Abstract
Objective
To present an evidence-based overview of the effectiveness of pharmaceutical interventions, including nonsteroidal anti-inflammatory drugs, corticosteroid injections, and other injections, used to treat the subacromial impingement syndrome (SIS). An overview can help physicians select the most appropriate pharmaceutical intervention, and it can identify gaps in scientific knowledge.
Data Sources
The Cochrane Library, PubMed, Embase, PEDro, and CINAHL databases.
Study Selection
Two reviewers independently selected relevant reviews and randomized clinical trials.
Data Extraction
Two reviewers independently extracted the data and assessed the methodologic quality.
Data Synthesis
A best evidence synthesis was used to summarize the results. Three reviews and 5 randomized clinical trials were included. Although we found limited evidence for effectiveness in favor of 2 sessions with corticosteroid injections versus 1 session, for the effectiveness of corticosteroid injections versus placebo, nonsteroidal anti-inflammatory drugs, or acupuncture, only conflicting and no evidence for effectiveness was found. Moderate evidence was found in favor of immediate release oral ibuprofen compared with sustained-released ibuprofen in the short-term. Also, moderate evidence for effectiveness was found in favor of glyceryltrinitrate patches versus placebo patches in the short-term and mid term. Furthermore, injections with disodium ethylene diamine tetraacetic acid plus ultrasound with ethylene diamine tetraacetic acid gel were more effective (moderate evidence) than was placebo treatment in the short- and long-term.
Conclusions
This article presents an overview of the effectiveness of pharmaceutical interventions for SIS. Some treatments seem to be promising (moderate evidence) to treat SIS, but more research is needed before firm conclusions can be drawn.
Keywords
List of abbreviations:
CANS (Complaints of the Arm, Neck, and/or Shoulder), CI (confidence interval), EDTA (ethylene diamine tetraacetic acid), GTN (glyceryltrinitrate), NSAIDs (nonsteroidal anti-inflammatory drugs), RCT (randomized clinical trial), ROM (range of motion), SIS (subacromial impingement syndrome)Musculoskeletal disorders of the shoulder, including tendinitis and bursitis, are difficult to differentiate in clinical practice. In the Complaints of the Arm, Neck, and/or Shoulder (CANS) model, the term subacromial impingement syndrome (SIS) is used for the rotator cuff syndrome, tendonosis of the Musculus infraspinatus, Musculus supraspinatus, and Musculus subscapularis, and bursitis in the shoulder area.
1
More than 50% of the patients suffering from chronic CANS reported complaints of the shoulder.2
The relation between shoulder complaints and work-related factors, such as repetitive work, working with the hand above the shoulder, and high psychosocial job demands, has been found positive by several authors.3
In general practice, SIS is the most frequently reported diagnosis of the shoulder, with a cumulative incidence of 5 per 1000 patients per year.
4
Patients with SIS are characterized by pain localized in the shoulder that is exacerbated when performing overhead activities.5
The first step in treatment for SIS by a general practitioner often includes an analgesic.6
Also, corticosteroid injections are an often-used intervention in primary care.7
New treatment modalities such as tenoxicam injections8
have been studied for their effectiveness. A systematic review on this subject is necessary to give an evidence-based overview of (new) studies8
, 9
, 10
, 11
, 12
and the effectiveness of pharmaceutical interventions, that is, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections, and other injections, to treat SIS.Methods
Search strategy
The Cochrane Library, PubMed, Embase, PEDro, and CINAHL were searched up to March 2009. Keywords related to SIS and interventions were included. The complete search strategy is available on request.
Inclusion criteria
Systematic reviews and randomized clinical trials (RCTs) were included if they fulfilled all of the following criteria: (a) acute or chronic SIS (grades I–IV), not caused by an acute trauma or any systemic disease as described in the definition of CANS, was studied; (b) an intervention for treating SIS was evaluated; (c) results on pain, function, or recovery were reported; and (d) a follow-up period of ≥2 weeks was reported. There were no language restrictions.
After the full-text articles were included, we divided the included studies into different treatment groups for which separate reviews could be conducted. One of these groups is pharmaceutical intervention. For this review, only those studies were included in which pharmaceutical therapy (oral, injected, or patched) was compared with placebo, no treatment, or another nonsurgical treatment.
Study selection
Two reviewers (B.M.H., L.G.) independently applied the inclusion criteria to select potential relevant studies from the title, abstracts, and full-text articles, respectively. A consensus method was used to solve any disagreements concerning inclusion of studies, and a third reviewer (B.W.K.) was consulted if disagreement persisted.
Categorization of the relevant literature
Relevant articles are categorized under 3 headers: Systematic reviews describes all (Cochrane) reviews; Recent RCTs contains all RCTs published after the search date of the systematic review on the same intervention; Additional RCTs describes all RCTs concerning an intervention that has not yet been described in a systematic review.
Data extraction
Three authors (L.G., R.S., B.M.H.) independently extracted data from the included articles. Information was collected on the study population, interventions, and outcome measures. A consensus procedure was used to solve any disagreement between the authors. Results were reported in short-term (≤3mo), midterm (4–6mo), and long-term (>6mo).
Methodologic quality assessment
Two reviewers (L.G., M.S.R.) independently assessed the methodologic quality of each RCT using Furlan's 12 criteria (table 1).
13
Each item was scored as “yes,” “no,” or “unclear.” “High-quality” was defined as a “yes” score of ≥50%. A consensus procedure was used to solve disagreement between the reviewers.Table 1Methodologic quality assessment: sources of risk bias
A. |
|
B. |
|
C. | Was knowledge of the allocated interventions adequately prevented during the study?
|
D. | Were incomplete outcome data adequately addressed?
|
E. |
|
F. | Other sources of potential bias:
|
In a (Cochrane) review, the use of a methodologic quality assessment is a standard procedure. We describe the methodologic quality scale/criteria that were used in the review, and used the authors' definitions of high and low quality for the included studies.
Data synthesis
A quantitative analysis of the studies was not possible due to heterogeneity of the outcome measures. Therefore, we summarized the results using a best-evidence synthesis.
14
The article was included in the best-evidence synthesis only if a comparison was made between the groups and the level of significance was reported. The results of the study were labeled “significant” if 1 of the 3 outcome measures on pain, function, or recovery reported significant results. The levels of evidence for effectiveness are given in table 2.Table 2Levels of evidence
Strong evidence: consistent (ie, when ≥75% of the trials report the same findings) positive (significant) findings within multiple higher quality RCTs |
Moderate evidence: consistent positive (significant) findings within multiple lower quality RCTs and/or 1 high-quality RCT |
Limited evidence for effectiveness: positive (significant) findings within 1 low-quality RCT |
Conflicting evidence: provided by conflicting (significant) findings in the RCTs (<75% of the studies reported consistent findings) |
No evidence: RCT(s) available, but no (significant) differences between the intervention and control groups were reported |
Results
Characteristics of the included studies
The initial search resulted in 5 reviews from the Cochrane library. Via PubMed 5 reviews and 215 RCTs, via Embase 21 reviews and 193 RCTs, via CINAHL 141 reviews/RCTs, and via PEDro 0 reviews and 13 RCTs were identified. Finally, 3 reviews and 5 RCTs reported on the effectiveness of pharmaceutical interventions and were included.
The review of Green et al
15
that studied the effectiveness of physiotherapy for shoulder pain included 26 trials; 11 trials reported on SIS and were included in the present review. Another review of Green et al16
studied the effectiveness of acupuncture for shoulder pain and included 9 trials; 2 trials reported on SIS and were included in the present review.The review of Buchbinder et al
17
studied the effectiveness of corticosteroid injections for shoulder pain. Seven of the 26 trials included in this review met our inclusion criteria and were included in the present review. The characteristics of the included studies are listed in appendices 1, 2, and 3.Methodologic quality assessment
The results of the methodologic quality assessment are presented in table 3.
Table 3Methodologic quality scores of the included recent and additional RCTs
Reference | Adequate Randomization? | Allocation Concealment? | Blinding? Patients? | Blinding? Caregiver? | Blinding? Outcome Assessors? | Incomplete Outcome Data Addressed? Dropouts? | Incomplete Outcome Data? ITT Analysis? | Free of Suggestions of Selective Outcome Reporting? | Similarity of Baseline Characteristics? | Cointerventions Avoided or Similar? | Compliance Acceptable in all Groups? | Timing of the Outcome Assessment Similar? | Maximum Score | Score Study | Percentage |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Paoloni et al 12 | + | + | + | − | + | + | + | + | + | + | + | + | 12 | 11 | 92 |
Akgun et al 9 | + | ? | + | − | + | + | + | + | + | + | + | + | 12 | 10 | 83 |
Friis et al 11 | + | ? | + | ? | ? | + | ? | + | + | + | + | + | 12 | 8 | 67 |
Cacchio et al 10 | + | ? | + | − | + | + | + | + | + | ? | ? | + | 12 | 8 | 67 |
Itzkowitch et al 8 | ? | ? | + | ? | ? | + | − | + | ? | ? | ? | + | 12 | 4 | 33 |
Methodologic quality scores of Green et al 15 | |||||||||||||||
Random Allocation? | Concealed Allocation? | Blind Subjects? | Blind Therapists? | Blind Assessors? | Between-group Comparisons? | Adequate Follow-up? | ITT Analysis? | Baseline comparability? | Availability of Point Estimates and Measures of Variability of Primary Outcome Measures? | Specification of Eligibility Criteria? | Score Maximum | Score Study | Percentage | ||
Ebenbichler 27 | + | + | + | + | + | + | + | − | + | + | + | 11 | 10 | 91 | |
Nykanen 28 | + | − | + | + | + | + | + | − | + | + | + | 11 | 9 | 82 | |
Saunders 29 | + | ? | + | + | + | + | − | + | + | + | + | 11 | 9 | 82 | |
Vecchio et al 23 | + | − | + | + | + | + | + | − | + | + | + | 11 | 9 | 82 | |
Berry et al 18 | + | − | − | − | + | + | + | − | + | + | + | 11 | 7 | 64 | |
Conroy 30 | + | − | − | − | + | + | + | − | + | + | + | 11 | 7 | 64 | |
Dal Conte 31 | + | − | + | + | − | + | + | − | + | − | + | 11 | 7 | 64 | |
England et al 19 | + | − | + | − | + | + | + | − | − | + | + | 11 | 7 | 64 | |
Bang 32 | + | − | − | − | − | + | + | − | + | + | + | 11 | 6 | 55 | |
Brox 33 | + | − | − | − | + | + | − | + | + | + | − | 11 | 6 | 55 | |
Perron 34 | + | − | − | − | + | + | + | − | + | + | − | 11 | 6 | 55 | |
Methodologic quality scores of Green et al 16 | |||||||||||||||
Berry et al 18 | + | − | − | n.p. | + | + | + | − | + | + | + | 10 | 7 | 70 | |
Methodologic quality scores of Buchbinder et al 17 | |||||||||||||||
Blind Participants? | Blind Assessors? | Acceptable Lost to Follow-up? | Appropriate Statistical Analysis? (ITT Analysis?) | Allocation Concealed | Score Maximum | Score Study | Percentage | ||||||||
Adebajo et al 20 | + | + | + | + | + | 5 | 4 | 80 | |||||||
Petri et al 22 | + | + | + | + | + | 5 | 4 | 80 | |||||||
Withrington et al 25 | + | + | + | + | ? | 5 | 4 | 80 | |||||||
Berry et al 18 | ? | + | + | + | ? | 5 | 3 | 60 | |||||||
Vecchio et al 23 | + | + | + | − | ? | 5 | 3 | 60 | |||||||
White et al 35 | + | + | − | + | − | 5 | 3 | 60 | |||||||
Blair et al 21 | + | + | ? | ? | ? | 5 | 2 | 40 | |||||||
Strobel 24 | ? | ? | − | − | ? | 5 | 0 | 0 |
Abbreviations: +, yes; −, no; ?, unclear/unsure; ITT, intention-to-treat; n.p., not possible.
∗ Based on the PEDro scale (specifically designed and validated for the assessment of validity for trials of physiotherapy interventions) (http://ptwww.cchs.usyd.edu.au/pedro/).
† Based on the Cochrane reviewer's handbook (Alderson P, Green S, Higgins JPT, editors. Cochrane reviewers' handbook. Chichester, UK: John Wiley & Sons, Ltd; December 2003).
‡ Adapted from the Cochrane reviewers' handbook (Clarke M, Oxman AD, editors. Cochrane reviewers' handbook 4.0 [updated July 1999]. In: The Cochrane Library [database on CDROM]. The Cochrane Collaboration. Oxford: Update Software; 2000, Issue 2, 1999).
§ Lost to follow-up: We defined this item as positive if the percentage of lost to follow-up is <20% for the short-term follow-up and <30% for the long-term follow-up.
Four (of the 5 included) RCTs were of high quality. Most prevalent methodologic flaws were (1) care provider not blinded and (2) unclear whether allocation was concealed.
The 3 reviews used a methodologic scoring list of 11 items
16
or 5 items17
: 18 of the 20 RCTs in these reviews scored ≥50% on the quality assessment and were classified as high quality. The RCT by Berry et al18
was included in all the 3 reviews.Effectiveness of pharmaceutical interventions for SIS
Table 4 shows the interventions for which moderate or strong evidence for effectiveness for pharmaceutical interventions for SIS was found. Table 5 presents a complete overview.
Table 4Evidence for the effectiveness of pharmaceutical interventions for SIS
SIS | |
---|---|
Conservative | |
Oral | √b |
Injection | √c,f |
Other | √a,d,e |
NOTE. √, strong or moderate evidence found; 0, RCT(s) found, but only limited, conflicting, or no evidence for the effectiveness of interventions was found; empty cells, no RCTs or reviews found.
Short-term:
a: Moderate evidence: NSAID vs laser therapy.
b: Moderate evidence: Ibuprofen vs sustained-release ibuprofen.
c: Moderate evidence: Disodium EDTA plus ultrasound vs placebo.
d: Moderate evidence: GTN patches vs placebo.
Midterm:
e: Moderate evidence: GTN patches vs placebo.
Long-term:
f: Moderate evidence: Disodium EDTA plus ultrasound vs placebo.
∗ In favor of.
Table 5CANS: Evidence for the effectiveness of pharmaceutical interventions for SIS
Oral Treatment | Injections | ||||
---|---|---|---|---|---|
Corticosteroid | Tenoxicam | ||||
NSAID | |||||
▸ NSAID vs laser therapy | ▸ Corticosteroid injection vs placebo | ▸ Tenoxicam injection vs placebo | |||
Short-term | ++ | Short-term | ± | Short-term | + |
Ibuprofen | Long-term | ± | |||
▸ Ibuprofen vs sustained-release ibuprofen | ▸ Corticosteroid injection 1 session vs 2 sessions | Disodium EDTA ▸ Disodium EDTA plus ultrasound (with EDTA gel) vs placebo | |||
Short-term | ++ | + | Short-term | ++ | |
Long-term | ++ | ||||
▸ Corticosteroid injection vs acupuncture plus moxibustion | |||||
Other conservative | Short-term | NE | |||
GTN patches | |||||
▸ GTN patches vs placebo | ▸ Corticosteroid injection vs NSAID | ||||
Short-term | ++ | ||||
Mid-term | ++ | ||||
Short-term | NE | ||||
▸ Corticosteroid injection plus NSAID vs placebo | |||||
Short-term | NE | ||||
▸ Corticosteroid injection plus NSAID vs NSAID | |||||
Short-term | NE | ||||
▸ Corticosteroid injection plus placebo NSAID vs acupuncture | |||||
Short-term | NE |
NOTE. +, limited evidence found; ++, moderate evidence found; +++, strong evidence found; ±, conflicting evidence for effectiveness; NE, no evidence found for effectiveness of the treatment: RCT(s) available, but no differences between intervention and control groups were found.
∗ In favor of.
Effectiveness of analgesics: NSAIDs versus laser therapy
In a systematic review, 1 high-quality RCT
19
(n=20) included in the review of Green et al15
compared NSAIDs (naproxen sodium 550mg 2 times a day for 2wk) with laser therapy (902nm) for shoulder tendinitis. Significantly less pain (mean difference, 2; 95% confidence interval [CI]=1–3.5) was reported for laser versus NSAIDs at 2-week follow-up. No significant results were found on function.There is moderate evidence for the effectiveness of laser therapy versus NSAIDs in the short-term (2wk).
Effectiveness of analgesics: ibuprofen tablet versus sustained-release ibuprofen
One high-quality RCT
11
(n=147) compared conventional tablets ibuprofen (600mg 4 times a day) with sustained-release tablets ibuprofen (1200mg 2 times a day). At 3-week follow-up, significant differences between the groups were found in favor of conventional tablets ibuprofen on complete pain relief of shoulder tendonitis (7% vs 21%, P=.02) and on patients' global assessment on a 5-point scale (no data given, P=.04); no significant differences were found on the patient's assessment concerning better or complete relief, or the physician's assessment.There is moderate evidence for effectiveness in favor of conventional ibuprofen tablets versus sustained-released ibuprofen tablets for SIS in the short-term (3wk).
Effectiveness of analgesics: glyceryltrinitrate transdermal patches versus placebo
A high-quality RCT
12
(n=53; 57 shoulders) compared glyceryltrinitrate (GTN) patches with placebo patches. Both groups also received a tendon rehabilitation program. Significant differences were found between the groups on decrease in pain at rest in favor of the GTN patches group at 12- (P=.04) and 24-week (P=.03) follow-up (no further data given). From baseline to 24 weeks, the range of motion (ROM) increased by 24% (17%–31%) in the GTN group versus 8% (4%–13%) in the placebo group (no P value given). Increases in force (supraspinatus, subscapularis, adduction, and external and internal rotation) were all significant in favor of the GTN group at 12- and 24-week follow-up (no exact data given, P value ranged from .001 to .02). At 24-week follow-up, there were significant differences between the groups for the outcome “asymptomatic shoulder” in favor of the GTN group (64% vs 24%, P=.007; weighted mean difference, .26; 95% CI=.19–.32).There is moderate evidence for the effectiveness of GTN patches versus placebo for SIS in the short- (12wk) and midterm (24wk).
Effectiveness of injections: coricosteroid injections versus placebo
Seven RCTs in the systematic review of Buchbinder et al
17
compared corticosteroid injections with placebo injections. Five of the 7 trials compared subacromial steroid injection with placebo.18
, 20
, 21
, 22
, 23
One trial compared intraarticular injection with placebo,24
and another trial compared supraspinatus tendon injection with placebo.25
Two high-quality trials
20
, 22
(n=90) reported a significant improvement between the groups in patients treated with corticosteroid injections with respect to pain (standard mean difference, .83; 95% CI=.39–1.26), ROM (abduction) (standard mean difference, .63; 95% CI=.20–1.06), and function (standard mean difference, .82; 95% CI=.39–1.25) at 4-week follow-up. A low-quality study21
(n=40) reported significantly better results (no exact data given) in the corticosteroid group versus placebo on pain and ROM at a mean of 33-week and 28-week follow-up, respectively. Furthermore, no significant differences between the groups were reported on improvement in daily activities (no exact follow-up time given).A high-quality trial
18
(n=24) found no significant differences on pain, ROM (abduction), or success rate between the 2 groups at 4-week follow-up. Another high-quality study26
(n=57) also found no significant differences on pain and ROM (abduction) between the 2 groups (no further data were given) at 12-week follow-up. Strobel (low quality)24
(n=40) reported significantly greater reduction in pain in the placebo group versus the treatment group at 90 and 360 days. Another high-quality study25
(n=25) studied treatment with supraspinatus tendon injection versus placebo in patients with supraspinatus tendonitis. No significant differences were found on pain improvement or analgesic consumption between the 2 groups at 2- and 8-week follow-up.A recent high-quality RCT
9
(n=48) compared 3 groups according to 2 therapeutic injections given at a 10-day interval: group 1 received corticosteroid injections at the first and second sessions, group 2 received corticosteroid injections at the first session and placebo injections at the second session, and group 3 received placebo injections at both sessions. Only on pain causing sleep disturbance, significant differences between the groups were found in favor of group 1 a month after treatment (P<.001). However, at 3-month follow-up, this significant difference was not sustained. Furthermore, no significant differences were found on the Constant score between the 3 groups at 1- and 3-month follow-up.We found conflicting evidence for the effectiveness of corticosteroid injections versus placebo for SIS in the short- (4wk) and long-term (12wk).
Effectiveness of injections: coricosteroid injections versus acupuncture
In a systematic review, 1 high-quality RCT
18
(n=24) included in the review of Green et al16
compared acupuncture with moxibustion (a form of fire heat treatment that stimulates specific acupuncture points of the body) with corticosteroid injections. Postintervention pain, range of abduction, and success in the short-term showed no significant differences between the 2 groups.There is no evidence for the effectiveness of corticosteroid injections versus acupuncture plus moxibustion in the short-term (4wk).
Effectiveness of injections: coricosteroid injections versus NSAIDs
In a systematic review, 3 high-quality trials
20
, 22
, 35
(n=120) included in the review of Buchbinder et al17
compared subacromial corticosteroid injections with NSAIDs. No significant differences between the groups were found on pain and ROM at 4- to 6-wk follow-up,20
, 22
, 35
on improvement in function at 4-week follow-up,20
, 22
and on global assessment at 6-week follow-up.35
There is no evidence for the effectiveness of corticosteroid injections versus NSAIDs for SIS in the short-term (4–6wk).
Effectiveness of injections: coricosteroid injection plus NSAID versus placebo
In a systematic review, Berry et al
18
(n=24) compared corticosteroid injection plus NSAID versus placebo. No significant differences between the 2 groups were found on pain and success rate at 4-week follow-up. On the range of abduction, significant differences were found in favor of placebo (weighted mean difference, −27.60; 95% CI=−49.99 to −5.21).There is no evidence for the effectiveness of corticosteroid plus NSAID versus placebo for SIS in the short-term (4wk).
Effectiveness of injections: coricosteroid injection plus NSAID versus NSAID
In a systematic review, Petri et al
22
(n=50) studied the effectiveness of corticosteroid plus NSAID versus NSAID alone. No significant differences were reported on pain, improvement in function, and improvement in range of abduction between the groups at 4-wk follow-up.There is no evidence for the effectiveness of corticosteroid injection plus NSAID versus NSAID alone for SIS in the short-term (4wk).
Effectiveness of injections: coricosteroid injection (plus placebo NSAID) versus acupuncture
In a systematic review, 1 high-quality RCT
18
(n=24) compared steroid injection plus placebo NSAID and steroid injection plus NSAID with acupuncture. No significant differences were found for postintervention pain or range of abduction.There is no evidence for the effectiveness of corticosteroid injection (plus placebo NSAID) versus acupuncture for SIS in the short-term (4wk).
Effectiveness of injections: tenoxicam injections versus placebo injections
One low-quality RCT
8
compared periarticular tenoxicam injections (20mg/2mL) with placebo injections once a week for up to 4 weeks in 80 patients with rotator cuff tendinitis. Significant results (P<.001) were found in favor of tenoxicam injections on pain at rest and on pain during active movement. Also, significant results (P<.001) were found on improvement of the active shoulder mobility in favor of the treatment group.There is limited evidence for the effectiveness of tenoxicam injections versus placebo for rotator cuff tendonitis in the short-term.
Effectiveness of injections: disodium ethylene diamine tetraacetic acid plus ultrasound versus placebo
A high-quality study
10
compared disodium ethylene diamine tetraacetic acid (EDTA) injections plus ultrasound (using disodium EDTA gel) with placebo in patients with calcific tendinitis (n=80). Disodium EDTA could bind and remove calcium deposits on the tendon. The treatment group showed significantly (P<.01) more improvements on pain (2.87±1.21 vs 6.95±.30) and on the Constant and Murley score (75.62±3.96 vs 45.85±6.25) at 1-week and 1-year follow-up (2.00±1.30 vs 7.01±.30 and 75.50±4.07 vs 46.42±8.52, respectively). The treatment group had a significantly (P<.01) smaller amount of calcification versus the placebo group after the treatment (3.16±3.28 vs 16.92±4.03).We found moderate evidence for the effectiveness of disodium EDTA plus ultrasound versus placebo in treating patients with calcific tendonitis in the short-term (1wk) and the long-term (52wk).
Discussion
In this review, we give an overview of the evidence for effectiveness of all pharmaceutical therapies—NSAIDs, corticosteroid injections, and other injections—studied in a randomized controlled setting in the treatment of SIS.
Analgesics
According to the results of this review, for physicians wishing to give analgesics to treat SIS we would recommend the use of oral ibuprofen rather than sustained-release ibuprofen (for 3wk; moderate evidence). However, our review has highlighted the lack of evidence regarding the use of simple analgesics (paracetamol/acetaminophen), mild opioids (eg, codeine phosphate), or other commonly used NSAIDs for SIS. Although we found moderate evidence for the short-term (3mo) and mid-term (6mo) benefits of GTN patches, the body's systemic responses on GTN or the pharmacokinetics are not entirely clear.
Injections
For other specific CANS, strong and moderate evidence was found in favor of the effectiveness of corticosteroid injections versus placebo in the short-term but not in the long-term.
36
, 37
In contrast to these findings, for SIS we found conflicting evidence in the short- and long-term. More research is needed to allow us to draw definite conclusions about the effectiveness of corticosteroid injections for treating SIS. Future research should also concentrate on the long-term benefits and disadvantages, as well as the accuracy and safety, of corticosteroid injections.A new treatment modality, an injection with disodium EDTA, seems to be promising in both the short-term (1wk) and the long-term. Disodium EDTA is a heavy metal and mineral chelator amino acid. EDTA can bind and remove calcium deposits on the rotator cuff tendon. Cacchio et al
10
concluded that disodium EDTA administered through single needle mesotherpy and ionopheresis is safe and effective for treating patients with calcific tendinitis. However, this conclusion is based on 1 RCT only and more research is needed to confirm the effectiveness and safety of disodium EDTA.Study limitations
The present review has some limitations. First, the methodologic quality assessment of the RCTs included in the reviews and our methodologic quality assessment of the recent and additional RCTs differ greatly; for example, we defined a study as “high quality” when the study scored ≥50% on the quality assessment. However, in the Cochrane reviews, no clear definition is given as to whether the study is considered to be of high or low quality. Buchbinder et al
17
used only 5 items, in contrast to the 12 items of Furlan et al13
that we used to assess the methodologic quality of the recent and additional RCTs. Therefore, a risk of bias can be introduced by categorizing some of the studies as high-quality studies. Second, some studies with a small sample size were categorized as high-quality studies. Therefore, the results must be viewed with caution. Furthermore, the RCTs in which corticosteroids are studied must be interpreted with the notion that different types and dosages of corticosteroids are compared with each other.Conclusions
Moderate evidence for effectiveness was found in the short-term in favor of oral ibuprofen versus sustained-release ibuprofen. Furthermore, promising results were found for the effectiveness of GTN and injections with disodium EDTA plus ultrasound with EDTA gel. GTN patches were more effective (moderate evidence) than placebo patches in the short- and midterm. Injections with disodium EDTA plus ultrasound with EDTA gel were more effective (moderate evidence) than placebo treatment in the short- and long-term.
Acknowledgment
We thank M.S. Randsdorp (M.S.R.), MD, for her participation in the quality assessment.
Appendix
Appendix 1Data extraction—systematic reviews
Author | Total Number of Patients | Treatment | Placebo | Control/Comparison | Outcome Measures | Effect Size |
---|---|---|---|---|---|---|
Buchbinder et al 17 | Corticosteroid injections | |||||
Corticosteroid vs placebo injection | ||||||
Adebajo et al 20 and Petri et al22 | 90 | Subacromial steroid injection (1mL of 80mg/mL triamcinolone hexacetomide) (n=45) | Placebo (n=45) | Pain improvement (VAS) (4wk) | SMD 0.83 (95% CI=0.39–1.26) ifo injection | |
Rotator cuff tendonitis | ||||||
Improvement in function (4wk) | SMD 0.63 (95% CI=0.20–1.06) ifo injection | |||||
Improvement in ROM abduction (4wk) | SMD 0.82 (95% CI=0.39–1.25) ifo injection | |||||
Blair et al 21 | 40 | Subacromial steroid injection (2mL of 40mg/mL triamcinolone acetonide) (n=19) | Placebo (n=21) | No data were given | At a mean of 33wk in corticosteroid group and 28wk in placebo group, the corticosteroid group was significantly better with respect to pain and ROM. No significant difference between the groups with respect to improvement (ADL) | |
SIS | ||||||
Berry et al 18 | 60 | Intraarticular steroid injection with 40mg methylprednisolone (n=12) | Placebo (n=12) | Pain (VAS) (4wk) | WMD 4.60 (95% CI=−15.99 to 25.19) | |
Rotator cuff lesion | ||||||
Range of abduction (4wk) | WMD −20.20 (95% CI=−47.50 to 7.10) | |||||
Success rate | RR 0.67 (95% CI=0.35–1.28) | |||||
Vecchio et al 23 | 57 | Subacromial steroid injection (40mg methylprednisolone) (n=29) | Placebo (n=28) | No data were given | No significant differences with respect to pain and ROM between the treatment and placebo groups | |
Rotator cuff tendonitis | ||||||
Strobel 24 | 40 | Subacromial steroid injection (20mg triamcinolone hexacetonide (n=20) | Placebo (n=20) | No data were given | Greater reduction in pain in the placebo group at 90 and 360d | |
Subacromial bursitis or supraspinatus tendinitis | ||||||
Withrington et al 25 | 25 | Supraspinatus injection with 80mg methylprednisolone (n=12) | Saline (n=13) | No data were given | No difference in improvement in pain or analgesic consumption between the 2 groups at 2 and 8wk | |
Supraspinatus tendonitis | ||||||
Corticosteroid vs acupuncture | ||||||
Berry et al 18 | Intraarticular steroid injection (40mg methylprednisolone) (n=12) | Acupuncture (once a week) (n=12) | Pain (VAS) (4wk) | WMD −7.50 (95% CI=−27.47 to 12.47) | ||
Rotator cuff lesion | ||||||
Range of abduction (4wk) | WMD −2.90 (95% CI=−32.63 to 26.83) | |||||
Success rate (4wk) | RR 0.83 (95% CI=0.35–2.00) | |||||
Corticosteroid vs NSAID | ||||||
Adebajo et al, 20 Petri et al,22 White et al35 | 200/120 | Subacromial steroid injection (1mL of 80mg/mL triamcinolone hexacetomide) (n=45) | NSAID (50mg diclofenac thrice a day for 28d) | Pain improvement (VAS) (4–6wk) | SMD −0.18 (95% CI= −0.54 to 0.18) | |
Improvement in function (4wk) | SMD 0.03 (95% CI=−0.39 to 0.44) | |||||
(n=60) | (n=60) | |||||
Rotator cuff tendonitis | (n=45) | (n=45) | Improvement in range of abduction (4–6wk) | SMD −0.17 (95% CI=−0.53 to 0.19) | ||
(n=60) | (n=60) | |||||
(n=15) | (n=15) | |||||
Global assessment score (sum of pain and motion deficit) (0–9 points) (6wk) | SMD −0.03 (95% CI=−0.75 to 0.68) | |||||
Corticosteroid plus NSAID vs placebo | ||||||
Berry et al 18 | 60 | Intraarticular steroid injection plus NSAID (40mg methylprednisolone plus 50mg diclofenac thrice a day (n=12) | Placebo (n=12) | Pain (VAS) (4wk) | WMD 7.20 (95% CI= −14.03 to 28.43) | |
Rotator cuff lesion | ||||||
Range of abduction (4wk) | WMD −27.60 (95% CI=−49.99 to −5.21) ifo placebo | |||||
Success rate | RR 0.56 (95% CI=0.26–1.17) | |||||
Corticosteroid plus NSAID vs NSAID | ||||||
Petri et al 22 | 100 | Subacromial steroid injection plus NSAID (1mL of 40mg/mL triamcinolone plus 500mg naproxen twice a day for 30d) (n=25) | NSAID (500mg naproxen twice a day for 30d) (n=25) | Pain improvement (0–5 scale) (4wk) | WMD 0.19 (95% CI=−0.73 to 1.11) | |
Rotator cuff tendonitis | ||||||
Improvement in function (4wk) | WMD −0.10 (95% CI=−0.96 to 0.76) | |||||
Improvement in range of abduction (4wk) | WMD 0.56 (95% CI=−0.15 to 1.27) | |||||
Corticosteroid plus NSAID vs acupuncture | ||||||
Berry et al 18 | 60 | Steroid (400mg tolmetin sodium thrice a day plus anterior injection of 40mg methylprednisolone) (n=12) | Acupuncture once a week with moxibustion (n=12) | Pain (VAS) (postintervention) | MD 7.50 (95% CI=−12.47 to 27.47) | |
Rotator cuff lesion | ||||||
Range of abduction (postintervention) | MD 2.90 (95% CI=−26.83 to 32.63) | |||||
Success rate (short term) | RR 0.83 (95% CI=0.35–2.00) |
Abbreviations: ADL, activities of daily living; ifo, in favor of; MD, mean difference; RR, relative risk; SMD, standardized mean difference; VAS, visual analog scale; WMD, weighted mean difference.
∗ Success rate = success or failure of the treatment at the end of 4wk defined as the need for a steroid injection.
Appendix 2Data extraction—recent RCTs
Author | Treatment | Placebo | Control Comparison | Outcome Measures and FU Time | Results—Statistical | Results—Words |
---|---|---|---|---|---|---|
Corticosteroid injections | ||||||
Corticosteroid vs placebo | ||||||
Akgun et al 9 | Group 1: 2 injections, 10-d interval: 10cc of 1% lignocaine + 40mg methylprednisolone for both injections (n=16) | Group 3: only lignocaine (n=16) | Rest pain | NS (no P value given) | Group 1: from 4.3±1.6 at baseline to 0.5±0.4 at 1-mo FU vs group 3: from 3.8±1.2 at baseline to 1.0±0.9 at 1-mo FU | |
SIS | ||||||
NS (no P value given) | At 3-mo FU: Group 1: 0.8±0.6 vs group 3: 0.7±0.6 | |||||
Activity pain | NS (no P value given) | Group 1: from 6.1±1.9 at baseline to 1.1±0.9 at 1-mo FU vs group 3: from 5.5±2.3 at baseline to 1.7±1.0 at 1-mo FU | ||||
NS (no P value given) | At 3-mo FU: Group 1: 0.8±0.7 vs group 3: 0.7±0.6 | |||||
Pain disturbing sleep | Significant (no P value given) | Group 1: from 4.5±1.2 at baseline to 0.8±0.7 at 1-mo FU vs group 3: from 4.6±1.1 at baseline to 2.0±1.2 at 1-mo FU ifo group 1 | ||||
NS (no P value given) | At 3-mo FU: | |||||
Group 1: 0.94±0.9 vs group 3: 0.9±0.7 | ||||||
Constant score | NS (no P value given) | Group 1: from 63.6±22.2 at baseline to 87.8±15.4 at 1-mo FU vs group 3: from 65.5± 21.4 at baseline to 82.1±16.1 at 1-mo FU | ||||
NS (no P value given) | At 3-mo FU: Group 1: 91.6±8.3 vs group 3: 91.6±9.1 | |||||
SIS | Group 1: 2 injections, 10-d interval: 10cc of 1% lignocaine + 40 mg methylprednisolone for both injections (n=16) | Group 2: first injection 10cc of 1% lignocaine +40mg methylprednisolone, second injection only lignocaine (n=16) | Rest pain | NS (no P value given) | Group 1: from 4.3±1.6 at baseline to 0.5±0.4 at 1-mo FU vs group 2: from 4.3±1.7 at baseline to 1.0±0.8 at 1-mo FU | |
NS (no P value given) | At 3-mo FU: | |||||
Group 1: 0.8±0.6 vs group 2: 1.3±0.9 | ||||||
Activity pain | NS (no P value given) | Group 1: from 6.1±1.9 at baseline to 1.1±0.9 at 1-mo FU vs group 2: from 6.4±1.5 at baseline to 1.4±1.1 at 1-mo FU | ||||
NS (no P value given) | At 3-mo FU: | |||||
Group 1: 0.8±0.7 vs group 2: 0.81±0.9 | ||||||
Pain disturbing sleep | S (no P value given) | Group 1: from 4.5±1.2 at baseline to 0.8±0.7 at 1-mo FU vs group 2: from 4.0±1.3 at baseline to 4.6±1.1 at 1-mo FU ifo group 1 | ||||
NS (no P value given) | At 3-mo FU: | |||||
Group 1: 0.94±0.9 vs group 2: 0.8±0.7 | ||||||
Constant score | NS (no P value given) | Group 1: from 63.6±22.2 at | ||||
baseline to 87.8±15.4 at 1-mo FU vs group 2: from 65.6± 23.4 at baseline to 84.1±16.2 at 1-mo FU | ||||||
NS (no P value given) | At 3-mo FU: Group 1: 91.6±8.3 vs group 2: 89.8±9.5 | |||||
Abbreviations: FU, follow-up; ifo, in favor of; NS, not significant; S, significant.
Appendix 3Data extraction—additional RCTs
Author | Treatment | Placebo | Control/Comparison | Outcome Measures and FU Time | Results—Statistical | Results—Words |
---|---|---|---|---|---|---|
Analgesics | ||||||
Ibuprofen tablet vs sustained-released ibuprofen | ||||||
Friis et al 11 | Conventional tablets ibuprofen (CTI) (600mg QID) plus 1 local injection with corticosteroid at day 0 (n=74) | Sustained-release tablets ibuprofen (SRTI) (1200mg BID) plus 1 local injection with corticosteroid at day 0 (n=73) | Patients' global assessment 5-point scale (3wk) | P=.04 | SRTI vs CTI ifo CTI | |
Shoulder tendonitis | (no exact data given) | |||||
Complete pain relief | P=.02 | SRTI 7% (no 95% CI given) vs CTI 21% (no 95% CI given) | ||||
(3wk) | ||||||
Improvement: better or complete relief (3wk) | .2<P<.3 | SRTI 67% (95% CI=55%–77%) vs CTI 77% (95% CI=65%–86%) | ||||
Improvement: (doctor's assessment) (3wk) | No P value given | SRTI 73% (no 95% CI given) vs CTI 79% (no 95% CI given) | ||||
GTN transdermal vs placebo | ||||||
Paoloni et al 12 | Placebo patch plus 24 tablets paracetamol 500mg for use with possible headache plus tendon rehabilitation program (n=27 [29 shoulders]) | Decrease in pain at rest (0–4) | P=.04 | 12wk: GTN vs placebo ifo GTN, no exact data given | ||
Chronic supraspinatus tendinopathy | GTN patch plus 24 tablets paracetamol 500mg for use with possible headache plus tendon rehabilitation program (n=26 [28 shoulders]) | |||||
P=.03 | 24wk: GTN vs placebo ifo GTN, no exact data given | |||||
Decrease in pain with activity (0–4) | P>.05 | 12wk: GTN vs placebo, no exact data given | ||||
P=.01 | 24wk: GTN vs placebo ifo of GTN, no exact data given | |||||
Decrease in pain at night (0–4) | P=.03 | 12wk: GTN vs placebo ifo of GTN, no exact data given | ||||
P=.01 | 24wk: GTN vs placebo ifo GTN, no exact data given | |||||
Patient-related pain scores (at rest, at night, with activity) | No P value given | GTN: from baseline to 24wk, a reduction of 65% (64%–67%) vs placebo: from baseline to 24wk, a reduction of 30% (27%–33%) | ||||
ROM | No P value given | GTN: from baseline to 24wk, an increase of 24% (17%–31%) vs placebo: from baseline to 24wk, an increase of 8% (4%–13%) | ||||
Increase in supraspinatus force | P=.001 | 12wk: GTN vs placebo ifo of GTN, no exact data given | ||||
P=.001 | 24wk: GTN vs placebo ifo of GTN, no exact data given | |||||
Increase in external rotation force | P=.01 | 12wk: GTN vs placebo ifo GTN, no exact data given | ||||
P=.01 | 24wk: GTN vs placebo ifo GTN, no exact data given | |||||
Increase in internal rotation force | P=.01 | 12wk: GTN vs placebo ifo GTN, no exact data given | ||||
P=.01 | 24wk: GTN vs placebo ifo of GTN, no exact data given | |||||
Increase in subscapularis force | P=.02 | 12wk: GTN vs placebo ifo GTN, no exact data given | ||||
P=.02 | 24wk: GTN vs placebo ifo GTN, no exact data given | |||||
Increase in adduction force | P=.003 | 12wk: GTN vs placebo ifo GTN, no exact data given | ||||
P=.003 | 24wk: GTN vs placebo ifo GTN, no exact data given | |||||
Increase in dynanometer-measured shoulder force | No P value given | GTN: from baseline to 24wk, an increase of 29% (10%–61%) vs placebo: from baseline to 24wk, an increase of 12% (5%– 32%) | ||||
Impingement signs | No P value given | GTN: from baseline to 24wk, a decrease of 76% (74%–78%) vs placebo: from baseline to 24wk, a decrease of 43% (40%–47%) | ||||
Asymptomatic at 24wk | P=.007 | 24wk: GTN 64% vs placebo 24%, no range given | ||||
24wk: mean estimated effect size GTN: 0.26 (95% CI=0.19–0.32) | ||||||
Other injections | ||||||
Tenoxicam injection vs placebo injection | ||||||
Itzkowitch et al 8 | Tenoxicam injection 20mg/2mL once per week for up to 4wk (n=38) | Placebo injection (n=39) | Pain at rest (VAS) (2–4wk) | NS | Baseline: | |
Tenoxicam: 4.68±2.7 vs placebo: 4.84±2.35 | ||||||
Rotator cuff tendinitis | ||||||
P<.001 | Last available score: | |||||
Tenoxicam: 1.73±2.41 | ||||||
vs placebo: 3.18±2.73 | ||||||
Pain on active movement (VAS) (2-4wk) | NS | Baseline: | ||||
Tenoxicam: 7.38±1.35 | ||||||
vs placebo: 6.98±1.65 | ||||||
P<.001 | Last available score: | |||||
Tenoxicam: 2.38±2.65 vs placebo: 4.99±2.95 | ||||||
Active abduction (degrees) (2–4wk) | NS | Baseline: | ||||
Tenoxicam: 111.2±39.7 vs placebo: 116.4±35.5 | ||||||
P<.001 | Last available score: | |||||
Tenoxicam: 141.8±35.4 vs placebo: 129±40.1 | ||||||
Disodium EDTA plus US vs placebo | Study group vs placebo | |||||
Cacchio et al 10 | Study-group: injection with 1mL disodium EDTA, 1mL of 1% procaine and 3mL injectable H2O (once a week for 3wk) plus 15-min pulsed-mode US (1MHz) using 15% solution disodium EDTA gel (5 times a week for 3wk) (n=40) | Sham injection plus sham US (n=40) | Pain (VAS) | P<.43 | Baseline: 6.78±0.28 vs 6.63±0.17 | |
Calcific tendinitis | ||||||
P<.01 | 1wk: 2.87±1.21 vs 6.95±0.30 | |||||
P<.01 | 1y: 2.00±1.30 vs 7.01±0.30 | |||||
Study group vs placebo | ||||||
Total Constant and Murley score | P<.53 | Baseline: 47.68±5.79 vs 46.57±6.94 | ||||
P<.01 | 1wk: 75.62±3.96 vs 45.85±6.25 | |||||
P<.01 | 1y: 75.50±4.07 vs 46.42±8.52 | |||||
Study group vs placebo | ||||||
Size of calcification (mm) (radiography) | P=.08 | Baseline: 18.5±1.57 vs 17.85±1.19 | ||||
P<.01 | After treatment: 3.16± 3.28 vs 16.92±4.03 | |||||
Abbreviations: BID, 2 times a day; CTI, conventional tablets ibuprofen; FU, follow-up; ifo, in favor of; NS, not significant; S, significant; SRTI, sustained-release tablets ibuprofen; US, ultrasound; VAS, visual analog scale (range, 0–10); QID, 4 times a day.
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Published online: December 13, 2012
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© 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.