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Subacromial Impingement Syndrome: Effectiveness of Pharmaceutical Interventions–Nonsteroidal Anti-Inflammatory Drugs, Corticosteroid, or Other Injections: A Systematic Review

Published:December 13, 2012DOI:https://doi.org/10.1016/j.apmr.2012.11.041

      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.
      • Huisstede B.M.
      • Miedema H.S.
      • Verhagen A.P.
      • Koes B.W.
      • Verhaar J.A.
      Multidisciplinary consensus on the terminology and classification of complaints of the arm, neck and/or shoulder.
      More than 50% of the patients suffering from chronic CANS reported complaints of the shoulder.
      • Huisstede B.M.
      • Wijnhoven H.A.
      • Bierma-Zeinstra S.M.
      • Koes B.W.
      • Verhaar J.A.
      • Picavet S.
      Prevalence and characteristics of complaints of the arm, neck, and/or shoulder (CANS) in the open population.
      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.
      • van Rijn R.M.
      • Huisstede B.M.
      • Koes B.W.
      • Burdorf A.
      Associations between work-related factors and specific disorders of the shoulder – a systematic review of the literature.
      In general practice, SIS is the most frequently reported diagnosis of the shoulder, with a cumulative incidence of 5 per 1000 patients per year.
      • van der Windt D.A.
      • Koes B.W.
      • de Jong B.A.
      • Bouter L.M.
      Shoulder disorders in general practice: incidence, patient characteristics, and management.
      Patients with SIS are characterized by pain localized in the shoulder that is exacerbated when performing overhead activities.
      • Koester M.C.
      • George M.S.
      • Kuhn J.E.
      Shoulder impingement syndrome.
      The first step in treatment for SIS by a general practitioner often includes an analgesic.

      Nederlands Huisartsen Genootschap (NHG) Standaard Schouderklachten: the Netherlands; 2008.

      Also, corticosteroid injections are an often-used intervention in primary care.
      • Rhon D.I.
      • Boyles R.E.
      • Cleland J.A.
      • Brown D.L.
      A manual physical therapy approach versus subacromial corticosteroid injection for treatment of shoulder impingement syndrome: a protocol for a randomised clinical trial.
      New treatment modalities such as tenoxicam injections
      • Itzkowitch D.
      • Ginsberg F.
      • Leon M.
      • Bernard V.
      • Appelboom T.
      Peri-articular injection of tenoxicam for painful shoulders: a double-blind, placebo controlled trial.
      have been studied for their effectiveness. A systematic review on this subject is necessary to give an evidence-based overview of (new) studies
      • Itzkowitch D.
      • Ginsberg F.
      • Leon M.
      • Bernard V.
      • Appelboom T.
      Peri-articular injection of tenoxicam for painful shoulders: a double-blind, placebo controlled trial.
      • Akgun K.
      • Birtane M.
      • Akarirmak U.
      Is local subacromial corticosteroid injection beneficial in subacromial impingement syndrome?.
      • Cacchio A.
      • De Blasis E.
      • Desiati P.
      • Spacca G.
      • Santilli V.
      • De Paulis F.
      Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA.
      • Friis J.
      • Jarner D.
      • Toft B.
      • et al.
      Comparison of two ibuprofen formulations in the treatment of shoulder tendonitis.
      • Paoloni J.A.
      • Appleyard R.C.
      • Nelson J.
      • Murrell G.A.
      Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial.
      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).
      • Furlan A.D.
      • Pennick V.
      • Bombardier C.
      • van Tulder M.
      2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group.
      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.
      • 1.
        Was the method of randomization adequate?
      B.
      • 2.
        Was the treatment allocation concealed?
      C.Was knowledge of the allocated interventions adequately prevented during the study?
      • 3.
        Was the patient blinded to the intervention?
      • 4.
        Was the care provider blinded to the intervention?
      • 5.
        Was the outcome assessor blinded to the intervention?
      D.Were incomplete outcome data adequately addressed?
      • 6.
        Was the dropout rate described and acceptable?
      • 7.
        Were all randomized participants analyzed in the group to which they were allocated?
      E.
      • 8.
        Are reports of the study free of suggestion of selective outcome reporting?
      F.Other sources of potential bias:
      • 9.
        Were the groups similar at baseline regarding the most important prognostic indicators?
      • 10.
        Were cointerventions avoided or similar?
      • 11.
        Was the compliance acceptable in all groups?
      • 12.
        Was the timing of the outcome assessment similar in all groups?
      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.
      • van Tulder M.
      • Furlan A.
      • Bombardier C.
      • Bouter L.
      Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group.
      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
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Physiotherapy interventions for shoulder pain.
      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 al
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Acupuncture for shoulder pain.
      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
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      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
      ReferenceAdequate 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 ScoreScore StudyPercentage
      Paoloni et al
      • Paoloni J.A.
      • Appleyard R.C.
      • Nelson J.
      • Murrell G.A.
      Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial.
      +++++++++++121192
      Akgun et al
      • Akgun K.
      • Birtane M.
      • Akarirmak U.
      Is local subacromial corticosteroid injection beneficial in subacromial impingement syndrome?.
      +?+++++++++121083
      Friis et al
      • Friis J.
      • Jarner D.
      • Toft B.
      • et al.
      Comparison of two ibuprofen formulations in the treatment of shoulder tendonitis.
      +?+??+?+++++12867
      Cacchio et al
      • Cacchio A.
      • De Blasis E.
      • Desiati P.
      • Spacca G.
      • Santilli V.
      • De Paulis F.
      Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA.
      +?++++++??+12867
      Itzkowitch et al
      • Itzkowitch D.
      • Ginsberg F.
      • Leon M.
      • Bernard V.
      • Appelboom T.
      Peri-articular injection of tenoxicam for painful shoulders: a double-blind, placebo controlled trial.
      ??+??++???+12433
      Methodologic quality scores of Green et al
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Physiotherapy interventions for shoulder pain.
      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/).
      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 MaximumScore StudyPercentage
      Ebenbichler
      • Ebenbichler G.R.
      • Erdogmus C.B.
      • Resch K.L.
      • et al.
      Ultrasound therapy for calcific tendinitis of the shoulder.
      ++++++++++111091
      Nykanen
      • Nykanen M.
      Pulsed ultrasound treatment of the painful shoulder: a randomized, double–blind, placebo–controlled study.
      +++++++++11982
      Saunders
      • Saunders L.
      The efficacy of low level laser therapy in supraspinatus tendinitis.
      +?++++++++11982
      Vecchio et al
      • Vecchio P.C.
      • Hazleman B.L.
      • King R.H.
      A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis.
      +++++++++11982
      Berry et al
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      +++++++11764
      Conroy
      • Conroy D.E.
      • Hayes K.W.
      The effect of mobilization as a component of comprehensive treatment for primary shoulder impingement syndrome.
      +++++++11764
      Dal Conte
      • Dal Conte G.
      • Rivoltini P.
      • Combi F.
      [Trattamento della periartrite calcarea di spalla con campi magnetici pulsanti: studio controllato] [Italian].
      +++++++11764
      England et al
      • England S.
      • Farrell A.J.
      • Coppock J.S.
      • Struthers G.
      • Bacon P.A.
      Low power laser therapy of shoulder tendonitis.
      +++++++11764
      Bang
      • Bang M.
      • Deyle G.
      Comparison of supervised exercise with and without manual physical therapy for patients with shoulder impingement syndrome.
      ++++++11655
      Brox
      • Brox J.
      • Staff P.
      • Ljunggren A.
      • Brevik J.
      Arthroscopic surgery compared with supervised exercises in patients with rotator cuff disease.
      ++++++11655
      Perron
      • Perron M.
      • Malouin F.
      Acetic acid iontophoresis and ultrasound for the treatment of calcifying tendinitis of the shoulder: a randomized control trial.
      ++++++11655
      Methodologic quality scores of Green et al
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Acupuncture for shoulder pain.
      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).
      Berry et al
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      +n.p.++++++10770
      Methodologic quality scores of Buchbinder et al
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      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).
      Blind Participants?Blind Assessors?Acceptable Lost to Follow-up?
      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.
      Appropriate Statistical Analysis? (ITT Analysis?)Allocation ConcealedScore MaximumScore StudyPercentage
      Adebajo et al
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      +++++5480
      Petri et al
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      +++++5480
      Withrington et al
      • Withrington R.H.
      • Girgis F.L.
      • Seifert M.H.
      A placebo-controlled trial of steroid injections in the treatment of supraspinatus tendonitis.
      ++++?5480
      Berry et al
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      ?+++?5360
      Vecchio et al
      • Vecchio P.C.
      • Hazleman B.L.
      • King R.H.
      A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis.
      +++?5360
      White et al
      • White R.H.
      • Paull D.M.
      • Fleming K.W.
      Rotator cuff tendinitis: comparison of subacromial injection of a long acting corticosteroid versus oral indomethacin therapy.
      +++5360
      Blair et al
      • Blair B.
      • Rokito A.S.
      • Cuomo F.
      • Jarolem K.
      • Zuckerman J.D.
      Efficacy of injections of corticosteroids for subacromial impingement syndrome.
      ++???5240
      Strobel
      • Strobel G.
      [Long-term therapeutic effect of different intra-articular injection treatments of the painful shoulder–effect on pain, mobility and work capacity] [German].
      ???500
      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
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Acupuncture for shoulder pain.
      or 5 items
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      : 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 al
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      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
       Oralb
       Injectionc,f
       Othera,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.
      In favor of.
      b: Moderate evidence: Ibuprofen
      In favor of.
      vs sustained-release ibuprofen.
      c: Moderate evidence: Disodium EDTA plus ultrasound
      In favor of.
      vs placebo.
      d: Moderate evidence: GTN patches
      In favor of.
      vs placebo.
      Midterm:
      e: Moderate evidence: GTN patches
      In favor of.
      vs placebo.
      Long-term:
      f: Moderate evidence: Disodium EDTA plus ultrasound
      In favor of.
      vs placebo.
      In favor of.
      Table 5CANS: Evidence for the effectiveness of pharmaceutical interventions for SIS
      Oral TreatmentInjections
      CorticosteroidTenoxicam
      NSAID
      ▸ NSAID vs laser therapy
      In favor of.
      ▸ Corticosteroid injection vs placebo▸ Tenoxicam
      In favor of.
      injection vs placebo
      Short-term++Short-term±Short-term+
      IbuprofenLong-term±
      ▸ Ibuprofen
      In favor of.
      vs sustained-release ibuprofen
      ▸ Corticosteroid injection 1 session vs 2 sessions
      In favor of.
      Disodium EDTA

      ▸ Disodium EDTA

      plus ultrasound (with EDTA gel) vs placebo
      Short-term+++Short-term++
      Long-term++
      ▸ Corticosteroid injection vs acupuncture plus moxibustion
      Other conservativeShort-termNE
      GTN patches
      ▸ GTN patches
      In favor of.
      vs placebo
      ▸ Corticosteroid injection vs NSAID
      Short-term++
      Mid-term++
      Short-termNE
      ▸ Corticosteroid injection plus NSAID vs placebo
      Short-termNE
      ▸ Corticosteroid injection plus NSAID vs NSAID
      Short-termNE
      ▸ Corticosteroid injection plus placebo NSAID vs acupuncture
      Short-termNE
      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
      • England S.
      • Farrell A.J.
      • Coppock J.S.
      • Struthers G.
      • Bacon P.A.
      Low power laser therapy of shoulder tendonitis.
      (n=20) included in the review of Green et al
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Physiotherapy interventions for shoulder pain.
      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
      • Friis J.
      • Jarner D.
      • Toft B.
      • et al.
      Comparison of two ibuprofen formulations in the treatment of shoulder tendonitis.
      (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
      • Paoloni J.A.
      • Appleyard R.C.
      • Nelson J.
      • Murrell G.A.
      Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial.
      (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
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      compared corticosteroid injections with placebo injections. Five of the 7 trials compared subacromial steroid injection with placebo.
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      • Blair B.
      • Rokito A.S.
      • Cuomo F.
      • Jarolem K.
      • Zuckerman J.D.
      Efficacy of injections of corticosteroids for subacromial impingement syndrome.
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      • Vecchio P.C.
      • Hazleman B.L.
      • King R.H.
      A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis.
      One trial compared intraarticular injection with placebo,
      • Strobel G.
      [Long-term therapeutic effect of different intra-articular injection treatments of the painful shoulder–effect on pain, mobility and work capacity] [German].
      and another trial compared supraspinatus tendon injection with placebo.
      • Withrington R.H.
      • Girgis F.L.
      • Seifert M.H.
      A placebo-controlled trial of steroid injections in the treatment of supraspinatus tendonitis.
      Two high-quality trials
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      (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 study
      • Blair B.
      • Rokito A.S.
      • Cuomo F.
      • Jarolem K.
      • Zuckerman J.D.
      Efficacy of injections of corticosteroids for subacromial impingement syndrome.
      (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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      (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 study
      • Vecchio P.
      • Cave M.
      • King V.
      • Adebajo A.O.
      • Smith M.
      • Hazleman B.L.
      A double-blind study of the effectiveness of low level laser treatment of rotator cuff tendinitis.
      (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)
      • Strobel G.
      [Long-term therapeutic effect of different intra-articular injection treatments of the painful shoulder–effect on pain, mobility and work capacity] [German].
      (n=40) reported significantly greater reduction in pain in the placebo group versus the treatment group at 90 and 360 days. Another high-quality study
      • Withrington R.H.
      • Girgis F.L.
      • Seifert M.H.
      A placebo-controlled trial of steroid injections in the treatment of supraspinatus tendonitis.
      (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
      • Akgun K.
      • Birtane M.
      • Akarirmak U.
      Is local subacromial corticosteroid injection beneficial in subacromial impingement syndrome?.
      (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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      (n=24) included in the review of Green et al
      • Green S.
      • Buchbinder R.
      • Hetrick S.
      Acupuncture for shoulder pain.
      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
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      • White R.H.
      • Paull D.M.
      • Fleming K.W.
      Rotator cuff tendinitis: comparison of subacromial injection of a long acting corticosteroid versus oral indomethacin therapy.
      (n=120) included in the review of Buchbinder et al
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      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,
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      • White R.H.
      • Paull D.M.
      • Fleming K.W.
      Rotator cuff tendinitis: comparison of subacromial injection of a long acting corticosteroid versus oral indomethacin therapy.
      on improvement in function at 4-week follow-up,
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      and on global assessment at 6-week follow-up.
      • White R.H.
      • Paull D.M.
      • Fleming K.W.
      Rotator cuff tendinitis: comparison of subacromial injection of a long acting corticosteroid versus oral indomethacin therapy.
      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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      (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
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      (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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      (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
      • Itzkowitch D.
      • Ginsberg F.
      • Leon M.
      • Bernard V.
      • Appelboom T.
      Peri-articular injection of tenoxicam for painful shoulders: a double-blind, placebo controlled trial.
      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
      • Cacchio A.
      • De Blasis E.
      • Desiati P.
      • Spacca G.
      • Santilli V.
      • De Paulis F.
      Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA.
      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.
      • Huisstede B.M.
      • Hoogvliet P.
      • Randsdorp M.S.
      • Glerum S.
      • van Middelkoop M.
      • Koes B.W.
      Carpal tunnel syndrome, part I: effectiveness of nonsurgical treatments–a systematic review.
      • Huisstede B.M.
      • van Middelkoop M.
      • Randsdorp M.S.
      • Glerum S.
      • Koes B.W.
      Effectiveness of interventions of specific complaints of the arm, neck, and/or shoulder: 3 musculoskeletal disorders of the hand. An update.
      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.
      • Holleman A.F.
      In organic chemistry.
      Cacchio et al
      • Cacchio A.
      • De Blasis E.
      • Desiati P.
      • Spacca G.
      • Santilli V.
      • De Paulis F.
      Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA.
      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
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      used only 5 items, in contrast to the 12 items of Furlan et al
      • Furlan A.D.
      • Pennick V.
      • Bombardier C.
      • van Tulder M.
      2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group.
      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
      AuthorTotal Number of PatientsTreatmentPlaceboControl/ComparisonOutcome MeasuresEffect Size
      Buchbinder et al
      • Buchbinder R.
      • Green S.
      • Youd J.M.
      Corticosteroid injections for shoulder pain.
      Corticosteroid injections
      Corticosteroid vs placebo injection
      Adebajo et al
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      and Petri et al
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      90Subacromial 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
      • Blair B.
      • Rokito A.S.
      • Cuomo F.
      • Jarolem K.
      • Zuckerman J.D.
      Efficacy of injections of corticosteroids for subacromial impingement syndrome.
      40Subacromial steroid injection (2mL of 40mg/mL triamcinolone acetonide) (n=19)Placebo (n=21)No data were givenAt 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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      60Intraarticular 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
      Success rate = success or failure of the treatment at the end of 4wk defined as the need for a steroid injection.
      RR 0.67 (95% CI=0.35–1.28)
      Vecchio et al
      • Vecchio P.C.
      • Hazleman B.L.
      • King R.H.
      A double-blind trial comparing subacromial methylprednisolone and lignocaine in acute rotator cuff tendinitis.
      57Subacromial steroid injection (40mg methylprednisolone) (n=29)Placebo (n=28)No data were givenNo significant differences with respect to pain and ROM between the treatment and placebo groups
      Rotator cuff tendonitis
      Strobel
      • Strobel G.
      [Long-term therapeutic effect of different intra-articular injection treatments of the painful shoulder–effect on pain, mobility and work capacity] [German].
      40Subacromial steroid injection (20mg triamcinolone hexacetonide (n=20)Placebo (n=20)No data were givenGreater reduction in pain in the placebo group at 90 and 360d
      Subacromial bursitis or supraspinatus tendinitis
      Withrington et al
      • Withrington R.H.
      • Girgis F.L.
      • Seifert M.H.
      A placebo-controlled trial of steroid injections in the treatment of supraspinatus tendonitis.
      25Supraspinatus injection with 80mg methylprednisolone (n=12)Saline (n=13)No data were givenNo difference in improvement in pain or analgesic consumption between the 2 groups at 2 and 8wk
      Supraspinatus tendonitis
      Corticosteroid vs acupuncture
      Berry et al
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      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,
      • Adebajo A.O.
      • Nash P.
      • Hazleman B.L.
      A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis.
      Petri et al,
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      White et al
      • White R.H.
      • Paull D.M.
      • Fleming K.W.
      Rotator cuff tendinitis: comparison of subacromial injection of a long acting corticosteroid versus oral indomethacin therapy.
      200/120Subacromial 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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      60Intraarticular 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
      Success rate = success or failure of the treatment at the end of 4wk defined as the need for a steroid injection.
      RR 0.56 (95% CI=0.26–1.17)
      Corticosteroid plus NSAID vs NSAID
      Petri et al
      • Petri M.
      • Dobrow R.
      • Neiman R.
      • Whiting-O'Keefe Q.
      • Seaman W.E.
      Randomized, double-blind, placebo-controlled study of the treatment of the painful shoulder.
      100Subacromial 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
      • Berry H.
      • Fernandes L.
      • Bloom B.
      • Clark R.J.
      • Hamilton E.B.
      Clinical study comparing acupuncture, physiotherapy, injection and oral anti-inflammatory therapy in shoulder-cuff lesions.
      60Steroid (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
      AuthorTreatmentPlaceboControl ComparisonOutcome Measures and FU TimeResults—StatisticalResults—Words
      Corticosteroid injections
      Corticosteroid vs placebo
      Akgun et al
      • Akgun K.
      • Birtane M.
      • Akarirmak U.
      Is local subacromial corticosteroid injection beneficial in subacromial impingement syndrome?.
      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 painNS (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 painNS (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 sleepSignificant (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 scoreNS (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
      SISGroup 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 painNS (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 painNS (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 sleepS (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 scoreNS (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
      AuthorTreatmentPlaceboControl/ComparisonOutcome Measures and FU TimeResults—StatisticalResults—Words
      Analgesics
      Ibuprofen tablet vs sustained-released ibuprofen
      Friis et al
      • Friis J.
      • Jarner D.
      • Toft B.
      • et al.
      Comparison of two ibuprofen formulations in the treatment of shoulder tendonitis.
      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=.04SRTI vs CTI ifo CTI
      Shoulder tendonitis(no exact data given)
      Complete pain reliefP=.02SRTI 7% (no 95% CI given) vs CTI 21% (no 95% CI given)
      (3wk)
      Improvement: better or complete relief (3wk).2<P<.3SRTI 67% (95% CI=55%–77%) vs CTI 77% (95% CI=65%–86%)
      Improvement: (doctor's assessment) (3wk)No P value givenSRTI 73% (no 95% CI given) vs CTI 79% (no 95% CI given)
      GTN transdermal vs placebo
      Paoloni et al
      • Paoloni J.A.
      • Appleyard R.C.
      • Nelson J.
      • Murrell G.A.
      Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial.
      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=.0412wk: GTN vs placebo ifo GTN, no exact data given
      Chronic supraspinatus tendinopathyGTN patch plus 24 tablets paracetamol 500mg for use with possible headache plus tendon rehabilitation program (n=26 [28 shoulders])
      P=.0324wk: GTN vs placebo ifo GTN, no exact data given
      Decrease in pain with activity (0–4)P>.0512wk: GTN vs placebo, no exact data given
      P=.0124wk: GTN vs placebo ifo of GTN, no exact data given
      Decrease in pain at night (0–4)P=.0312wk: GTN vs placebo ifo of GTN, no exact data given
      P=.0124wk: GTN vs placebo ifo GTN, no exact data given
      Patient-related pain scores (at rest, at night, with activity)No P value givenGTN: from baseline to 24wk, a reduction of 65% (64%–67%) vs placebo: from baseline to 24wk, a reduction of 30% (27%–33%)
      ROMNo P value givenGTN: 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 forceP=.00112wk: GTN vs placebo ifo of GTN, no exact data given
      P=.00124wk: GTN vs placebo ifo of GTN, no exact data given
      Increase in external rotation forceP=.0112wk: GTN vs placebo ifo GTN, no exact data given
      P=.0124wk: GTN vs placebo ifo GTN, no exact data given
      Increase in internal rotation forceP=.0112wk: GTN vs placebo ifo GTN, no exact data given
      P=.0124wk: GTN vs placebo ifo of GTN, no exact data given
      Increase in subscapularis forceP=.0212wk: GTN vs placebo ifo GTN, no exact data given
      P=.0224wk: GTN vs placebo ifo GTN, no exact data given
      Increase in adduction forceP=.00312wk: GTN vs placebo ifo GTN, no exact data given
      P=.00324wk: GTN vs placebo ifo GTN, no exact data given
      Increase in dynanometer-measured shoulder forceNo P value givenGTN: from baseline to 24wk, an increase of 29% (10%–61%) vs placebo: from baseline to 24wk, an increase of 12% (5%– 32%)
      Impingement signsNo P value givenGTN: from baseline to 24wk, a decrease of 76% (74%–78%) vs placebo: from baseline to 24wk, a decrease of 43% (40%–47%)
      Asymptomatic at 24wkP=.00724wk: 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
      • Itzkowitch D.
      • Ginsberg F.
      • Leon M.
      • Bernard V.
      • Appelboom T.
      Peri-articular injection of tenoxicam for painful shoulders: a double-blind, placebo controlled trial.
      Tenoxicam injection 20mg/2mL once per week for up to 4wk (n=38)Placebo injection (n=39)Pain at rest (VAS) (2–4wk)NSBaseline:
      Tenoxicam: 4.68±2.7 vs placebo: 4.84±2.35
      Rotator cuff tendinitis
      P<.001Last available score:
      Tenoxicam: 1.73±2.41
      vs placebo: 3.18±2.73
      Pain on active movement (VAS) (2-4wk)NSBaseline:
      Tenoxicam: 7.38±1.35
      vs placebo: 6.98±1.65
      P<.001Last available score:
      Tenoxicam: 2.38±2.65 vs placebo: 4.99±2.95
      Active abduction (degrees) (2–4wk)NSBaseline:
      Tenoxicam: 111.2±39.7 vs placebo: 116.4±35.5
      P<.001Last available score:
      Tenoxicam: 141.8±35.4 vs placebo: 129±40.1
      Disodium EDTA plus US vs placeboStudy group vs placebo
      Cacchio et al
      • Cacchio A.
      • De Blasis E.
      • Desiati P.
      • Spacca G.
      • Santilli V.
      • De Paulis F.
      Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA.
      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<.43Baseline: 6.78±0.28 vs 6.63±0.17
      Calcific tendinitis
      P<.011wk: 2.87±1.21 vs 6.95±0.30
      P<.011y: 2.00±1.30 vs 7.01±0.30
      Study group vs placebo
      Total Constant and Murley scoreP<.53Baseline: 47.68±5.79 vs 46.57±6.94
      P<.011wk: 75.62±3.96 vs 45.85±6.25
      P<.011y: 75.50±4.07 vs 46.42±8.52
      Study group vs placebo
      Size of calcification (mm) (radiography)P=.08Baseline: 18.5±1.57 vs 17.85±1.19
      P<.01After 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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