This is not the most recent version of the article. View current version (26 MAY 2015)

Intervention Protocol

You have free access to this content

Injection therapies for Achilles tendinopathy

  1. Rebecca S Kearney1,*,
  2. Nick Parsons2,
  3. David Metcalfe3,
  4. Matthew L Costa4

Editorial Group: Cochrane Bone, Joint and Muscle Trauma Group

Published Online: 5 FEB 2014

DOI: 10.1002/14651858.CD010960


How to Cite

Kearney RS, Parsons N, Metcalfe D, Costa ML. Injection therapies for Achilles tendinopathy (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD010960. DOI: 10.1002/14651858.CD010960.

Author Information

  1. 1

    University of Warwick, Warwick Medical School, Coventry, UK

  2. 2

    University of Warwick, Warwick Orthopaedics, Warwick Medical School, Coventry, UK

  3. 3

    Warwick Medical School, University of Warwick, Warwick Orthopaedics, Coventry, UK

  4. 4

    University of Warwick, Warwick Clinical Trials Unit, Coventry, Warwickshire, UK

*Rebecca S Kearney, Warwick Medical School, University of Warwick, Clifford Bridge Road, Coventry, CV2 2DX, UK. R.S.Kearney@warwick.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 5 FEB 2014

SEARCH

This is not the most recent version of the article. View current version (26 MAY 2015)

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Description of the condition

The Achilles tendon connects the calf muscles (gastrocnemius, soleus and plantaris) to the heel bone (calcaneus). It transmits muscular forces that effect plantarflexion of the ankle against resistance (such as when standing on tiptoes). It has a fundamental role in walking and locomotion in general. The tendon is composed of a parallel alignment of cross-linked collagen fibres that have a crimped configuration at rest but straighten when under tension (Evans 2000). When the Achilles tendon is subject to greatly increased forces (e.g. sudden increase in intensity of an exercise activity) or repetitive submaximal forces over a prolonged duration, such as in long-distance running, these cross-links begin to fail. This process is followed by a period of remodelling and repair of the damaged tendon (Riley 2008). When there is an imbalance between these two processes, the tendon may begin to exhibit characteristics associated with Achilles tendinopathy, which is sometimes known as 'tendinitis'.

Achilles tendinopathy occurs at either the heel bone (insertion) or mid-portion (3 to 6 cm from the heel bone). The insertion of the Achilles tendon is thought to be predisposed to developing tendinopathy because of the excessive shear and compressive forces that occur at this site. Tendinopathy at the mid-portion (also 'mid-substance') has been attributed to decreased vascularity as the tendon fibres spiral laterally through 90 degrees at this point (Riley 2008). Factors associated with Achilles tendinopathy include biomechanical faults (hyperpronation of the foot), systemic diseases (such as diabetes), smoking, age, activity level and obesity; however, the aetiology is probably multifactorial rather than the result of any one of these considerations (Van Sterkenburg 2011).

Common features of Achilles tendinopathy include pain and stiffness, particularly over the lower portion of the calf. There may also be thickening of the tendon and swelling. Although classically worse in the morning, the pain may be constant or intermittent and aggravated either during or after weight-bearing exercise (Maffulli 2010). Pain on weight bearing in previously active people may cause considerable disruption to activities of daily living, work and sports.

One study in the Netherlands estimated the annual incidence of symptoms attributable to Achilles tendinopathy in the general population at 2.01 per 1000 people (De Jonge 2011). The annual incidence rate for mid-portion Achilles tendinopathy was 1.85 per 1000 people. The annual median age at presentation for mid-portion tendinopathy was 43.4 years; in 34.6% of cases, a specific relationship to sporting activities was noted. However, this study used Dutch general practitioner (GP) practice records and is likely to have underestimated the true incidence as people may have presented to other healthcare practitioners (e.g. physiotherapists) or not presented at all.

 

Description of the intervention

There is a large array of non-surgical (conservative) interventions available for the management of Achilles tendinopathy (Andres 2008; Kearney 2010; Sussmilch-Leitch 2012). Examples include eccentric exercises, cryotherapy, extracorporeal shockwave therapy, low-level laser therapy, ultrasound, orthotics, splints, topical nitroglycerin, injections and non-steroidal anti-inflammatory drugs (NSAIDS). Our review focuses on injection therapies, of which there are a growing number in use (Coombes 2010).

Injection therapies include a range of options such as corticosteroids, high-volume saline, prolotherapy, autologous blood, platelet-rich plasma, aprotinin, botulinum toxin, sodium hyaluronate, polysulphated glycosaminoglycan and polidocanol (Coombes 2010).

Injection therapies can be guided by real-time ultrasound imaging or unguided; they can be administered in isolation or in combination with any of the above interventions; they can be administered in a single dose or consist of a course, and they can be injected locally into the tendon or targeted at specific sites (such as areas of vascular ingrowth). There is no consensus on many of these factors and the exact intervention is at the discretion of the administering professional (Maffulli 2010).

 

How the intervention might work

All injection therapies are used to deliver a drug directly to the damaged tendon. In general, these substances are thought to act either pharmacologically (e.g. corticosteroids) or mechanically (e.g. high volume saline to stimulate neovascular growth).

The injection therapies reported in previous systematic reviews (Coombes 2010; DTB 2012) are listed below together with a brief description of their proposed mechanism of action. In broad terms, they have been classified into those targeting the promotion of repair activity through the introduction of substances to act directly on the repair pathway and those promoting repair activity through causing injury or destruction of new vascular ingrowth, or both.

 

Agents acting directly on the repair pathway

  1. Autologous blood: injected locally to promote repair activity through the administration of growth factors (present in a person's own blood) directly to the site of injury.
  2. Platelet-rich plasma: injected locally to promote repair activity through the administration of concentrated growth factors (present in a person's own blood that has been spun at a high speed to separate out the platelet-rich plasma layer) directly to the injury site.
  3. Aprotinin: injected locally to inhibit collagenase which would otherwise break down collagen and has been found to be increased in tendinopathy.
  4. Polysulphated glycosaminoglycan: injected locally to prevent destruction and facilitate repair through inhibiting metalloproteinase enzyme activity.
  5. Botulinum toxin: injected locally to decrease tensile stress through the tendon and inhibit substance P, which is increased in tendinopathy.
  6. Sodium hyaluronate: injected locally to absorb mechanical stress and provide a protective buffer for tissues.
  7. Corticosteroid: injected locally to down regulate (acting to decrease) inflammation in the affected tendon.

 

Agents causing injury or disrupting vascular ingrowth to promote repair activity

  1. High volume saline: a saline solution is injected along the surface of Achilles tendon, with or without local anaesthetic. The injection produces a mechanical effect on the new vascular ingrowth associated with tendinopathy, resulting in the new blood vessels stretching and breaking.
  2. Polidocanol: targeted disruption of new vasculature by administration of a scelerosant to precipitate blood vessel fibrosis.
  3. Prolotherapy: hypertonic glucose injected locally to initiate repair activity by causing local tissue trauma.

Injection therapies have a common suite of potential adverse effects, including local infection, bleeding, swelling and tendon rupture. Adverse effects may be the consequence of the injection itself (e.g. local bleeding and weakening of the tendon) or the substance injected.

 

Why it is important to do this review

Achilles tendinopathy is a common condition, often with significant functional consequences. A review of the evidence from randomised trials of injection therapies to help inform treatment decisions is warranted in the light of the wide range of available treatments, together with an exponential increase in their use (Kaux 2011). A synthesis of the available evidence may also help to direct future research in this area.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

To assess the effects (benefits and harms) of injection therapies for Achilles tendinopathy.

We plan to compare injection therapy versus no treatment, placebo (sham) treatment or other conservative treatment (injection or otherwise). Use of supplementary conservative treatments across study groups will be acceptable.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Criteria for considering studies for this review

 

Types of studies

We will include randomised and quasi-randomised (using a method of allocating participants to a treatment that is not strictly random, e.g. by hospital number) controlled clinical trials evaluating injection therapies for Achilles tendinopathy.

 

Types of participants

We will include people with an investigator-reported diagnosis of Achilles tendinopathy (or related terminology, e.g. tendinitis). We will exclude trials focusing on the treatment of individuals with systemic conditions (e.g. rheumatoid arthritis and diabetes).

We will exclude mixed population trials, including other conditions, unless the proportion of the population with other conditions is small and comparable between the intervention groups, or separate data are available for people with Achilles tendinopathy.

 

Types of interventions

As described above, there are many different types of injection therapies. In the first instance, we will attempt to group the therapies by mode of action; for example, grouping could include all methods of autologous blood injections (administration of growth factors) or sclerosing agents (aimed at destruction of new vascular growth). Sclerosing agents are those that cause inflammation and subsequent fibrosis of new blood vessels. As these modes of action are postulated rather than established facts, we will explore clinical heterogeneity on this basis.

Our main comparisons will be injection therapy versus no treatment or placebo (sham) treatment; and injection therapy versus other conservative treatment (such as exercises or orthoses). Use of supplementary conservative treatments across study groups will be acceptable.

We will also compare different injection therapies, again attempting to group these by mode of action; and different doses or number of injections for the same injection therapy. No single injection therapy is well established or in common use as a treatment for Achilles tendinopathy. This makes it difficult to choose a meaningful control intervention when comparing different injection therapies. However, we will adopt the following provisional rules when selecting the control intervention in any comparison: this will be the older, more traditional therapy (e.g. corticosteroid would be selected for a comparison of platelet rich plasma versus corticosteroid); the less destructive; or the less intensive of the interventions under test.

 

Types of outcome measures

The review will focus on functional recovery, together with reported adverse events.

 

Primary outcomes

  1. Function measured by validated patient-reported measure for Achilles tendinopathy (e.g. VISA A: an Achilles tendinopathy specific questionnaire, which contains eight questions that cover three domains of pain, function and activity. An asymptomatic person would score 100; the lower the score, the greater the disability (Robinson 2001)).
  2. Serious adverse events (e.g. tendon rupture).

 

Secondary outcomes

  1. Patient-reported quality of life (e.g. EQ-5D, 12-Item Short Form Health Survey (SF-12)).
  2. Non-validated patient-reported functional outcomes for Achilles tendinopathy.
  3. Pain (e.g. as measured by a visual analogue scale (VAS)).
  4. Return to previous level of activity.
  5. Other (transient) adverse events (e.g. post-injection discomfort).
  6. Patient rating of acceptability or satisfaction.
  7. Resource use.

 

Timing of outcome measurement

It is expected that functional outcome scores will be reported at multiple time points; for example, six weeks, three months and six months. Dependent on the nature of reporting, we will perform separate analyses representing short-, medium- and long-term follow-up time points.

 

Search methods for identification of studies

 

Electronic searches

We will search the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to present), the Cochrane Central Register of Controlled Trials (CENTRAL, current issue), MEDLINE (1946 to present), AMED (1985 to present), CINAHL (1981 to present), SPORTDiscus (1985 to present) and EMBASE (1980 to present). We will also search the World Health Organization International Clinical Trials Registry platform and Current Controlled Trials for ongoing and recently completed studies. We will apply no restrictions based on language or publication status.

In MEDLINE (Ovid Online), we will combine a subject-specific strategy with the sensitivity-maximising version of the Cochrane Highly Sensitive Search Strategy for identifying randomised trials (Lefebvre 2011). Search strategies for the CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and SPORTDiscus are shown in Appendix 1 .

 

Searching other resources

We will search reference lists of articles retrieved from the electronic searches and contact experts in the field for any additional published or unpublished articles.

 

Data collection and analysis

 

Selection of studies

Two review authors (RK and DM) will independently screen search results for potentially eligible studies, for which full-text reports will be obtained. The same two review authors will independently select articles for inclusion based on the inclusion criteria listed above. We will resolve any disagreements through discussion, with arbitration by a third review author (MC) if required.

 

Data extraction and management

Two review authors (RK and DM) will independently extract data using a piloted data extraction form. We will resolve any disagreements through discussion, with arbitration by a third review author (MC) if required. The review statistician (NP), who is independent from the study selection discussions, will collate and manage the data.

 

Assessment of risk of bias in included studies

Two review authors (RK and DM) will independently assess the risk of bias using The Cochrane Collaboration's 'Risk of bias' tool (Higgins 2011). This tool includes the assessment of selection bias (random allocation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data), reporting bias (selective reporting) and other sources of bias. We will determine the risk of bias from blinding of subjective and objective outcome measures separately. We will resolve any disagreements through discussion and consensus between those conducting the review.

 

Measures of treatment effect

For continuous data, such as functional scores, we will calculate mean differences with 95% confidence intervals (CI). For dichotomous outcomes, such as adverse events, we will calculate risk ratios with 95% CI. When pooling continuous data from outcomes measured in different ways, we will use standardised mean differences and 95% CIs.

 

Unit of analysis issues

We plan to analyse the data by individual participant. We anticipate that studies will exclude cases of bilateral Achilles tendinopathy and thus unit of analysis issues associated with a disparity between unit of randomisation (person) and analysis (feet) will not arise. We will record where exceptions arise and take appropriate statistical measures, including conducting sensitivity analyses to test the effects of including incorrectly reported trials.

We anticipate simple parallel group designs; however, in the unlikely event that cross-over trials are reported, we will only analyse the first phase of the results.

 

Dealing with missing data

Where there is missing data for binary outcomes, we will categorise them as failures, providing an overall conservative analysis. For continuous data, we will analyse data that are available and explore the effect of missing data through sensitivity analyses.

However, we will endeavour to acquire missing data from the articles directly from the study authors where appropriate. Finally, if standard deviations are not available, we will, if possible, calculate these from exact P values, CIs or standard errors.

 

Assessment of heterogeneity

We will assess statistically heterogeneity between studies by visual inspection of the overlap of the CIs on the forest plots, and consideration of the Chi2 test (P value < 0.1 will be interpreted as significant heterogeneity) and the I2 statistic. We will base our interpretation of the I2 results as suggested in Higgins 2011: 0% to 40% might not be important, 30% to 60% may represent moderate heterogeneity, 50% to 90% may represent substantial heterogeneity and 75% to 100% may represent considerable (very substantial) heterogeneity.

 

Assessment of reporting biases

Where at least 10 studies contribute data to a meta-analysis, we will generate a funnel plot to explore the potential for publication bias.

 

Data synthesis

When considered appropriate, we will pool results of comparable groups of trials using both fixed-effect and random-effects models. The choice of the model to report will be guided by a careful consideration of the extent of heterogeneity and whether it can be explained, in addition to other factors such as the number and size of studies. If there is substantial unexplained heterogeneity (I2 > 75%), we will not perform a meta-analysis and will present a narrative description instead.

 

Subgroup analysis and investigation of heterogeneity

If sufficient data are available, we will perform the following subgroup analyses.

We will investigate whether the results of subgroups are significantly different by inspecting the overlap of CIs and performing the test for subgroup differences available in Review Manager 5 (RevMan 2012).

As the actual substance injected may be a key determinant of outcome, this is likely to be a great source of heterogeneity. Therefore, we will explore clinical heterogeneity according to the substance injected.

If the heterogeneity statistic indicates that one or more of the studies is a clear outlier, then we will conduct a meta-analysis with and without the outliers. All such decisions will be carefully documented.

 

Sensitivity analysis

If sufficient trials are available, we will perform sensitivity analyses to examine various aspects of trial and review methodology, including the effects of missing data (see Dealing with missing data); of presenting results at different time points, as defined in Types of outcome measures; of including trials at high or unclear risk of bias, such as selection bias arising from lack of allocation concealment; the selection of a statistical model (fixed-effect versus random-effects) for pooling; and including and excluding study outliers.

 

'Summary of findings' tables

Where there is sufficient evidence, we will prepare 'Summary of findings' tables for the main comparisons. We will use the GRADE approach to assess the quality of evidence related to each of the key outcomes listed in the Types of outcome measures (Chapter 12.2, Higgins 2011).

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

We would like to thank the external referees (Nicola Maffulli and Stephen Pribut), and the two editors (Nigel Hanchard and Helen Handoll) and editorial staff (Joanne Elliott, Lindsey Elstub and Laura MacDonald) of the Cochrane Bone, Joint and Muscle Trauma Group for help and feedback on the protocol.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Appendix 1. Search strategies

 

The Cochrane Library (Wiley Online Library)

#1 MeSH descriptor: [Achilles Tendon] this term only
#2 Achilles or calcan*:ti,ab,kw  (Word variations have been searched)      
#3 #1 or #2      
#4 [mh Tendinopathy] or [mh ^"Athletic Injuries"] or [mh ^"Tendon Injuries"] or [mh ^"Soft Tissue Injuries"]      
#5 tend?nitis or tenosynovitis or tendinopath* or tendinosis or paratend?nitis or peritend?nitis:ti,ab,kw  (Word variations have been searched)      
#6 #4 or #5      
#7 #3 and #6    
#8 [mh ^Injections] or [mh ^"Injections, Intralesional"]     
#9 injection*:ti,ab,kw  (Word variations have been searched)        
#10 MeSH descriptor: [Adrenal Cortex Hormones] explode all trees and with qualifiers: [Administration & dosage - AD, Pharmacology - PD, Therapeutic use - TU] 
#11 MeSH descriptor: [Steroids] explode all trees and with qualifiers: [Administration & dosage - AD, Pharmacology - PD, Therapeutic use - TU]
#12 MeSH descriptor: [Anti-Inflammatory Agents] this term only     
#13 glucocorticoid* or corticoster* or methylprednisolone or prednisolone or betamethasone or triamcinolone or cortisone or hydrocortisone:ti,ab,kw  (Word variations have been searched)
#14 "high volume":ti,ab,kw  (Word variations have been searched)  
#15 prolotherapy or "proliferation therapy":ti,ab,kw  (Word variations have been searched)        
#16 autologous near/3 blood:ti,ab,kw  (Word variations have been searched)        
#17 MeSH descriptor: [Blood Transfusion, Autologous] this term only
#18 ((platelet rich near/3 (plasma or therap*)) or PRP):ti,ab,kw  (Word variations have been searched) 
#19 MeSH descriptor: [Platelet-Rich Plasma] this term only    
#20 MeSH descriptor: [Aprotinin] this term only
#21 Aprotinin:ti,ab,kw  (Word variations have been searched)
#22 MeSH descriptor: [Botulinum Toxins] explode all trees    
#23 "botulinum toxin":ti,ab,kw  (Word variations have been searched)        
#24 "sodium hyaluronate":ti,ab,kw  (Word variations have been searched)  
#25 MeSH descriptor: [Glycosaminoglycans] this term only    
#26 Glycosaminoglycan*:ti,ab,kw  (Word variations have been searched)    
#27 [mh ^"Sclerosing Solutions"] or [mh ^Sclerotherapy]    
#28 MeSH descriptor: [Polyethylene Glycols] this term only   
#29 polidocanol:ti,ab,kw  (Word variations have been searched)      
#30 lauromacrogol:ti,ab,kw  (Word variations have been searched)  
#31 "hyperosmolar dextrose":ti,ab,kw  (Word variations have been searched)       
#32 {or #8-#31}
#33 #7 and #32  

 

MEDLINE (Ovid Online)

1 Achilles Tendon/
2 (Achilles or calcan*).tw.
3 1 or 2
4 exp Tendinopathy/ or Athletic Injuries/ or Tendon Injuries/ or Soft Tissue Injuries/
5 (Tend#nitis or tenosynovitis or tendinopath* or tendinosis or paratend#nitis or peritend#nitis).tw.
6 4 or 5
7 3 and 6
8 Injections/ or Injections, Intralesional/
9 injection*.tw. (394404)
10 exp Adrenal Cortex Hormones/ad, dt, pd, tu [Administration & Dosage, Drug Therapy, Pharmacology, Therapeutic Use]
11 exp steroids/
12 Anti-Inflammatory Agents/
13 (glucocorticoid* or corticoster* or methylprednisolone or prednisolone or betamethasone or triamcinolone or cortisone or hydrocortisone).tw.
14 "high volume".tw.
15 (prolotherapy or "proliferation therapy").tw.
16 (autologous adj3 blood).tw.
17 Blood Transfusion, Autologous/
18 ((platelet rich adj3 (plasma or therap*)) or PRP).tw.
19 Platelet-Rich Plasma/
20 Aprotinin/
21 Aprotinin.tw.
22 exp Botulinum Toxins/
23 "botulinum toxin".tw.
24 "sodium hyaluronate".tw.
25 Glycosaminoglycans/
26 glycosaminoglycan.tw.
27 Sclerosing Solutions/ or Sclerotherapy/
28 Polyethylene Glycols/
29 polidocanol.tw.
30 lauromacrogol.tw.
31 "hyperosmolar dextrose".tw.
32 or/8-31
33 7 and 32
34 Randomized controlled trial.pt.
35 Controlled clinical trial.pt.
36 randomized.ab.
37 placebo.ab.
38 Drug therapy.fs.
39 randomly.ab.
40 trial.ab.
41 groups.ab.
42 or/34-41
43 exp Animals/ not Humans/
44 42 not 43
45 33 and 44

 

EMBASE (Ovid Online)

1 Achilles Tendinitis/
2 Achilles Tendon/
3 (Achill* or calcan*).tw.
4 2 or 3
5 Tendinitis/ or Tenosynovitis/ or Sport Injury/ or Tendon Injury/ or Soft Tissue Injury/
6 (tend#nitis or tenosynovitis or tendinopath* or tendinosis or paratend#nitis or peritend#nitis).tw.
7 5 or 6
8 4 and 7
9 1 or 8
10  Injection/ or Intralesional Drug Administration/
11 injection*.tw.
12 exp Corticosteroid/
13 exp Antiinflammatory Agent/
14 (glucocorticoid* or corticoster* or methylprednisolone or prednisolone or betamethasone or triamcinolone or cortisone or hydrocortisone).tw.
15 "high volume".tw.
16 (prolotherapy or "proliferation therapy").tw.
17 (autologous adj3 blood).tw.
18 exp Blood Transfusion/
19 ((platelet rich adj3 (plasma or therap*)) or PRP).tw.
20 Plasma Transfusion/ or Thrombocyte Rich Plasma/
21 Aprotinin/
22 aprotinin.tw.
23 Botulinum Toxin/
24 "botulinum toxin".tw.
25 "sodium hyaluronate".tw.
26 Glycosaminoglycan/
27 glycosaminoglycan.tw.
28 Sclerosing Agent/ or Sclerotherapy/
29 Macrogol Derivative/
30 Polidocanol/
31 polidocanol.tw.
32 lauromacrogol.tw.
33 "hyperosmolar dextrose".tw.
34 or/10-33
35 and/9,34
36 exp Randomized Controlled Trial/ or exp Single Blind Procedure/ or exp Double Blind Procedure/ or Crossover Procedure/ (378735)
37 (random* or RCT or placebo or allocat* or crossover* or 'cross over' or trial or (doubl* adj1 blind*) or (singl* adj1 blind*)).ti,ab.
38 36 or 37
39 (exp Animal/ or animal.hw. or Nonhuman/) not (exp Human/ or Human Cell/ or (human or humans).ti.)
40 38 not 39
41 35 and 40

 

AMED (Ovid Online)

1 Achilles Tendon/
2 (Achilles or calcan*).tw.
3 1 or 2
4 Tendinopathy/ or Tenosynovitis/ or exp Athletic Injuries/ or Tendon Injuries/
5 (tend#nitis or tenosynovitis or tendinopath* or tendinosis or paratend#nitis or peritend#nitis).tw.
6 4 or 5
7 3 and 6
8 Randomized controlled trial.pt.
9 Controlled clinical trial.pt.
10 Randomized Controlled Trials/
11 Random Allocation/
12 Double-Blind Method/
13 or/8-12
14 exp Animals/ not Humans/
15 13 not 14
16 Clinical trial.pt.
17 exp Clinical Trials/
18 (clinic* adj25 trial*).tw.
19 ((singl* or doubl* or trebl* or tripl*) adj (mask* or blind*)).tw.
20 Placebos/
21 placebo*.tw.
22 random*.tw.
23 exp Research Design/
24 (latin adj square).tw.
25 or/16-24
26 25 not 14
27 26 not 15
28 7 and 27

 

CINAHL (EBSCO)

S1 (MH "Achilles Tendinopathy")
S2 (MH "Achilles Tendon")
S3 TI ( Achill* or calcan* ) OR AB ( Achill* or calcan* )
S4 S2 OR S3
S5 (MH "Tendinopathy") OR (MH "Tenosynovitis") OR (MH "Athletic Injuries") OR (MH "Tendon Injuries") OR (MH "Soft Tissue Injuries")
S6 TX tendinitis ot tendonitis or tenosynovitis or tendinopath* or tendinosis or paratendinitis or paratendonitis or peritendinitis or peritendonitis
S7 S5 OR S6
S8 S4 AND S7
S9 S1 AND S8
S10 (MH "Injections") OR (MH "Injections, Intralesional")
S11 TI injection* OR AB injection*
S12 (MH "Adrenal Cortex Hormones+")
S13 (MH "Antiinflammatory Agents")
S14 TX (glucocorticoid* or corticoster* or methylprednisolone or prednisolone or betamethasone or triamcinolone or cortisone or hydrocortisone)
S15 TX "high volume"
S16 TX (prolotherapy or "proliferation therapy")
S17 TX (autologous n3 blood)
S18 (MH "Blood Transfusion, Autologous")
S19 ((platelet rich n3 (plasma or therap*)) or PRP)
S20 (MH "Platelet-Rich Plasma")
S21 (MH "Aprotinin")
S22 TX aprotinin
S23 (MH "Botulinum Toxins")
S24 TX "botulinum toxin"
S25 TX "sodium hyaluronate"
S26 (MH "Glycosaminoglycans")
S27 TX glycosaminoglycan*
S28 (MH "Sclerosing Solutions") OR (MH "Sclerotherapy")
S29 (MH "Polyethylene Glycols")
S30 TX polidocanol
S31 TX lauromacrogol
S32 TX "hyperosmolar dextrose"
S33 S3 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32
S34 S9 AND S33
S35 (MH "Clinical Trials+")
S36 (MH "Evaluation Research+")
S37 (MH "Comparative Studies")
S38 (MH "Crossover Design")
S39 PT Clinical Trial
S40 (MH "Random Assignment")
S41 S35 or S36 or S37 or S38 or S39 or S40
S42 TX ((clinical or controlled or comparative or placebo or prospective or randomi?ed) and (trial or study))
S43 TX (random* and (allocat* or allot* or assign* or basis* or divid* or order*))
S44 TX ((singl* or doubl* or trebl* or tripl*) and (blind* or mask*))
S45 TX ( crossover* or 'cross over' ) or TX cross n1 over
S46 TX ((allocat* or allot* or assign* or divid*) and (condition* or experiment* or intervention* or treatment* or therap* or control* or group*))
S47 S42 or S43 or S44 or S45 or S46
S48 S41 or S47
S49 S34 AND S48

 

SPORTDiscus (EBSCO)

S1 DE "ACHILLES tendinitis"
S2 (DE "ACHILLES tendon") OR (DE "ACHILLES tendon -- Wounds & injuries")
S3 TX Achill* or calcan*
S4 S2 OR S3
S5 (DE "TENDINITIS") OR (DE "TENOSYNOVITIS") OR (DE "SOFT tissue injuries") OR (DE "SPORTS injuries")
S6 TX tendinitis ot tendonitis or tenosynovitis or tendinopath* or tendinosis or paratendinitis or paratendonitis or peritendinitis or peritendonitis
S7 S5 OR S6
S8 S4 AND S7
S9 S1 OR S8
S10 DE "INJECTIONS"
S11 TX injection*
S12 DE "ANTI-inflammatory agents"
S13 TX (glucocorticoid* or corticoster* or methylprednisolone or prednisolone or betamethasone or triamcinolone or cortisone or hydrocortisone)
S14 TX "high volume"
S15 TX (prolotherapy or "proliferation therapy")
S16 TX (autologous n3 blood)
S17 TX ((platelet rich n3 (plasma or therap*)) or PRP)
S18 TX aprotinin
S19 DE "BOTULINUM toxin"
S20 TX "botulinum toxin"
S21 TX "sodium hyaluronate"
S22 TX glycosaminoglycan*
S23 TX sclerosing solution* or sclerotherap*
S24 TX polyethylene glycol*
S25 TX polidocanol
S26 TX lauromacrogol
S27 TX hyperosmolar dextrose
S28 S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27
S29 S9 AND S28
S30 TX ( (clinic* N3 trial) or (controlled N3 trial) or (comparative N3 trial) or (placebo N3 trial) or (prospective N3 trial) or (randomi?ed N3 trial) ) or TX ( (clinic* N3 study) or (controlled N3 study) or (comparative N3 study) or (placebo N3 study) or (prospective N3 study) or (randomi?ed N3 study) )
S31 (random* N7 allot*) or (random* N7 assign*) or (random* N7 basis*) or (random* N7 divid*) or (random* N7 order*)
S32 TX ( (singl* N7 blind*) or (doubl* N7 blind*) or (trebl* N7 blind*) or (tripl* N7 blind*) ) or TX ( (singl* N7 mask*) or (doubl* N7 mask*) or (trebl* N7 mask*) or (tripl* N7 mask*) )
S33 TX (cross#over*) or TX (cross N1 over*)
S34 TX randomi?ed control* trial*
S35 TX ( (allocat* N3 condition*) or (allocat* N3 experiment*) or (allocat* N3 intervention*) or (allocat* N3 treatment*) or (allocat* N3 therap*) or (allocat* N3 control*) or (allocat* N3 group*) ) or TX ( (allot* N3 condition*) or (allot* N3 experiment*) or (allot* N3 intervention*) or (allot* N3 treatment*) or (allot* N3 therap*) or (allot* N3 control*) or (allot* N3 group*) ) or TX ( (assign* N3 condition*) or (assign* N3 experiment*) or (assign* N3 intervention*) or (assign* N3 treatment*) or (assign* N3 therap*) or (assign* N3 control*) or (assign* N3 group*) ) or TX ( (divid* N3 condition*) or (divid* N3 experiment*) or (divid* N3 intervention*) or (divid* N3 treatment*) or (divid* N3 therap*) or (divid* N3 control*) or (divid* N3 group*) )
S36 TX placebo*
S37 S30 or S31 or S32 or S33 or S34 or S35 or S36
S38 S29 AND S37

 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

RK: drafted protocol and contributed to the search strategy, and is guarantor of the review.
NP: drafted protocol and contributed to the search strategy.
DM: drafted protocol and contributed to the search strategy.
MC: drafted protocol and contributed to the search strategy.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

Rebecca S Kearney: none known.
Nick Parsons: none known.
David Metcalfe: none known.
Matthew L Costa: My institution, University of Warwick, has received research grants and PRP [platelet-rich plasma] materials at cost price for studies related to the treatment of Achilles tendinopathy and rupture, including injection studies. However, I have no personal interest to declare.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Internal sources

  • University of Warwick, UK.
    Salaries for the authors to support the development of the protocol.

 

External sources

  • No sources of support supplied

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Acknowledgements
  7. Appendices
  8. Contributions of authors
  9. Declarations of interest
  10. Sources of support
  11. Additional references
Andres 2008
Coombes 2010
  • Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet 2010;376(9754):1751-67.
De Jonge 2011
  • De Jonge S, Van den Berg C, De Vos R, Van der Heide H, Weir A, Verhaar J, et al. Incidence of midportion Achilles tendinopathy in the general population. British Journal of Sports Medicine 2011;45(13):1026-8.
DTB 2012
  • Anonymous. Management of chronic Achilles tendinopathy. Drugs and Therapy Bulletin 2012;50(8):93-6.
Evans 2000
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Kaux 2011
  • Kaux JF, Forthomme B, Le Goff C, Crielaard JM, Croiser JL. Current opinions on tendinopathy. Journal of Sports Science and Medicine 2011;10:238-53.
Kearney 2010
Kraemer 2012
  • Kraemer R, Wuerfel W, Lorenzen J, Busche M, Vogt PM, Knobloch K. Analysis of hereditary and medical risk factors in Achilles tendinopathy and Achilles tendon ruptures: a matched pair analysis. Archives of Orthopaedic and Trauma Surgery 2012;132:847-53.
Lefebvre 2011
  • Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Maffulli 2010
  • Maffulli N, Longo UG, Denaro V. Novel approaches for the management of tendinopathy. Journal of Bone and Joint Surgery - American Volume 2010;92(15):2604-13.
Narici 2008
RevMan 2012
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Riley 2008
Robinson 2001
  • Robinson JM, Cook JL, Purdam C, Visentini PJ, Ross J, Maffulli N, et al. The VISA-A questionnaire: a valid and reliable index of the clinical severity of Achilles tendinopathy. British Journal of Sports Medicine 2001;35(5):335-41.
Sussmilch-Leitch 2012
  • Sussmilch-Leitch S, Collins N, Bialocerkowski A, Warden S, Crossley K. Physical therapies for Achilles tendinopathy: systematic review and meta-analysis. Journal of Foot and Ankle Research 2012;5(1):15.
Van Sterkenburg 2011
  • Van Sterkenburg MN, Van Dijk CN. Mid-portion Achilles tendinopathy: why painful? An evidence-based philosophy. Knee Surgery, Sports Traumatology, Arthroscopy 2011;19(8):1367-75.