intervention arm,31,47 and from 40 to 1852
patients in the control arm.23,51 The most common
study design was a pre–post intervention design,
used in 20 studies.27,28,30–32,35–37,40,44–54 Nine studies
were randomised controlled trials (RCTs.21,23–
26,38,39,41,43 There were two quality improvement
studies,42,29 one study involved a prospective chart
review with a historical control,22 one study involved
an interrupted time series design34 and one study
comprised a prospective observational design.33
A total of 9 studies involved implementation of
interventions in both medical and surgical units;
21 studies were conducted in medical units while
4 studies were conducted in surgical units. Chart
review was the most common data collection

Note. Some studies examined more than one type of medication
error.
Records identified through database
searching
(n=1980)
S
cr
ee
n
in
g
In
cl
u
d
ed
E
li
g
ib
il
it
y
Id
en
ti
fi
ca

ti
on
Additional records identified through reference
lists from systematic reviews
(n=5)
Records after duplicates removed
(n=1503)
Titles and abstract records
screened
(n=1503)
Records excluded with
reasons
(n = 1368)
Wrong outcome (n=1368)
Full-text articles assessed for
eligibility
(n=135)
Full-text articles excluded
with reasons
(n = 101)
Wrong outcome (n=59)
Wrong setting (n=24)
Conference abstract (n=9)
Wrong population (n=6)
Wrong study design (n=3)Studies included in qualitative

synthesis
(n=34)
Studies included in
quantitative synthesis
(meta-analysis) for
administration errors
(n=11)
Studies included in
(meta-analysis) for
prescribing errors (n=26)
Studies included in
(meta-analysis) for
dispensing errors (n=2)
Figure 1. PRISMA flow diagram. Some studies examined more
than one type of medication error.
PRISMA, preferred reporting items for systematic reviews and
meta-analyses.
method used to obtain information about medica-
tion errors (n = 19), followed by observations
(n = 8) and patient and family interviews (n = 5).
Other methods used included review of discharge
summaries (n = 2), electronic medical record
review (n = 2), participation in ward rounds (n = 1),
clinical incident reports (n = 1), the inpatient phar-
macy system (n = 1), prescription coverage plan

(n = 1), health provider interviews (n = 1), patient
notes (n = 1) and the preadmission medication list
(n = 1). In six studies, more than one method was
used to collect data on medication errors. Out of
the 34 included studies, 21 contained details
about the clinical significance of the medication
errors. This information was mainly in the form of
severity of the medication errors in causing harm.
Other studies provided details about clinical sig-
nificance in relation to the medication errors pro-
longing length of hospital stay (n = 2), or
contributing to hospital readmission (n = 1),
patient mortality (n = 2) and falls (n = 1) (Table 1).
Quality of studies
A total of 9 randomised controlled studies
scored 49–70% using the CONSORT guideline
(Table 2). The quality improvement studies
scored 48–80% using the SQUIRE guideline
(Table 3); 23 studies scored 36–73% according
to the TREND guideline (Table 4). Figure 2
contains the risk of bias graph while Figure 3
shows the risk of bias summary.
Ta
b
le

2
.
Q
u
al
it
y
as
se
ss
m
en
t
fo
r
ra
n
d
om
iz
ed
c
on
tr

ol
le
d
t
ri
al
s
an
d
c
lu
st
er
r
an
d
om
iz
ed
c
on
tr
ol
le

d
t
ri
al
s
u
si
n
g
th
e
C
O
N
S
O
R
T
g
u
id
el
in
es

(
n
=
9)
.
R
ef
er
en
ce
(C
ou
n
tr
y)
(i
n
te
rv
en
ti
on

)
S
tu
d
y
d
es
ig
n
Ti
tl
e
an
d
A
bs
t
In
tr
o
Tr
ia
l

D
es
ig
P
ar
t
In
t
O
u
tc
S
p
S
z
R
an
d
S
eq
G
en

R
an
d
A
ll
oc
R
an
d
Im
p
l
B
li
n
d
S
ta
t.
M
et

h
P
ar
t
F
lo
w
R
ec
ru
B
as
.
D
at
a
N
u
m
A
n
a
O

u
t
&
E
st
A
n
c
A
n
al
H
ar
m
L
im
.
G
en
In
tp
R
eg

P
ro
t
F
u
n
d
n/
N
%
A
l-
H
as
h
ar
et
a
l.2
1
(O
m
an

)
(P
L
-M
R
)
P
ro
sp
ec
ti
ve
ra
n
d
om
is
ed
co
n
tr
ol

le
d
st
u
d
y
1/
2
2/
2
1/
2
2/
2
1/
1
1/
2
1/
2
2/
2

1/
1
1/
1
0/
2
1/
2
2/
2
1/
2
1/
1
1/
1
1/
2
1/
1
0/
1
1/
1

1/
1
1/
1
1/
1
0/
1
1/
1
26
/3
7
70
%
B
ec
ke
tt
et
a
l.2
3

(U
S
)
(P
L
-M
R
)
P
ro
sp
ec
ti
ve
ra
n
d
om
is
ed
,
n
on

-b
li
n
d
ed
st
u
d
y
1/
2
2/
2
1/
2
2/
2
1/
1
1/
2
0/
2

1/
2
0/
1
1/
1
0/
2
1/
2
1/
2
1/
2
1/
1
1/
1
1/
2
0/
1
0/
1

1/
1
1/
1
1/
1
0/
1
0/
1
1/
1
20
/3
7
54
%
B
oo
ck
va
r
et

a
l.2
4
(U
S
)
(P
L
-M
R
)
C
lu
st
er
-
ra
n
d
om
is
ed
co

n
tr
ol
le
d
tr
ia
l
2/
2
2/
2
2/
2
2/
2
1/
1
1/
2
1/
2
0/

2
0/
1
0/
3
1/
2
2/
2
2/
2
1/
2
1/
1
1/
1
1/
2
1/
1
0/
1
1/

1
1/
1
1/
1
1/
1
1/
1
1/
1
27
/3
9
69
%
C
ad
m
an
et
a
l.2

5
(U
K
)
(P
L
-M
R
)
P
il
ot
ra
n
d
om
is
ed
co
n
tr

ol
le
d
tr
ia
l
2/
2
2/
2
2/
2
2/
2
1/
1
1/
2
1/
2
2/
2
1/

1
1/
1
0/
2
2/
2
1/
2
1/
2
0/
1
1/
1
1/
2
0/
1
0/
1
1/
1
1/

1
1/
1
1/
1
0/
1
1/
1
26
/3
7
70
%
T
on
g
et
a
l.2
6
(A
u
st

ra
li
a)
(P
L
-M
R
)
U
n
b
li
n
d
ed
,
cl
u
st
er
ra
n
d

om
is
ed
,
co
n
tr
ol
le
d
st
u
d
y
2/
2
2/
2
1/
2
2/
2

1/
1
1/
2
1/
2
1/
2
1/
1
2/
3
0/
2
1/
2
2/
2
1/
2
1/
1
1/
1

1/
2
0/
1
0/
1
1/
1
1/
1
1/
1
1/
1
0/
1
1/
1
26
/3
9
66
%
G

u
rs
an
sc
ky
et
a
l.3
8
(A
u
st
ra
li
a)
(P
E
)
C
lu
st
er

ra
n
d
om
is
ed
tr
ia
l
in
vo
lv
in
g
p
re
sc
ri
b
er
s
1/
2

2/
2
2/
2
2/
2
1/
1
0/
2
0/
2
1/
2
1/
1
1/
3
1/
2
2/
2
1/
2

1/
2
0/
1
1/
1
1/
2
1/
1
0/
1
1/
1
1/
1
1/
1
0/
1
0/
1
0/
1

22
/3
9
56
%
W
ei
n
ga
rt
et
a
l.3
9
(U
S
)
(P
T
E
)
P

ro
sp
ec
ti
ve
ra
n
d
om
is
ed
,
co
n
tr
ol
le
d
p
il
ot
t

ri
al
1/
2
2/
2
1/
2
2/
2
1/
1
0/
2
0/
2
1/
2
1/
1
1/
1
1/
2

2/
2
2/
2
1/
2
1/
1
1/
1
1/
2
1/
1
0/
1
1/
1
1/
1
1/
1
0/
1

1/
1
1/
1
25
/3
7
68
%
G
re
en
go
ld
et
a
l.4
1
(U
S
)
(T

M
E
)
R
an
d
om
is
ed
,
d
ir
ec
t
ob
se
rv
at
io
n
st
u
d

y
2/
2
2/
2
1/
2
1/
2
1/
1
1/
2
0/
2
1/
2
1/
1
1/
1
0/
2
1/

2
0/
2
1/
2
0/
1
1/
1
1/
2
0/
1
0/
1
1/
1
1/
1
1/
1
0/
1
0/

1
0/
1
18
/3
7
49
%
S
ch
n
ei
d
er
et
a
l.4
3
(U
S
)
(T
M

E
)
R
an
d
om
is
ed
,
co
n
tr
ol
le
d
,
n
on
-b
li
n
d
ed

st
u
d
y
1/
2
1/
2
2/
2
2/
2
1/
2
1/
2
1/
2
2/
2
0/
1
0/
1

0/
2
1/
2
1/
2
0/
2
2/
2
2/
2
2/
2
1/
1
0/
1
0/
1
0/
1
1/
1

0/
1
0/
1
1/
1
22
/3
7
59
%
A
n
c
A
n
al
, a
n
ci
ll
ar
y

an
al
ys
es
;
B
as
D
at
a,
b
as
el
in
e
d
at
a;
B
li
n
d
, b
li

n
d
in
g;
F
u
n
d
, f
u
n
d
in
g;
G
en
, g
en
er
al
iz
ab
il
it

y;
H
ar
m
, h
ar
m
s,
In
t,
in
te
rv
en
ti
on
s;
In
tp
, i
n
te
rp
re

ta
ti
on
;
In
tr
o,
in
tr
od
u
ct
io
n
;
L
im
, l
im
it
at
io
n
s;

N
u
m
A
n
a,
n
u
m
b
er
s
an
al
ys
ed
;
O
u
t
&
E
st
,

ou
tc
om
es
a
n
d
e
st
im
at
io
n
;
O
u
tc
, o
u
tc
om
es
;
P

ar
t,
p
ar
ti
ci
p
an
ts
;
P
ar
t
F
lo
w
, p
ar
ti
ci
p
an
t
fl

ow
;
P
E
, p
re
sc
ri
b
er
e
d
u
ca
ti
on
;
P
L
-M
R
, p
h
ar

m
ac
is
t-
le
d
m
ed
ic
at
io
n
r
ec
on
ci
li
at
io
n
;
P
ro
t,

p
ro
to
co
l;
P
T
E
, p
at
ie
n
t
ed
u
ca
ti
on
;
R
an
d
A
ll

oc
, r
an
d
om
is
at
io
n
a
ll
oc
at
io
n
;
R
an
d
Im
p
l,
r
an

d
om
is
at
io
n
im
p
le
m
en
ta
ti
on
;
R
an
d
S
eq
G
en
, r
an

d
om
is
at
io
n
s
eq
u
en
ce
g
en
er
at
io
n
;
R
ec
ru
, r
ec
ru

it
m
en
t;
R
eg
, r
eg
is
tr
at
io
n
;
S
p
S
z,
s
am
p
le
s
iz

e;
S
ta
t
M
et
h
, s
ta
ti
st
ic
al
m
et
h
od
s;
T
it
le
&
A
b

st
, t
it
le
a
n
d
a
b
st
ra
ct
;
T
M
E
;
tr
ai
n
ed
m
ed
ic

at
io
n
ex
p
er
ts
;
Tr
ia
l
D
es
ig
, t
ri
al
d
es
ig
n
;
U

S
, U
n
it
ed
S
ta
te
s.
Ta
b
le
3
.
Q
u
al
it
y

as
se
ss
m
en
t
fo
r
th
e
q
u
al
it
y
im
p
ro
ve
m
en
t
st
u

d
y
u
si
n
g
th
e
S
Q
U
IR
E
g
u
id
el
in
es
(
n
=
2)
.

R
ef
er
en
ce
(C
ou
n
tr
y)
(i
n
te
rv
en
ti
on
)
T
it
le
A

b
st
P
ro
b
.
d
es
c
A
va
il
k
n
ow
R
at
io
n
S
p
ec

ai
m
s
C
on
te
xt
In
te
rv
S
tu
d
y
of
t
h
e
in
te
rv
M
ea
su

A
n
al
y
E
th
co
n
si
d
R
es
u
lt
s
S
u
m
m
ar
y
In
te

rp
L
im
it
C
on
cl
u
F
u
n
d
n/
N
%
S
ch
n
ip
p
er
et
a

l.2
9
(U
S
)
(M
R
)
1/
1
2/
2
1/
1
1/
1
1/
1
1/
1
1/
1
1/
2

2/
2
1/
3
2/
2
0/
1
5/
6
2/
2
5/
5
3/
3
2/
5
1/
1
32
/4
0
80

%
N
gu
ye
n
et
a
l.4
2
(U
S
)
(T
M
E
)
1/
1
1/
1
1/
1

1/
1
0/
1
0/
1
0/
1
1/
2
1/
2
1/
3
0/
2
1/
1
3/
6
1/
2
2/
5

2/
3
2/
5
1/
1
19
/4
0
48
%
A
b
st
, a
b
st
ra
ct
;
A
n
al
y,

a
n
al
ys
is
;
A
va
il
K
n
ow
, a
va
il
ab
le
k
n
ow
le
d
ge
;

C
on
cl
u
, c
on
cl
u
si
on
s;
E
th
C
on
si
d
, e
th
ic
al
c
on
si

d
er
at
io
n
;
F
u
n
d
, f
u
n
d
in
g;
In
te
rp
, i
n
te
rp
re

ta
ti
on
;
In
te
rv
, i
n
te
rv
en
ti
on
;
L
im
it
, l
im
it
at
io
n

s,
M
ea
su
, m
ea
su
re
s;
M
R
, m
ed
ic
at
io
n
r
ec
on
ci
li
at
io

n
;
P
ro
b
D
es
c,
p
ro
b
le
m
d
es
cr
ip
ti
on
;
R
at
io
n

, r
at
io
n
al
e;
S
p
ec
A
im
s,
s
p
ec
if
ic
a
im
s;
S
tu
d
y

of
t
h
e
In
te
rv
, s
tu
d
y
of
t
h
e
in
te
rv
en
ti
on
;
T
M

E
, t
ra
in
ed
m
ed
ic
at
io
n
e
xp
er
ts
;
U
S
, U
n
it
ed
S
ta

te
s.
Identified interventions
The 12 intervention types identified were: phar-
macist-led medication reconciliation, computer-
ised medication reconciliation, medication
reconciliation by trained mentors, computerised
physician order entry (CPOE) with or without a
clinical decision support system, pharmacist part-
nership, prescriber education, patient education,
trained medication experts, medication dispens-
ing, use of an automated drug distribution system
with or without electronic medication administra-
tion record, interdisciplinary collaboration and
electronic administration system (Table 5).
Various combinations of interventions were also
identified.
Prescribing error rates were reduced in 14 out
of 26 studies, while administration error rates
were reduced in 4 out of 11 studies. Out of two
studies using interventions for dispensing, no
studies reported a significant reduction in dis-
pensing errors. Figure 4 shows a summary of
risk ratios for studies that reported on prescrib-
ing errors as categorical variables. Figure 5
shows the mean differences for studies report-
ing on prescribing errors as continuous varia-
bles, whereas Figures 6 and 7 present the risk
ratio summaries for administration and dis-
pensing errors respectively.
Pharmacist-led medication reconciliation
Six studies investigated the effect of pharmacist-

led medication reconciliation on prescribing
errors, with two out of the six studies reporting a
reduction in prescribing error rates. Al-Hashar
et al. showed a reduction of preventable adverse
drug events (ADEs) from 16% to 9.1%
(p = 0.008).21 The percentage of patients with
prescribing errors reduced from 35.1% to 16.7%
in the work of Batra et al.22 A pilot randomised
controlled trial reported a reduction of uninten-
tional discrepancies (UDs) from 2.71 errors per
patient in the intervention group (268 UDs in 99
patients) to 0.02 errors per patient in the control
group (2 UDs in 91 patients).25 There was no
significant difference in prescribed medication
discrepancies in the study by Beckett et al., with
45 medication discrepancies in the control group
and 71 in the intervention group (p = 0.074).23
Boockvar et al. reported no difference in mean
medication discrepancy (3.0 versus 3.2,
p = 0.452).24
Ta
b
le
4
.
Q

u
al
it
y
as
se
ss
m
en
t
fo
r
q
u
as
i-
ex
p
er
im
en
ta
l
st

u
d
ie
s
u
si
n
g
th
e
T
R
E
N
D
g
u
id
el
in
es
(
n
=

23
).
R
ef
er
en
ce
(C
ou
n
tr
y)
(i
n
te
rv
en
ti
on
)
T
it

le
an
d
ab
st
B
g
d
P
ar
ti
c
In
t
O
b
j
O
u
tc
S

p
S
z
A
ss
ig
n
.
m
td
B
ld
U
n
it
o
f
an
al
S
ta
t
m
td

P
ar
t
fl
ow
R
ec
ru
B
as
el
d
at
a
B
as
el
eq
u
iv
N
o

an
al
O
u
tc
&
es
ti
m
A
n
c
an
al
A
d
v
ev
In
te
r
G
en

O
v
ev
id
n/
N
%
B
at
ra
e
t
al
.2
2
(U
S
)
(P
L
-M
R
)
2/

3
1/
2
4/
4
3/
9
1/
1
1/
3
0/
1
0/
3
0/
1
1/
2
3/
4
2/
7
1/

1
1/
4
0/
1
1/
2
1/
3
0/
1
0/
1
2/
4
0/
1
1/
1
25
/5
9
42
%

A
ll
is
on
e
t
al
.2
7
(U
S
)
(I
T
-M
R
)
1/
3
1/
2
4/
4

5/
9
1/
1
2/
3
0/
1
0/
3
0/
1
1/
2
3/
4
4/
7
1/
1
3/
4
1/
1

1/
2
1/
3
0/
1
0/
1
3/
4
1/
1
1/
1
34
/5
9
58
%
S
m
it
h
e

t
al
.2
8
(U
S
)
(I
T
-M
R
)
2/
3
1/
2
4/
4
4/
9
1/
1
2/
3

1/
1
0/
3
0/
1
1/
2
2/
4
1/
7
1/
1
3/
4
1/
1
1/
2
3/
3
1/
1

0/
1
3/
4
0/
1
1/
1
33
/5
9
56
%
H
er
n
an
d
ez
et
a
l.3

0
(F
ra
n
ce
)
(C
P
O
E
)
2/
3
1/
2
4/
4
4/
9
1/
1
1/
3
0/

1
0/
3
1/
1
1/
2
2/
4
1/
7
1/
1
3/
4
0/
1
1/
2
2/
3
1/
1
0/

1
3/
4
0/
1
1/
1
30
/5
9
51
%
M
il
an
i e
t
al
.3
1
(U
S
)
(C

P
O
E
+
C
D
S
S
)
2/
3
1/
2
4/
4
4/
9
1/
1
1/
3
0/
1

0/
3
0/
1
1/
2
3/
4
3/
7
1/
1
2/
4
1/
1
1/
2
1/
3
1/
1
0/
1

3/
4
1/
1
1/
1
32
/5
9
54
%
P
et
ti
t
et
a
l.3
2
(U
S
)
(C
P

O
E
)
2/
3
1/
2
4/
4
4/
9
1/
1
1/
3
0/
1
0/
3
0/
1
1/
2
2/

4
1/
7
1/
1
0/
4
0/
1
1/
2
1/
3
1/
1
0/
1
3/
4
0/
1
1/
1
25

/5
9
42
%
S
h
aw
ah
n
a
et
a
l.3
3
(U
S
)
(C
P
O
E
)
3/
3

1/
2
2/
4
5/
9
1/
1
2/
3
0/
1
1/
3
1/
1
0/
2
2/
4
0/
7
0/
1

0/
4
0/
1
1/
2
2/
3
1/
1
1/
1
2/
4
0/
1
1/
1
26
/5
9
44
%

va
n
D
oo
rm
aa
l
et
a
l.3
4
(T
h
e
N
et
h
er
la
n
d
s)
(C

P
O
E
)
2/
3
1/
2
2/
4
7/
9
1/
1
3/
3
1/
1
2/
3
0/
1
1/
2

2/
4
5/
7
1/
1
3/
4
1/
1
2/
2
2/
3
1/
1
1/
1
3/
4
1/
1
1/
1

43
/5
9
73
%
G
ar
ci
a-
M
ol
in
a
S
ae
z
et
a
l.3
5
(S
p
ai
n

)
(P
P
)
2/
3
1/
2
4/
4
5/
9
1/
1
1/
3
0/
1
0/
3
0/
1
1/
2

3/
4
2/
7
1/
1
3/
4
1/
1
1/
2
1/
3
1/
1
0/
1
3/
4
1/
1
1/
1

33
/5
9
56
%
H
as
sa
n
e
t
al
.3
6
(M
al
ay
si
a)
(P
P
)
2/

3
1/
2
4/
4
4/
9
1/
1
1/
3
0/
1
0/
3
0/
1
1/
2
3/
4
0/
7
1/

1
1/
4
1/
1
1/
2
1/
3
0/
1
0/
1
3/
4
1/
1
1/
1
27
/5
9
46
%

L
ie
d
tk
e
et
a
l.3
7
(U
S
)
(P
P
)
3/
3
1/
2
4/
4
4/
9

1/
1
2/
3
0/
1
0/
3
1/
1
1/
2
3/
4
2/
7
1/
1
3/
4
0/
1
1/
2

1/
3
0/
1
0/
1
3/
4
1/
1
1/
1
33
/5
9
56
%
D
ea
n
a
n
d

B
ar
b
er
44
(
U
K
)
(M
D
)
1/
3
1/
2
2/
4
4/
9
1/
1
3/
3

1/
1
2/
3
0/
1
2/
2
3/
4
2/
7
0/
1
0/
4
0/
1
1/
2
3/
3
1/
1

1/
1
4/
4
1/
1
1/
1
34
/5
9
58
%
S
ch
im
m
el
et
a
l.
45

(N
et
h
er
la
n
d
)
(M
D
)
2/
3
1/
2
3/
4
4/
9
1/
1
2/
3

1/
1
0/
3
0/
1
1/
2
3/
4
2/
7
1/
1
2/
4
1/
1
1/
2
2/
3
0/
1

0/
1
3/
4
0/
1
1/
1
31
/5
9
53
%
(C
on
ti
nu
ed
)

R
ef
er
en
ce
(C
ou
n
tr
y)
(i
n
te
rv
en
ti
on
)
T
it
le

an
d
ab
st
B
g
d
P
ar
ti
c
In
t
O
b
j
O
u
tc
S
p
S
z

A
ss
ig
n
.
m
td
B
ld
U
n
it
o
f
an
al
S
ta
t
m
td
P
ar
t

fl
ow
R
ec
ru
B
as
el
d
at
a
B
as
el
eq
u
iv
N
o
an
al
O

u
tc
&
es
ti
m
A
n
c
an
al
A
d
v
ev
In
te
r
G
en
O
v
ev

id
n/
N
%
B
aq
ir
e
t
al
.4
0
(U
K
)
2/
3
1/
2
4/
4
5/
9
1/

1
2/
3
0/
1
0/
3
0/
1
1/
2
3/
4
3/
7
1/
1
0/
4
0/
1
1/
2
1/

3
0/
1
0/
1
4/
4
1/
1
1/
1
31
/5
9
53
%
C
an
n
e
t
al
.4
7

(A
u
st
ra
li
a)
(P
P
, P
E
)
2/
3
1/
2
3/
4
5/
9
1/
1
2/
3

0/
1
0/
3
0/
1
1/
2
2/
4
1/
7
1/
1
0/
4
0/
1
1/
2
2/
3
0/
1

0/
1
3/
4
1/
1
1/
1
27
/5
9
46
%
D
an
ie
ls
e
t
al
.4
8
(U
S

)
(P
E
, C
P
O
E
)
2/
3
1/
2
4/
4
5/
9
1/
1
2/
3
0/
1
0/
3

0/
1
1/
2
0/
4
0/
7
1/
1
0/
4
0/
1
1/
2
1/
3
0/
1
0/
1
3/
4

1/
1
1/
1
24
/5
9
41
%
G
im
en
ez
-
M
an
zo
rr
o
et
a
l.4
9

(S
p
ai
n
)
(C
P
O
E
, I
T
-M
R
)
2/
3
1/
2
4/
4
4/
9
1/
1

2/
3
1/
1
1/
3
0/
1
1/
2
3/
4
5/
7
1/
1
3/
4
1/
1
1/
2
1/
3

0/
1
0/
1
4/
4
1/
1
1/
1
38
/5
9
64
%
G
ri
m
es
e
t
al
.5
0

(I
re
la
n
d
)
(P
L
-M
R
, P
P
)
2/
3
1/
2
4/
4
5/
9
1/
1
2/

3
0/
1
1/
3
0/
1
1/
2
3/
4
1/
7
1/
1
3/
4
1/
1
1/
2
3/
3
1/

1
0/
1
3/
4
1/
1
1/
1
36
/5
9
61
%
M
ou
ra
e
t
al
.5
1
(B
ra

zi
l)
(C
P
O
E
, P
P
)
2/
3
1/
2
4/
4
4/
9
1/
1
2/
3
0/
1

0/
3
0/
1
1/
2
3/
4
0/
7
1/
1
1/
4
0/
1
1/
2
1/
3
0/
1
0/
1

2/
4
0/
1
1/
1
25
/5
9
42
%
S
h
ea
e
t
al
.5
2
(U
S
)
(P
E

, P
L
-M
R
)
2/
3
1/
2
4/
4
4/
9
1/
1
2/
3
0/
1
0/
3
0/
1
1/

2
3/
4
3/
7
1/
1
0/
4
0/
1
1/
2
1/
3
0/
1
0/
1
3/
4
1/
1
1/

1
29
/5
9
49
%
S
an
d
er
s
et
a
l.
53
(U
S
)
(C
O
P
E
, P

E
, I
C
)
2/
3
1/
2
4/
4
5/
9
1/
1
1/
3
0/
1
0/
3
0/
1
1/
2

3/
4
1/
7
1/
1
3/
4
1/
1
1/
2
3/
3
1/
1
0/
1
3/
4
0/
1
0/
1

32
/5
9
54
%
C
ou
se
in
e
t
al
.4
6
(F
ra
n
ce
)
(D
D
)
2/

3
1/
2
3/
4
4/
9
1/
1
1/
3
0/
1
0/
3
1/
1
1/
2
3/
4
0/
7
1/

1
3/
4
1/
1
1/
2
1/
3
0/
1
0/
1
3/
4
0/
1
1/
1
28
/5
9
47
%

Jh
ee
ta
e
t
al
.5
4
(U
K
)
(C
P
O
E
, C
A
)
2/
3
1/
2
1/
4

4/
9
1/
1
1/
3
0/
1
0/
3
0/
1
1/
2
1/
4
2/
7
1/
1
0/
4
0/
1

1/
2
1/
3
0/
1
0/
1
3/
4
0/
1
1/
1
21
/5
9
36
%
A
d
v
E

v,
a
d
ve
rs
e
ev
en
ts
;
A
n
c
A
n
al
, a
n
ci
ll
ar
y
an
al

ys
es
;
A
ss
ig
n
M
td
, a
ss
ig
n
m
en
t
m
et
h
od
;
B
as
el

D
at
a,
b
as
el
in
e
d
at
a;
B
as
el
E
q
u
iv
, b
as
el
in
e
eq

u
iv
al
en
ce
;
B
gd
, b
ac
kg
ro
u
n
d
;
B
ld
, b
li
n
d
in
g;

C
A
, e
le
ct
ro
n
ic
ad
m
in
is
tr
at
io
n
s
ys
te
m
, C
D
S

S
, c
li
n
ic
al
d
ec
is
io
n
s
u
p
p
or
t
sy
st
em
;
C
P
O

E
, c
om
p
u
te
ri
ze
d
p
h
ys
ic
ia
n
o
rd
er
e
n
tr
y;
D
D

, a
u
to
m
at
ed
d
ru
g
d
is
tr
ib
u
ti
on
s
ys
te
m
, G
en
, g
en

er
al
iz
ab
il
it
y;
In
t,
in
te
rv
en
ti
on
s;
In
te
r,
in
te
rp
re

ta
ti
on
;
IT
-M
R
, c
om
p
u
te
ri
ze
d
m
ed
ic
at
io
n
r
ec
on

ci
li
at
io
n
;
M
D
, m
ed
ic
at
io
n
d
is
p
en
si
n
g;
N
o
A

n
al
, n
u
m
b
er
s
an
al
ys
ed
;
O
b
j,
ob
je
ct
iv
es
;
O
u

t,
o
u
tc
om
es
;
O
u
tc
&
E
st
im
, o
u
tc
om
es
a
n
d
e
st

im
at
io
n
;
O
v
E
vi
d
, o
ve
ra
ll
ev
id
en
ce
;
P
ar
t
F

lo
w
, p
ar
ti
ci
p
an
t
fl
ow
;
P
ar
ti
c,
p
ar
ti
ci
p
an
ts
;

P
E
, p
re
sc
ri
b
er
e
d
u
ca
ti
on
;
P
L
-M
R
, p
h
ar
m
ac

is
t-
L
ed
m
ed
ic
at
io
n
r
ec
on
ci
li
at
io
n
;
P
P
, p
h
ar

m
ac
is
t
p
ar
tn
er
sh
ip
;
R
ec
ru
, r
ec
ru
it
m
en
t;
S
p
S

z,
s
am
p
le
s
iz
e;
S
ta
t
M
td
, s
ta
ti
st
ic
al
m
et
h
od

s;
T
it
le
&
A
b
st
, t
it
le
a
n
d
a
b
st
ra
ct
;
T
M
E
, t

ra
in
ed
m
ed
ic
at
io
n
e
xp
er
ts
;
U
n
it
o
f
A
n
al
, u
n

it
o
f
an
al
ys
is
;
U
K
, U
n
it
ed
K
in
gd
om
;
U
S
, U
n
it

ed
S
ta
te
s.
Ta
b
le
4
. (
C
on
ti
n
u
ed
)
Computerised medication reconciliation
Two studies employed computerised medication
reconciliation to reduce medication errors at dis-

charge and only one showed a significant reduc-
tion in errors. In a medication antimicrobial
reconciliation program at discharge, Allison et al.
undertook a retrospective examination of patients’
medical records to investigate the presence of
intravenous antibiotics in their discharge orders
before and after the implementation of the inter-
vention.27 Patients with at least one discharge
medication error decreased from 23/100 in the
pre-intervention period to 11/100 in the post-
intervention period (p-value was not reported).
Smith et al. conducted a quasi-experimental
study and reported a significant reduction
(p < 0.001) in discharge medication errors from
645 errors/3490 medication variance in the pre-
intervention period to 359 errors/2823 medica-
tion variance in the post-intervention period.28
The study also found no change in medication
errors having the potential to produce serious or
life-threatening harm with 1.4% (9/645 errors) at
pre-intervention and 3.1% (11/359 errors at post-
intervention, p = 0.10).
Medication reconciliation by trained mentors
One study specified that trained mentors com-
prising physicians with medication safety experi-
ence carried out medication reconciliation.29
Three hospitals were intervention sites and two
hospitals were concurrent controls. The outcome
was reported as potentially harmful discrepancies
in admission and discharge orders per patient.
Only two sites (sites 2 and 3) out of five had
results for both control units and intervention
units. In site 2, the mean number of errors per
patient decreased from 1.00 to 0.88. A similar

result was found in site 3 where the mean number
of errors per patient decreased from 0.30 to 0.18.
CPOE with or without a clinical decision support
system
Five studies examined the use of CPOE and
reported significant improvements in reduction of
medication errors. Hernandez et al. conducted a
before-and-after observational study in an ortho-
paedic surgery unit using CPOE without a clinical
decision support system.30 Prescribing errors
decreased from 30.1% (479 errors/1593 prescribed
medications) in the pre-intervention period to
2.4% (33 errors/1388 prescribed medications) in
the post-intervention period (p < 0.0001). The
study also found a significant reduction in adminis-
tration errors (p < 0.05) but showed no significant
change in dispensing errors. CPOE with a clinical
decision support system was employed by Milani
et al. for patients with chronic kidney disease who
were admitted with acute coronary syndrome.31
The number of patients with contraindicated medi-
cations decreased from 8/47 in the control group to
0/33 in the intervention group (p = 0.01). Pettit
et al. found a significant reduction in the number of
patients with prescribing errors from 84/167
(50.2%) in the pre-intervention period to 37/131
(28.2%) in the post-intervention period (p < 0.01).32
Shawahna et al. compared paper based with elec-
tronic prescribing in Pakistan in a prospective chart
review.33 They found prescribing errors differed
significantly between control and intervention
wards with a mean prescription errors of 21.4%
and 6.9% errors respectively. van Doormaal et al.
undertook an interrupted time series design and
found following CPOE, prescribing errors reduced

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