Review

Br J Sports Med: first published as 10.1136/bjsports-2015-094879 on 21 July 2015. Downloaded from http://bjsm.bmj.com/ on December 21, 2024 by guest. Protected by copyright.
Efficacy of rehabilitation (lengthening) exercises,
platelet-rich plasma injections, and other
Editor’s choice
conservative interventions in acute hamstring
Scan to access more
free content injuries: an updated systematic review and
meta-analysis
Haiko IMFL Pas,1,2 Gustaaf Reurink,1,3,4 Johannes L Tol,1,5,6 Adam Weir,4
Marinus Winters,7 Maarten H Moen1,8

▸ Additional material is ABSTRACT were not effective.1 Since the publication of this
published online only. To view Background Our 2012 review on therapeutic review, several new randomised controlled trials
please visit the journal online
(http://dx.doi.org/10.1136/ interventions for acute hamstring injuries found a lack (RCTs) have been published. After the 2012
bjsports-2015-094879). of high-quality studies. The publication of new studies Cochrane review of Mason et al2 no new systematic
1 warranted an update. reviews have been published warranting an update.
The Sports Physician Group,
Department of Sports Objectives To update and reanalyse the efficacy of Given the new evidence, we adjusted the inclusion
Medicine, St Lucas Andreas conservative treatments for hamstring injury. criteria of our original review1 to include only RCTs.
Hospital, Amsterdam, Data sources PubMed, EMBASE, Web of Science, The purpose of this updated systematic review is to
The Netherlands Cochrane library, CINAHL and SPORTDiscus were reassess the available literature concerning the conser-
2
Department of Cardiology,
Alrijne Hospital Leiden, Leiden,
searched till mid-February 2015. vative management of HI, to review their efficacy
The Netherlands Study eligibility criteria Randomised controlled and perform meta-analysis, where possible.
3
Department of Orthopaedics, trials (RCTs) on the effect of conservative interventions
Erasmus Medical Centre, versus a control group or other intervention for MATERIALS AND METHODS
Rotterdam, The Netherlands hamstring injuries (HI) were included. Literature search
4
Department of Orthopaedic
Surgery, Academic Medical Data analysis The search results were screened A literature search was performed in mid-February
Centre, Amsterdam, independently by two authors. Risk of bias assessment 2015 in PubMed, EMBASE, Web of Science core
The Netherlands
5
was performed using a modified Downs and Black scale collection, Cochrane library, CINAHL and
Aspetar, Orthopedic and with a maximum score of 28. Meta-analysis was SPORTDiscus. A modified version of the 2012
Sports Medicine Hospital,
Doha, Qatar
performed, where possible. search was used (see online supplementary appen-
6
Amsterdam Center of Main results 10 RCTs (526 participants), including dix 1). Searches were performed by one author
Evidence Based Sports 6 new RCTs, were identified. Two RCTs were of good/ (HP) with no limits. The references of the selected
Medicine, Academic Medical excellent quality, the rest were fair or poor (median articles were manually searched for additional
Center, Amsterdam, Downs and Black score 16 (IQR 9)). Meta-analysis of references.
The Netherlands
7
Department of Rehabilitation, two studies on rehabilitation (lengthening) exercises All studies identified by the search were imported
Nursing Science & Sports, showed a significantly reduced time to return to play in a citation database (EndNote 7.1, Thomson
University Medical Centre (HR 3.22 (95% CI 2.17 to 4.77), p<0.0001) but no Reuters, New York, USA) and duplicates were
Utrecht, Utrecht, difference in risk of re-injury. Meta-analysis of three removed. Additionally, co-authors of this review, with
The Netherlands
8
Bergman Clinics, Naarden, studies investigating platelet-rich plasma (PRP) showed a specific interest in hamstring injury, were asked
The Netherlands no effect when compared to control (HR 1.03 (95% CI about internationally known recently completed and/
0.87 to 1.22), p=0.73). Limited evidence was found that or submitted RCTs up to February 2015.
Correspondence to progressive agility and trunk stability training may reduce
Haiko IMFL Pas, The Sports
re-injury rates. Study selection
Physician Group, Department
of Sports Medicine, St Lucas Conclusions Meta-analysis showed superior efficacy All titles were screened by two independent assessors
Andreas Hospital, mailbox for rehabilitation exercises. PRP injection had no effect (HP and JLT). Full texts of possibly eligible articles
9243, Amsterdam 1006 AE, on acute hamstring injury. Limited evidence was found were obtained and assessed independently using the
The Netherlands; that agility and trunk stabilisation may reduce re-injury inclusion criteria presented in box 1. Both reviewers
[email protected]
rates. The limitations identified in the majority of RCTs compared the articles identified and consensus was
Accepted 26 June 2015 should improve the design of new hamstring RCTs. reached. If no consensus was reached, a third
Published Online First reviewer (MHM) was consulted.
21 July 2015
Data extraction
INTRODUCTION Using a standardised data extraction form, study
In 2012, we systematically reviewed the evidence for characteristics, patient characteristics and outcome
conservative interventions in the treatment of acute measures were recorded by one author (HP). Point
hamstring injuries (HI).1 We found limited evidence measures and estimations of variance of the selected
To cite: Pas HIMFL, to support the use of agility and trunk stabilisation, outcomes were recorded to evaluate therapy efficacy.
Reurink G, Tol JL, et al. Br J (slump) stretching and Actovegin injections.1 Limited In the case of multiple measurements, the data of the
Sports Med 2015;49: evidence was found that sacroiliac manipulations and last measurement were used. If necessary, authors
1197–1205. non-steroidal anti-inflammatory drugs (NSAIDs) were contacted for additional data.
Pas HIMFL, et al. Br J Sports Med 2015;49:1197–1205. doi:10.1136/bjsports-2015-094879 1 of 10
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time-to-event data. HRs were calculated such that HR>1 indi-
Box 1 Inclusion criteria cated faster RTP in the treatment group as compared to the
control group. Risk ratios (RR) with 95% CI were calculated for
dichotomous outcomes. RR<1 expressed a smaller risk for
▸ Participants in the study had an acute hamstring injury,
re-injury in the treatment group as compared to the control group.
diagnosed by physical examination, MRI or ultrasound
A fixed effects model was used to pool data when studies were stat-
▸ The studies included were randomised controlled trials
istically homogenous. We visually inspected the forest plots for
▸ There was a well-described conservative therapeutic
heterogeneity, along with the I2-statistic which was considered to
intervention which was compared to another intervention
represent substantial heterogeneity for I2>50%.9 Heterogeneity
or a control group
was considered present when the χ2 was significant (p<0.1).9 We
▸ Full text of the article was available
planned a metaregression analysis or subgroup analysis when stat-
▸ The article was written in English, German or Dutch
istical heterogeneity was present and ≥10 studies were available. A
▸ In the article at least one of the following outcome
random effects model was used when statistical heterogeneity was
measures had to be reported:
present. However, when <5 studies were available for data synthe-
– Time to return to sport or normal function
sis we used a fixed effects model.
– Re-injury rate
We planned a sensitivity analysis to explore the effect of study
– Pain scores
quality by excluding studies with low D&B scores (<20) from
– Hamstring force: isometric or isokinetic testing
the meta-analysis.
– Hamstring flexibility testing
If meta-analysis was not possible, a qualitative analysis of the
– Patient satisfaction
data was carried out using the five levels of evidence used in
– Adverse effects
2012.1 10 Meta-analysis was considered superior to qualitative
levels of evidence.
1. Strong evidence: provided by two or more studies with high
Quality assessment quality and by generally consistent findings in all studies
Two reviewers (MHM and GR) independently assessed the (≥75% of the studies reported consistent findings).
selected studies for risk of bias using a modified version of the 2. Moderate evidence: provided by one study with high quality
Downs and Black scale (D&B)3 (see online supplementary and/or two or more studies with low quality, and by gener-
appendix 2). The original scale consists of 27 questions and ally consistent findings in all studies (≥75% of the studies
allows a maximal score of 32 points. Based on previous litera- reported consistent findings).
ture we modified this scale to a 28-point scale4–7 by converting 3. Limited evidence: provided by only one study with low
it to a binary scale and by adding one additional question evalu- quality.
ating therapist blinding. This was identified as an important 4. Conflicting evidence: inconsistent findings in multiple
form of bias based on the studies we identified in our previous studies (<75% of the studies reported consistent findings).
review.1 Most studies evaluated physical therapy interventions 5. No evidence: when no studies could be found.
or complementary therapies, adding a possibly biased party if We evaluated the possible presence of publication bias in this
he/she was not blinded. Especially in return to play (RTP) review by assessing the symmetry of the funnel plot.
decision-making, lack of therapist blinding is an important
source of bias.8 One point was given if therapist blinding was RESULTS
ensured. Lastly, question 21 was only scored when both time to Literature search
RTP and re-injury rate were reported in the trial. This was done In total 2190 titles and abstracts were screened; 16 studies were
because we feel that trials reporting both these outcome mea- selected for full-text assessment. Reference tracking yielded no
sures give a more complete and less biased outcome of the additional titles. After full-text assessment, six studies were
therapy success.1 excluded11–15 and nine studies met the inclusion criteria.16–24
A maximum of 28 points could be scored. We adopted the Two, at that time unpublished, articles were found through
following quality levels based on previous literature4 5 7: excel- co-authors ( JLT and GR).25 26 The manuscripts were obtained
lent (26–28); good (20–25); fair (15–19) and poor (≤14). with permission of the authors. One of these trials26 reported
If there was a difference in opinion on a D&B item score, the secondary outcomes of a trial identified in the literature
consensus was reached by consulting a third reviewer ( JLT). search;24 we did not consider it as a separate trial, but rather as
When at least one of the primary D&B assessors was involved additional information of the first trial.24 Figure 1 illustrates the
as co-author in the RCT, an independent experienced assessor selection process.
(AS), scored it as the third assessor.
Description of the included studies
The funnel plot showed no evidence of publication bias when
Data synthesis taking the symmetrical distribution of the studies in the funnel
One author (HP) calculated weighted means and SDs for demo- plot (figure 2) into account.
graphic information using SPSS V.22.0 (IBM statistics, Table 1 summarises the characteristics of the included studies.
New York, New York, USA). After assessing normality using the Compared to 2012,1 two case–control trials were not evaluated13 27
Kolmogorov-Smirnov ( p<0.05) test mean or median, D&B and six new RCTs were found.20–26 Five studies21–26 were rated as
scores were calculated. homogenous and judged to be suitable for meta-analysis. The data
We considered pooling data when studies were sufficiently statis- of these trials were pooled per intervention.
tically and clinically homogeneous (ie, intervention and outcome).
Data pooling was carried out with RevMan V.5.3 (The Nordic Quality assessment
Cochrane Centre, Copenhagen, Denmark) by two authors (HP Table 2 shows the overall D&B scores (detailed information in
and MW). We calculated hazard ratios (HR) with 95% CI for online supplementary appendix 3). Scores ranged from 14 to 27
2 of 10 Pas HIMFL, et al. Br J Sports Med 2015;49:1197–1205. doi:10.1136/bjsports-2015-094879
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Participants
A total of 526 participants were included with a mean of
65 (SD 23) per study. The mean and median ages reported
across the studies ranged between 20 and 32 years. The majority
of participants were males comprising a weighted mean of 86%
(SD 13) of the population (range 65–100). Participants from dif-
ferent sports were used in seven studies,17–20 23–26 two studies
used a specific sport population,21 22 one study did not expli-
citly mention using a sporting population.16
Table 3 summarises the examinations performed on patients
to diagnose hamstring injury.

Interventions and outcomes

Table 4 summarises the interventions used in the studies, the
outcomes that were measured and their effect. Two studies eval-
uated the efficacy of exercises aimed at loading and lengthening
the muscle during eccentric actions in addition to a physiother-
apy programme.21 22 Two studies assessed a physical therapy
programme focused on agility and trunk stabilisation.19 20
Three studies compared platelet-rich plasma (PRP) injections
and a standardised physiotherapy programme with placebo
injections, platelet-poor plasma injections or no injection.23–26
The remaining studies examined the efficacy of stretching,18
sacroiliac manipulation16 and the use of NSAIDs (meclofena-
mate and diclofenac).17

Figure 1 Flow chart of article selection (RCT, randomised controlled Data synthesis
trial). We performed a meta-analysis on five studies.21–25 Two studies
evaluated the effect of a partially supervised physiotherapy pro-
with a median of 16 (IQR 9). One three-arm RCT was given gramme21 22 with either a lengthening protocol (L-protocol) or
two separate D&B scores25 as it used two different control inter- a conventional protocol (C-protocol). Of the three RCTs evalu-
ventions which were blinded in different ways. The third assessor ating the efficacy of PRP injections in addition to physiotherapy,
was asked to assess all trials concerning questions 11–13 which we did not pool the platelet-poor plasma data from Hamilton
were found to be highly subjective. An independent assessor (AS) et al25 due to doubts about the validity and the unknown effects
was asked to score one trial,24 26 as the primary D&B assessors of this product.
were involved as co-authors in the trial. The total score of the Two studies19 20 evaluating physical therapy programmes
independent assessor was identical to our consensus assessment based on agility and trunk stabilisation were not pooled because
though there was a slight variance between individual items (see of differences in the content of the intervention and control
online supplementary appendix 3). programmes.

Figure 2 Publication bias funnel

plot.

Pas HIMFL, et al. Br J Sports Med 2015;49:1197–1205. doi:10.1136/bjsports-2015-094879 3 of 10

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Review
Table 1 Article characteristics
Author N Population Intervention(s) Follow-up Primary outcome Results
19
Sherry and Best 24 Athletes with acute hamstring strain, grades 1 and 2 I1: rehabilitation programme consisting of PATS exercises 1 year Time to RTP I1: 22.2 days (SD 8.3)
based on physical examination and icing Re-injury I2: 37.4 days (SD 27.6)
I2: rehabilitation programme consisting of static stretching, I1: 0/13
isolated progressive resistance exercise and icing (STST) I2: 7/10
Silder et al20 29 Athletes with suspected HI within the past 10 days I1: rehabilitation programme consisting of PATS programme 1 year Time to RTP I1: 25.2 days (SD 6.3)
confirmed by physical examination and MRI I2: rehabilitation programme consisting of PETS Craniocaudal length of I2: 28.8 days(SD 11.4)
injury I1: 7.9 cm (95% CI 2.7 to 13.1)
I2: 15.9 cm (95% CI 8.4 to 23.4)
Reynolds et al17 44 Patients with sports-related tear of the hamstring, I1: two capsules 50 mg meclofenamate and two diclofenac 7 days Sum of pain score (VAS) in I1: 7.9 (SD 6.6)
<48 h after injury placebo capsules 3 times/day for 7 days the last 24 h I2: 8.8 (SD 7.7)
I2: two 25 mg diclofenac and two meclofenamate placebo C: 3.9 (SD 3.3)
capsules 3 times/day for 7 days
C: meclofenamate and diclofenac placebo capsules
Malliaropoulos et al18 80 Athletes with a ultrasonographic grade 2 hamstring I1+I2: during first 48 h PRICE followed by rehabilitation RTP Time required for full I1: 13.27 days (SD 0.71)
strain programme rehabilitation I2: 15.05 days (SD 0.81)
I1: four stretching sessions daily Time to equalisation of I1: 5.57 days (SD 3.3)
I2: one stretching session daily knee ROM I2: 7.23 days (SD 0.525)
Cibulka et al16 20 Patients with a clinical diagnosis of hamstring muscle I: moist heat, passive stretching and manipulation of None Hamstring peak torque I1: 46.4 ft lbs (SD 17.47
strain and sacroiliac joint dysfunction sacroiliac joint reported Passive knee extension I2: 45.7 ft lbs (SD 22.70)
Pas HIMFL, et al. Br J Sports Med 2015;49:1197–1205. doi:10.1136/bjsports-2015-094879

C: moist heat, passive stretching ROM I1: 155.0° (SD 14.2)

I2: 144.6° (SD 16.7)
Askling et al21 75 Elite Swedish football players with MRI (<5 days after I1: L-protocol aimed at loading the hamstrings during extensive 1 year Time to RTP I1: 28 days (SD 15)
injury) confirmed HI lengthening, mainly during eccentric muscle actions Re-injury I2: 51 days (SD 21)
I2: C-protocol consisting of conventional exercises for the I1: 0/37
hamstrings with less emphasis on lengthening I2: 1/38
Askling et al22 56 Swedish elite sprinters and jumpers with MRI (<5 days I1: L-protocol aimed at loading the hamstrings during extensive 1 year Time to RTP I1: 49 days (SD 26)
after injury) confirmed HI lengthening, mainly during eccentric muscle actions Re-injury I2: 86 days (SD 34)
I2: C-protocol consisting of conventional exercises for the I1: 0/28
hamstrings with less emphasis on lengthening I2: 2/28
Reurink et al24 80 Athletes with acute hamstring injuries confirmed by I: two 3 mL platelet-rich plasma injections and a standard 1 year Time to RTP I: 42 days (IQR 30–58)
physical examination and MRI rehabilitation programme C: 42 days (IQR 37–56)
C: two 3 mL saline placebo injections and a standard
rehabilitation programme
Hamid et al23 28 Athletes diagnosed with an acute ultrasonographic I: one 3 mL platelet-rich plasma injection and a rehabilitation RTS Time to RTP I: 26.7 days (SD 7.0)
grade 2 hamstring injury programme C: 42.5 days (SD 20.6)
C: rehabilitation programme only
Hamilton et al25 90 Athletes with acute posterior thigh pain confirmed by I1: one 3 mL platelet-rich plasma injection and a rehabilitation 6 months Time to RTP I1: 21 days (95% CI 17.9 to 24.1)
MRI as grade 1 or 2 hamstring lesion programme I2: 27 days (95% CI 20.6 to 33.4)
I2: one 3 mL platelet-poor plasma injection and a rehabilitation C: 25 days (95% CI 21.5 to 28.5)
programme
C: rehabilitation programme only
C, control; C-protocol, conventional rehabilitation protocol; I, intervention; L-protocol, loading and lengthening rehabilitation protocol; PATS, progressive agility and trunk stabilisation; PETS, progressive running and eccentric strengthening; ROM, range of
motion; RTP, return to play; RTS, return to sport; STST, stretching and strengthening; VAS, visual analogue scale.

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 Review

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risk of re-injury (figure 3A, B). The pooled effect showed that
Table 2 Total D&B scores (maximal 28)*
the L-protocol significantly reduced RTP compared to the
D&B Level of C-protocol with an HR of 3.22 ((95% CI 2.17 to 4.77),
Reference score evidence Z=5.83, p<0.0001) (figure 2). No difference was found
Sherry and Best19 16 Fair
between the two protocols for the risk of re-injury ((RR)=0.25,
Silder et al20 18 Fair
95% CI 0.03 to 2.20, Z=1.25, p=0.21) (figure 3). No statistical
Reynolds et al17 16 Fair
heterogeneity was present (I2=0%).
Malliaropoulos et al18 14 Poor
Cibulka et al16 15 Fair
Meta-analysis: PRP
Askling et al21 15 Fair
Three studies evaluated the effect of PRP injections23–25 with
Askling et al22 15 Fair
standardised rehabilitation. Hamid et al23 performed an
Reurink et al24 25 Good
assessor-blinded study comparing patients receiving a single
Hamid et al23 19 Fair
3 mL PRP injection (Biomet, mean 1297×103 platelets/μL,
Hamilton et al25 (PRP vs no injection) 24 Good
mean 38.3×103 leucocytes/μL) within 7 days after injury, to
Hamilton et al25 (PRP vs platelet-poor plasma) 27 Excellent
patients who received no injection. Both groups followed a stan-
dardised rehabilitation programme. Hamilton et al25 performed
*Scores for all 28 questions are listed in the online supplementary table S3. Hamilton
et al25 was given two separate D&B scores because it used two different controls a double-blinded trial comparing one 3 mL injection of PRP
which were blinded in two different ways. (Biomet, mean 765.8±423.6×103 platelets/μL, mean 26.1±
D&B, Downs and Black; PRP, platelet-rich plasma. 13.7×103 leucocytes/μL) and platelet-poor plasma (mean 30.3±
23.0×103 platelets/μL, mean 0.03±0.03×103 leucocytes/μL)
Meta-analysis: lengthening exercises (also referred to as within 5 days after injury and a single-blinded comparison study
‘rehabilitative’ for the general reader) arm with no injection. All three groups underwent a six-stage
Askling et al21 22 evaluated the effect of adding exercises aimed criteria-based standardised rehabilitation. All treating phy-
at progressively loading the injured muscle (L-protocol) to a siotherapists were blinded for group allocation and MRI find-
conventional physiotherapy programme. The hamstrings were ings. Patients were randomised to receive either 3 mL of PRP or
lengthened extensively during eccentric muscle actions. This platelet-poor plasma or no injection. Reurink et al24 26 under-
was compared to exercises which had less emphasis on muscle took a double-blind RCT in which patients were randomised to
lengthening (C-protocol). Both protocols contained three types receive either two injections with 3 mL of PRP, respectively,
of exercises aimed at increasing flexibility, strengthening the within 5 days after injury onset and 5–7 days after the first injec-
muscle, and a combination of strengthening and trunk/pelvic tion (Arthrex mean 433±128×103 platelets/μL, mean 1.9±
stabilisation, but the exact exercises differed between groups. 2.1×103 leucocytes/μL), or saline placebo injections in addition
Both groups received a standard general rehabilitation pro- to a standardised rehabilitation programme.
gramme in addition to their exercises (checked with the author). The D&B scores of the trials differed. Two24–26 were rated as
Patients were cleared for return to sport when there were no good or excellent (D&B scores 25 and 24/27, respectively) and
signs of injury during physical examination and when they one23 as fair (D&B 19). We, therefore, performed a sensitivity
could perform the Askling H-test (a rapid straight leg raise in a analysis.
special knee brace) without hesitation.28 Additional data from A fixed effects model was used to estimate the HR of RTP in
the author was requested for meta-analysis. the PRP group compared to the non-injected control group.
Fixed effects models were used to estimate the effect of the The pooled effect showed no significant effect of PRP compared
L-protocol versus the C-protocol for RTP (number of days) and to control with an HR of 1.03 ((95% CI 0.87 to 1.22),
Z=0.35, p=0.73) (figure 4A). There was substantial heterogen-
eity (I2=75%), which was significant (p=0.02). Sensitivity ana-
Table 3 Clinical examinations used to diagnose hamstring injury lysis revealed that the decision of including high risk of bias
studies in the meta-analysis did not affect the effect of PRP
Physical
when compared to including low risk of bias studies only. When
Reference examination Ultrasound MRI* Grading system
analysing low risk of bias studies only, the HR was 1.00 ((95%
Sherry and Best19 Yes No No Based on physical CI 0.85 to 1.19), Z=0.04, p=0.97) (figure 4B). The risk of
exam findings re-injury at 6 months was pooled for two trials24–26 as one
Silder et al20 Yes No Yes None trial23 did not report re-injury. This showed no difference
Reynolds et al17 Yes No No None between PRP and control (RR=0.88, (95% CI 0.45 to 1.71),
Malliaropoulos Yes Yes No Based on Z=0.39, p=0.70) (figure 4C). No heterogeneity was present for
et al18 ultrasound findings re-injury. Owing to the small number of studies investigating the
Cibulka et al16 Yes† No No None interventions, no meta-regression or subgroup analysis was
Askling et al21 Yes No Yes None possible.
Askling et al22 Yes No Yes None
Reurink et al24 Yes No Yes Based on MRI Descriptive synthesis
findings
Progressive agility and trunk stabilisation
Hamid et al23 Yes Yes No Based on
ultrasound findings
Two studies19 20 evaluated a rehabilitation programme, which
Hamilton et al25 Not reported No Yes Based on MRI
focused on progressive agility and trunk stabilisation (PATS).
findings Sherry and Best19 compared PATS to a rehabilitation pro-
*Abnormally high intensity on T2-weighted and/or STIR-weighted images.
gramme focusing on stretching and strengthening (STST). Both
†Also evaluated sacroiliac dysfunction defined as pelvic asymmetry, positive standing programmes consisted of two discrete phases. Compliance was
flexion test and prone knee flexion test. monitored through self-recorded exercise logs. A mean of
STIR, short tau inversion recorvery.
22.2 days (SD 8.3) for the PATS group and 37.4 days (SD 27.6)
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Table 4 Interventions and outcomes of RCTs
Intervention Outcome Effect Best evidence synthesis Quality ratings of studies

Progressive loading during Time to RTP21 22 + Meta-analysis Fair21 22

eccentric lengthening Re-injury21 22 = Meta-analysis

PATS exercises Time to RTS19 20 = Moderate Fair19 20

Re-injury19 + Limited
Craniocaudal length of injury at RTS20 + Limited
Physical examination at RTS20 = Limited
MRI characteristics at RTS20 = Limited
Stretching exercises Time to RTP18 + Limited Poor18
Time to equalisation of knee ROM18 + Limited
Platelet-rich plasma Time to RTP23–25 = Meta-analysis Good24 26
Re-injury24 25 = Meta-analysis Fair23
Adverse events23–25 = Strong Good/excellent25
Change in pain score23 = Limited
Isokinetic testing25 = Limited
Changes in T2-weighted MRI after 3 weeks25 = Limited
Adherence to rehabilitation programme25 26 = Strong
Physical examination26 = Limited
Hamstring outcome score26 = Limited
Patient satisfaction26 = Limited
oedema on MRI26 = Limited
NSAIDs Pain score17 = Limited Fair17
Isokinetic testing17 = Limited
Swelling17 = Limited
Adverse events17 − Limited
Sacroiliac manipulation Hamstring flexibility16 = Limited Fair16
Isokinetic testing16 = Limited
=, No effect of intervention compared to control or no differences between intervention and control; +, favours intervention; −, favours control; NSAID, non-steroidal anti-inflammatory
drug; PATS, progressive agility and trunk stabilisation; RCT, randomised controlled trial; ROM, range of motion; RTP, return to play; RTS, return to sport.

for the STST group was reported, which was not statistically sig- PATS and 3/13 for the PRES group. Significance was not
nificant ( p=0.2455). Re-injury rates between groups were statis- reported. Several other outcome measures based on MRI finding
tically significant in favour of PATS (0/13 re-injuries within and physical examination were reported in the study. Of these,
16 days after RTP and 1/13 within 1 year, vs 6/10 and 7/10, only the craniocaudal length of injury at RTP on MRI was signifi-
respectively in the STST group ( p<0.001 in both cases)). cantly shorter for the PATS group at RTP ( p=0.037).
Silder et al20 compared PATS with a progressive running and
eccentric strengthening (PRES) programme. Both programmes Stretching
consisted of three phases. No statistically significant difference in Malliaropoulos et al18 compared two different intensities of
RTP was found (PATS: mean of 25.2 days (SD 6.3), PRES: static stretching (four times vs once daily) in 80 patient with
28.8 days (SD 11.4), p=0.346). Re-injury rates were 1/16 in the grade 2 hamstring injury. Full active knee extension was reached

Figure 3 (A) Pooled HRs of return to play for adding lengthening exercises (L-protocol) and conventional exercises (C-protocol) Log natural
logarithm; IV, inverse variance;, square size indicates the size of the population investigated in each study; diamond estimated pooled effect: width
indicates the 95% CI. (B) Pooled risk ratio for re-injury (<1 year) for adding lengthening exercises (L-protocol) and conventional exercises (C-protocol).
square size indicates the size of the population investigated in each study; diamond estimated pooled effect: width indicates the 95% CI.
6 of 10 Pas HIMFL, et al. Br J Sports Med 2015;49:1197–1205. doi:10.1136/bjsports-2015-094879
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Figure 4 (A) Pooled HRs for return to play for platelet-rich protein (PRP) and control interventions. Log natural logarithm; IV, inverse variance;
square size indicates the size of the population investigated in each study; diamond estimated pooled effect: width indicates the 95% CI. Data using
platelet-poor plasma (PPP) as control were excluded from analysis. (B) Sensitivity analysis, the HR for return to play for PRP and control based on
high-quality randomised controlled trials (RCTs) only. Log natural logarithm; IV, inverse variance; square size indicates the size of the population
investigated in each study; diamond estimated pooled effect: width indicates the 95% CI. Data using platelet-poor plasma (PPP) as control were
excluded from analysis. (C) Pooled risk ratio for re-injury for platelet-rich plasma (PRP) and control. IV, inverse variance; square size indicates the
size of the population investigated in each study; diamond estimated pooled effect: width indicates the 95% CI. Data using platelet-poor plasma as
control were excluded.

earlier in the high-intensity group with a mean of 5.57 (SD had no effect on change in pain scores or pain intensity scores.
0.71) days vs 7.32 (SD 0.53) days ( p<0.001). Time to RTP was No adverse events were reported. Re-injury rates were not
shorter in the high-intensity group (mean of 13.27 days (SD reported.
0.71) days compared to 15.05 (SD 0.81) days ( p<0.001)). Both Hamilton et al25 and Reurink et al24 26 found no signifi-
cant differences between other secondary outcomes. Both
Sacroiliac manipulation reported no significant adverse events.
Cibulka et al16 found no effect of sacroiliac manipulation on Hamilton et al25 found that RTP in the platelet-poor plasma
peak quadriceps torque and passive knee extension after group was significantly longer when compared to PRP
manipulation compared to non-manipulated controls. A signifi- (−5.7 days ((95% CI −10.1 to −1.4), p=0.01). No difference
cant difference in peak torque change was reported in favour of was found between platelet-poor plasma and no injection
manipulation (8.1 (sacroiliac mobilisation group) vs 0.4 ft lbs (2.8 days (95% CI −1.6 to 7.2), p=0.210).
(control)). It should be noted that significantly lower pre-test
peak torques of the experimental group were reported
(8.4 ft lbs lower, p<0.005). DISCUSSION
Main findings
Non-steroidal anti-inflammatory drugs We systematically reviewed 10 RCTs that evaluated the effects
Reynold et al17 evaluated the effect of 50 mg meclofenamate of different interventions for acute hamstring injuries. These
and placebo (group 1) versus 25 mg diclofenac twice daily, and studies were generally of fair quality with one poor quality18
placebo (Group 2) versus placebo only (group 3) for a period of and two good/excellent quality studies.24–26 The poor-quality
7 days. No significant effects on pain scores (measured with a and fair-quality studies mostly lacked adequate blinding, were
visual analogue scale), swelling and isokinetic hamstring tests underpowered and did not properly adjust for loss to follow-up.
( peak torque, total work and average power) were found. Based on the meta-analysis of two studies of fair quality,21 22 we
Adverse events were reported in 5/13 patients in group 1, 6/17 found that adding lengthening exercises reduce the time to RTP
in group 2 and 2/14 in group 3. None of these required alter- when compared to conventional exercises. Meta-analysis of the
ation or reduction of the medication. Statistical analysis was not PRP trials23–26 showed no additional effect for PRP injections
performed for adverse events. on RTP or in reducing re-injury. For re-injury reduction, limited
evidence from one trial19 was found for agility and trunk stabil-
PRP injections isation exercises; however, moderate evidence from two fair
Hamid et al23 found that although the PRP group showed sig- quality trials19 20 showed no reduction in time to RTP for these
nificantly lower pain severity scores during the rehabilitation, it exercises.
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Limited evidence, through one poor-quality study,18 is available (1297×103/μL). However, this study risked bias due to a lack of
to support high-frequency compared with low-frequency stretch- a placebo or any attempt to mask the lack of injection allowing
ing in grade 2 HI. Based on fair-quality studies, limited evidence is for a placebo effect among patients. Re-injury rates were not
available that NSAIDs17 and sacroiliac mobilisation16 have no reported, making the assessment of a possible premature RTP
therapeutic effect in acute hamstring injury rehabilitation. and the long-term efficacy impossible.
Several previous reviews30–33 have found a dearth of evidence
Physical therapeutic interventions to support PRP as a treatment for muscle injury. Considering
Meta-analysis showed that adding lengthening exercises to a our quantitative and qualitative findings, higher levels of evi-
standard physical therapy programme was more effective than dence are now available to discourage the use of PRP injections
using conventional exercises in reducing time to RTP, but had in the rehabilitation of hamstring injuries.
no effect on re-injury rate. These results should be interpreted
with care and require reproduction by other research groups Other interventions
and different athlete populations. It should also be noted that Limited evidence was found that NSAIDs17 and sacroiliac
both trials were unblinded and the D&B scores indicate that manipulation16 have no effect on outcome. Furthermore, the
both trials were of fair quality (D&B scores of 15) making them study by Cibulka et al16 contains several methodical shortcom-
prone to detection and performance bias. Several differences ings (unclear definitions, differences in baseline characteristics)
were found between trials (unequal male/female distributions, making it prone to bias. Also, its findings with regard to ham-
age, proportion of stretch type injury, length of injury and string peak torque can be explained by the difference in pre-test
sports type) but these did not influence statistical heterogeneity peak torques between groups.
of the data. NSAIDs are often proposed as an analgesic in the early phase
We found moderate evidence that PATS does not reduce the of muscle injury.34–37 Although the evidence is limited,17 we
time to RTP. Both studies19 20 used different control (STST and found no evidence to support the use of NSAIDs for pain man-
PRES) interventions and the content of the PATS programmes agement. Furthermore, there is increasing evidence that NSAIDs
differed (two vs three phases). It should also be noted that both may be counterproductive for muscle healing.29 Considering the
trials used small sample sizes (n=2419 and n=2920). Sherry and lack of support for their efficacy and the possible detrimental
Best19 did prove its superiority over STST with regard to effect on muscle healing, NSAIDs are not recommended in HI.
re-injury rate. However, as previously observed,1 the re-injury
rate in the STST group was remarkably high (70%), suggesting Limitations
a possible adverse effect of this programme. Our review has several limitations. First, we did not perform a
We found limited evidence that static stretching four times a grey literature search. We did find one on-going trial through
day was superior to once daily stretching.18 No other studies the co-authors. It is possible that other pending trials are
evaluated static stretching or used it as a control making it available.
impossible to state whether stretching itself is efficacious. Second, we used a modified D&B scale to assess the quality
in trials. In 2012, the PEDro scale was used1 making compari-
Platelet-rich plasma son of the trial quality more difficult. However, the association
Our meta-analysis and descriptive synthesis show that there is between both scales was previously found to be moderately high
no superior efficacy for PRP injections. The results from the (r 0.71, p<0.01)38 and after the modifications to our D&B
meta-analysis should be considered carefully as there is substan- scale, all questions from the PEDro scale were assessed as part
tial heterogeneity in the data. First, two trials23 25 used a non- of the D&B. We, therefore, feel that the use of our modified
blinded, no injection group as control whereas Reurink et al D&B scale was valid. We compared the effect on quality assess-
used a blinded placebo group (saline) as control group,24 26 ment between both scales and found no difference in 50%. In
allowing for performance bias in the results. This actually the remaining 50%, the PEDro scale always showed higher
strengthens the results presented because no effect could be quality ratings, suggesting our current review was more critical
found despite the presence of bias. Second, all trials differed in assessing the available evidence.
slightly in injection techniques and PRP content. Third, we did We altered a few keyword combinations because we found
not pool the platelet-poor plasma data from Hamilton et al25 that the original search included too many irrelevant articles
because there were concerns about its validity as placebo. There and that the number of hits using this search had in some cases
is little experience with platelet-poor plasma and due to its quadrupled. Each alteration was checked for potentially missed
content ( pH, osmolality, remaining leucocytes and platelets), articles. We are confident that no relevant articles were missed.
myotoxic effects cannot be excluded and its enhancing effect Lastly, we excluded all clinical controlled trials since enough
remains unclear. Saline was considered a more valid placebo as RCTs were now available to focus specifically on randomised
ample evidence is available that it has no myotoxic effect on studies, adding to the level of evidence of this review. Owing to
muscle tissue.29 Lastly, there were differences in patient this exclusion criterion, two treatment options were not
characteristics. Thus, no meta-regression or subgroup analysis reviewed compared to 2012.1
was possible to investigate the effect of patient characteristics.
The RCTs by Reurink et al24 26 and Hamilton et al,25 were of Updated clinical relevance: what should be implemented
high quality. Please note that members of this review group are in clinical practice
co-authors of these studies. The D&B score of the independent New evidence is available to assist in clinical decision-making
assessor (AS) was comparable and did not affect the quality cat- for the treatment of hamstring injuries. Askling’s et al21 22
egory of Reurink et al24 26 (good) and the co-author involved lengthening protocol enhances RTP compared to conventional
with the Hamilton et al25 trial ( JLT) was not involved in the therapy (meta-analysis), and PATS might be implemented for
D&B scoring. reducing the re-injury rate (limited evidence). Statistical evi-
Hamid et al23 reported that PRP shortened the time to RTP. dence suggests that PRP injections have no added effect on RTP
The PRP preparation in this study had the highest platelet count or re-injury rate (meta-analysis).
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Future directions Provenance and peer review Not commissioned; externally peer reviewed.
The quality of the RCTs included was generally relatively low.
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