Accepted Manuscript Title: Predictors of chronic ankle instability after an index lateral ankle sprain: A systematic review Author: Fereshteh Pourkazemi Claire E. Hiller Jacqueline Raymond Elizabeth J. Nightingale Kathryn M. Refshauge PII: DOI: Reference:
S1440-2440(14)00024-3 http://dx.doi.org/doi:10.1016/j.jsams.2014.01.005 JSAMS 989
To appear in:
Journal of Science and Medicine in Sport
Received date: Accepted date:
8-12-2013 25-1-2014
Please cite this article as: Pourkazemi F, Hiller CE, Raymond J, Nightingale EJ, Refshauge KM, Predictors of chronic ankle instability after an index lateral ankle sprain: A systematic review, Journal of Science and Medicine in Sport (2014), http://dx.doi.org/10.1016/j.jsams.2014.01.005 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.
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Predictors of chronic ankle instability after an index lateral ankle sprain: A systematic
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review
3 Fereshteh Pourkazemi,a Claire E. Hiller,a Jacqueline Raymond,b Elizabeth J Nightingale,a Kathryn M.
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Refshauge a
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Discipline of Physiotherapy, Faculty of Health Sciences, University of Sydney, Australia
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Discipline of Exercise and Sport Science, Faculty of Health Sciences, University of Sydney, Australia
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Corresponding author: Fereshteh Pourkazemi
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e-mail:
[email protected] an
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Word count: 3037
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The Abstract word count: 234
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Number of tables: 2
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Number of figures: 1
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Supplemental files: 2
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Predictors of chronic ankle instability after an index lateral ankle sprain: A systematic
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review
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Abstract
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Objective: To identify the predictors of CAI after an index lateral ankle sprain.
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Design: Systematic review
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Methods: The data bases of MEDLINE, CINAHL, AMED, Scopus, SPORTDiscus, Embase, Web of
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Science, PubMed, PEDro, and Cochrane Register of Clinical Trials were searched from the earliest
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record until May 2013. Prospective studies investigating any potential intrinsic predictors of chronic
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ankle instability (CAI) after an index ankle sprain were included. Eligible studies had a prospective
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design (follow-up of at least three months), participants of any age with an index ankle sprain, and
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had assessed ongoing impairments associated with CAI. Eligible studies were screened and data
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extracted by two independent reviewers.
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Results: Four studies were included. Three potential predictors of CAI, i.e., postural control,
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perceived instability, and severity of the index sprain, were investigated. Decreased postural control
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measured by number of foot lifts during single-leg stance with eyes closed and perceived instability
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measured by Cumberland Ankle Instability Tool (CAIT) were not predictors of CAI. While the results
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of one study showed that the severity of the initial sprain was a predictor of re-sprain, another study
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did not.
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Conclusion: Of the three investigated potential predictors of CAI after an index ankle sprain, only
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severity of initial sprain (grade II) predicted re-sprain. However, concerns about validity of the
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grading system suggest that these findings should be interpreted with caution.
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Key words: ankle sprains, joint instability, sprain severity, postural balance
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1. Introduction
43 Ankle sprain injuries, particularly sprain of the lateral ligaments, are among the most common lower
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limb injuries in the general1,2 and athletic populations3 as well as among military personnel.4 High
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recurrence rate, along with residual impairments, are the consequence of ankle sprain for up to 54% of
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individuals.5 The most common residual impairments include re-sprain, perceived instability and
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episodes of giving way (also referred to as functional instability), joint laxity (also referred to as
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mechanical instability), pain, swelling, a feeling of weakness and subsequently reduced level of
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physical activity.5 These residual impairments, alone or in combination, are frequently termed chronic
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ankle instability (CAI).6 Prevention of CAI, particularly re-sprain, is the main treatment goal for many
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studies of ankle sprain,7 however, prevention is only possible if people at risk of developing CAI can
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be identified. That is, to determine the most effective prevention strategy it is essential to understand
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the underlying causes leading to CAI, and the factors increasing the risk of CAI.
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History of a previous sprain is the most frequently reported risk factor for lateral sprain.8-10 Basketball
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players with history of an ankle sprain were found to be five times more likely to re-sprain, although
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the reasons for the increased risk are unknown.9 Hertel11 suggested that ankle sprains cause various
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sensorimotor deficits that can lead to instability, and that the presence of instability increases the risk
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of further sprain. Many studies have investigated this theory, but the findings are inconsistent.12-14
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There are few studies of predictors of CAI, however two systematic reviews have evaluated closely
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related questions and some information can be derived from their findings. One systematic review
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found decreased dorsiflexion range of motion to be a strong predictor of lateral ankle sprain.15 The
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second systematic review investigated the clinical course of acute ankle sprain,5 finding only one
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study that reported on prognostic factors for development of CAI16. Based on this study,16 athletes
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competing at a higher level of competition were at greater risk of persisting impairments after an
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acute sprain than athletes competing at lower levels. Severity of pain, number of re-sprains, as well as
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level of perceived instability and self-reported recovery after an acute lateral ankle sprain were found
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to be independent of the severity of the initial sprain. Furthermore, men were reported to have a
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greater risk of developing residual impairments than women. However, not all studies included in
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these two systematic reviews investigated the risk factors contributing to CAI after an index ankle
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sprain.
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Research to date has tended to focus more on changes associated with CAI rather than predictors of
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CAI. Sensorimotor, functional, anatomical or biomechanical changes associated with CAI have been
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analysed in a number of systematic reviews.14,17,18 Postural instability,17,18 prolonged time to balance
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after a jump,14 lower limb muscle weakness or muscle imbalance19 were found to be associated with
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CAI. Whether these impairments cause CAI or develop as a result of CAI is not clear. Therefore, the
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objective of the present systematic review was to identify predictors of CAI (e.g., age, sex, body mass
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index (BMI), level of physical activity, balance, postural control, proprioception, motor control,
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severity of ankle sprain, perceived ankle instability, feeling of giving way, ligament laxity, pain, or
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swelling) after an index ankle sprain. Prospective studies investigating any of these variables as
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potential predictors of CAI after an index ankle sprain might enable health providers to design more
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effective treatments to prevent ongoing problems.
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2. Methods
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The study protocol was developed based on the framework outlined in the guidelines provided by the
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PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement.20 The
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protocol of this systematic review is registered on PROSPERO (registration number
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CRD42012002990).
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2.1. Eligibility criteria
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Studies were included if they met the following inclusion criteria: i) longitudinal design, ii) follow-up
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length of at least three months since the sprain, iii) participants of any age who had sustained an index
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ankle sprain only, iv) measuring at least one of the potential predictors of CAI, v) reporting on any re-
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sprain or residual symptoms after the initial ankle sprain during the follow-up period, vi) published
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full paper; abstracts were included if the authors provided the raw data for further analysis. Papers
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where it was possible that at least some of the participants had suffered an index sprain were
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considered for inclusion, however if the data from this sub-group could not be isolated, then the paper
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was excluded.
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For randomised controlled trials, we included the minimal intervention group (e.g. conservative treatment of lateral ankle sprains, such as modified footwear and associated supports, taping, adapted
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training programmes, and education). Randomised clinical trials were excluded if there was no
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minimal intervention group e.g., if surgery or immobilisation for more than three days were
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investigated.
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2.2. Information Sources
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Studies were identified through a search of the MEDLINE, CINAHL, AMED, Scopus,
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SPORTDiscus, Embase, Web of Science, PubMed, PEDro, and Cochrane Register of Clinical Trials
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to May 2013. Abstracts from the International Ankle Symposium (IAS) and International Foot and
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Ankle Biomechanics (i-FAB) conference proceedings, and bibliographies of eligible studies were
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hand searched. In addition, relevant experts were contacted to identify any unpublished studies that
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may exist and to review the list of identified studies for completeness. No language restriction was
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imposed, however, if a translation could not be arranged, the paper was excluded.
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2.3. Search Strategy
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Key terms used in our search strategy are presented in supplemental file 1. Search protocols were
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specifically designed to target prospective studies.
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2.4. Study Selection
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All studies identified by the search strategy were screened against the eligibility criteria independently
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by the first author (FP) and by one other author (CH, JR or KR). Titles and abstracts were inspected
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and clearly ineligible studies were removed. Full copies of potentially eligible papers were retrieved.
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Any inconsistencies regarding inclusion of trials were resolved by consensus.
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2.5. Potential Predictors of CAI
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The following predictors, identified from previous studies of risk factors for lateral ankle sprain, were
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considered as potential risk factors of developing CAI: age, sex, height, weight, BMI, leg dominance,
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foot type, foot and lower limb alignment, ankle joint laxity, general ligamentous laxity, postural
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control, muscle weakness or muscle strength/power imbalance in lower limbs, lower limb muscle
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reaction time, range of motion at lower limb joints, physical fitness, gait biomechanics, and severity
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of symptoms after the initial sprain (e.g., pain, swelling, laxity, feeling of instability).
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2.6. Outcome measures
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Any measures that assessed ongoing impairments associated with CAI after the initial sprain during
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the follow up period (e.g., re-sprain, swelling, pain, mechanical instability, perceived instability,
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feeling of giving way, or feeling of weakness) were considered as outcome measures.
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2.7. Data Extraction Process
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Data were extracted independently by two authors (FP and CH) and confirmed by one other author
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(either JR or KR). Any discrepancies were settled by further discussion and consensus. Study
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characteristics extracted were study type, target population (setting, sex, age), sample size, inclusion
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criteria, follow-up duration, prognostic factors measured, interventions (if any) and all reported
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outcome measures.
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2.8. Quality Assessment
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Risk of bias and methodological quality of included studies were assessed using the quality
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assessment tool developed by Pengel21 et al. This tool consists of 7 items rated as either ‘yes’, ‘no’ or
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‘N/A’ (not applicable). Four items relate to control of bias (items 1-4), two to appropriate
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measurement of variables (items 5 and 6) and one to control of confounding variables (item 7). Two
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raters (FP and JR) independently assessed the quality and a third author (CH) resolved disagreements.
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2.9. Synthesis of Results
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Study outcomes were statistically pooled if the studies were considered to be sufficiently
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homogeneous. For homogeneous studies, raw data were used in a direct logistic regression to assess
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whether the predictor variables increased the likelihood of re-sprain. If the studies were considered
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too heterogeneous, data were not pooled and the outcomes were described.
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3. Results
151 The search strategy identified 8085 titles. Following title and abstract screening, 210 potentially
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relevant articles were identified, of which 16 met all the inclusion criteria. The data required for
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analysis were reported in two of the included studies.22,23 The authors of the remaining 14 articles,
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which included participants with one or more ankle sprains, were contacted for data related to the
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participants with only an index ankle sprain. Seven authors replied, of whom only two were able to
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provide raw data for analysis.24,25 Therefore, four studies22-25 were included in this review (Figure 1).
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3.1. Study Characteristics
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All included studies were prospective cohort trials, with follow-up periods that varied between 8 and
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24 months. Participants were adults in two studies,23,24 adolescents in one study25 and children and
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adolescents in the fourth study.22 In two studies the inclusion criterion was an acute index ankle sprain
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of less than two days duration.22,23 The other two studies24,25 included a heterogeneous group of
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participants, with a history that varied between multiple ankle sprains to no history of sprain, and the
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time since sprain was not standardised. Separate data of the participants with an index ankle sprain
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were provided by the authors of these two studies.24,25 Participants were recruited from various
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settings, including a university,24 dance school,25 and primary care practice(s).22,23 The predictors of
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CAI measured were perceived instability and balance24,25 in two of the studies and severity of index
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sprain22,23 in the other two. The severity of injury was measured by either clinical symptoms and
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anterior drawer stress x-ray23 or clinical symptoms and magnetic resonance imaging (MRI).22 The
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outcomes reported were re-sprain in three studies23-25 and pain, mobility and perceived instability in
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the remaining study.22 Details of the included studies are presented in Table 1.
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3.2. Quality Assessment
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No study was rated as having excellent methodological quality. Methodological quality was moderate
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in three studies, with scores of 5 25 and 4.23,24 The fourth study22 had low methodological quality, with
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a score of 3 (supplemental file 2).None of these studies used statistical adjustment for potentially
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confounding factors. Only one study used blinded outcome assessor(s).22
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177 3.4. Predictive Factors of CAI
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Data for two of the studies24,25 were pooled, because they investigated perceived instability and
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balance as predictors for re-sprain. We were not able to pool data for the two other studies22,23
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because, although they both investigated severity of initial sprain, they used different grading systems
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and reported on different outcome measures.
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Perceived instability and balance: Two studies24,25 investigated perceived instability and static balance
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on both legs as a predictor of re-sprain. Perceived instability was measured using the Cumberland
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Ankle Instability Tool (CAIT) and balance was measured recording the number of foot movements
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during single-leg stance with eyes closed for 30 seconds. Hiller25 et al and de Noronha24 et al provided
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raw data for 44 participants with history of an index ankle sprain. After the follow-up periods of 12-
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13 months, 11 participants had re-sprained their ankles. Raw data from these two studies were pooled
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and logistic regression was performed, finding that the predictive capacity of the model was not
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statistically significant (Table 2). That is, CAIT score and number of foot lifts during single-leg stance
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with eyes close did not predict re-sprain.
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Severity of the index ankle sprain: Two studies investigated severity of the index sprain as a predictor
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of CAI. Malliaropoulos23 et al used an expanded grading system26 (I, II, IIIA and IIIB) to determine
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severity of sprain. They found significant differences in rate of re-sprain between athletes with
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different grades of injury during a 24 month follow-up period. Elite track and field athletes with less
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severe ankle sprain (grade I or II) had a higher rate of re-sprain than athletes with more severe ankle
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sprain (grade IIIA or IIIB). To further analyse the results of this study, we performed direct logistic
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regression to assess the impact of the severity of index sprain on the likelihood of re-sprain. The
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predictive capacity of the model was statistically significant, X²(3, n=202) = 14.71, P=0.002. The
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severity of sprain (grades I to IIIB) explained between 7% (Cox and Snell R2) and 11.4% (Nagelkerke
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R2) of the variance in re-sprain status, and correctly classified 81.7% of cases. However, only grade I
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and II made a unique statistically significant contribution to the model (Table 2). The strongest
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predictor of re-sprain was grade II injury, recording an odds ratio (OR) of 2.6. This indicates that
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athletes with grade II injury were 2.6 times more likely to re-sprain their ankles.
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In the second study, Endele22 et al divided 30 children with an acute ankle sprain into three groups
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based on the severity of their clinical symptoms (I, II or III). Only children with grade II and III were
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followed up for eight months. Endele22 et al reported no significant differences between children with
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grades II or III of ankle sprain, with regard to limitation of mobility, pain or instability, three months
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after the index injury. These outcome measures were not reported at eight months follow up. Due to
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the small number of participants in this study (n=15) no further analysis was performed.
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4. Discussion
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The present systematic review found that only three potential predictors of CAI (severity of sprain,
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balance and perceived instability) had been investigated in longitudinal studies after an index ankle
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sprain. Although recent evidence from cross-sectional studies shows that postural sway, time to
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balance after a jump, foot position during gait, strength, and proprioception are altered in participants
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with CAI,14,15,19 none of these factors has been investigated in a longitudinal study after the index
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sprain.
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Two studies investigated the severity of the index ankle sprain as a potential predictor of CAI, with
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conflicting results. Although there are factors limiting comparisons between these studies, including
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the use of different grading systems, different age groups (adults23 vs. children22), and different
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duration of follow-up (24 months23 vs. 8 months22), a critique of the two studies highlights some
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critical issues.
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Malliaropoulos23 et al, classified the severity of index sprains into four grades based on the patients’
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clinical symptoms (dorsiflexion range of motion and swelling). Participants were referred for stress
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radiography only if they were diagnosed with a grade III sprain. In the second study, Endele22 et al
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also classified the sprains as grades I, II or III based on the clinical symptoms (weight bearing status
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and swelling), however, they performed additional MRI investigations. Interestingly, they found that
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clinical symptoms were not well correlated with the grade of injury. The amount of swelling and
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ability to weight bear were highly correlated with bone bruising, based on their MRI findings.
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Furthermore, six (50%) children with sprains classified as grade II based on the clinical symptoms,
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had complete ligament rupture and three had a Salter I injury. These findings raise concerns about the
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validity of the grading systems based on symptoms, alone.
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The second study22 provides valuable information regarding the severity of ankle sprain in 30
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children. In this study however, only children with sprains classified as grade II or III were followed
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up, and the follow-up was at eight months, potentially an inadequate period when investigating re-
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sprain and CAI. In this study, anatomical changes were reported in the MRIs of 10 children at eight
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months, but Endele 22 et al did not re-assess pain, mobility or instability at eight months follow up.
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Since the main aim of this study was to compare symptoms with MRI findings, the outcomes of pain,
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instability or mobility were not reported.
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Based on the results of these two studies, it is not possible to conclude definitively that ankle sprains
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classified as grades I or II predict development of CAI. To be able to determine whether the severity
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of an initial sprain predicts CAI, a valid grading system, a large sample size and adequate follow-up
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are required.
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Pooled data from the two other studies24,25 showed that CAIT scores do not predict re-sprain. CAIT is
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a measure of perceived instability27 and previous studies demonstrated that perceived ankle instability
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is related to ankle sprain.28 However, based on the new model of sub-groups of CAI developed by
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Hiller29 et al, there is a sub-group of participants with CAI who have perceived instability without
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recurrence of sprain. The findings of Hiller25 et al and de Noronha24 et al support the proposed model,
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and explain the lack of predictive value of the CAIT score. Decreased CAIT score, or presence of
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perceived instability, may increase risk of re-sprain in some subgroups, but not others.
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The results of this systematic review also show that postural control, measured as the number of foot
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lifts during single-leg stance with eyes closed was not a predictor of CAI. Many studies have
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investigated postural control as a predictor of acute ankle sprain.25,30,31 These studies however, used
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different measurement methods and found different results. While most of these studies found
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decreased postural control as a predictor of acute ankle sprains,25,32 several found no relationship
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between postural control scores and the risk of ankle sprain.30,31,33 In a recent systematic review,
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Witchalls34 et al reported that the studies in which postural control was tested by scoring the number
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of errors during a test, did not show that poorer postural control increased the risk of ankle sprain.
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They suggested that the increased subjectivity of these methods may increase the variability in scores
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and render them less meaningful for measuring postural control.
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While it seems the number of foot lifts during single-leg stance might not predict re-sprain, these
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results should be interpreted with caution. Firstly, the different populations in these two studies
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(adolescent dancers25 vs. active university students24) may have been a confounding factor. In
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addition, the time from the index ankle sprain was not controlled for, potentially constituting another
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confounding factor. Finally, the aim of these studies was not to predict CAI after an index sprain, and
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therefore data were a subset. This resulted in a small number of participants in these two studies with
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consequent lack of power for our re-analysis.
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The strength of this systematic review was that no language limitations were imposed. Where
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required, a translation in different languages was made (e.g. German, Italian, Japanese, and French).
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We also included the grey literature. However, several studies could not be included because
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reporting was insufficient and the data were not available for further analysis.
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We found that of the three potential predictors of CAI that have been investigated prospectively after
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an index ankle sprain, only severity of initial sprain (grade II) predicted re-sprain. However, concerns
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about validity of the grading system suggest that these findings should be interpreted with caution.
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Consequently, there is a large gap in the literature. Anatomical, central, physiological and
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psychosocial changes have yet to be investigated after an initial sprain and the relationship of such
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variables to re-injury and other residual symptoms remains unknown.
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Practical Implications
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Severity of the initial ankle sprain does not necessarily predict the likelihood of
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developing chronic ankle instability. •
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Perceived ankle instability and static balance do not appear to predict future ankle
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sprains. •
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Currently there is limited research investigating predictors of chronic ankle instability after
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an index ankle sprain.
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292 Acknowledgment
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The authors would like to thank Dr Markus Hübscher, Ms Naomi Kusano, and Ms Alexandra Di Lallo
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for their assistance in translation of non-English papers.
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Table 1. Characteristics of included studies
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Tables
Type of Study
Followup length
Participants
Inclusion/Exclusion criteria
Predictor
Interventions
Outcome measures
Hiller et al 2008
Prospective Cohort
13 mths
33 adolescents dancers with an index sprain Age: 14 ± 1.8 yrs (total study participants: 115)
Inclusion: Dance and ballet students Exclusion criteria: None
Cumberland Ankle Instability tool, Foot movement during singleleg stance with eyes closed (30 s)
None
Re-sprain
Malliaropoulos et al 2009
Prospective Cohort
24 mths
202 elite Greek track and field athletes Age: 19 ± 4.1 yrs
Inclusion criteria: Acute index lateral ankle sprain, no history of ankle and foot injury Exclusion criteria: syndesmotic injury or a lower limb fracture
Severity of the initial sprain (I, II, IIIA or IIIB)
Common rehabilitation program
Re-sprain
de Noronha et al 2011
Prospective Cohort
12 mths
11 active university students with an index sprain Age: 20.9 ± 2.7 yrs (total study participants: 125)
Inclusion criteria: regular exercise (≥2/week) Exclusion criteria: sprain ≤ 1 month
CAIT, Foot movement during single-leg stance with eyes closed (30 s)
None
Re-sprain
8 mths
30 children presenting to ER(15 followed up for 8 mths ) Age: 11.2 yrs (range: 7-15)
Inclusion criteria: Acute index inversion sprain (≤ 2 days) with open epiphyseal plate Exclusion criteria: fracture or recurrent sprains
Severity of the initial sprain (I,II, III)
Initially:elastic compression wraps, AirSport Ankle brace, forearm crutches (if required). After 2 weeks: common rehabilitation program
Pain, mobility and instability* MRI
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Author, Year
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Endele et al 2012
Prospective Cohort
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CAIT: Cumberland ankle instability tool, ER: Emergency room, MRI: magnetic resonance imaging, Mths: months, S: seconds, Yr: year
377
*The method of measurement for pain, mobility and instability was not explained in the study 18
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Table 2. Odds ratio of re-sprains associated with CAIT scores, balance, and severity of the initial sprain Variables
OR
95% CI for odds ratio
P-value
0.839
0.664-1.061
0.142
CAIT score (non-injured side)
1.037
0.800-1.346
0.782
Foot-lifts (injured side)
0.958
0.897-1.057
0.391
Foot-lifts (non-injured side) Constant
1.017
0.914-1.132
0.756 0.403
15.887
Severity of the initial sprain
0.004
Grade II
2.603
1.175-5.768
0.018
Grade III
0.364
0.065-1.466
0.139
Constant 0.162 OR: odds ratio, CI: confidence interval
< 0.01
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Grade I
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Step 1
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CAIT score (injured side)
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CAIT scores and balance
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Figure Legends Figure 1: Flow chart of the review process
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Figure(s)
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