21

Japanese Journal of Comprehensive Rehabilitation Science (2020)

Original Article

The impact of lesion location on medication self-management ability
in patients with cerebrovascular disease
Hisato Fujihara, Ph, PhD,1,2 Keiya Goto, Ph,3 Mayumi Higashino, Ph,2 Shoko Nakamura, Ph,1,2
Eriko Tanaka, Ph,1 Tomiko Sunaga, Ph, PhD,2 Nobuyuki Kawate, MD, PhD,4
Kazuyoshi Kawazoe, Ph, PhD,3 Toru Watanabe, Ph, PhD,2 Tadanori Sasaki, Ph, PhD2
Department of Pharmacy, Showa University Fujigaoka Rehabilitation Hospital, Yokohama, Japan
Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan3
Department of Clinical Pharmacy, Division of Natural Medicine and Therapeutics, School of Pharmacy, Showa
University, Tokyo, Japan
4
Department of Rehabilitation Medicine, School of Medicine, Showa University, Tokyo, Japan1
2

ABSTRACT
Fujihara H, Goto K, Higashino M, Nakamura S,
Tanaka E, Sunaga T, Kawate N, Kawazoe K, Watanabe
T, Sasaki T. The impact of lesion location on medication
self-management ability in patients with cerebrovasculardisease. Jpn J Compr Rehabil Sci 2020; 11: 21‐27.
Objective: To elucidate the impact of cerebrovascularlesion location on patients’ ability to manage their own
medications, we retrospectively investigated thedifferences in ability between the left hemispheredamage group (Group L) and the right hemispheredamage group (Group R).
Methods: In patients with cerebrovascular disease
who were discharged from the Kaifukuki rehabilitation
ward of our hospital between October 2011 and March2013 and between January 2016 and December 2017,
Group L and Group R were compared.
Results: The study subjects were 282 patients, andboth Group L and Group R had 141 patients each. The
length of time required for achieving medication selfmanagement was longer in Group L than in Group R(p = 0.02), showing a significant difference.
Conclusion: The delay in achieving medication selfmanagement in Group L was considered due toimpairment of the dominant arm by right hemiplegia,
which, unlike in Group R, hindered the dexterity
required for taking medications. In order for patientswith cerebrovascular disease to become capable ofCorrespondence: Hisato Fujihara, Ph, PhD
Department of Pharmacy, Showa University Fujigaoka
Rehabilitation Hospital, 2‐1‐1 Fujigaoka, Aoba-ku,
Yokohama, Kanagawa 227‐8518, Japan.
E-mail: h-fujihara@cmed.showa-u.ac.jp
Accepted: December 27, 2019
The authors have no conflict of interest directly relevant tothe content of this article.
©Kaifukuki Rehabilitation Ward Association 2020
doi.org/10.11336/jjcrs.11.21

managing their own medications, it is consideredessential to assist in developing medication support
plans according to lesion location.
Key words: medication self-management, cerebrovasculardisease, cerebrovascular lesion location, Kaifukuki
rehabilitation ward
Introduction
The cerebrum is broadly divided into the right andleft hemispheres, and cerebral vascular territories are
separated between the hemispheres. Cerebrovasculardisease damages each hemisphere individually.
Depending on the location of the lesion in the brain,patients exhibit various symptoms involving visual
perception[1], body[2], and cognitive function[3],as well as movement disorders[4], and theyalso experience different outcomes of subsequent
rehabilitation. Patients with right hemisphere damage
have been reported to have poor rehabilitation
outcomes[5, 6], and psychiatric symptoms such asattention impairment and affective flattening arepresumed to be one of the causes. Problems associatedwith rehabilitation in patients with right hemispheredamage are considered not due to clinical symptomsof the damage, but rather to characteristic behavioral
reactions caused by the clinical symptoms, such as
inattention, lowered insight, disorders of emotion/
motivation, and communication disorders. Whiledifferences in symptoms and roles between thehemispheres are becoming clear, there is no report on
the impact of lesion location in the brain on patients’
medication-taking behaviors. Such behaviors include
adherence, obtainment of medication knowledge, andself-management ability. In this study, we aimed
to elucidate the length of time required from the onsetof cerebrovascular damage to the introduction of
Jpn J Compr Rehabil Sci Vol 11, 2020

22 Fujihara H et al.: The impact of lesion location on medication self-management ability in patients with cerebrovascular disease
medication self-management for each lesion locationand factors influencing the patients’ ability to manage
their own medications by retrospectively investigating
differences in the ability between the left hemispheredamage group (Group L) and the right hemispheredamage group (Group R). Using the length of timerequired for medication self-management presumably
resulting from differences between Group L and GroupR as clinical indicators, we also analyzed factors
influencing the time period from the onset date of
cerebrovascular damage to the introduction of
medication self-management.
Methods
1. Study patients
In the Kaifukuki rehabilitation ward of Showa
University Fujigaoka Rehabilitation Hospital (hereafter“our hospital”), we retrospectively investigated thosepatients with cerebrovascular disease (cerebral
infarction, cerebral hemorrhage) who were discharged
between October 2011 and March 2013 and between
January 2016 and December 2017. Among the patients
who had achieved medication self-management, those
who subsequently had medication errors, such asincorrect medication dosage and usage, duringhospitalization were excluded from the study.
This study was conducted after review and approvalby the Institutional Review Board of Showa University
Fujigaoka Hospital (Approval No: F2017C74).
2. Investigation items
We investigated the following data from thepatients’ medical records: patient demographics (sex,age on admission), medication-related factors (thenumber of medications taken on admission, number of
medications taken per day, number of as-needed
medications taken on admission, number of topical
medications used on admission, use/nonuse of singledose packaging, achievement/non-achievement of

medication self-management at discharge, time period
from the onset date of cerebrovascular damage tothe introduction of medication self-management),
and disease-related factors (the disease, time period
from the onset date of cerebrovascular damage toadmission to our hospital and presence/absence of
dementia, aphasia, dysphagia, dyslalia, or hemiplegia).
Additionally, using the functional independence
measure (FIM) for the evaluation of activities of dailyliving (ADL), the patients’ scores on each FIM item on
admission were investigated. The patients’ admission
FIM scores were given by nurses or physical therapists
who worked in the Kaifukuki rehabilitation ward.
During the investigation period, data were collectedfrom paper medical records from October 2011
to March 2013 and from electronic medical records
from January 2016 to December 2017, but there were
no differences in the patients’ characteristics orrehabilitation program.
3. Criteria for the introduction of medication selfmanagement
The introduction of medication self-management
for inpatients in our hospital was indicated for patients
who had achieved all the eight items necessary for
medication-taking behaviors shown in Figure 1 andwere deemed capable of safely self-administering
medications after discussion with physicians,
pharmacists, nurses, and occupational therapists.
Medication self-management in this study was defined
as: “being able to take the correct medications asprescribed by the physician, at the right dose and at theright time, in the absence of the caregiver.” Patients
failing to do so were defined as noncompliant.
4. Comparison between Group L and Group R
Univariate analysis was performed to compare
the patient demographic factors, medication-related
factors, disease-related factors, and scores on each
FIM item between Group L and Group R.

Figure 1. Eight items that are necessary to introduce medication self-management.
Jpn J Compr Rehabil Sci Vol 11, 2020

Fujihara H et al.: The impact of lesion location on medication self-management ability in patients with cerebrovascular23
disease

5. Analysis of factors influencing medication selfmanagement in Group L and Group R
In Group L and Group R, subjects were divided into
self-management and non-self-management withineach group, and univariate analysis was performed.
In consideration of multicollinearity, the FIM item
was defined as the total score of the admission
FIM motor items and the admission FIM cognitive
items, and each FIM item was not used as afactor. Subsequently, logistic regression analysis was
performed using achievement/non-achievement of
medication self-management as an objective variable
and factors with significant differences noted by
univariate analysis as explanatory variables. Stepwise
backward selection was used for the selection of
explanatory variables. The validity of the regression
model was evaluated by the lack-of-fit (LOF) test andthe area under the receiver operating characteristic(ROC) curve, which is an indicator of the relationshipbetween estimated sensitivity and specificity.
6. Analysis of factors influencing the time period
from the onset date of cerebrovascular damage tothe introduction of medication self-management
Multiple regression analysis was performed using
the time period from the onset date of cerebrovasculardamage to the introduction of medication selfmanagement as an objective variable and patient
demographic factors, medication-related factors, diseaserelated factors, and FIM item scores as explanatory
variables. In consideration of multicollinearity, aphasia
and left/right hemiplegia were excluded from the factors,
and the FIM item was defined as the total score ofadmission FIM motor items and admission FIM cognitive
items. Stepwise backward selection was used for theselection of explanatory variables. In addition, thevariance inflation factor (VIF) was calculated to evaluate
the multicollinearity between the factors.
7. Statistical analysis
For comparisons between the two groups, theShapiro-Wilk W test was performed for continuous
variables. If data followed a normal distribution, thet-test was used; otherwise, the Wilcoxon rank-sum test
was used. Among categorical variables, the chisquared test was used for the presence/absence ofhemiplegia, Fisher’s exact test for other factors, and
the Wilcoxon rank-sum test for the comparison of FIM
item scores. The significance level was p < 0.05 for all
tests.
The statistical software used was JMP® Pro 14 (SASInstitute Inc., Cary, NC, USA).
Results
1. Patient backgroundThe study subjects were 282 patients with a mean
age of 69.9 ± 12.0 years, consisting of 186 men and 96
Table 1. Characteristics of the patients: host-related
factors (n = 282).
Variablen (%) or Mean ± SD

Age (years)
Sex
Male
FemaleDiagnosis
Cerebral infarction
Cerebral hemorrhage

69.9 ± 12.0
186 (66.0)
96 (34.0)
189 (67.0)
93 (33.0)

women. Of these, both Group L and Group R had 141
subjects each (Table 1).
2. Comparison between Group L and Group R
As a result of the Shapiro-Wilk W test, it was confirmedthat the data did not follow a normal distribution for anyof the investigation items. In the comparison of patient
background on admission between the self-management
and the non-self-management groups, significant
differences were observed in age, time period from theonset date of cerebrovascular damage to the introductionof medication self-management, presence/absence ofaphasia, and presence/absence of left/right hemiplegia.
Medication self-management was introduced to 50
patients in Group L and 56 patients in Group R (Table 2).
3. Analysis of factors influencing medication selfmanagement in Group L and Group R
Factors significantly different between the selfmanagement and non-self-management groups inGroup L were age, number of medications taken perday, number of as-needed medications taken on
admission, number of topical medications used on
admission, presence/absence of dysphagia, FIM motor
items, and FIM cognitive items, whereas those inGroup R were age, time period from the onset date of
cerebrovascular damage to admission to our hospital,
number of as-needed medications taken on admission,
number of topical medications used on admission,presence/absence of dementia and dysphagia, FIM
motor items, and FIM cognitive items (Table 3).
Results of the logistic regression analysis showed thatfactors associated with the introduction of medication
self-management in patients with cerebrovasculardisease were age and FIM cognitive items in Group L
and age, FIM motor items, and FIM cognitive items inGroup R (Table 4).
Evaluation of the validity of the regression model
showed that the p-value by LOF was 0.78 in Group L
and 0.99 in Group R; as both were greater than 0.05,
the estimated model was confirmed to be appropriate.
The values of the area under the ROC curve were 0.84
in Group L and 0.91 in Group R; as both were close to
1, the model was confirmed to be highly accurate.

Jpn J Compr Rehabil Sci Vol 11, 2020

24 Fujihara H et al.: The impact of lesion location on medication self-management ability in patients with cerebrovascular disease
Table 2. Comparison of variables between Group L and Group R.
Group L(n＝141)

Group R
(n＝141)n, Mean ± SD

n, Mean ± SD

Age (years)
Sex: Male/Female

68.3±12.1
98/43

71.5±11.6
88/53

0.02*
0.26

Number of drugs
Number of doses per day
Number of doses of medicine to betaken only once
Number of external medicines
One-dose packages
SM at discharge
Post-onset introduction of medication
self-management day (days)
Post-onset rehabilitation hospital day(days)
Dementia
Aphasia
Dysphagia
Dysarthria
Hemiplegia: left/right

5.9±3.4
3.5±2.0

5.7±3.5
3.5±1.90.43
0.93

0.6±0.9

0.7±0.90.42

0.7±1.2
9450

0.8±1.3
91
56

0.42
0.80
0.54

80.8±44.1

65.6±45.9

0.02*

28.1±17.2

27.9±16.0

0.87

7
65
39
59
6/110

15
12
44
58
114/8

0.12
<0.01*
0.60
1.00<0.01*

EatingGrooming
Bathing
Dressing upper body
Dressing lower body
Toileting
BladderBowel
Bed chair transfer
Toilet transfer
Tub shower transfer
Walking/wheelchair mobility
StairsComprehension
Expression
Social interaction
Problem-solving
MemoryMotor
Cognitive
Total

4.9±2.1
4.4±2.3
3.6±2.1
3.8±2.1
3.6±2.1
4.0±2.3
4.8±2.6
4.6±2.5
4.2±2.1
4.1±2.1
3.6±1.9
3.5±2.3
1.8±1.75.2±2.1
5.1±2.1
5.4±2.3
4.7±2.3
4.9±2.250.9±24.4
25.2±10.375.8±32.6

5.2±1.94.5±2.0
3.5±2.1
3.7±2.0
3.5±2.1
4.1±2.3
4.7±2.5
4.5±2.4
4.1±1.9
4.0±2.0
3.4±1.9
3.3±2.3
1.9±1.85.4±1.95.5±1.95.7±2.0
5.0±2.1
5.0±2.1
50.5±23.7
26.5±9.1
77.0±31.0

0.43
0.98
0.75
0.79
0.68
0.55
0.84
0.52
0.84
0.77
0.37
0.71
0.62
0.61
0.19
0.49
0.47
0.75
0.89
0.47
0.86

Variable
Characteristics of thepatients

Medication-related
items

Disease-related items

FIM items

p Value

SM, medication self-management group.
Significant difference, *p Value < 0.05.
4. Analysis of factors influencing the time period
from the onset date of cerebrovascular damage tothe introduction of medication self-management
As a result of the multiple regression analysis, thetime period from the onset date of cerebrovasculardamage to admission to our hospital, use/nonuse of
single-dose packaging, and FIM motor item scores
were extracted. The standard regression coefficients
Jpn J Compr Rehabil Sci Vol 11, 2020

were 56.62, 11.18, and －49.12, respectively, showingthat the time period from the onset date of
cerebrovascular damage to admission to our hospital
had the greatest influence. VIF was calculated to be ≤2 for each factor, confirming no influence ofmulticollinearity (Table 5).



5.4±3.3
2.9±2.1
0.5±0.9
0.4±0.93624.5±14.3
0
20
7
20
1
63.6±17.1
31.2±6.3

Number of drugs
Number of doses per day
Number of doses of medicine to be taken only once
Number of external medicines
One-dose packages

Post-onset rehabilitation hospital day (days)
Dementia
Aphasia
Dysphagia
Dysarthria
Hemiplegia: left/rightMotor
Cognitive

Medication-related items

Disease-related items

FIM items

SM, medication self-management group.
Significant difference, *p Value < 0.05.

63.2±12.2
39/11

43.8±25.1
21.9±10.730.1±18.3
7
45
32
39
5

6.3±3.4
3.9±1.9
0.7±0.8
0.9±1.35871.1±11.1
59/32

n, Mean ± SD

n, Mean ± SD

Age (years)
Sex: Male/Female

non-SM(n＝91)

SM(n＝50)

Characteristics of the patients

VariableGroup L

Table 3. Comparison of variables between medication self-management and non-medication self-management groups.

<0.01*<0.01*

0.06
0.05
0.30
<0.01*
0.86
0.39

0.11
<0.01*
0.04*<0.01*
0.36<0.01*
0.13

p Value69.4±15.7
32.8±3.422.9±9.9
2
3
11
28
43

5.4±3.4
3.1±1.6
0.5±0.7
0.5±1.03666.2±11.6
37/19

n, Mean ± SD

SM
(n＝56)

38.1±19.4
22.4±9.3

31.2±18.3
13
9
33
30
71

6.0±3.6
3.7±2.1
0.9±1.0
1.0±1.45574.9±10.3
51/34

n, Mean ± SD

non-SM(n＝85)

Group R

<0.01*<0.01*<0.01*
0.03*
0.36
0.02*
0.12
0.60

0.25
0.07
0.04*
0.02*
1.00

<0.01*
0.48

p ValueFujihara H et al.: The impact of lesion location on medication self-management ability in patients with cerebrovascular25
diseaseJpn J Compr Rehabil Sci Vol 11, 2020

26 Fujihara H et al.: The impact of lesion location on medication self-management ability in patients with cerebrovascular disease
Table 4. Results of stepwise multiple regression analyses.
Group L (n＝141)
Variable

Regression coefficient

Odds ratio

95% confidence
interval

－0.08
0.15
0.50

0.92
1.16

0.89‐0.96
1.09‐1.24

Regression coefficient

Odds ratio

95% confidence
interval

－0.05
0.07
0.15
－5.26

0.95
1.07
1.16

0.91‐1.00
1.04‐1.11
1.03‐1.31

Age (years)
Cognitive FIM
Intercept

p Value
0.04
<0.01
0.05

LOF: 0.78.
Area under ROC curve: 0.84.
Group R (n＝141)
VariableAge (years)
Motor FIM
Cognitive FIM
Intercept

p Value
0.03
<0.01
0.02
0.05

LOF: 0.99.
Area under ROC curve: 0.91.
Table 5. Multiple regression analysis for post-onset introduction of medication self-management day.
Variable
Post-onset rehabilitation
hospital day (days)
One-dose packages
Motor FIM
Intercept

Parameter
estimate

Standarderror

t Valuep Value

VIF

Standardized
estimate

95% confidence
interval

1.22

0.25

4.91

<0.01

1.03

56.62

33.76‐79.47

11.18
－1.42
134.87

3.35
0.19
14.91

3.34
－7.55
9.05

<0.01
<0.01
<0.01

1.13
1.12
―

11.18
－49.12
68.79

4.54‐17.81－62.02‐－36.21
62.50‐75.07

VIF, variance inflation factor.

Discussion
In this study, we used data on patients withcerebrovascular disease, including FIM items andmedication-related information on admission, andexamined differences in the medication selfmanagement ability between Group L and Group R.
In the comparison between Group L and GroupR, significant differences were observed in the“presence/absence of aphasia,” “presence/absence ofhemiplegia,” and “time period from the onset date of
cerebrovascular damage to the introduction of
medication self-management.” It was confirmed that
medication self-management was introduced to GroupR more than 2 weeks earlier on average than to GroupL. Previous studies have indicated that patients inGroup R have poor adaptation in rehabilitation after
cerebrovascular damage despite the advantages ofbeing less likely to exhibit aphasia and having thedominant hand unaffected [5, 6]. However, in thisstudy, medication self-management was achieved
Jpn J Compr Rehabil Sci Vol 11, 2020

earlier in Group R than in Group L. This may be
associated with the presence/absence of aphasia andhemiplegia. Regarding aphasia, there is a report on
medication guidance for patients with the disorder.
Horikawa et al. pointed out that because understanding
medication guidance depends on the ability tounderstand language, it takes time for aphasia patientsto learn its contents and establish a relationship withpharmacists, which consequently shortens the lengthof time spent on medication guidance for aphasia
patients compared to other patients[7]. Medication
guidance for aphasia patients requires collaboration
with speech-language-hearing therapists, andpharmacists need to establish relationships withpatients and provide appropriate medication guidance
after understanding the patients’ language disorder.
In addition, many patients in Group L have impaired
right-hand performance due to right hemiplegia, which
may hinder the dexterity required for taking
medications, such as “removal of medications.” In an
investigation that conducted a handedness test inFujihara H et al.: The impact of lesion location on medication self-management ability in patients with cerebrovascular27
diseaseJapanese subjects, 90.5% of the subjects were reported
to be right-handed[8], indicating a high likelihood of
impaired dominant hand function in Group L.
Therefore, the length of time required for a switch inhandedness in occupational therapy was considered toplay a part in the delay in introducing medication selfmanagement.
The common factors associated with the introductionof medication self-management in Group R and GroupL were age and FIM cognitive score. The FIM motorscore was also identified in Group R. In a preceding
study on the introduction of medication selfmanagement in stroke patients, age, FIM motor items(walk/wheelchair), and FIM cognitive items (memory)
were reported to be factors influencing the introductionof medication self-management[9], which are similar
to our findings. However, the present study confirmedthat “FIM motor items” affect Group R but have little
association with Group L. This is because, sincepatients in Group L suffer impairment in the rightarm, which is dominant for most patients, the inability
to maintain dexterity presumably led to greater
dependence on cognitive skills than motor skills. On
the other hand, patients in Group R retain their
dominant hand function and thus, much of their motor
function remains along with their cognitive function.
This was suggested to be a factor leading to theintroduction of medication self-management.
Factors influencing the length of time required forachieving medication self-management were “timeperiod from the onset date of cerebrovascular damage
to admission to our hospital,” “single-dose packaging,”and “FIM motor items.” “Time period from the onset
date of cerebrovascular damage to hospital admission”
has been reported as a factor contributing to a decline
in the rate of successful return to home and prolongationof hospital stay, and similar results were also obtainedin this study. This may be because the severity of thedisease requiring prolongation of acute treatment anddelayed patient transfer to the Kaifukuki rehabilitation
ward delay the initiation of intensive rehabilitation,consequently delaying an elevation in ADL.
“Single-dose packaging” was also a factor
contributing to the delayed introduction of medication
self-management. This may be due to the backgroundleading to the use of single-dose packaging or thecondition of the packaging itself. There is a reportclaiming that patients’ awareness of what they aretaking affects their medication-taking behaviors[10].
Patients may not be able to recognize the types of
medications they are taking due to the single-dose
packaging, which can be a factor hindering medication
compliance. Single-dose packaging is a useful method
for patients who have trouble removing medications
from the packages due to paralysis and otherconditions, but needlessly suggesting its use should be
avoided. Instead, it would be worth identifying patients
who truly need single-dose packaging and workingwith them to solve the problem while providing
appropriate information.
One limitation of this study is that there was asignificant difference in age in the patient backgroundbetween Group L and Group R. Age has been reported
to be a negative factor in the achievement of medication
self-management in stroke patients[9]. In this study,
the mean age was higher in Group R than in Group L,
and thus data on the non-self-management in Group R
unavoidably affected the analysis. Additionally, as
this study was conducted retrospectively, patients’
dominant hand could not be identified from their
medical records. Since the discussion in this study
was based on the report that “a large proportionof the population are right-handed,” a prospective
investigation encompassing patients’ handedness is
considered necessary. Although this study was acomparison between Group L and Group R, further
investigations and analyses are needed taking into
consideration the impact of disease and severity.

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