- Email: [email protected]
Risk Factors for Falls in Community Stroke Survivors: A Systematic Review and Meta-Analysis
Accepted Manuscript Risk factors for falls in community stroke survivors: A systematic review and metaanalysis Tianma Xu, MOT, Lindy Clemson, PhD, Kate O’Loughlin, PhD, Natasha A. Lannin, PhD, Catherine Dean, PhD, Gerald Koh, MD, PhD PII:
S0003-9993(17)30528-2
DOI:
10.1016/j.apmr.2017.06.032
Reference:
YAPMR 56975
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 26 March 2017 Revised Date:
19 June 2017
Accepted Date: 25 June 2017
Please cite this article as: Xu T, Clemson L, O’Loughlin K, Lannin NA, Dean C, Koh G, Risk factors for falls in community stroke survivors: A systematic review and meta-analysis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/j.apmr.2017.06.032. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Running head: Fall risk factors after stroke
ACCEPTED MANUSCRIPT
Risk factors for falls in community stroke survivors: A systematic review and metaanalysis Tianma Xu, MOT,
a,b
a
a
Lindy Clemson, PhD, Kate O’Loughlin, PhD, Natasha A. Lannin,
c
d
e
RI PT
PhD, Catherine Dean, PhD, Gerald Koh, MD, PhD a
From the Ageing Work and Health Research Group, Faculty of Health Sciences, University of Sydney, Sydney, Australia;
b
Health & Social Sciences Cluster, Singapore Institute of Technology, Singapore;
c
SC
Department of Community and Clinical Allied Health, La Trobe Clinical School La Trobe University, d
e
M AN U
Melbourne, Australia; Department of Health Professions, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia; Saw Swee Hock School of Public Health, National University of Singapore, Singapore;
Presented with preliminary results to the National Occupational Therapy Conference, 10
TE D
October 2015, Singapore; and full findings to the 7th Biennial Australian and New Zealand Falls Prevention Conference, 29 November 2016, Melbourne, Australia.
EP
Acknowledgement
AC C
Tianma Xu is supported by Singapore Institute of Technology for his Ph.D. study at the University of Sydney. We also would like to thank Professor Deborah Black from the University of Sydney for her statistical support in the meta-analysis.
Conflicts of interest We have no conflict of interest.
Corresponding author:
Running head: Fall risk factors after stroke
ACCEPTED MANUSCRIPT
Tianma Xu (MOT) Ageing Work & Health Research Unit Faculty of Health Sciences
75 East St, Lidcombe, NSW, 2141, Australia
RI PT
The University of Sydney,
Telephone: +61290367483 or +6565928673
AC C
EP
TE D
M AN U
Systematic Review Registration No.: CRD42015023389
SC
Email address: [email protected] or [email protected]
ACCEPTED MANUSCRIPT Risk factors for falls in community stroke survivors: A systematic review and metaanalysis
Abstract
RI PT
Objective: To identify the risk factors for falls in community stroke survivors.
Data Sources: A comprehensive search for articles indexed on MEDLINE, EMBASE,
CINAHL, PsychINFO, Cochrane Library, and Web of Science databases was conducted.
SC
Study Selection: Prospective studies investigating fall risk factors in community stroke survivors were included. Reviewers in pair independently screened the articles and
M AN U
determined inclusion through consensus. Studies meeting acceptable quality rating using the Q-Coh were included in the meta-analysis.
Data Extraction: Data extraction was done in duplicate by four reviewers using a standardized data extraction sheet, and confirmed by another independent reviewer for
TE D
completeness and accuracy.
Data Synthesis: Twenty-one articles met the minimum criteria for inclusion; risk factors investigated by three or more studies (n=16) were included in a meta-analysis. The following
EP
risk factors had strong association with all fallers: impaired mobility (OR 4.36, CI 2.68-7.10);
AC C
reduced balance (OR 3.87, CI 2.39-6.26); use of sedative / psychotropic medications (OR 3.19, CI 1.36-7.48); disability in self-care (OR 2.30, CI 1.51-3.49); depression (OR 2.11, CI 1.18-3.75); cognitive impairment (OR 1.75, CI 1.02-2.99); and history of fall (OR 1.67, CI 1.03-2.72). A history of falling (OR 4.19, CI 2.05-7.01) had a stronger association with recurrent fallers. Conclusions: This study confirms that balance and mobility problems, assisted self-care, taking sedative or psychotropic medications, cognitive impairment, depression, and history of falling are associated with falls in community stroke survivors. We recommend that any
1
ACCEPTED MANUSCRIPT future research into falls prevention programs should consider addressing these modifiable risk factors. As the risk factors for falls in community stroke survivors are multifactorial,
Keywords: Community; Stroke; Accidental falls; Risk factors; Rehabilitation
SC
List of Abbreviations:
RI PT
interventions should be multi-dimensional.
activities of daily living
OR
odds ratios
CI
confidence interval
RR
Relative Risk, Risk Ratio or Rate Ratio
MMSE
Mini-Mental State Examination
BBS
Berg Balance Scale
10MWT
10 metre walk test
TUG
timed up and go
FIM
Functional Independence Measure
AC C
EP
TE D
M AN U
ADL
2
ACCEPTED MANUSCRIPT Falls are one of the most frequent complications after stroke.1 Stroke survivors are more likely to
2
fall than the general aging population and this could lead to greater deficits in activities of daily
3
living (ADL) and mobility functions.2-4 The prevalence of falls among stroke survivors during the
4
first six months after discharge from hospital is between 36% and 73%,5-7 and fall rates remain
5
high between 40% and 58% among these individuals one year after stroke.8-11 More stroke
6
survivors report falls in the first months post-stroke after discharge from the hospital and almost
7
one out of three have a near-fall each month.12 Two-thirds of the stroke survivors fall indoors13-15
8
and ambulatory stroke survivors are more likely to fall compared to those with higher dependency
9
levels and reduced mobility.16 Among those who fall, walking and transfers are the most
SC
frequently mentioned activities at the time of fall.2
M AN U
10
RI PT
1
11
The consequences of falls can cause further physical complications among stroke survivors in the
13
community, such as soft tissue injuries,7 fractures,17 and restriction in functional activities.17 Once
14
stroke survivors sustain a hip fracture, they are less likely to regain independent mobility than the
15
general population.18 At the same time, stroke survivors often develop psychosocial issues from
16
falling. The most common are depression19 and fear of falling,20 which can further reduce their
17
level of activity leading to further physical deconditioning and loss of independence.21
EP
AC C
18
TE D
12
19
Understanding the risk factors for falls among community stroke survivors is crucial to
20
developing an effective community falls prevention program. A number of cohort and case-
21
control studies have reported that the risk of falls among community stroke survivors may
22
increase with reduced balance,6 fear of falling,22, 23 depressive symptoms,24 a fall history during
23
hospitalization,6, 7 motor and sensory impairment,23 and environmental safety hazards.24 However,
24
there has been no systematic comprehensive review on fall predictors among stroke survivors
25
after their discharge from hospital. A previous systematic review25 in 2009 published in the Dutch
26
language included stroke participants from both hospital and community settings. However, it had 3
ACCEPTED MANUSCRIPT 27
broader inclusion criteria and did not include meta-analysis, presenting the results as a descriptive
28
review. Furthermore, they did not distinguish between hospital and community settings.25 This
29
systematic review and meta-analysis aims to identify the risk factors for falls in stroke survivors
30
discharged from hospital and residing in the community, the setting where most falls occur.
RI PT
31
Methods
33
A systematic review protocol was developed before the review commenced. The detail of the
34
protocol was registered on the PROSPERO database under registration number
35
CRD42015023389. Review methods followed the Preferred Reporting Items for Systematic
36
Reviews and Meta-Analysis (PRISMA)26 and Meta-Analysis of Observational Studies in
37
Epidemiology (MOOSE)27 guidelines.
38
M AN U
SC
32
Search Strategy
40
A broad search strategy was used; combinations included Medical Subject Headings, text words
41
and word variants for three main themes: “stroke”, “falls”, and “study type”. As in similar
42
reviews,25, 28, 29 title and abstract were searched (up to June 2015) in the following electronic
43
databases: MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library (Cochrane Database of
44
Systematic Review) and Web of sciences. For example, under “study type”, we included the
45
following key words in our comprehensive search: prospective or cohort or case-control or
46
follow-up or observational or cohort study or case-control study or observational study. Full
47
search terms are available upon request. Additionally, bibliographies of identified publications
48
and published reviews were hand searched for potentially relevant articles. An email alert function
49
in electronic databases was created to keep track of any later published articles that may meet the
50
selection criteria based on saved search history up to 31 May 2016.
AC C
EP
TE D
39
51
4
ACCEPTED MANUSCRIPT Study Selection
53
We included prospective cohort studies and case-control studies where all participants were 18
54
years and above and clinically diagnosed with either first stroke or recurrent stroke. There was no
55
restriction on the year of publication but was limited to English literature. Studies were included if
56
at least 80% of the stroke participants in the study were being followed up in the community or
57
non-institutionalized setting for a minimum period of three months. Clinical trials and
58
retrospective studies were excluded. Studies conducted only during the hospitalization period or at
59
residential care facilities were excluded. The primary outcomes were the risk factors for all fallers
60
defined as community stroke survivors with at least one fall during follow-up. The secondary
61
outcomes were the risk factors for recurrent fallers defined as community stroke survivors with
62
two or more falls during follow-up.
63
M AN U
SC
RI PT
52
Data Extraction
65
One reviewer (TX) screened titles and based on inclusion criteria, rated them as relevant, not
66
relevant or maybe relevant. Abstracts for titles indicated with “yes” and “maybe” were
67
independently scrutinized by a pair of reviewers (TX & LC). The selected articles were then
68
reviewed independently in full text by two reviewers (TX, LC, KO, CD or NL). Any disagreement
69
was discussed among at least three reviewers until consensus was reached. The following data
70
was abstracted in duplicate by four reviewers (TX, LC, CD, and KO) using a standardized data
71
extraction sheet. The data extraction sheet included year of publication, country of study, sample
72
size, mean age of the participants, mean time since stroke at baseline assessment (duration of
73
stroke), frequency of fall assessment, duration of follow-up, proportion of fallers, and risk factors
74
for falls. The binary outcome variables reporting odds ratio (OR) with 95% Confidence Intervals
75
(CI) for each risk factor were extracted. Results reported in non-ORs, such as Relative Risk, Risk
76
Ratio or Rate Ratio (RR), were also extracted. When raw data is available to calculate the OR in
77
another study,30 we calculated the OR with 95% confidence intervals using an online statistical
AC C
EP
TE D
64
5
ACCEPTED MANUSCRIPT OR calculator (Appendix A, Table 1).31 The different categories of frequency of fall assessment
79
used in our data extraction were based on the Deandera et al’s systematic review.28 All extracted
80
data on proportions of fallers and risk factors were categorized into all fallers and recurrent fallers.
81
All findings from the selected studies were collated based on the common characteristics of
82
participants, and the primary and secondary outcomes of this review. Another independent
83
reviewer (NL) confirmed all data entries and checked for completeness and accuracy.
RI PT
78
84
Quality Assessment
86
The evaluation of the methodological quality of primary studies is a key process in systematic
87
review and meta-analysis. Strengthening the Reporting of Observational Studies in Epidemiology
88
statement (STROBE)32 was used as a general guide for the reviewers to determine whether the
89
selected observational studies were well reported. The quality assessment tool for cohort studies
90
called “Q-Coh”33 has established its inter-rater reliability (kappa: 0.68 to 0.87) and acceptable
91
validity, and it classifies methodological quality as either good, satisfactory or low.33 Hence, it
92
was used to select studies with good or satisfactory methodological quality to be included in the
93
meta-analysis. The Q-Coh tool was adapted by creating a standardized approach to decisions
94
when reviewing components and determining rating scales relevant to falls. A list of confounders
95
considered important to be controlled in fall studies was also defined before conducting the
96
quality assessment and they were age, gender, falls before stroke, falls in the hospital, length of
97
stay in the hospital, rehabilitation before and during the study.34 All selected studies were assessed
98
for risk of bias using the adapted Q-Coh by two independent reviewers (TX, LC, KO, CD). All
99
disagreements were solved in a consensus meeting. Any studies with good or satisfactory
100
AC C
EP
TE D
M AN U
SC
85
methodological quality were included in the meta-analysis.
101 102
Statistical analysis
6
ACCEPTED MANUSCRIPT In view of the wide range of potential risk factors being investigated across studies, only binary
104
outcome variables with 95% CI investigated by at least three studies in a comparable manner were
105
included in the meta-analysis. Decisions regarding inclusion of studies that can be meaningfully
106
compared were based on the validity of the outcome measures for measuring the domain of
107
interest. When different statistical analysis (e.g. both univariate analysis and multivariate analysis)
108
was used for the same risk factor in the study, the unadjusted results from the univariate statistical
109
analysis were pooled in the meta-analysis. However, when only adjusted results or results from
110
multivariate statistical analysis were presented in the study, these were included in the meta-
111
analysis.
SC
RI PT
103
M AN U
112
Since falls are more common in the studied population, the OR will considerably overestimate the
114
relative risk, or in other words, the relative risk will underestimate the OR if we combine both in
115
the meta-analysis.35, 36 Hence, we analysed all outcome variables reported in ORs and non-ORs
116
separately using the Comprehensive Meta-Analysis software (version 2.0)37 to generate pooled
117
estimates of effect sizes for each risk factor. We used the random-effects model with 95% CI for
118
all analyses in consideration of the diverse effect sizes of the included studies. The random-effects
119
model allowed us to estimate the mean of a distribution of effects from the selected studies in
120
meta-analysis.38 The i²-test was used to test the level of heterogeneity among the included studies.
121
The i²-test has been recommended as one of the most preferred and reliable tests for
122
heterogeneity,39 which represents the degree of variation in estimated effects across studies. It has
123
proposed that low heterogeneity is if the i² value falls lower than 50%, moderate for 50-75%, and
124
high for above 75%.40 All binary outcome variables or the risk factors reported in ORs were
125
pooled together for analyses and the respective risk factors reported in non-ORs were analysed
126
separately to support the findings from pooled ORs.
AC C
EP
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113
127 128
Results 7
ACCEPTED MANUSCRIPT Study selection
130
Figure 1 summarises the flow of searches, inclusions, and exclusions. It included one eligible
131
study41 that was found from the database email alert system. Twenty-one studies including 19
132
cohort studies and two case-control studies met the selection criteria and were assessed for risk of
133
bias using the adapted Q-Coh tool.33
134
RI PT
129
135
Methodological quality
137
The summary of quality assessment is presented in appendix A, table 2. A study was considered
138
as “good” quality if at least six domain items in Q-Coh were given positive ratings and
139
“acceptable” quality if four or five domain items were rated as positive. Anything below was
140
considered as “low” quality. Out of the 21 papers, seven papers4, 5, 8, 24, 41-43 were rated as “good”
141
quality and nine papers6, 10, 11, 16, 30, 44-47 were rated as “acceptable” quality. The remaining five
142
papers7, 12, 48-50 were rated as “low” quality and excluded in the meta-analysis.
M AN U
TE D
143
SC
136
Characteristics of included studies
145
Study characteristics of the 16 included studies are displayed in table 1. Studies were conducted
146
in the community settings across different continents (Asia Pacific, Europe, and North America)
147
with a mean cohort age of sixty-nine years old, mean sample size less than 300 (range: 3011 –
148
117445), and published between 200224 and 2015.41 The range of follow-up period was from four
149
months24 to two years.44, 45 Out of the 16 studies, 11 studies5, 11, 16, 24, 30, 41-43, 45-47 identified risk
150
factors for all fallers, three studies4, 6, 8 identified risk factors for recurrent fallers, and two
151
studies10, 44 reported risk factors for both all fallers and recurrent fallers. A total number of 4,160
152
stroke participants from 16 studies and 1,116 (27%) stroke participants were classified as fallers.
153
The proportion of all fallers across studies ranged from 23%24 to 55%,8 and recurrent fallers from
154
5%44 to 42%.8 Summary characteristics of the included studies are shown in appendix A, table 3.
AC C
EP
144
8
ACCEPTED MANUSCRIPT 155
S0003-9993(17)30528-2
DOI:
10.1016/j.apmr.2017.06.032
Reference:
YAPMR 56975
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 26 March 2017 Revised Date:
19 June 2017
Accepted Date: 25 June 2017
Please cite this article as: Xu T, Clemson L, O’Loughlin K, Lannin NA, Dean C, Koh G, Risk factors for falls in community stroke survivors: A systematic review and meta-analysis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/j.apmr.2017.06.032. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Running head: Fall risk factors after stroke
ACCEPTED MANUSCRIPT
Risk factors for falls in community stroke survivors: A systematic review and metaanalysis Tianma Xu, MOT,
a,b
a
a
Lindy Clemson, PhD, Kate O’Loughlin, PhD, Natasha A. Lannin,
c
d
e
RI PT
PhD, Catherine Dean, PhD, Gerald Koh, MD, PhD a
From the Ageing Work and Health Research Group, Faculty of Health Sciences, University of Sydney, Sydney, Australia;
b
Health & Social Sciences Cluster, Singapore Institute of Technology, Singapore;
c
SC
Department of Community and Clinical Allied Health, La Trobe Clinical School La Trobe University, d
e
M AN U
Melbourne, Australia; Department of Health Professions, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia; Saw Swee Hock School of Public Health, National University of Singapore, Singapore;
Presented with preliminary results to the National Occupational Therapy Conference, 10
TE D
October 2015, Singapore; and full findings to the 7th Biennial Australian and New Zealand Falls Prevention Conference, 29 November 2016, Melbourne, Australia.
EP
Acknowledgement
AC C
Tianma Xu is supported by Singapore Institute of Technology for his Ph.D. study at the University of Sydney. We also would like to thank Professor Deborah Black from the University of Sydney for her statistical support in the meta-analysis.
Conflicts of interest We have no conflict of interest.
Corresponding author:
Running head: Fall risk factors after stroke
ACCEPTED MANUSCRIPT
Tianma Xu (MOT) Ageing Work & Health Research Unit Faculty of Health Sciences
75 East St, Lidcombe, NSW, 2141, Australia
RI PT
The University of Sydney,
Telephone: +61290367483 or +6565928673
AC C
EP
TE D
M AN U
Systematic Review Registration No.: CRD42015023389
SC
Email address: [email protected] or [email protected]
ACCEPTED MANUSCRIPT Risk factors for falls in community stroke survivors: A systematic review and metaanalysis
Abstract
RI PT
Objective: To identify the risk factors for falls in community stroke survivors.
Data Sources: A comprehensive search for articles indexed on MEDLINE, EMBASE,
CINAHL, PsychINFO, Cochrane Library, and Web of Science databases was conducted.
SC
Study Selection: Prospective studies investigating fall risk factors in community stroke survivors were included. Reviewers in pair independently screened the articles and
M AN U
determined inclusion through consensus. Studies meeting acceptable quality rating using the Q-Coh were included in the meta-analysis.
Data Extraction: Data extraction was done in duplicate by four reviewers using a standardized data extraction sheet, and confirmed by another independent reviewer for
TE D
completeness and accuracy.
Data Synthesis: Twenty-one articles met the minimum criteria for inclusion; risk factors investigated by three or more studies (n=16) were included in a meta-analysis. The following
EP
risk factors had strong association with all fallers: impaired mobility (OR 4.36, CI 2.68-7.10);
AC C
reduced balance (OR 3.87, CI 2.39-6.26); use of sedative / psychotropic medications (OR 3.19, CI 1.36-7.48); disability in self-care (OR 2.30, CI 1.51-3.49); depression (OR 2.11, CI 1.18-3.75); cognitive impairment (OR 1.75, CI 1.02-2.99); and history of fall (OR 1.67, CI 1.03-2.72). A history of falling (OR 4.19, CI 2.05-7.01) had a stronger association with recurrent fallers. Conclusions: This study confirms that balance and mobility problems, assisted self-care, taking sedative or psychotropic medications, cognitive impairment, depression, and history of falling are associated with falls in community stroke survivors. We recommend that any
1
ACCEPTED MANUSCRIPT future research into falls prevention programs should consider addressing these modifiable risk factors. As the risk factors for falls in community stroke survivors are multifactorial,
Keywords: Community; Stroke; Accidental falls; Risk factors; Rehabilitation
SC
List of Abbreviations:
RI PT
interventions should be multi-dimensional.
activities of daily living
OR
odds ratios
CI
confidence interval
RR
Relative Risk, Risk Ratio or Rate Ratio
MMSE
Mini-Mental State Examination
BBS
Berg Balance Scale
10MWT
10 metre walk test
TUG
timed up and go
FIM
Functional Independence Measure
AC C
EP
TE D
M AN U
ADL
2
ACCEPTED MANUSCRIPT Falls are one of the most frequent complications after stroke.1 Stroke survivors are more likely to
2
fall than the general aging population and this could lead to greater deficits in activities of daily
3
living (ADL) and mobility functions.2-4 The prevalence of falls among stroke survivors during the
4
first six months after discharge from hospital is between 36% and 73%,5-7 and fall rates remain
5
high between 40% and 58% among these individuals one year after stroke.8-11 More stroke
6
survivors report falls in the first months post-stroke after discharge from the hospital and almost
7
one out of three have a near-fall each month.12 Two-thirds of the stroke survivors fall indoors13-15
8
and ambulatory stroke survivors are more likely to fall compared to those with higher dependency
9
levels and reduced mobility.16 Among those who fall, walking and transfers are the most
SC
frequently mentioned activities at the time of fall.2
M AN U
10
RI PT
1
11
The consequences of falls can cause further physical complications among stroke survivors in the
13
community, such as soft tissue injuries,7 fractures,17 and restriction in functional activities.17 Once
14
stroke survivors sustain a hip fracture, they are less likely to regain independent mobility than the
15
general population.18 At the same time, stroke survivors often develop psychosocial issues from
16
falling. The most common are depression19 and fear of falling,20 which can further reduce their
17
level of activity leading to further physical deconditioning and loss of independence.21
EP
AC C
18
TE D
12
19
Understanding the risk factors for falls among community stroke survivors is crucial to
20
developing an effective community falls prevention program. A number of cohort and case-
21
control studies have reported that the risk of falls among community stroke survivors may
22
increase with reduced balance,6 fear of falling,22, 23 depressive symptoms,24 a fall history during
23
hospitalization,6, 7 motor and sensory impairment,23 and environmental safety hazards.24 However,
24
there has been no systematic comprehensive review on fall predictors among stroke survivors
25
after their discharge from hospital. A previous systematic review25 in 2009 published in the Dutch
26
language included stroke participants from both hospital and community settings. However, it had 3
ACCEPTED MANUSCRIPT 27
broader inclusion criteria and did not include meta-analysis, presenting the results as a descriptive
28
review. Furthermore, they did not distinguish between hospital and community settings.25 This
29
systematic review and meta-analysis aims to identify the risk factors for falls in stroke survivors
30
discharged from hospital and residing in the community, the setting where most falls occur.
RI PT
31
Methods
33
A systematic review protocol was developed before the review commenced. The detail of the
34
protocol was registered on the PROSPERO database under registration number
35
CRD42015023389. Review methods followed the Preferred Reporting Items for Systematic
36
Reviews and Meta-Analysis (PRISMA)26 and Meta-Analysis of Observational Studies in
37
Epidemiology (MOOSE)27 guidelines.
38
M AN U
SC
32
Search Strategy
40
A broad search strategy was used; combinations included Medical Subject Headings, text words
41
and word variants for three main themes: “stroke”, “falls”, and “study type”. As in similar
42
reviews,25, 28, 29 title and abstract were searched (up to June 2015) in the following electronic
43
databases: MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library (Cochrane Database of
44
Systematic Review) and Web of sciences. For example, under “study type”, we included the
45
following key words in our comprehensive search: prospective or cohort or case-control or
46
follow-up or observational or cohort study or case-control study or observational study. Full
47
search terms are available upon request. Additionally, bibliographies of identified publications
48
and published reviews were hand searched for potentially relevant articles. An email alert function
49
in electronic databases was created to keep track of any later published articles that may meet the
50
selection criteria based on saved search history up to 31 May 2016.
AC C
EP
TE D
39
51
4
ACCEPTED MANUSCRIPT Study Selection
53
We included prospective cohort studies and case-control studies where all participants were 18
54
years and above and clinically diagnosed with either first stroke or recurrent stroke. There was no
55
restriction on the year of publication but was limited to English literature. Studies were included if
56
at least 80% of the stroke participants in the study were being followed up in the community or
57
non-institutionalized setting for a minimum period of three months. Clinical trials and
58
retrospective studies were excluded. Studies conducted only during the hospitalization period or at
59
residential care facilities were excluded. The primary outcomes were the risk factors for all fallers
60
defined as community stroke survivors with at least one fall during follow-up. The secondary
61
outcomes were the risk factors for recurrent fallers defined as community stroke survivors with
62
two or more falls during follow-up.
63
M AN U
SC
RI PT
52
Data Extraction
65
One reviewer (TX) screened titles and based on inclusion criteria, rated them as relevant, not
66
relevant or maybe relevant. Abstracts for titles indicated with “yes” and “maybe” were
67
independently scrutinized by a pair of reviewers (TX & LC). The selected articles were then
68
reviewed independently in full text by two reviewers (TX, LC, KO, CD or NL). Any disagreement
69
was discussed among at least three reviewers until consensus was reached. The following data
70
was abstracted in duplicate by four reviewers (TX, LC, CD, and KO) using a standardized data
71
extraction sheet. The data extraction sheet included year of publication, country of study, sample
72
size, mean age of the participants, mean time since stroke at baseline assessment (duration of
73
stroke), frequency of fall assessment, duration of follow-up, proportion of fallers, and risk factors
74
for falls. The binary outcome variables reporting odds ratio (OR) with 95% Confidence Intervals
75
(CI) for each risk factor were extracted. Results reported in non-ORs, such as Relative Risk, Risk
76
Ratio or Rate Ratio (RR), were also extracted. When raw data is available to calculate the OR in
77
another study,30 we calculated the OR with 95% confidence intervals using an online statistical
AC C
EP
TE D
64
5
ACCEPTED MANUSCRIPT OR calculator (Appendix A, Table 1).31 The different categories of frequency of fall assessment
79
used in our data extraction were based on the Deandera et al’s systematic review.28 All extracted
80
data on proportions of fallers and risk factors were categorized into all fallers and recurrent fallers.
81
All findings from the selected studies were collated based on the common characteristics of
82
participants, and the primary and secondary outcomes of this review. Another independent
83
reviewer (NL) confirmed all data entries and checked for completeness and accuracy.
RI PT
78
84
Quality Assessment
86
The evaluation of the methodological quality of primary studies is a key process in systematic
87
review and meta-analysis. Strengthening the Reporting of Observational Studies in Epidemiology
88
statement (STROBE)32 was used as a general guide for the reviewers to determine whether the
89
selected observational studies were well reported. The quality assessment tool for cohort studies
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called “Q-Coh”33 has established its inter-rater reliability (kappa: 0.68 to 0.87) and acceptable
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validity, and it classifies methodological quality as either good, satisfactory or low.33 Hence, it
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was used to select studies with good or satisfactory methodological quality to be included in the
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meta-analysis. The Q-Coh tool was adapted by creating a standardized approach to decisions
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when reviewing components and determining rating scales relevant to falls. A list of confounders
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considered important to be controlled in fall studies was also defined before conducting the
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quality assessment and they were age, gender, falls before stroke, falls in the hospital, length of
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stay in the hospital, rehabilitation before and during the study.34 All selected studies were assessed
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for risk of bias using the adapted Q-Coh by two independent reviewers (TX, LC, KO, CD). All
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disagreements were solved in a consensus meeting. Any studies with good or satisfactory
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methodological quality were included in the meta-analysis.
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Statistical analysis
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outcome variables with 95% CI investigated by at least three studies in a comparable manner were
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included in the meta-analysis. Decisions regarding inclusion of studies that can be meaningfully
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compared were based on the validity of the outcome measures for measuring the domain of
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interest. When different statistical analysis (e.g. both univariate analysis and multivariate analysis)
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was used for the same risk factor in the study, the unadjusted results from the univariate statistical
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analysis were pooled in the meta-analysis. However, when only adjusted results or results from
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multivariate statistical analysis were presented in the study, these were included in the meta-
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analysis.
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Since falls are more common in the studied population, the OR will considerably overestimate the
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relative risk, or in other words, the relative risk will underestimate the OR if we combine both in
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the meta-analysis.35, 36 Hence, we analysed all outcome variables reported in ORs and non-ORs
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separately using the Comprehensive Meta-Analysis software (version 2.0)37 to generate pooled
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estimates of effect sizes for each risk factor. We used the random-effects model with 95% CI for
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all analyses in consideration of the diverse effect sizes of the included studies. The random-effects
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model allowed us to estimate the mean of a distribution of effects from the selected studies in
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meta-analysis.38 The i²-test was used to test the level of heterogeneity among the included studies.
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The i²-test has been recommended as one of the most preferred and reliable tests for
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heterogeneity,39 which represents the degree of variation in estimated effects across studies. It has
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proposed that low heterogeneity is if the i² value falls lower than 50%, moderate for 50-75%, and
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high for above 75%.40 All binary outcome variables or the risk factors reported in ORs were
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pooled together for analyses and the respective risk factors reported in non-ORs were analysed
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separately to support the findings from pooled ORs.
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Figure 1 summarises the flow of searches, inclusions, and exclusions. It included one eligible
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study41 that was found from the database email alert system. Twenty-one studies including 19
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cohort studies and two case-control studies met the selection criteria and were assessed for risk of
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bias using the adapted Q-Coh tool.33
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Methodological quality
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The summary of quality assessment is presented in appendix A, table 2. A study was considered
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as “good” quality if at least six domain items in Q-Coh were given positive ratings and
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“acceptable” quality if four or five domain items were rated as positive. Anything below was
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considered as “low” quality. Out of the 21 papers, seven papers4, 5, 8, 24, 41-43 were rated as “good”
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quality and nine papers6, 10, 11, 16, 30, 44-47 were rated as “acceptable” quality. The remaining five
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papers7, 12, 48-50 were rated as “low” quality and excluded in the meta-analysis.
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Characteristics of included studies
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Study characteristics of the 16 included studies are displayed in table 1. Studies were conducted
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in the community settings across different continents (Asia Pacific, Europe, and North America)
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with a mean cohort age of sixty-nine years old, mean sample size less than 300 (range: 3011 –
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117445), and published between 200224 and 2015.41 The range of follow-up period was from four
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months24 to two years.44, 45 Out of the 16 studies, 11 studies5, 11, 16, 24, 30, 41-43, 45-47 identified risk
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factors for all fallers, three studies4, 6, 8 identified risk factors for recurrent fallers, and two
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studies10, 44 reported risk factors for both all fallers and recurrent fallers. A total number of 4,160
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stroke participants from 16 studies and 1,116 (27%) stroke participants were classified as fallers.
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The proportion of all fallers across studies ranged from 23%24 to 55%,8 and recurrent fallers from
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5%44 to 42%.8 Summary characteristics of the included studies are shown in appendix A, table 3.
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