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Adverse Drug Events In High Risk Older Outpatients

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To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy. A cohort study. General Medicine Clinic at the Durham Veterans Affairs Medical Center. A total of 167 high risk (taking > or = 5 scheduled medications) ambulatory older veterans who participated in a year long health service intervention trial. Potential ADEs were identified by asking patients during closeout interviews whether, in the past year, they had experienced any side effects, unwanted reactions, or other problems from any medication. All reported medications and corresponding adverse experiences were assessed for plausibility by a research clinical pharmacist using two standard pharmacological textbooks and categorized by predictability, therapeutic class, and organ system. Eighty self-reported ADEs involving 72 medications taken by 58 (35%) of 167 patients were textbook confirmed. Seventy-six of 80 (95%) ADEs were classified as Type A (predictable) reactions. Cardiovascular (33.3%) and central nervous system (27.8%) medication classes were most commonly implicated. Gastrointestinal (30%) and central nervous system (28.8%) ADE symptoms were common. Sixty-three percent of patients with ADEs required physician contacts, 10% emergency room visits, and 11% hospitalization. Twenty percent of medications implicated with ADEs required dosage adjustments, and 48% of ADE-related medications were discontinued. No significant differences (P > .05) were observed when ADE reporters (n = 58) and nonreporters (n = 109) were compared. Predictable ADEs are common in high risk older outpatients, resulting in considerable medication modification and substantial healthcare utilization.
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Adverse Drug Events In High
Risk
Older Outpatients
Joseph
T.
Hanlon, PharmD,
MS,'ty
'I#
Kenneth
E.
Schmader, MD,*tm
I'
Michael]. Koronkowski,
PharmD,' Morris Weinberger, PhD,tt Pamela
B.
Landsman,
MPH,f'
Gregory
P.
Samsa, PbD,t§y
and Ingrid
K.
Lewis, PharrnD'"#
_____
~_~__~~_-~-
OBJECTIVE:
To
describe the prevalence, types, and conse-
quences
of
adverse drug events
(ADEs)
in older outpatients
with polypharmacy.
DESIGN: A
cohort study.
SETTING:
General Medicine Clinic at the Durham Veterans
Affairs Medical Center.
PATIENTS: A
total
of
167 high
risk
(taking
2
5
scheduled
medications) ambulatory older veterans who participated in
a year long health service intervention trial.
MEASUREMENTS:
Potential
ADEs
were identified by ask-
ing patients during closeout interviews whether, in the past
year, they had experienced any side effects, unwanted reac-
tions,
or
other problems from any medication.
All
reported
medications and corresponding adverse experiences were
assessed for plausibility by a research clinical pharmacist
using two standard pharmacological textbooks and catego-
rized by predictability, therapeutic class, and organ system.
RESULTS:
Eighty self-reported
ADEs
involving 72 medica-
tions taken by 58
(35%))
of
167
patients were textbook
confirmed. Seventy-six
of
80
(
~WO)
ADEs
were classified as
Type
A
(predictable) reactions. Cardiovascular
(33.3%)
and
central nervous system
(27.8%)
medication classes were most
commonly implicated. Gastrointestinal
(30%)
and central
nervous system (28.8%)
ADE
symptoms were common.
Sixty-three percent
of
patients with
ADEs
required physician
contacts,
10%
emergency room visits, and
1
1
%
hospitaliza-
tion. Twenty percent
of
medications implicated with
ADEs
required dosage adjustments, and 48% of ADE-related med-
__
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.-
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-
-
-
-
-
-
From The *Center
for
the Study
of
Aging and Human Development, the
tDe-
partments
of
Medicine, khnniunity and Family Medicine, and the SCenter
for
Health Policy Research and Education, Duke University Medical Centcr.
Durham, North Carolina; the ?Center
for
Health Services Research in Primary
Care, and the IIGeriatric Research, Education and Clinical Center, Veterans Af-
fairs Medical Center, Durham, North Carolina;
#School
of
Pharmacy, University
of
North Carolina, Chapel Hill, North Carolina; and ttRoudehush Veterans
Af-
fairs Medical Center, Regenstrief Institute
for
Health Care, and Department
of
Medicine, Indiana University Medical Center, Indianapolis, Indiana.
'This work was supported hy Grants R01-AC08380,
AG00526,
and
P60AC1126R from the National Institute on Aging.
Presented at the American Geriatrics Society Meeting, New Orleans, I.ouisiana,
November 199.3.
Current addresses: Dr. Koronkowski, School
of
Pharmacy, University
of
Illinois,
(M/C)
833
South Wood
St.,
Chicago,
II
60612. Ms. Landsman: Merck
&
Co.,
PO
Box
4, WP.39-106, South Broad St.
&
Sumneytown Pike, West Point, PA
19486.
Address corrcspondcnce to Joseph
T.
Hanlon, PharmD, MS,
Box
300.3,
DUMC.
Durham, NC 27710.
ications were discontinued.
No
significant differences
(P
>
.05)
were observed when
ADE
reporters
(n
=
58) and
non-
reporters
(n
=
109)
were compared.
CONCLUSION:
Predictable
ADEs
are common in high risk
older outpatients, resulting in considerable medication mod-
ification and substantial healthcare utilization.
J
Am
Geriatr
SOC
45:945-948,1997.
linicians prescribe medications to treat geriatric condi-
C
tions, but medication use exposes older patients
to
the
threat of adverse drug events
(ADEs). ADEs
can be defined as
noxious and unintended patient events (i.e., symptoms, signs,
or
laboratory abnormalities) caused by a drug.'
ADEs
are
important because they cause significant morbidity and can
increase the cost
of
care in this population by increasing
health care utilization.2-'
A
panel of geriatrics experts iden-
tified adverse effects of drugs as one of the five most impor-
tant quality-of-care problems in older people.'"
Although various risk factors have been associated with
ADEs,
linked most consistently is polypharmacy
or
the use of
multiple
medication^.^*'.'
'*I2
In
fact, the risk of
ADEs
has
been shown
to
increase exponentially as the number
of
med-
ications
increase^.^^"^"
Polypharmacy is prevalent in both
institutionalized and community-dwelling older people and is
considered one
of
the principal drug safety issues
for
the next
decade.'
'
While numerous studies have examined the epidemiol-
ogy
of
ADEs
leading
to
hospitalization
or
in institutionalized
patients, few have examined
ADEs
in ambulatory care set-
ting~.~.' Previous investigators have reported widely dispar-
ate prevalence rates for
ADEs
in ambulatory older adults,
ranging from
2.5
to 50.6%.4-h,'4-'8 Th ese dramatic differ-
ences are likely attributable to variation in both methods used
to
ascertain
ADEs
and study samples.
Of
note, only a few
studies focused primarily
on
those
65
years
of
age and older,
and
none
has carefully examined incident
ADEs
in
commu-
nity-dwelling older people at high risk
to
experience
an
ADE
(i.e., those with polypharmacy).'
'*16
In
order to provide more information
on
ADEs
in this
group of patients, the purpose of the current study was to
describe the prevalence, types, and healthcare consequences
of
ADEs
and
to
identify risk factors for
ADEs
in ambulatory
older outpatients with polypharmacy.
To
address this ques-
tion, we analyzed
ADE
data collected during a randomized,
.
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JAGS
45:945-948, 1997
0
1997 by the American Geriatrics Society 0002-86 14/97/$3..50
946 HANLON
ET
AL.
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~_-
AUGUST
1997-VOL. 45, NO.
8
JAGS
controlled trial
of
a clinical pharmacist intervention for older
veterans with polypharmacy.”
METHODS
Study Setting, and Sample
This investigation was part of a randomized, controlled
health services trial examining the impact
of
a clinical phar-
macist intervention in the General Medicine Clinic (GMC) at
the Durham Veterans Affairs Medical Center (VAMC).”
In
the GMC,
13
internal medicine faculty and
17
internal med-
icine residents, paired with faculty physicians, provided
lon-
gitudinal primary care
to
approximately
3000
patients. Pa-
tients were eligible
if
they were
65
years
of
age or older,
taking five or more regularly scheduled medications at enroll-
ment, and receiving primary care from the GMC. Patients
with cognitive impairment
(n
=
21)
were determined by use
of
the Mental Status Questionnaire, and they were eligible
only
if
a caregiver was available to be involved in the inter-
vention.20
Of
208
patients who were eligible and random-
ized, closeout interviews were completed with
172 (83%),
who constituted the sample for this study. Thirty-six patients
were not interviewed because they were institutionalized
(lo),
deceased
(17),
lost
to
follow-up
(6),
refused
(l),
or were
no
longer under GMC care
(2).
The study was approved by
the Durham VAMC Research and Human Subjects Committee.
Data Collection
Medical and sociodemographic data, self-perceived
health status, information
on
multiple prescribers, and previ-
ous
adverse drug event histories were collected from the
patients before randomi~ation.’~,~’ Medication lists were
obtained from the patient’s “action profile” which is a com-
puter listing of their current VAMC medications.
In
addition,
a research assistant prepared an abstract
of
each patient’s VA
medical chart that included progress notes, laboratory re-
sults, medications, clinic appointments, procedures, emer-
gency room visits and hospitalizations from the previous
2
years and for the year
of
the study. Closeout telephone
interviews conducted by a clinical pharmacist collected infor-
mation about non-VA health services use, and information
about emergency room visits and hospitalization were veri-
fied by obtaining written copies
of
discharge summaries.
Moreover, adverse drug events were reported during this
closeout interview. Specifically patients were asked whether
in the past year they had experienced any side effects,
un-
wanted reactions, or other problems with their medica-
tion~.”,’~ For those answering “yes,” the interviewer used a
semi-structured questionnaire to determine the name
of
the
medication involved, obtain a full description
of
the problem,
and find out whether the patient talked to a doctor about the
reaction and what was advised (i.e., medication modification,
emergency room visit, or hospitalization) or whether the
patient,
on
their own, modified the use
of
the medication in
question.
Assessment ofAdverse
Drug
Events
To
determine the occurrence of ADEs, a research clinical
pharmacist (MJK) reviewed the ADE questionnaire, ab-
stracted the medical chart and medication list
of
each patient
with a suspected ADE, and assessed each adverse event and
putative drug pair for plausibility. The research clinical phar-
macist confirmed or refuted whether the patient’s symptom
was a known adverse effect
of
the implicated medication by
its listing in either of two standard pharmacological
text^.^^,'^
These
two
texts were chosen since they have com-
prehensive information about the pharmacological effects of
both brand name and generic prescription and over-the
counter medications that could be prescribed at this VAMC.
Uncertain or problematic cases were reviewed by two inves-
tigators
(JTH,
KES) and were resolved by group consensus.
This approach replicates the methods used in previous ADE
studie~.~*~’
The research clinical pharmacist then categorized the
event as being either a Type A or
B
rea~tion.’~ Type
A
(“augmented”) reactions are defined as those that are predict-
able, dose-dependent, and an exaggeration
of
the expected
pharmacological effect of a drug.
In
contrast, Type
B
(“bi-
zarre”) reactions are defined as idiosyncratic or caused by
allergic reactions, that are not predictable, and are associated
with low morbidity but high mortality. Implicated medica-
tions were categorized into major therapeutic classes accord-
ing to the VA Medication Classification Sy~tem.~’ Adverse
drug events were categorized into major organ systems ac-
cording to the ICD-9 Classification System.26
Statistical Analysis
Descriptive statistics for all continuous variables are
presented as means and standard deviations, and those for
dichotomous variables as frequencies and percents
of
the
respective totals. For purposes
of
presentation, medication
classes with less than
2%
and organ systems involved with
ADEs with less than
3
prevalence were combined into mis-
cellaneous categories.
For purposes of analysis, the dependent variable was
di-
chotomized (i.e., patients having or not having any confirmed
ADEs). The independent variables, chosen based
upon
previ-
ously reported associations with
ADEs,
included age, race, edu-
cation, number
of
chronic medications, number
of
medical
conditions, self-perceived health status (range
0-loo),
whether
the patient received prescriptions from more than one provider
and whether the patient had a previous history
of
experiencing
an adverse drug e~ent.~-~,~,~~-~~~~-~~ Bivariate analyses were
performed with the patient as the unit
of
analysis
using
chi-
square tests for categorical variables and Wilcoxon rank sum
tests for continuous
variable^.^'
SAS@ software was utilized for
all
RESULTS
Of
the
172
patients who completed closeout interviews,
167
(97%)
had evaluable ADE questionnaires. Two patients
were excluded because of proxy interviews, and three be-
cause
of
incomplete interviews. Ninety-three potential ADEs
were self-reported,
80 (86%)
of
which were textbook con-
firmed by the clinical pharmacist. These
80
ADEs were re-
ported
to
involve
72
medications, with some medications
involving more than one ADE. The most common drug
classes in rank order were cardiovascular
(33.3%),
central
nervous system drugs
(27.8%),
musculoskeletal
(9.7%),
re-
spiratory
(5.6%),
endocrine
(4.2%),
gastrointestinal
(2.8
%),
and miscellaneous
(16.7%).
The most common organ sys-
tems involved, in rank order, were the gastrointestinal system
(30.0%),
central nervous system
(28.8%),
cardiovascular
(15.00/),
respiratory
(6.2%),
endocrine
(6.2%),
dermato-
logic
(3.8%),
and miscellaneous
(10.0%).
Seventy-six
of
80
(950/)
ADEs were classified as Type A (predictable) reactions.
Fifty-eight
(35%)
of
167
patients experienced the
80
textbook-confirmed
ADEs
(some patients experienced more
than one
ADE).
Of these
58
patients,
49
(84%)
required
health care services:
37 (63%)
required physician contacts,
seven
(1
1
Yo)
required hospitalizations, and
5
(loo/)
emer-
gency room visits. Sixty-eight percent
of
medications associ-
ated with
ADEs
required modifications:
20%
dosage adjust-
ments, and
48%
medication discontinuations. Table
1
describes the drugs and events associated with the
12
patient
cases requiring either emergency room visits or hospitaliza-
tion.
Table
2
presents bivariate analyses examining potential
associations between selected independent variables and the
risk of experiencing an
ADE.
No statistically significant dif-
ferences
(P
>
.05)
were observed comparing
ADE
reporters
(n
=
58)
to nonreporters
(n
=
109)
with respect
to
age, race,
education, number
of
medications, self-perceived health sta-
tus, or having multiple prescribing physicians. There were
trends
(P
<
.lo)
suggesting that those with greater numbers
of
chronic conditions and those with a previous history
of
ADE
were more likely
to
experience an
ADE.
DISCUSSION
A
substantial proportion
(35%)
of
older ambulatory
patients with polypharmacy experienced a confirmed
ADE
over a 1-year period. This finding should alert clinicians to
the fact that
ADEs
are common in outpatients taking multiple
medications. The reported
35%
rate
of
ADEs
in this sample
of high risk older outpatients is higher than seen in a previous
study of community-dwelling older adults using similar
ADE
ascertainment methodology.'" Chrischilles et al. documented
that
10%
of
3170
rural Iowa subjects reported one or more
ADEs
in the previous year. The high
ADE
rate we observed
may be attributed to our sample being comprised of clinic
patients rather than community-dwelling subjects. Another
explanation may be that the difference in average drug use
between the current study and the Iowa study was substantial
(approximately
8.0
vs
3.0
drugs per person, re~pectively)."~~~
The most clinically significant
ADEs
are those that re-
quire urgent medical attention via emergency room visits or
hospitalizations. Among those who experienced an
ADE,
emergency room and in-hospital care represented a consider-
Table
1.
Adverse
Drug
Events In Patients With Emergency
Room
Visits
or
Hospitalization
Case
Number Drug Implicated Adverse Event
(s)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
amiodarone
aspirin
atenolol
carbamazepine
colestipol
cotrimoxazole
cotrimoxazole
hydrochlorothiazide
imiprarnine
piroxicam
theophylline
warfarin
dyspnea, blurry vision
bleeding
blurry vision
rash
epigastric pain
rash
diarrhea
hypotension
decreased functional status
gastrointestinal ulcer
arrhythmia
bleeding
ADVERSE
DRUG
EVENTS
IN
OLDER OUTPATIENTS
947
____
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-
__
-
-
Table
2.
Comparison
of
Adverse Drug and Nonadverse
Drug
Event Reporting Groups
Reporters Nonreporters
P
Factor
(n=58)
(n=
109)
Value*
Age, years
68.9
2
3.3
%
Black race
24.1
%
High school
77.6
No. Chronic
9.7
2
3.8
No.
Chronic
8.3
2
3.0
Self-perceived health
33.5
2
20.0
%
Multiple
55.2
%
Adverse event
77.6
education
conditions
medications
score+
prescribers
history
69.8
2
3.6
22.9
68.5
8.6
2
3.0
8.0
2
2.7
37.1
2
22.8
48.6
64.8
0.1 39
0.861
0.231
0.067
0.459
0.31 2
0.420
0.097
*
Categorical data analyzed using chi-square testing and continuous data ann-
t
Self-perceived health status score ranges from
0
to
100.
lyzed
using Wilcoxon rank sum testing.
able proportion
of
all
ADE
consequences
(1
0%
and
11
%,
respectively). The proportion
of
hospitalized participants
with
ADEs
in the current study was more than two times
higher than that reported in the Iowa study
(11%
vs
5%,
respectively).1s
Of
the remaining
ADEs,
a large proportion
(63%)
of
patients contacted their physicians either by tele-
phone or through clinic visits. Whereas these
ADEs
were less
serious, they did indicate that patients experienced a high
level
of
distress with a medication and utilized physician time.
Notably, the majority
of
the medications
(68%)
associated
with
ADEs
required modification.
None
of
eight potential risk factors examined was signif-
icantly associated with
ADEs.
However, previous
ADE
his-
tory and number
of
chronic conditions showed a trend
sug-
gesting an association. It is controversial whether previous
history
of
ADE
is or is not a risk factor for the occurrence of
a future
ADE
occurrence.1s72Y In contrast, number
of
chronic
health conditions has been reported
to
be an important
independent predictor in previous studies
of
ambulatory and
institutionalized older
person^.'^-^^
Noteworthy in this study
of patients with polypharmacy, number of drugs was not
significantly associated with
ADEs.
This sample excluded
patients taking fewer than five medications and, therefore,
limited our ability
to
fully examine this relationship.
How are the results of this study
of
use to geriatricians
and other health care professionals? First, any symptoms that
patients with polypharmacy report may be related to
ADEs,
particularly symptoms referable
to
the gastrointestinal, cen-
tral nervous, and cardiovascular systems. Second, cardiovas-
cular and central nervous system drugs are the most likely
culprits in causing
ADEs
in this group although other high
risk drugs, such as musculoskeletal (e.g., nonsteroidal antiin-
flammatory agents), and respiratory (e.g., bronchodilators)
and endocrine (e.g., hypoglycemics) drugs may be involved.
Of
the drugs causing
ADEs
that resulted in emergency room
visits or hospitalizations, most
(75%)
were in a group
of
drugs considered high risk for
ADEs.4327*28.'0-'4.39
Examples
of high risk cardiac drugs resulting in an emergency room
visit or hospitalization were atenolol and amiodarone, and
examples
of
high risk CNS medications were carbamazepine
and imipramine. Third,
it
is
important
to
recognize that the
majority
of
these ADEs are potentially preventable;
95%
of
ADEs were categorized as type A or predictable reactions.
The importance
of
preventability
of
ADEs is underscored by
a recent study of hospitalized adults in which
28%
of
ADEs
were judged to be preventable.’
There are several potential limitations worth noting. Our
retrospective questionnaire approach to ADE ascertainment
could have lead to an underestimation
of
ADEs that partici-
pants experienced but did not recall. There is also another
potential limitation with the use
of
this method
to
determine
the
plausibility/probability
of ADEs. ADEs can be difficult to
determine in the older patient because they often present
nonspecifically and may be attributed to a pre-existing dis-
ease(s), to a new disease, or
to
a “normal” consequence
of
aging.
In
contrast, a symptom
of
a disease may be attributed
incorrectly
to
an ADE. However,
it
is
likely that the assess-
ment approach used in the current study did capture clinically
meaningful ADEs, especially those requiring physician inter-
vention. The small sample size may have limited our ability to
detect small differences between groups and precluded con-
ducting multivariate analyses. Finally, the generalizability
of
our findings is unknown as
it
involved VAMC patients man-
aged by academic medical center physicians.
Despite these potential limitations, we conclude that
ADEs are common in high risk older outpatients, with poly-
pharmacy often resulting in substantial drug therapy modifi-
cation and health services utilization. Given that the majority
of
ADEs are predictable reactions, clinicians should consider
the benefit
of
periodic systematic drug regimen reviews in an
effort
to
reduce the occurrence
of
this problem in older
people. Additional research
is
needed to further identify risk
factors for experiencing ADEs in older outpatients.
ACKNOWLEDGMENTS
The authors thank Marti E. Doyle, MS, and Becky
Nagle, PharmD, for their technical assistance with data col-
lection and management and Kay Uttech, PharmD, Patricia
A. Cowper, PhD, Harvey J. Cohen, MD, and John
R.
Feuss-
ner, MD, for their advice and contributions to other aspects
of
this study.
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... A substantial proportion of hospital consultations is attributable to adverse drug events. During 1990-2020, the proportion of outpatient visits and hospitalizations due to adverse drug events has varied from 5.5 to 35.0% (Hanlon et al., 1997;Honigman et al., 2001;Gandhi et al., 2003) and 1.3 to 30.4% (Dartnell et al., 1996;Chan et al., 2001;Senst et al., 2001;Onder et al., 2002;Wawruch et al., 2009;Ruiter et al., 2012;Parameswaran Nair et al., 2017), respectively. In Japan, 1.7% of hospitalizations are attributable to inappropriate drug use (Koinuma et al., 2006). ...
... Adverse drug events were the reason for 9.0% of all outpatient visits in Japan. This is consistent with the findings of various other studies reporting that adverse drug events are the reason for 5.5-53% of outpatient visits (Hanlon et al., 1997;Honigman et al., 2001;Gandhi et al., 2003). Furthermore, they accounted for 14.4% of all hospitalizations in this study, which is higher than the finding of another Japanese study that reported only 1.7% of hospitalizations owing to adverse drug events (Koinuma et al., 2006). ...
Article
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In Japan, medical costs are increasing annually, and the increase in national medical costs, particularly in the direct cost of managing adverse drug events, is high. An in-depth understanding of these costs is important for their reduction. This study aimed to calculate the direct cost of managing adverse drug events in all ages, including older adults, and that of avoidable adverse drug events in older adults. We conducted a retrospective survey on patients aged 1 year or older who visited Gifu Municipal Hospital in Japan. We investigated and calculated the direct cost of managing adverse drug events and that of avoidable adverse drug events based on the Beers Criteria Japanese version (BCJ) and “Guidelines for medical treatment and its safety in the elderly 2015” (GMTSE-2015) in inpatients and outpatients. Among 6,504 patients, 11.1% visited the hospital or were hospitalized due to adverse drug events. The direct costs per patient with adverse drug events were 21,281 and 22,590 yen (166 and 176 euros as on September 13, 2021) for outpatients, and 853,175 and 874,582 yen (6,648 and 6,815 euros) for inpatients of all ages and older adults, respectively. The direct costs of avoidable adverse drug events per patient using drugs listed in the BCJ and GMTSE-2015 for older adults were 3,212 and 3,341 yen (25 and 26 euros) for outpatients, and 55,548 and 80,246 yen (433 and 625 euros) for inpatients, respectively. In sum, considering both inpatients and outpatients in the whole country, the direct costs of managing adverse drug events were 804.53 billion and 597.19 billion yen (6,269 million and 4,653 million euros) per year for all ages and older ages, respectively. The direct cost of avoidable adverse drug events in older adults was 83.43–258.44 billion yen (650–2,013 million euros) per year. We found that, in Japan, high medical costs are often caused by managing adverse drug events, and that the costs of avoidable adverse drug events in older adults based on the BCJ and GMTSE-2015 account for a substantial proportion of the medical cost. Therefore, by using the BCJ and GMTSE-2015, avoiding adverse drug events and reducing medical costs may be possible.
... Within the framework of multimorbidity, polypharmacy acquires special importance. It is defined as the simultaneous consumption of ≥ 5 drugs and is considered the main determinant of potentially inappropriate prescription (PIP) in the elderly; this term encompasses excessive, incorrect, and insufficient prescriptions [8,9]. Currently, it is estimated that 40% of the elderly population are polymedicated, having 36.5% of them PIP. ...
Article
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Background The progressive ageing of the population is leading to an increase in multimorbidity and polypharmacy, which in turn may increase the risk of hospitalization and mortality. The enhancement of care with information and communications technology (ICT) can facilitate the use of prescription evaluation tools and support system for decision-making (DSS) with the potential of optimizing the healthcare delivery process. Objective To assess the effectiveness and cost-effectiveness of the complex intervention MULTIPAP Plus, compared to usual care, in improving prescriptions for young-old patients (65-74 years old) with multimorbidity and polypharmacy in primary care. Methods/design This is a pragmatic cluster-randomized clinical trial with a follow-up of 18 months in health centres of the Spanish National Health System. Unit of randomization: family physician. Unit of analysis: patient. Population Patients aged 65–74 years with multimorbidity (≥ 3 chronic diseases) and polypharmacy (≥ 5 drugs) during the previous 3 months were included. Sample size n = 1148 patients (574 per study arm). Intervention Complex intervention based on the ARIADNE principles with three components: (1) family physician (FP) training, (2) FP-patient interview, and (3) decision-making support system. Outcomes The primary outcome is a composite endpoint of hospital admission or death during the observation period measured as a binary outcome, and the secondary outcomes are number of hospital admission, all-cause mortality, use of health services, quality of life (EQ-5D-5L), functionality (WHODAS), falls, hip fractures, prescriptions and adherence to treatment. Clinical and sociodemographic factors will be explanatory variables. Statistical analysis The main result is the difference in percentages in the final composite endpoint variable at 18 months, with its corresponding 95% CI. Adjustments by the main confounding and prognostic factors will be performed through a multilevel analysis. All analyses will be carried out in accordance to the intention-to-treat principle. Discussion It is important to prevent the cascade of negative health and health care impacts attributable to the multimorbidity-polypharmacy binomial. ICT-enhanced routine clinical practice could improve the prescription process in patient care. Trial registration ClinicalTrials.gov NCT04147130 . Registered on 22 October 2019
... The focus on individuals over 65 years old is not unexpected as individuals over the age of 65 years are considered 'older' people in healthcare (NHS England, n.d.-b), and it is older people that are generally targeted for medication review services as they are at greater risk of poor health outcomes as a result of medications (Hanlon et al., 1997;Leipzig et al., 1999aLeipzig et al., , 1999b. ...
Thesis
Medication reviews are recognised as essential to identifying and optimising problematic polypharmacy. Domiciliary medication reviews (DMRs) which have become more prevalent in recent years, are identified as comprehensive and patient-centric medication reviews. Despite their popularity, there is little evidence on where the value of DMRs lies. This research aimed to understand the value of domiciliary medication reviews using mixed methods. The research was underpinned by a systematic review of the literature to understand the existing landscape around DMRs. Correlational techniques were used to explore the relationships between demographics and intervention variables. The deeper service-based perceptions and views of both patients and DMR pharmacists were sought using semi-structured interviews and focus groups. The systematic review revealed a very profession-centric view of DMRs that suggested the impact of these services could be measured using traditional clinical outcomes. The literature rarely went beyond describing clinical process measures. The quantitative analysis revealed that individuals have differing needs that go beyond the scope of the medications they take. Results suggested that a ‘one size fits all’ approach to service delivery will not work optimally, and instead a holistic and more comprehensive approach is needed. The qualitative analysis suggested that conducting medication reviews in the domiciliary setting afforded advantages over traditional healthcare settings. For individuals the medicines expertise of professionals is important but so too is the socialisation aspect of the review. The time spent conducting a review was essential for a comprehensive review and ensuring individuals felt heard. This multi-method and multi-perspective study enabled a richer understanding of where the added value of DMRs services might lie. It is suggested that the value lies in a well thought out service, delivered by knowledgeable medicines experts (pharmacists), who are able to connect with patients and understand their needs, even when they are not medication related.
... The inappropriate use of medication increases the risk of adverse drug events (ADEs) [1]. While ADEs are associated with an increased risk of hospital readmission [2,3], studies also suggest that most events are predictable and preventable [4][5][6], particularly through the integration of transitional care services [7,8] and the use of medication risk prediction tools [6]. ...
Article
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(1) Background: Adverse drug events and inappropriate use of medications lead to hospitalizations, medication-related morbidity, and mortality. This study examined whether a novel medication risk prediction tool, the MedWise Risk Score™, was associated with medication safety-related problem (MRP) identification and whether integration into an existing innovative transitions of care (TOC) service could decrease readmissions. (2) Methods: This retrospective comparator group study assessed patients discharged from a hospital in southern Arizona between January and December 2020. Participants were included in the study if they were 18 years of age or older, referred to the pharmacist for TOC services, and received a pharmacist consultation within one-week post discharge. Patients were categorized into two groups: (1) medication safety review (MSR)-TOC service (intervention) or (2) existing innovative TOC service (control). (3) Results: Of 164 participants, most were male (57%) and were between 70–79 years of age. Overall, there were significantly more drug-drug interactions (DDI) MRPs identified per patient in the intervention vs. control group for those who were readmitted (3.7 ± 1.5 vs. 0.9 ± 0.6, p < 0.001) and those who were not readmitted (2 ± 1.3 vs. 1.3 ± 1.2, p = 0.0120). Furthermore, of those who were readmitted, the average number of identified MRPs per patient was greater in the intervention group compared to the control (6.3 vs. 2.5, respectively, p > 0.05). Relative to the control, the readmission frequency was 30% lower in the treatment group; however, there was insufficient power to detect significant differences between groups. (4) Conclusions: The integration of a medication risk prediction tool into this existing TOC service identified more DDI MRPs compared to the previous innovative TOC service, which lends evidence that supports its ability to prevent readmissions. Future work is warranted to demonstrate the longitudinal impact of this intervention in a larger sample size.
... The prevalence and significance of drug-induced illness in old age have been well described [2][3][4][5][6][7][8][9][10] . Studies in different countries have shown that hospitalized elderly patients are two to three times more likely to experience an adverse drug reaction(ADR) than patients aged 20 to 30 years 6 . ...
Article
Full-text available
Kong T-K. Iatrogenesis - still a geriatric giant. J Hong Kong Geriatr Soc. 1997;8(1):3-5.
... Older adults who tend to be on polypharmacy show non-specific symptoms such as depression, falls, constipation, light-headedness, confusion, lethargy. [16] Hence, it becomes difficult to detect ADR in older adults. The ADR rate in older adults is at least three times that of the general population. ...
Article
Full-text available
The present manuscript highlights Beers guidelines till date and puts them at a single platform to enable the physicians, academicians, and patients for the safe and timely use of medicines. Potentially inappropriate medications (PIM) are medications in which adverse risks exceed its health benefits. Complex and multiple comorbidities in older adults make them use multiple drugs that further become a reason for exclusion from randomized clinical trials (RCT). Hence, no set guidelines or RCT-based scientific shreds of evidence are available to support prescription decisions. PIM has become an increasingly common problem in older adults; hence the American Geriatric Society updated Beers criteria; the most crucial strategy to check its use/misuse. The Beers criteria have been formulated in 1991 with the help of validated and appropriate screening tools that explain the use/avoidance of various drugs in older adults based on their health status and are being further updated as and when required. This change in Beers criteria is due to some limitations in the study population, emerging adverse drug reactions/new drug molecules, change in pharmacodynamics of medicines with changing physiology of older adults. Beers guidelines are being updated; however, few significant issues that are not being touched by the committee responsible for constituting the criteria.
... The criteria are applicable to older adults with the exception being those in palliative or hospice care. By some estimates, up to 30 percent of hospital admissions in elderly patients may be linked to drug related complications or side effects and so the choice to use these medications identi ied as higher risk must be weighed against possible harms [5]. As a result of this, therapeutic options for treatment of dizziness in the elderly population are limited. ...
Article
Full-text available
Background: Meclizine is a commonly prescribed medication for patients discharged from the Emergency Department (ED) with a diagnosis of peripheral vertigo, however it is on the Beers list of medications to avoid in elderly patients. Objectives: This study aims to determine the correlation between use of meclizine and return visits to the ED within 1 week in patients > 65 years old. Methods: This is a retrospective observational study conducted at 2 urban tertiary care EDs over 5 years. Inclusion criteria included patients > 65 years who were given meclizine in the ED or discharged with a prescription. Charts were reviewed for diagnosis, prescriptions and return visits within 7 days. Results: There were a total of 1608 patients over 65 years of age who met inclusion criteria, 669 patients identified as receiving meclizine in the ED and 962 who received no meclizine (ED or ED plus home prescription). Of the meclizine patients, 548 (84.8%) were given home prescriptions, of which there were 36 (6.6%) return visits within 7 days. Patients who were given meclizine while in the ED without home prescriptions (121) had 16 return visits (13.2%). Among the non-meclizine group, 102 patients (10.6%) had a return visit within 7 days. Conclusion: There was no increase in return visits in elderly patients discharged from the ED with a prescription for meclizine after a diagnosis of benign dizziness. Meclizine prescriptions at discharge were associated with fewer return visits to the ED within 1 week. Ongoing dizziness was the most common reason for return visits; there were no documented chief complaints of weakness, syncope/falls, or hypotension.
Article
Context Simplifying medication regimens by tapering and/or withdrawing unnecessary drugs is important to optimize quality of life and safety for patients with serious illness. Few resources are available to educate clinicians, patients and family caregivers about this process. Objective To describe the development of an educational program called Shared Medication PLanning In (SIMPLIfy) Home Hospice. Methods An environmental scan identified a state-of-the-art educational program for home hospice deprescribing that we adapted using a stakeholder panel engagement process. The stakeholder panel (2 hospice administrators, 3 nurses, 2 physicians, 2 pharmacists, and 2 former family caregivers) drawn from 2 geographically diverse hospice agencies reviewed the educational program and recommended additional content. Results Iterative rounds of review and feedback resulted in: (a) a 3-part clinician educational program (total duration=1.5 hour) that presents a standardized, goal-concordant, medication review approach to align medications and conversations about regimen simplification with patient and family caregiver goals of care; (b) a patient-family caregiver medication management educational notebook that presents common symptoms, hospice medications, and medication regimen simplification principles; and (c) a brief guide including helpful phrases to use as conversation starters for key steps in the program. A professional designer created thematic coherence for all materials that was well received by stakeholder panelists and hospice staff. Conclusion Educational materials can support hospice programs’ and clinicians’ efforts to implement goal-concordant medication simplification that optimizes end-of-life outcomes for patients and family caregivers. Evaluation of outcomes including medication appropriateness and family caregiver medication administration burden are not yet available.
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Background Adverse drug reactions (ADRs) represent a major cause of iatrogenic morbidity and mortality in patient care. While a substantial body of work has been undertaken to characterise ADRs in the hospital setting, the overall burden of ADRs in the primary care remains unclear. Objectives To investigate the prevalence of ADRs in the primary care setting and factors affecting the heterogeneity of the estimates. Methods Studies were identified through searching of Medline, Embase, CINAHL and IPA databases. We included observational studies that reported information on the prevalence of ADRs in patients receiving primary care. Disease and treatment specific studies were excluded. Quality of the included studies were assessed using Smyth ADRs adapted scale. A random-effects model was used to calculate the pooled estimate. Potential source of heterogeneity, including age groups, ADRs definitions, ADRs detection methods, study setting, quality of the studies, and sample size, were investigated using sub-group analysis and meta-regression. Results Thirty-three studies with a total study population of 1,568,164 individuals were included. The pooled prevalence of ADRs in the primary care setting was 8.32% (95% CI, 7.82, 8.83). The percentage of preventable ADRs ranged from 12.35–37.96%, with the pooled estimate of 22.96% (95% CI, 7.82, 38.09). Cardiovascular system drugs were the most commonly implicated medication class. Methods of ADRs detection, age group, setting, and sample size contributed significantly to the heterogeneity of the estimates. Conclusion ADRs constitute a significant health problem in the primary care setting. Further research should focus on examining whether ADRs affect subsequent clinical outcomes, particularly in high-risk therapeutic areas. This information may better inform strategies to reduce the burden of ADRs in the primary care setting.
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Background Potentially inappropriate prescribing which may lead to adverse drug events and linked to polypharmacy is becoming increasingly common in older patients. Objective This study applied the STOPP/START criteria to a clinical registry to determine the burden and profile of potentially inappropriate prescribing among patients attending a falls clinic. Setting University of Malaya Medical Centre Falls Clinic Method Data of individuals aged ≥ 65 years referred to the falls and syncope clinic were extracted from the falls registry. Potentially inappropriate prescribing was determined with the STOPP/START version 2 criteria. The relationship between potentially inappropriate prescribing with polypharmacy (≥ 5 medications), comorbidities and clinical variables were determined using Pearson’s chi-square and potential confounders adjusted for with multivariate regression. Main outcome measure Potentially inappropriate medicines and/or omitted medicines using STOPP/START criteria Results Data from 421 individuals, aged 77.8 ± 6.7 years and 53.4% women, were included. Potentially inappropriate prescribing was present in 311 (74%). Potentially inappropriate medicines use accounted for 84.6% of the 325 prescriptions. 361/659 instances (54.8%) were falls-risk-increasing drugs, with vasodilators (49.3%) being the main potentially inappropriate medicine identified. Of the 177/421 with polypharmacy, 169/177 (95.5%) were exposed to ≥ one potentially inappropriate medicine. 129 instances of potentially omitted medicines were observed in 109 prescriptions (25.9%). Conclusion STOPP/START criteria are useful to identify potentially inappropriate prescribing at the falls and syncope clinic. This finding has important implications for medication review strategies at falls clinic. Future research should determine whether identifying potentially inappropriate prescribing may reduce adverse falls outcomes among patients in this setting.
Article
• We interviewed 315 consecutive elderly patients admitted to an acute care hospital to determine the percentage of elderly hospital admissions due to noncompliance with medication regimens or adverse drug reactions, their causes, consequences, and predictors. Eighty-nine of the elderly admissions (28.2%) were drug related, 36 due to noncompliance (11.4%), and 53 due to adverse drug reactions (16.8%). One hundred three patients had a history of noncompliance (32.7%). Factors statistically associated with a higher risk of hospitalization due to noncompliance were poor recall of medication regimen, seeing numerous physicians, female, medium income category, use of numerous medications, and having the opinion that medications are expensive. Factors associated with an increased risk of an admission due to an adverse drug reaction were use of numerous different medications, higher medication costs, receiving Medicaid, and not receiving any home services. In conclusion, many elderly admissions are drug related; noncompliance accounting for a substantial fraction of these. Elders at high risk of being noncompliant are identifiable using a variety of criteria. Economic factors were important in predicting admissions due to noncompliance as well as adverse drug reactions. (Arch Intern Med. 1990;150:841-845)
Article
To select topics for quality assurance activities focusing on older patients, we convened a 14-member panel of physicians and experts in quality assurance. In two rounds of ratings, panelists rated 42 medical conditions (eg, pneumonia) in terms of their effects on patient outcomes, the availability of beneficial interventions, and the health benefits from improving current quality. They rated 27 health services (eg, adult day-care) on similar dimensions. The feasibility of doing quality assurance work on each condition and service also was rated. Using the ratings, the conditions selected for quality assurance work were congestive heart failure, hypertension, pneumonia, breast cancer, adverse effects of drugs, incontinence, and depression. Health care services selected were hospital discharge planning, acute inpatient care for the frail elderly, long-term—care facilities (intermediate-care facilities and skilled nursing facilities), home health care services, and case management. (JAMA 1987;258:1905-1908)
Article
Objectives. —To assess incidence and preventability of adverse drug events (ADEs) and potential ADEs. To analyze preventable events to develop prevention strategies.Design. —Prospective cohort study.Participants. —All 4031 adult admissions to a stratified random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical intensive care units and four medical and two surgical general care units.Main Outcome Measures. —Adverse drug events and potential ADEs.Methods. —Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented ADEs or potential ADEs and as to severity and preventability.Results. —Over 6 months, 247 ADEs and 194 potential ADEs were identified. Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions, for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs. Of all ADEs, 1% were fatal (none preventable), 12% life-threatening, 30% serious, and 57% significant. Twenty-eight percent were judged preventable. Of the life-threatening and serious ADEs, 42% were preventable, compared with 18% of significant ADEs. Errors resulting in preventable ADEs occurred most often at the stages of ordering (56%) and administration (34%); transcription (6%) and dispensing errors (4%) were less common. Errors were much more likely to be intercepted if the error occurred earlier in the process: 48% at the ordering stage vs 0% at the administration stage.Conclusion. —Adverse drug events were common and often preventable; serious ADEs were more likely to be preventable. Most resulted from errors at the ordering stage, but many also occurred at the administration stage. Prevention strategies should target both stages of the drug delivery process.(JAMA. 1995;274:29-34)
Article
Background: Preventable drug-related morbidity and mortality represent a serious medical problem that urgently requires expert attention. The costs to society of the misuse of prescription medications, in terms of morbidity, mortality, and treatment, can be immense. To date, research has primarily documented increased rates of hospitalization secondary to medication noncompliance and/or adverse drug effects.Objectives: To develop a conceptual model of drug-related morbidity and mortality, and to estimate the associated costs in the ambulatory setting in the United States.Methods: A probability pathway model was developed to estimate the cost of drug-related morbidity and mortality in the United States. Pharmacist practitioners were surveyed to determine conditional probabilities of therapeutic outcomes owing to drug therapy. Health care utilization and associated costs owing to negative therapeutic outcomes were estimated.Results: Drug-related morbidity and mortality was estimated to cost $76.6 billion in the ambulatory setting in the United States. The largest component of this total cost was associated with drug-related hospitalizations. When assumptions of the model were varied, the estimated cost ranged from a conservative estimate of $30.1 to $136.8 billion in a worst-case scenario.Conclusions: The cost of drug-related morbidity and mortality in the ambulatory setting in the United States is considerable and should be considered in health policy decisions with regard to pharmaceutical benefits. Policies and services should be developed to reduce and prevent drug-related morbidity and mortality.(Arch Intern Med. 1995;155:1949-1956)