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The Cochrane Database of Systematic... May 2015Achilles tendinopathy is a common condition, often with significant functional consequences. As a wide range of injection treatments are available, a review of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Achilles tendinopathy is a common condition, often with significant functional consequences. As a wide range of injection treatments are available, a review of randomised trials evaluating injection therapies to help inform treatment decisions is warranted.
OBJECTIVES
To assess the effects (benefits and harms) of injection therapies for people with Achilles tendinopathy.
SEARCH METHODS
We searched the following databases up to 20 April 2015: the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL and SPORTDiscus. We also searched trial registers (29 May 2014) and reference lists of articles to identify additional studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials evaluating injection therapies in adults with an investigator-reported diagnosis of Achilles tendinopathy. We accepted comparison arms of placebo (sham) or no injection control, or other active treatment (such as physiotherapy, pharmaceuticals or surgery). Our primary outcomes were function, using measures such as the VISA-A (Victorian Institute of Sport Assessment-Achilles questionnaire), and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included studies. We assessed treatment effects using mean differences (MDs) and 95% confidence intervals (CIs) for continuous variables and risk ratios (RRs) and 95% CIs for dichotomous variables. For follow-up data, we defined short-term as up to six weeks, medium-term as up to three months and longer-term as data beyond three months. We performed meta-analysis where appropriate.
MAIN RESULTS
We included 18 studies (732 participants). Seven trials exclusively studied athletic populations. The mean ages of the participants in the individual trials ranged from 20 years to 50 years. Fifteen trials compared an injection therapy with a placebo injection or no injection control, four trials compared an injection therapy with active treatment, and one compared two different concentrations of the same injection. Thus no trials compared different injection therapies. Two studies had three trial arms and we included them twice in two different categories. Within these categories, we further subdivided injection therapies by mode of action (injury-causing versus direct repair agents).The risk of bias was unclear (due to poor reporting) or high in six trials published between 1987 and 1994. Improved methodology and reporting for the subsequent trials published between 2004 and 2013 meant that these were at less risk of bias.Given the very low quality evidence available from each of four small trials comparing different combinations of injection therapy versus active treatment and the single trial comparing two doses of one injection therapy, only the results of the first comparison (injection therapy versus control) are presented.There is low quality evidence of a lack of significant or clinically important differences in VISA-A scores (0 to 100: best function) between injection therapy and control groups at six weeks (MD 0.79, 95% CI -4.56 to 6.14; 200 participants, five trials), three months (MD -0.94, 95% CI -6.34 to 4.46; 189 participants, five trials) or between six and 12 months (MD 0.14, 95% CI -6.54 to 6.82; 132 participants, three trials). Very low quality evidence from 13 trials showed little difference between the two groups in adverse events (14/243 versus 12/206; RR 0.97, 95% CI 0.50 to 1.89), most of which were minor and short-lasting. The only major adverse event in the injection therapy group was an Achilles tendon rupture, which happened in a trial testing corticosteroid injections. There was very low quality evidence in favour of the injection therapy group in short-term (under three months) pain (219 participants, seven trials) and in the return to sports (335 participants, seven trials). There was very low quality evidence indicating little difference between groups in patient satisfaction with treatment (152 participants, four trials). There was insufficient evidence to conclude on subgroup differences based on mode of action given that only two trials tested injury-causing agents and the clear heterogeneity of the other 13 trials, which tested seven different therapies that act directly on the repair pathway.
AUTHORS' CONCLUSIONS
There is insufficient evidence from randomised controlled trials to draw conclusions on the use, or to support the routine use, of injection therapies for treating Achilles tendinopathy. This review has highlighted a need for definitive research in the area of injection therapies for Achilles tendinopathy, including in older non-athletic populations. This review has shown that there is a consensus in the literature that placebo-controlled trials are considered the most appropriate trial design.
Topics: Achilles Tendon; Adrenal Cortex Hormones; Adult; Aprotinin; Athletes; Fibroblasts; Glycosaminoglycans; Hemodialysis Solutions; Humans; Injections, Intralesional; Middle Aged; Platelet Transfusion; Polidocanol; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sodium Chloride; Tendinopathy; Young Adult
PubMed: 26009861
DOI: 10.1002/14651858.CD010960.pub2 -
British Medical Bulletin Mar 2015Several pharmacological interventions have been proposed for the management of Achilles tendinopathy, with no agreement on which is the overall best option available.... (Review)
Review
INTRODUCTION
Several pharmacological interventions have been proposed for the management of Achilles tendinopathy, with no agreement on which is the overall best option available. This systematic review investigates the efficacy and safety of different local pharmacological treatments for Achilles tendinopathy.
SOURCES OF DATA
We included only randomized controlled studies (RCTs) focusing on clinical and functional outcomes of therapies consisting in injection of a substance or local application. Assessment of the methodological quality was performed using a modified version of the Coleman methodology score (CMS) to determine possible risks of bias.
AREAS OF AGREEMENT
Thirteen RCTs were included with a total of 528 studied patients. Eleven studies reported the outcomes of injection therapies. Two studies examined the outcomes of patients who applied glyceryl trinitrate patch. The mean modified CMS was 70.6 out of 90.
AREAS OF CONTROVERSY
There was no significant evidence of remarkable benefits provided by any of the therapies studied.
GROWING POINTS
There is not univocal evidence to advise any particular pharmacological treatment as the best advisable non-operative option for Achilles tendinopathy as equivalent alternative to the most commonly used eccentric loading rehabilitation program. However, potential was shown by the combination of different substances administered with physical therapy.
RESEARCH
There is a need for more long-term investigations, studying large enough cohort with standardized scores and evaluations shared by all the investigations to confirm the healing potential, and provide a stronger statistical comparison of the available treatments.
Topics: Achilles Tendon; Blood Transfusion, Autologous; Humans; Pain; Platelet-Rich Plasma; Polidocanol; Polyethylene Glycols; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Sclerosing Solutions; Tendinopathy; Treatment Outcome; United Kingdom; Wound Healing
PubMed: 25583629
DOI: 10.1093/bmb/ldu040 -
Cardiovascular and Interventional... Aug 2014Because the best possible treatment for venous malformations is unclear, this study systematically reviews the available literature regarding the effectiveness of... (Review)
Review
PURPOSE
Because the best possible treatment for venous malformations is unclear, this study systematically reviews the available literature regarding the effectiveness of different treatment options for the patient group. Venous malformations result from incorrect development of the veins during embryogenesis and are present at birth. Venous malformations may exhibit symptoms, such as pain, swelling, and inflammation of the vessel.
MATERIALS AND METHODS
A systematic literature search in PubMed and Embase was performed. Data regarding the design, participants, intervention and, treatment outcome (success and complications) were extracted. The validity of the studies was assessed with the Cochrane Collaboration's risk of bias tool.
RESULTS
Thirty-five studies were identified studying the effectiveness of eight treatments: sclerotherapy/embolization with ethanol, gelified ethanol, bleomycin, polidocanol, sodium tetradecyl sulfate (STS), Ethibloc, surgery, and laser therapy. All of the included studies have a high or unclear risk of bias. The average biased reported success rates for ethanol, gelified ethanol, bleomycin, polidocanol, STS, Ethibloc, surgery, and laser therapy were 74, 89, 88, 90, 86, 65, 90, and 94 %, respectively.
CONCLUSION
Until more valid evidence is available, the choice for treatment remains a shared decision between the patient and a multidisciplinary treatment group. From a cost perspective, sclerotherapy with STS or polidocanol should be the treatment of choice.
Topics: Humans; Laser Therapy; Risk Factors; Sclerosing Solutions; Sclerotherapy; Vascular Malformations; Vascular Surgical Procedures
PubMed: 24196269
DOI: 10.1007/s00270-013-0764-2 -
Phlebology Apr 2013The objective of the study was to review the literature reporting visual disturbance (VD)following sclerotherapy for varicose veins. Underlying mechanisms will be... (Review)
Review
The objective of the study was to review the literature reporting visual disturbance (VD)following sclerotherapy for varicose veins. Underlying mechanisms will be discussed. A literature search of the databases Medline and Google Scholar was performed. Original articles including randomized trials, case series and case reports reporting VD in humans following sclerotherapy for varicose veins were included. Additional references were also obtained if they had been referenced in related publications. The search yielded 4948 results of which 25 reports were found to meet the inclusion criteria. In larger series with at least 500 included patients the prevalence of VD following sclerotherapy ranges from 0.09% to 2%. In most reports foam sclerotherapy was associated with VD (19); exclusive use of liquid sclerosant was reported in two cases, some reports included foam and liquid sclerosant (4). There were no persistent visual disorders reported. VD occurred with polidocanol and sodium tetradecyl sulphate in different concentrations (0.25–3%). Various forms of foam preparation including various ways of foam production and the liquid –air ratio (1 or 2 parts of liquid mixed with 3, 4 or 5 parts of air) were reported in association with the occurrence of VD. VDs following sclerotherapy for varicose veins are rare and all reported events were transient. Bubble embolism or any kind of embolism seems unlikely to be the only underlying mechanism. A systemic inflammatory response following sclerotherapy has been suggested. Further research to clarify the mechanism of action of sclerosants is required.
Topics: Embolism; Female; Humans; MEDLINE; Male; Polidocanol; Polyethylene Glycols; Sclerosing Solutions; Sclerotherapy; Sodium Tetradecyl Sulfate; Telangiectasis; Varicose Veins; Vision Disorders
PubMed: 23761921
DOI: 10.1258/phleb.2012.012051 -
The American Journal of Sports Medicine Jun 2013Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection therapies have become available.
PURPOSE
To assess the comparative effectiveness and safety of injection therapies in patients with lateral epicondylitis.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
Randomized controlled trials comparing different injection therapies for lateral epicondylitis were included provided they contained data for change in pain intensity (primary outcome). Trials were assessed using the Cochrane risk of bias tool. Network (random effects) meta-analysis was applied to combine direct and indirect evidence within and across trial data using the final end point reported in the trials, and results for the arm-based network analyses are reported as standardized mean differences (SMDs).
RESULTS
Seventeen trials (1381 participants; 3 [18%] at low risk of bias) assessing injection with 8 different treatments-glucocorticoid (10 trials), botulinum toxin (4 trials), autologous blood (3 trials), platelet-rich plasma (2 trials), and polidocanol, glycosaminoglycan, prolotherapy, and hyaluronic acid (1 trial each)-were included. Pooled results (SMD [95% confidence interval]) showed that beyond 8 weeks, glucocorticoid injection was no more effective than placebo (-0.04 [-0.45 to 0.35]), but only 1 trial (which did not include a placebo arm) was at low risk of bias. Although botulinum toxin showed marginal benefit (-0.50 [-0.91 to -0.08]), it caused temporary paresis of finger extension, and all trials were at high risk of bias. Both autologous blood (-1.43 [-2.15 to -0.71]) and platelet-rich plasma (-1.13 [-1.77 to -0.49]) were also statistically superior to placebo, but only 1 trial was at low risk of bias. Prolotherapy (-2.71 [-4.60 to -0.82]) and hyaluronic acid (-5.58 [-6.35 to -4.82]) were both more efficacious than placebo, whereas polidocanol (0.39 [-0.42 to 1.20]) and glycosaminoglycan (-0.32 [-1.02 to 0.38]) showed no effect compared with placebo. The criteria for low risk of bias were only met by the prolotherapy and polidocanol trials.
CONCLUSION
This systematic review and network meta-analysis of randomized controlled trials found a paucity of evidence from unbiased trials on which to base treatment recommendations regarding injection therapies for lateral epicondylitis.
Topics: Blood Transfusion, Autologous; Botulinum Toxins; Glucocorticoids; Humans; Hyaluronic Acid; Platelet-Rich Plasma; Polidocanol; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sclerosing Solutions; Tennis Elbow; Viscosupplements
PubMed: 22972856
DOI: 10.1177/0363546512458237 -
The Cochrane Database of Systematic... Dec 2011Sclerotherapy has been used in clinical practice for centuries, but there is still no consensus about which, if any, sclerosing agent provides the best results. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sclerotherapy has been used in clinical practice for centuries, but there is still no consensus about which, if any, sclerosing agent provides the best results.
OBJECTIVES
To assess the effectiveness and safety of sclerosing agents in the treatment of telangiectasias of the lower limbs.
SEARCH METHODS
The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialised Register (last searched 26 May 2011) and CENTRAL (2011, Issue 2). We searched references within identified studies and from the Cited References in the Web of Science. We contacted study authors and pharmaceutical companies. There were no language restrictions.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials on the treatment of telangiectasias comparing sclerotherapy with a normal saline placebo, no treatment or an alternative sclerotherapy regimen.
DATA COLLECTION AND ANALYSIS
Both authors determined which studies to include, extracted the data and rated risk of bias. One author (LS) contacted study authors and pharmaceutical companies and analysed the results.
MAIN RESULTS
Ten studies involving 484 patients were included. There was no evidence suggesting superior efficacy of any one sclerosant over another, but there was evidence of superiority of sclerotherapy to placebo.The evidence did not suggest an increase in patient satisfaction with any one agent versus another, but there was evidence that patients were less satisfied with placebo.There was some evidence suggesting that polidocanol (POL) was more likely to cause adverse reactions at a concentration of 1% compared with lower concentrations or hypertonic saline, and that sodium tetradecyl sulfate (STS) was more likely to cause adverse reactions at a concentration of 1% compared with POL at 0.5%.There was some evidence suggesting that STS was more painful than POL, heparsal (20% saline mixed with heparin 100 units/mL) or placebo, and that POL was no more painful than placebo. Evidence from one study suggested that hypertonic saline (HS) was more painful than POL.The data were not suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The evidence did not suggest superior efficacy or patient satisfaction for any one sclerosing agent used in the treatment of telangiectasias of the lower limbs, but the agents studied showed superiority to a normal saline placebo. However, the amount of available evidence in this field is small and the overall methodological quality of the research was poor, as was the quality of reporting. More research is needed to determine the optimal agent(s) and the ideal dosing to achieve the best results and maximize patient satisfaction. Future research efforts should incorporate more demographic data and symptom measures to allow for comparison with findings from observational studies, thereby aiding assessment of how various risk groups respond to treatment.
Topics: Heparin; Humans; Leg; Patient Satisfaction; Polidocanol; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sclerosing Solutions; Sclerotherapy; Sodium Chloride; Sodium Tetradecyl Sulfate; Telangiectasis
PubMed: 22161437
DOI: 10.1002/14651858.CD008826.pub2 -
Lancet (London, England) Nov 2010Few evidence-based treatment guidelines for tendinopathy exist. We undertook a systematic review of randomised trials to establish clinical efficacy and risk of adverse... (Review)
Review
BACKGROUND
Few evidence-based treatment guidelines for tendinopathy exist. We undertook a systematic review of randomised trials to establish clinical efficacy and risk of adverse events for treatment by injection.
METHODS
We searched eight databases without language, publication, or date restrictions. We included randomised trials assessing efficacy of one or more peritendinous injections with placebo or non-surgical interventions for tendinopathy, scoring more than 50% on the modified physiotherapy evidence database scale. We undertook meta-analyses with a random-effects model, and estimated relative risk and standardised mean differences (SMDs). The primary outcome of clinical efficacy was protocol-defined pain score in the short term (4 weeks, range 0-12), intermediate term (26 weeks, 13-26), or long term (52 weeks, ≥52). Adverse events were also reported.
FINDINGS
3824 trials were identified and 41 met inclusion criteria, providing data for 2672 participants. We showed consistent findings between many high-quality randomised controlled trials that corticosteroid injections reduced pain in the short term compared with other interventions, but this effect was reversed at intermediate and long terms. For example, in pooled analysis of treatment for lateral epicondylalgia, corticosteroid injection had a large effect (defined as SMD>0·8) on reduction of pain compared with no intervention in the short term (SMD 1·44, 95% CI 1·17-1·71, p<0·0001), but no intervention was favoured at intermediate term (-0·40, -0·67 to -0·14, p<0·003) and long term (-0·31, -0·61 to -0·01, p=0·05). Short-term efficacy of corticosteroid injections for rotator-cuff tendinopathy is not clear. Of 991 participants who received corticosteroid injections in studies that reported adverse events, only one (0·1%) had a serious adverse event (tendon rupture). By comparison with placebo, reductions in pain were reported after injections of sodium hyaluronate (short [3·91, 3·54-4·28, p<0·0001], intermediate [2·89, 2·58-3·20, p<0·0001], and long [3·91, 3·55-4·28, p<0·0001] terms), botulinum toxin (short term [1·23, 0·67-1·78, p<0·0001]), and prolotherapy (intermediate term [2·62, 1·36-3·88, p<0·0001]) for treatment of lateral epicondylalgia. Lauromacrogol (polidocanol), aprotinin, and platelet-rich plasma were not more efficacious than was placebo for Achilles tendinopathy, while prolotherapy was not more effective than was eccentric exercise.
INTERPRETATION
Despite the effectiveness of corticosteroid injections in the short term, non-corticosteroid injections might be of benefit for long-term treatment of lateral epicondylalgia. However, response to injection should not be generalised because of variation in effect between sites of tendinopathy.
FUNDING
None.
Topics: Anti-Inflammatory Agents; Aprotinin; Botulinum Toxins; Glucocorticoids; Glycosaminoglycans; Humans; Hyaluronic Acid; Injections; Patellar Ligament; Platelet-Rich Plasma; Polyethylene Glycols; Randomized Controlled Trials as Topic; Rotator Cuff; Tendinopathy; Tennis Elbow
PubMed: 20970844
DOI: 10.1016/S0140-6736(10)61160-9 -
British Journal of Sports Medicine Jul 2009To appraise existing evidence for prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injection therapies for lateral epicondylosis (LE). (Review)
Review
OBJECTIVE
To appraise existing evidence for prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injection therapies for lateral epicondylosis (LE).
DESIGN
Systematic review.
DATA SOURCES
Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine.
SEARCH STRATEGY
names and descriptors of the therapies and LE.
STUDY SELECTION
All human studies assessing the four therapies for LE.
MAIN RESULTS
Results of five prospective case series and four controlled trials (three prolotherapy, two polidocanol, three autologous whole blood and one platelet-rich plasma) suggest each of the four therapies is effective for LE. In follow-up periods ranging from 9 to 108 weeks, studies reported sustained, statistically significant (p<0.05) improvement in visual analogue scale primary outcome pain score measures and disease-specific questionnaires; relative effect sizes ranged from 51% to 94%; Cohen's d ranged from 0.68 to 6.68. Secondary outcomes also improved, including biomechanical elbow function assessment (polidocanol and prolotherapy), presence of abnormalities and increased vascularity on ultrasound (autologous whole blood and polidocanol). Subjects reported satisfaction with therapies on single-item assessments. All studies were limited by small sample size.
CONCLUSIONS
There is strong pilot-level evidence supporting the use of prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injections in the treatment of LE. Rigorous studies of sufficient sample size, assessing these injection therapies using validated clinical, radiological and biomechanical measures, and tissue injury/healing-responsive biomarkers, are needed to determine long-term effectiveness and safety, and whether these techniques can play a definitive role in the management of LE and other tendinopathies.
Topics: Blood Transfusion, Autologous; Humans; Injections; Naturopathy; Platelet-Rich Plasma; Polidocanol; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sclerosing Solutions; Tennis Elbow
PubMed: 19028733
DOI: 10.1136/bjsm.2008.052761 -
The Cochrane Database of Systematic... Oct 2006Injection sclerotherapy is widely used for superficial varicose veins. The treatment aims to obliterate the lumen of varicose veins or thread veins. There is limited... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Injection sclerotherapy is widely used for superficial varicose veins. The treatment aims to obliterate the lumen of varicose veins or thread veins. There is limited evidence regarding its efficacy.
OBJECTIVES
To determine whether sclerotherapy is effective in improving symptoms and cosmetic appearance and has an acceptable complication rate; to define rates of symptomatic or cosmetic varicose vein recurrence following sclerotherapy.
SEARCH STRATEGY
We searched the Cochrane Peripheral Vascular Diseases Group trials register (April 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2006), MEDLINE and EMBASE (both inception to April 2006) and reference lists of articles. Manufacturers of sclerosants were contacted for additional trial information.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of injection sclerotherapy versus graduated compression stockings (GCS) or 'observation', or comparing different sclerosants, doses, formulations and post-compression bandaging techniques on people with symptomatic and/or cosmetic varicose veins or thread veins were considered for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Data were extracted by authors and Review Group Co-ordinators independently.
MAIN RESULTS
Seventeen studies were included. One study comparing sclerotherapy to GCS in pregnancy found that sclerotherapy improved symptoms and cosmetic appearance. Three studies comparing sodium tetradecyl sulphate (STD) to alternative sclerosants found no significant differences in outcome or complication rates; another study found that sclerotherapy with STD led to improved cosmetic appearance compared with polidocanol, although there was no difference in symptoms. Sclerosant plus local anaesthetic reduced the pain from injection (one study) but had no other effects. Two studies compared foam- to conventional sclerotherapy; one found no difference in failure rate or recurrent varicose veins; a second showed short-term benefit from foam in terms of elimination of venous reflux. The recanalisation rate was no different between the two treatments. One study comparing Molefoam and Sorbo pad pressure dressings found no difference in erythema or successful sclerosis. The degree and duration of elastic compression had no significant effect on varicose vein recurrence rates, cosmetic appearance or symptomatic improvement.
AUTHORS' CONCLUSIONS
Evidence from RCTs suggests that the choice of sclerosant, dose, formulation (foam versus liquid), local pressure dressing, degree and length of compression have no significant effect on the efficacy of sclerotherapy for varicose veins. The evidence supports the current place of sclerotherapy in modern clinical practice, which is usually limited to treatment of recurrent varicose veins following surgery and thread veins. Surgery versus sclerotherapy is the subject of a further Cochrane Review.
Topics: Bandages; Humans; Randomized Controlled Trials as Topic; Sclerosing Solutions; Sclerotherapy; Varicose Veins
PubMed: 17054141
DOI: 10.1002/14651858.CD001732.pub2