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Physical Therapy in Sport 49 (2021) 243e249
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Physical Therapy in Sport
journal homepage: www.elsevier .com/ptsp
Review Article
Effectiveness of cryotherapy on pain intensity, swelling, range of
motion, function and recurrence in acute ankle sprain: A systematic
review of randomized controlled trials
Júlio Pascoal Miranda a, Whesley Tanor Silva a, Hytalo Jesus Silva b,
Rodrigo Oliveira Mascarenhas a, Vinícius Cunha Oliveira c, *
a Department of Physiotherapy, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
b Postgraduate Program in Health Sciences, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Brazil
c Postgraduate Program in Rehabilitation and Functional Performance, Postgraduate Program in Health Sciences, Universidade Federal dos Vales do
Jequitinhonha e Mucuri (UFVJM), Diamantina, Brazil
a r t i c l e i n f o
Article history:
Received 8 February 2021
Received in revised form
17 March 2021
Accepted 21 March 2021
Keywords:
Acute ankle sprain
Cryotherapy
Systematic review
* Corresponding author. Postgraduate Program in R
Performance Universidade Federal dos Vales do Jequ
Campus JK - Rodovia MGT 367 e Km 583, nº 5000. Bair
000, Diamantina, Brazil.
E-mail addresses: juliopascoal09@gmail.com (J.P
gmail.com (W.T. Silva), hytalo-silva@hotmail.com (H
(R.O. Mascarenhas), vcunhaoliveira@gmail.com, v
(V.C. Oliveira).
https://doi.org/10.1016/j.ptsp.2021.03.011
1466-853X/© 2021 Elsevier Ltd. All rights reserved.
a b s t r a c t
Objective: Investigate effectiveness of cryotherapy on pain intensity, swelling, range of motion, function
and recurrence in acute ankle sprain.
Methods: Searches were conducted on six databases for randomized or quasi-randomized controlled
trials (RCTs) evaluating effectiveness of cryotherapy for pain intensity, swelling, range of motion, function
and recurrence in acute ankle sprain. Selection of trials, data extraction and methodological quality
assessment of included trials were conducted independently by two reviewers with discrepancies
resolved by a third reviewer. Estimates were presented as mean differences (MDs) with 95% confidence
intervals (CIs). The quality of the evidence was assessed using the Grading of Recommendations
Assessment (GRADE) approach.
Results: Two RCTs with high risk of bias were included. Both evaluated the additional effects of cryo-
therapy, comparing cryotherapy combined with other intervention versus other intervention stand-
alone. Uncertain evidence shows that cryotherapy does not enhance effects of other intervention on
swelling (MD ¼ 6.0; 95%CI: 0.5 to 12.5), pain intensity (MD ¼ �0.03; 95%CI: 0.34 to 0.28) and range of
motion (p > 0.05).
Conclusions: Current literature lacks evidence supporting the use of cryotherapy on management of
acute ankle sprain. There is an urgent call for larger high-quality randomized controlled trials.
© 2021 Elsevier Ltd. All rights reserved.
1. Introduction
Ankle sprain is a common condition in the general population
and athletes (Gribble et al., 2016). The ankle sprain incidence is
estimated in seven sprains per 1000 expositions in athletes, being
higher in young women (bib_Doherty_et_al_2014,Doherty et al.,
ehabilitation and Functional
itinhonha e Mucuri (UFVJM),
ro Alto da Jacuba, CEP 39100-
. Miranda), whesleytanor@
.J. Silva), rdmasc@gmail.com
inicius.oliveira@ufvjm.edu.br
2014). After a new episode of ankle sprain, there is a high fre-
quency of chronic ankle instability and recurrence (Gribble et al.,
2016). Moreover, it is a musculoskeletal injury that causes direct
(expenses with medical consultations and medicines) and indirect
costs (absence from work, reducing productivity) (Gribble et al.,
2016). Effective therapies to improve pain intensity, swelling,
range of motion and decrease recurrence are important for this
health condition.
Available treatment options after an acute ankle sprain comprise
cryotherapy (Bleakley et al., 2010; Van Dijk, 1999), surgical treat-
ment (Doherty, Bleakley, Delahunt, & Holden, 2017) joint mobili-
zation (Cosby, Koroch, Grindstaff, Parente, & Hertel, 2011),
kinesiotherapy (Bleakley et al., 2010; Cleland et al., 2013), brace
(Beynnon, Renstr€om, Haugh, Uh, & Barker, 2006), acupuncture
(Doherty et al., 2017), among others. Cryotherapy has often been
mailto:juliopascoal09@gmail.com
mailto:whesleytanor@gmail.com
mailto:whesleytanor@gmail.com
mailto:hytalo-silva@hotmail.com
mailto:rdmasc@gmail.com
mailto:vcunhaoliveira@gmail.com
mailto:vinicius.oliveira@ufvjm.edu.br
http://crossmark.crossref.org/dialog/?doi=10.1016/j.ptsp.2021.03.011&domain=pdf
www.sciencedirect.com/science/journal/1466853X
http://www.elsevier.com/ptsp
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https://doi.org/10.1016/j.ptsp.2021.03.011
J.P. Miranda, W.T. Silva, H.J. Silva et al. Physical Therapy in Sport 49 (2021) 243e249
recommended by clinical practice guidelines and used by health
professionals in acute ankle sprain management because it has low
cost, easy application, and is considered potentially effective in
clinical practice settings (Doherty et al., 2017; Van Dijk, 1999;
Vuurberg et al., 2018). However, current evidence supporting
cryotherapy is still unclear.
Previous systematic reviews (Bleakley, McDonough, &
MacAuley, 2004; bib_van_den_Bekerom_et_al_2012,van den
Bekerom et al., 2012; Doherty et al., 2017) that investigated the
efficacy of cryotherapy in acute ankle sprain, included trials
without appropriate comparator to isolate effects of therapies (i.e.,
placebo, sham, waiting list or no intervention) or to investigate
whether cryotherapy enhances effects of other intervention (i.e.,
cryotherapy combined with other active intervention compared
with the other active intervention stand-alone). Besides, these re-
views had methodological limitations that could have impacted on
the estimates, which in some cases rendered themmisleading (e.g.,
unclear inclusion criteria for the population of interest, lack of
heterogeneity investigation and inclusion of non-randomized
controlled trials). Thus, a new systematic review addressing these
issues is necessary to inform clinicians and patients about current
quality of the evidence for the effectiveness of cryotherapy in
management of acute ankle sprain. Our systematic review aims to
investigate the effectiveness of cryotherapy on pain intensity,
swelling, range of motion, function and recurrence in people with
an acute episode of ankle sprain.
2. Methods
2.1. Study design
This systematic review of randomized or quasi-randomized
controlled trials is reported following the PRISMA checklist
(Liberati et al., 2009) and some stages were conducted according to
the Cochrane recommendations (Higgins et al., 2020). Protocol was
prospectively registered in PROSPERO (CRD42020166411) and
Open Science Framework (https://osf.io/x6p23) (Miranda, Silva,
Mascarenhas, & Oliveira, 2020).
2.2. Eligibility criteria
We included trials that investigated the efficacy of cryotherapy
in people of both sexes, regardless of age, from any health care
setting, diagnosed with a new episode of ankle sprain, with dura-
tion of the injury up to seven days
(bib_Bleakley_et_al_2007,Bleakley et al., 2007; van Den Bekerom
et al., 2016). Cryotherapy was considered any conservative inter-
vention which includes low temperature components such as the
combination of protection, rest, ice, compression and elevation
(PRICE) and rest, ice, compression and elevation (RICE) (Bleakley
et al., 2007; Hing, Lopes, Hume, & Reid, 2011), protection, opti-
mum load, ice, compression and elevation (POLICE) (Salim, Umar,&
Shaharudin, 2018), ice pack therapy (Bleakley, McDonough, &
MacAuley, 2006; bib_Enwemeka_et_al_2002,Enwemeka et al.,
2002), whole body immersion therapy (Banfi, Lombardi,
Colombini, & Melegati, 2010). The comparators of interest to
investigate the isolated effect of cryotherapy were no intervention,
waiting list, placebo or sham. Inaddition, we included trials that
evaluated whether combination of cryotherapy with other active
intervention could enhance effects of the other investigated active
intervention stand-alone. Our outcomes of interest were pain in-
tensity, swelling, function, range of motion and recurrence assessed
using any valid instrument such as Visual Analog Scale - VAS
(Bleakley et al., 2007) and Numerical Rating Scales - NRS (Cohen
et al., 2017) - for pain intensity; volumetry
244
(bib_Nunes_et_al_2015,Nunes et al., 2015), perimeter and the figure
of eight technique for swelling (Bleakley et al., 2007); Lower Ex-
tremity Functional Scale - LEFS (Bleakley et al., 2010), Foot & Ankle
Disability Index - FADI (Cosby et al., 2011), American Orthopaedic
Foot & Ankle Society - AOFAS (bib_Prado_et_al_2014,Prado et al.,
2014), Foot and Ankle Outcome Score - FAOS (Brison et al., 2016)
for function; goniometry (Weerasekara, Tennakoon, & Suraweera,
2016), and weight bearing lunge test (Gogate, Satpute, & Hall,
2020) for range of motion; and self-reported occurrence for
recurrence (Hupperets, Verhagen, & Van Mechelen, 2009).
2.3. Search strategy and study selection
Search strategies were conducted in MEDLINE, COCHRANE,
EMBASE, AMED, PSYCINFO and PEDRO, without language or date
restrictions, up to January 25th, 2021. Search terms were related to
“randomized controlled trials”, “ankle sprain” and “cryotherapy”.
Detailed search strategy was presented in Appendix 1. In addition,
we hand searched identified systematic reviews published in the
field for potentially relevant full texts. After searches, retrieved
references were exported to an Endnote® file and duplicates were
removed. Then, two independent reviewers (JPM and WTS)
screened titles and abstracts and assessed potential full texts. Trials
fulfilling our eligibility criteria were included in our review.
Between-reviewer discrepancies were resolved by a third reviewer
(VCO).
2.4. Data extraction
Two independent reviewers (JPM and WTS) extracted charac-
teristics and outcome data from the included trials and any dis-
crepancies was resolved by a third reviewer (VCO). Characteristics
extracted from trials included: study design; source of participants;
age; description of cryotherapy and control groups; outcomes; in-
strument measurements; and time points. For our outcomes of
interest, we extracted post-intervention means (first option) or
within-group mean changes over time, standard deviations (SDs)
and sample sizes for each of our groups of interest to investigate
effects at short-, medium- and long-term. Short-term effects were
considered follow-up up three months after baseline, medium-
term effects were considered follow-up over three months but
less than twelve months after baseline, and long-term effects were
considered follow-up of at least twelve months after baseline. If
more than one-time point was available within the same follow-up
period, the one closer to the end of the intervention was consid-
ered. When outcome data was not reported, authors were con-
tacted to provide the non-reported data. When authors did not
respond, we imputed mean and SD from individual scores, p-value
and sample size. When contacted authors did not answer or im-
putations were not possible, the trial was excluded from the
quantitative analysis. All procedures followed recommended
methods (Higgins et al., 2020; Wan, Wang, Liu, & Tong, 2014).
2.5. Risk of bias assessment
Two independent reviewers (JPM and WTS) assessed method-
ological quality of included trials using the 0e10 PEDro scale
(http://www.pedro.org.au/) (bib_Macedo_et_al_2010,Macedo et al.,
2010). A third reviewer (VCO) resolved between-reviewer dis-
crepancies. When available, we used scores already rated on the
PEDro database.
2.6. Data analysis
Planned meta-analysis using a random-effects model was not
https://osf.io/x6p23
http://www.pedro.org.au/
J.P. Miranda, W.T. Silva, H.J. Silva et al. Physical Therapy in Sport 49 (2021) 243e249
possible because of the small number of included trials. Mean dif-
ferences (MDs) with 95% confidence intervals (CIs) were presented.
All analyses were conducted using the Comprehensive Meta-
analysis software, version 2.2.04 (Biostat, Englewood, NJ).
Two independent reviewers (JPM andWTS) assessed the quality
of the current evidence using the Grading of Recommendations
Assessment (GRADE) approach (Balshem et al., 2011; Guyatt et al.,
2008). According to the four-level GRADE system, evidence may
range from high to very-low quality, with low levels indicating that
future high-quality trials are likely to change estimated effects. In
the current review, evidence began from high quality and was
downgraded in one point for each of the following issues: serious
imprecision when analyzed sample less than 400 (Mueller,
Montori, Bassler, Koenig, & Guyatt, 2007); serious risk of bias
when more than 25% of the analyzed participants were from trials
with a high risk of bias (i.e., PEDro score less than 6 out of 10) (Foley,
Teasell, Bhogal, & Speechley, 2003); and serious inconsistency of
results when I2 statistics was higher than 50% or when pooling was
not possible (Higgins et al., 2020). Publication bias was not assessed
Fig. 1. Flow of studies through the review. *Articles could be exclud
245
because of the small number of included trials, i.e., less than ten
trials (Guyatt et al., 2011; Ioannidis & Trikalinos, 2007). Between-
reviewer discrepancies were resolved by a third reviewer (VCO).
We planned subgroup analyzes to investigate the impact of
different types/dosages of cryotherapy and of different character-
istics of participants. Besides, sensitivity analyzes were planned to
investigate whether high risk of bias impacted on the estimates. For
subgroup and sensitivity analyzes, we intended to use meta-
regression, if it was possible (i.e., at least 10 trials analyzed);
otherwise, qualitative analysis could have been used, following
recommendations (Higgins et al., 2020).
3. Results
We retrieved 377 records from our searches, 134 duplicates
were removed, and the remaining 243 titles and abstracts were
screened. Then, 19 potential full texts were assessed and two ran-
domized controlled trials were included (Laba & Roestenburg,
1989; Sloan, Hain, & Pownall, 1989). Flow of studies in the review
ed for more than one reason; RCT: randomized controlled trial.
J.P. Miranda, W.T. Silva, H.J. Silva et al. Physical Therapy in Sport 49 (2021) 243e249
is available in Fig. 1.
3.1. Characteristics of included trials and assessment of risk of bias
No study has evaluated the effectiveness of cryotherapy
compared with placebo, sham, waiting list or no intervention. The
two included trials evaluated the additional effects of cryotherapy
on pain intensity and swelling (Laba & Roestenburg, 1989; Sloan
et al., 1989), and one trial assessed range of motion (Sloan et al.,
1989). Both trials investigated outcomes at short-term. None of
the included trials assessed effects of cryotherapy on function and
recurrence. The form of cryotherapy used in both trials was ice pack
with the duration of application varying from 20 to 30 min as
adjunct of non-steroidal medication, elevation and rest (Sloan et al.,
1989) or ultrasound therapy, standardized exercise program and
support (Laba & Roestenburg, 1989). Detailed description of in-
terventions is in Table 1.
The two included trials had high risk of bias, scoring three out of
10 on the PEDro scale. Main reasons for increasing risk of bias were
not performing concealed allocation (2 trials [100%]); not blinding
therapists and subjects (2 trials [100%]); not adequate follow-up (2
trials [100%]); and not performing an intention-to-treat analysis (2
trials [100%]). Detailed characteristics of the included trials are
presented in Table 1.
3.2. Effects of cryotherapy on swelling, pain intensity, and range of
motion in acute ankle sprain
It was not possible to perform a meta-analysis due to the het-
erogeneity and missing data. Authors were contacted bye-mail to
provide mean and SD data, but one of them did not respond (Sloan
et al., 1989) and the other (Laba& Roestenburg, 1989) reported that
Table 1
Characteristics of included trials and assessment of risk of bias (n ¼ 2).
STUDY PARTICIPANTS INTERVENTION
Sloan (1989) People with diagnosis of acute
ankle sprain within the
previous 24 h from Accident
and Emergency Department of
the University Hospital,
Nottingham;
Exclusion criteria: history of
asthma or upper
gastrointestinal disturbance;
chronic relapsing injuries;
fracture (excluded by
radiological examination);
n ¼ 116; age ¼ 16e50 years;
gender: 79% M/21% F
Experimental group:
steroidal
medication þ Rest þ Ic
with ankle elevation d
30 min.
Control group: Non-st
medication þ Rest þ A
brace with no ice pack
elevation for 30 min.
Laba (1989) People from Accident and
Emergency Department of
Dunedin Hospital.
Inclusion criteria: Diagnosis of
acute ankle sprain within the
previous 2 days; 3 and 4 grade
of injury classification (Hocutt
et al., 1982); and fracture
discarded by X-ray
examination.
n ¼ 30 (IG: 14; NI: 16); Grade of
injury: Grade 3: 19 (IG: 8; NI:
11); Grade 4: 11 (IG: 6; NI: 5)
Experimental Group:
pack þ Ultrasound
therapy þ Exercises.
Control Group: Ultras
therapy þ Exercises.
Age in years; n ¼ sample size; M ¼ male; F ¼ female; IG ¼ Ice group; NI ¼ No Ice.
a Random allocation: Yes, concealed allocation: No, baseline comparability: Yes, blin
intention-to-treat analysis: No, between-group comparisons: No, point estimates and va
b Random allocation: Yes, concealed allocation: No, baseline comparability: No, blind
intention-to-treat analysis: No, between-group comparisons: Yes, point estimates and v
246
was not possible to provide the missing data because it has been a
long time since the trial was completed. For the results of individual
studies, mean and SD were imputed from individual scores and
sample size for pain intensity (Laba & Roestenburg, 1989), and SD
frommean, p-value and sample size for swelling (Sloan et al., 1989).
Summary of findings with GRADE recommendations are reported
in Table 2.
3.3. Swelling
In one trial (Sloan et al., 1989), swelling was assessed by the ratio
between the swelling and the intermalleolar distance calculated
from X-ray image. There was a within-group improvement of 46%
when cryotherapy was combined with the other active interven-
tion and of 40% when applied the other active intervention stand-
alone after seven days. There was no between-group difference
(MD¼ 6, 95%IC: 0.5 to 12.5, p¼ 0.07). In the trial conducted by Laba
and Roestenburg (1989), swelling was assessed by volumetry
through the percentage of increase on volume compared with the
contralateral limb. Participants were classified in three levels cat-
egories: 15-10%; 10-5%; and 5-0%. All the participants in both
groups improved up to 10% when compared with the contralateral
limb, but there was no between-group difference (p > 0.05).
3.4. Pain intensity
Sloan et al. (1989) showed no between-group difference on pain
intensity but did not report outcome data or how it was measured.
In Laba and Roestenburg (1989), pain intensity was assessed using a
5-point Likert scale that ranged from “no pain” to “very severe
pain”. Mean post-intervention scores were 0.21 (SD: 0.41) on the 5-
point scale for combination of cryotherapy with the other active
OUTCOME MEASURES PEDRO SCALE (0e10)
Non-
e pack
uring
eroidal
nkle
and no
Swelling: Ratio between the
swelling and the intermalleolar
distance calculated from X-ray
image;
Pain Intensity: Not reported.
Ankle range of motion:
Purpose-built goniometer;
Follow up: 7 days.
3/10a
Ice
ound
Swelling: Volumetry
Pain intensity: 5-point Likert
scale varying from ‘No Pain’ to
‘Very severe pain’
Follow-up: Participants were
discharged when they reached
grade of injury 1 or 2. No time
from the enrollment until
discharge was reported
. 3/10b
d subjects: No, blind therapists: No, blind assessors: No, adequate follow-up: No,
riability: Yes.
subjects: No, blind therapists: No, blind assessors: Yes, adequate follow-up: No,
ariability: No.
J.P. Miranda, W.T. Silva, H.J. Silva et al. Physical Therapy in Sport 49 (2021) 243e249
intervention and 0.25 (SD: 0.44) for the other intervention stand-
alone. There was no between-group difference on pain intensity
at short-term (MD ¼ �0.03, 95%CI: 0.34 to 0.28, p ¼ 0.84).
3.5. Range of motion
Sloan et al. (1989) showed no between-group difference at
short-term on range of motion assessed by goniometry (p > 0.05).
Outcome data was not provided in the trial.
4. Discussion
Our findings show that literature lacks evidence supporting the
effectiveness of cryotherapy for the management of acute ankle
sprain. Very-low quality of evidence from two randomized
controlled trials suggests that efficacy of cryotherapy on acute
ankle sprain is uncertain. The findings of this systematic review is
of great importance as it is a “call to action” for more appropriate
larger high-quality trials to investigate the efficacy of cryotherapy
on acute ankle sprain.
Previous systematic reviews reported that cryotherapy is
effective in acute ankle sprain (Bleakley et al., 2004) or recommend
its use in clinical practice if this decision is based on national
clinical practice guidelines or on expert decision (van den Bekerom
et al., 2012). However, their conclusions based on basic research
and expert opinion are biased and do not inform reliable estimates
of effect sizes for cryotherapy on different outcomes at different
time points. Moreover, previous reviews included non-randomized
controlled trials (Basur, Shephard,&Mouzas,1976; Cot�e, Prentice Jr,
Hooker, & Shields, 1988; Hocutt, Jaffe, Rylander, & Beebe, 1982;
Table 2
Summary of findings for cryotherapy and GRADE recommendations.
Additional effects of cryotherapy for acute ankle sprain
Patient or population: Participants with acute ankle sprain previous 24h (one study);
Setting: Accident and Emergency Department
Intervention: Ice pack applied for 20e30 min (two studies);
Comparison: Same interventions of experimental group but without the ice pack (two
Outcomes WMD or MD (95% IC) Nº of
participan
(studies)
Swelling
Ratio (%) between the swelling and intermalleolar
distance calculated from X-ray image;
Follow up: 7 days.
6.0 (�0.5 to 12.5)
P-value ¼ 0.07
143 (1 RC
Swelling
Volumetry
Follow-up: Until discharge
Not estimated 30 (1 RCT
Pain Intensity
Follow up: 7 days.
Not estimated 143 (1 RC
Pain intensity
Pain after treatment rated in 0e4
Follow-up: Until discharge
�0.03 (�0.34 to 0.28)
p-value ¼ 0.84
30 (1 RCT
Ankle range of motion
Goniometry
Follow up: 7 days.
Not estimated 143 (1 RC
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the esti
Moderate certainty:We are moderately confident in the effect estimate: The true effec
substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be
Very low certainty: We have very little confidence in the effect estimate: The true eff
Explanations.
a Downgraded owing to imprecision: less than 400 participants included in the analys
two levels).
b Downgraded owing to inconsistency: I2 statistic was higher than 50% or pooling was
included studies in the meta-analysis.
c Downgraded owing to risk of bias: analysis were from trials with a high risk of bias
247
Wilkerson & Horn-Kingery, 1993), did not compare cryotherapy
with an appropriate comparator to isolate the effects of cryo-
therapy (Ard�evol, Bolíbar, Belda, & Argilaga, 2002; Bleakley et al.,
2010; bib_Cot�e_et_al_1988,Cot�e, Prentice, Hooker, & Shields,
1988; Esch, Gerngross, & Fabian, 1989; Green, Refshauge, Crosbie,
& Adams, 2001; Hocutt et al., 1982; Prado et al., 2014; Wilkerson
& Horn-Kingery, 1993). Our systematic review is the first to eval-
uate the effectiveness of cryotherapy for the management of acute
ankle sprain. The adoption of appropriate inclusion and exclusion
criteria allowedus to inform the current evidence on the efficacy of
cryotherapy, and whether it enhances effects of other active
intervention in this health condition.
There are recommendations for the use of cryotherapy on
management of acute ankle sprain from clinical practice guidelines
(Van Dijk, 1999; Vuurberg et al., 2018), but these recommendations
are not based on high-quality clinical research from randomized
controlled trials. Vuurberg et al. (2018) recommend cryotherapy to
enhance effects of other active intervention, based on a randomized
controlled trial (Bleakley et al., 2010); however, comparators of this
trial were not appropriate to clarify it (i.e., compared cryotherapy
stand-alone with cryotherapy combined with exercise).
Clinicians have used cryotherapy in acute ankle sprain man-
agement based on findings from basic research, suggesting that
cryotherapy might decrease inflammatory processes by reducing
themacrophage infiltration, and the accumulation of TNF-a, NF-k B,
TGF-b and MMP-9 mRNA levels (bib_Nemet_et_al_2009,Nemet
et al., 2009; bib_Takagi_et_al_2011,Takagi et al., 2011); hypothe-
sizing that it might also lead to improvement on clinical outcomes.
However, this hypothesis is controversial because other basic
research hypothesizes that cryotherapy might delay migration of
participants with acute ankle sprain previous 48h (one study)
studies).
ts
Certainty of the
evidence (GRADE)
Comments
T) 222
VERY LOWa,b,c
The difference is not statistically significant.
) 222
VERY LOWa,b,c
The difference is not statistically significant.
T) 222
VERY LOWa,b,c
The outcome measure was not clearly stated. The
difference is not statistically significant.
) 222
VERY LOWa,b,c
The difference is not statistically significant.
T) 222
VERY LOWa,b,c
The difference is not statistically significant
mate of the effect
t is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different from the estimate of the effect
ect is likely to be substantially different from the estimate of effect
is (sample of less than 200 was considered serious imprecision and downgraded in
not possible or poor overlap between the confidence intervals of the effects of the
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	Effectiveness of cryotherapy on pain intensity, swelling, range of motion, function and recurrence in acute ankle sprain: A ...
	1. Introduction
	2. Methods
	2.1. Study design
	2.2. Eligibility criteria
	2.3. Search strategy and study selection
	2.4. Data extraction
	2.5. Risk of bias assessment
	2.6. Data analysis
	3. Results
	3.1. Characteristics of included trials and assessment of risk of bias
	3.2. Effects of cryotherapy on swelling, pain intensity, and range of motion in acute ankle sprain
	3.3. Swelling
	3.4. Pain intensity
	3.5. Range of motion
	4. Discussion
	5. Conclusions
	Ethical approval
	Funding
	Declaration of competing interest
	Acknowledgments
	Appendix A. Supplementary data
	References