Journal of Sport Rehabilitation, 2015, 24, 327 -331 http://dx.doi.org/10.1123/jsr.2014-0172 © 2015 Human Kinetics, Inc.
Critically Appraised Topic
The Effect of Dexamethasone Iontophoresis on Decreasing Pain and Improving Function in Patients With Musculoskeletal Conditions Christopher D. Brown, Christine A. Lauber, and Thomas Cappaert Clinical Scenario: Iontophoresis is a method of local transfer of ionized medicated and nonmedicated substances through the skin and into the target tissues using magnetic polarization. The anti-inflammatory properties exhibited by dexamethasone sodium phosphate (DEX) combined with iontophoresis make it a potentially desirable treatment for clinicians wishing to administer a noninvasive localized drug concentration without having a large systemic concentration of that drug. Since concurrent treatments are commonly used in clinical practice, many of the published studies that included the use of DEX also used concurrent treatments. However, this may make it difficult for clinicians to determine the individual effectiveness of DEX iontophoresis in treating musculoskeletal conditions. Focused Clinical Question: Does DEX iontophoresis, alone, decrease pain and improve function in patients with musculoskeletal conditions when compared with placebo or control? Keywords: corticosteroid, transdermal drug delivery, therapeutic modalities
Clinical Scenario Iontophoresis is a method of local transfer of ionized medicated and nonmedicated substances through the skin and into the target tissues using magnetic polarization. The anti-inflammatory properties exhibited by dexamethasone sodium phosphate (DEX) combined with iontophoresis make it a potentially desirable treatment for clinicians wishing to administer a noninvasive localized drug concentration without having a large systemic concentration of that drug. Since concurrent treatments are commonly used in clinical practice, many of the published studies that included the use of DEX also used concurrent treatments. However, this may make it difficult for clinicians to determine the individual effectiveness of DEX iontophoresis in treating musculoskeletal conditions.
Focused Clinical Question Does DEX iontophoresis, alone, decrease pain and improve function in patients with musculoskeletal conditions when compared with placebo or control? Brown is with the Athletic Training Program, University of Southern Mississippi, Hattiesburg, MS. Lauber is with Athletic Training, University of Indianapolis, Indianapolis, IN. Cappaert is with Rocky Mountain University of Health Professions, Provo, UT. Direct correspondence to Christopher Brown at [email protected].
Summary of Search, “Best Evidence” Appraised, and Key Findings • The literature was searched for clinical trials that investigated the effect of dexamethasone iontophoresis on reducing pain and/or improving function in patients with musculoskeletal conditions. • Three high-quality randomized controlled trials were included. • Two of the 3 included studies did not note any difference in outcomes for DEX compared with a placebo or control. • Age bias was identified in the included studies, as the average age of study participants was 54 ± 10, 45 to 50 median years, and 49.9 ± 10.3/50.9 ± 9.6 years.
Clinical Bottom Line There is little evidence to support the use of dexamethasone iontophoresis to reduce pain and/or improve function in patients with musculoskeletal conditions. Strength of Recommendation: Level B evidence exists that dexamethasone iontophoresis is not effective in reducing pain or improving function when compared with a placebo in patients with musculoskeletal conditions.
327
328 Brown, Lauber, and Cappaert
Search Strategy Terms Used to Guide Search Strategy • Patient/Client group: musculoskeletal conditions • Intervention: dexamethasone and iontophoresis • Comparison: alternate treatments and placebo and control • Outcomes: reduce pain and improve function
Table 1 Summary of Study Designs of Articles Retrieved Level of evidence
Number Study design located Reference
2
Randomized controlled trial
5
Gökoglu et al2 Karatay et al3 Nirschl et al4 Runeson and Haker5
Sources of Evidence Searched
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
Amirjani et al1
• PubMed • PEDro • CINAHL (EBSCO) • SPORTDiscus • Additional resources obtained via review of reference lists and hand search
Inclusion and Exclusion Criteria Inclusion Criteria • The literature was searched for studies of level 2 evidence or higher investigating dexamethasone iontophoresis and its effect on pain and function in musculoskeletal conditions. • All ages and genders. • Musculoskeletal conditions in the extremities. • Limited to the English language. • Limited to humans. • PEDro score of at least 5/10.
Exclusion Criteria • Studies examining other drugs • Studies investigating iontophoresis in conjunction with other treatments • Studies examining the torso, head, neck, or face • Reviews practice acts or meta-analysis
Results of Search Five studies were located and categorized as shown in Table 1 (based on Levels of Evidence, Centre for Evidence Based Medicine, 2011).1–5 Two of these studies were excluded because of PEDro scores of less than 5/10.2,3
Best Evidence The following studies were identified as the “best” evidence and selected for inclusion in the CAT (Table 2). Reasons for selecting these studies were
• No concurrent treatments • Uniform treatment parameters • PEDro scores of at least 5/10
Implications for Practice, Education, and Future Research Two of the 3 studies demonstrated that DEX iontophoresis was not significantly more effective than a placebo.1,5 The third study demonstrated DEX was more effective than a placebo during a 2-day follow-up session but was not more effective 1 month later.4 This could have been influenced by the decision to allow participants the freedom to use other methods of treatment after the 2-day follow-up session. It could also have been influenced by the fact that all 3 studies used a placebo group in comparison with their DEX group. While placebo effects are still somewhat controversial in the medical fields, researchers have found that the simple awareness of being treated is potentially enough for an analgesic effect in some patients.6 Another factor that may have led to the results seen in the included studies could have been the type of conditions used to test DEX iontophoresis. The 3 included studies examined elbow epicondylitis,4 carpal tunnel syndrome, 1 and lateral epicondylalgia. 5 Of those conditions, only epicondylitis is commonly associated with inflammation, due to small tears that appear in muscle fibers over time.7 Carpal tunnel syndrome is by definition the entrapment of the median nerve. This condition can be caused by inflammation, but it also has many other possible causes including alcohol abuse, obesity, infections, fractures, cysts, tumors, or a congenitally small carpal tunnel.8 Since the authors did not report the cause of the carpal tunnel condition, it cannot be certain that that the condition was caused by inflammation. Lateral epicodylalgia is a musculoskeletal disorder characterized by pain and mechanical hyperalgesia at the lateral epicondyle. While inflammation may be present along with the condition, it is not a diagnostic criterion. An understanding of the cause of the condition to be treated is important to achieve positive patient outcomes with DEX iontophoresis. Conditions that are not inflammatory in nature do not result in positive patient
JSR Vol. 24, No. 3, 2015
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329
Subjects were eligible if they were between 18 and 75 y of age and had clinical signs leading to a diagnosis of medial or lateral humeral epicondylitis, if they had a duration of symptoms of 3 mo or less during the most recent episode before the screening evaluation, and if the investigator’s global evaluation of the severity of epicondylitis at screening and at the baseline evaluation was rated moderate or greater intensity.
Subjects were eligible if they presented with mild to moderately severe median nerve compression at the wrist that was confirmed by electrophysiological studies.
At least 85% of subjects were available for follow-up.
Groups were comparable at baseline
Subjects were eligible if they had pain with at least 2 tests (middle finger test, resisted wrist extension, hand grip test) and a history of pain of at least 1 mo.
Patients were randomized using sequentially numbered, opaque-sealed envelopes.
65 patients initially recruited. 1 patient dropped out—64 patients used for study (placebo group 45 y, experimental group 50 y).
Randomized controlled trial
Runeson and Haker5
At least 85% of subjects were available for follow-up.
Groups were comparable at baseline. (continued)
Subjects were excluded if they had any treatment during the last month for elbow Subjects were excluded if they had recurrent injury of the subject area, bilateral pain; had any demonstrated dysfunction of or multiple affected areas; had an injection of a steroid into the affected area shoulder, neck, and/or thoracic region; local within the past year, prior surgery to correct the problem; use of nonsteroidal or generalized arthritis, neurological deficit, anti-inflammatory medications, systemic and local corticosteroids, or analradial nerve entrapment, bilateral epicongesics within 3 d of study participation; involvement in a lawsuit or workers’ dylalgia, pregnancy, previous surgeries to compensation claim for any medical condition; or history of rheumatoid arthri- the elbow, or a pacemaker. tis, degenerative arthritis, polyarthritis, carpal tunnel syndrome, rotator-cuff Groups were comparable at baseline. tendinitis, neurologic abnormalities in the affected area, muscular dysfunction, 64.1% of subjects were available for 3-mo peripheral neuropathy, radial nerve entrapment, or fracture or tumor of the follow-up affected area.
Patients were randomized according to a computer-generated randomization schedule, and randomization was stratified according to initial disease severity so that equal numbers of patients with a disease severity of “very severe” at baseline would receive each treatment.
Patients were randomized according to a random-number-generator function of a commercially available software program.
Subjects were excluded if they had thenar atrophy, previous carpal tunnel decompression surgery, previous corticosteroid injection to the carpal tunnel, other neurological disorders contributing to symptoms, or a history of trauma to wrist or arm.
199 patients from 11 centers across the USA (experimental group 49.9 ± 10.3 y, placebo group 50.9 ± 9.6 y).
17 patients from a university teaching hospital (36–73 y, mean = 54 ± 10).
Randomized controlled trial
Randomized controlled trial
Participants
Nirschl et al4
Study design
Amirjani et al1
Table 2 Characteristics of Included Studies
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
330
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2
PEDro 10/10
Both groups had significant reduction in severity of symptoms throughout the trial but neither differed from the other. Nerve conduction did not change significantly throughout the study.
Level of evidence
Validity score
Conclusion
Semmes-Weinstein: no significant improvement in either group.
PEDro 7/10 There was no statistical difference between the placebo and iontophoresis groups throughout the study.
The results of a 2-d follow-up after the last treatment showed that patients who were treated with dexamethasone significantly improved their pain and global function compared with control group. These results were not applicable to a 1-mo follow-up.
2
Patients in both groups reported improvement throughout the study but not statistically significant.
No statistical significance between the 4 outcomes after treatment and at the followups.
PEDro 8/10
2
No significant difference in measures between groups at 1-mo follow-up.
Nerve-conduction studies: No significant Dexamethasone group significantly improved in investigator’s assessment of improvement in either group over course symptoms (P = .019) and investigator tenderness evaluation (P = .001) comof the study. pared with placebo during 2-d follow-up.
Levine Self-Assessment Questionnaire: no significant differences between groups at any time frame.
Dexamethasone group significantly improved in investigator’s global improvement (P = .013) and patient pain evaluation (P = .012) compared with placebo during 2-d follow-up.
Blinding of therapists, assessors, and subjects.
Treatments given at Mon/Wed/Fri/Mon or Wed/Fri/Mon/Wed schedule.
4 treatments were given over a 2-wk period.
Iontophoresis treatments were provided with the following parameters: 40 mA-min, 0.4% dexamethasone solution.
Main findings
investigator’s tenderness evaluation, and investigator’s assessment of disease severity.
Subjects could not begin concurrent treatments during their evaluative period.
Blinding of therapists, assessors, and subjects.
Treatments were spaced 1–3 d apart.
6 treatments given within 15 d.
Iontophoresis treatments were provided with the following parameters: 40 mA-min, 0.4% dexamethasone solution.
Runeson and Haker5
Primary Outcomes: Evaluation of global improvement by patient, evaluation of Primary Outcomes: Palpation at lateral epiglobal improvement by investigators, patient pain evaluations after treatment. condyle, resisted wrist extension, middlefinger test, handgrip strength. Secondary Outcomes: Evaluations of symptoms by patient and investigators,
Blinding of therapists, assessors, and subjects.
Treatments were given on alternate days.
6 treatments were given over a 2-wk period.
Iontophoresis treatments were provided with the following parameters: 80 mA-min, 0.4% dexamethasone solution.
Nirschl et al4
Outcome measures Primary Outcomes: Levine Self-assessment Questionnaire, nerve-conduction studies, Semmes-Weinstein monofilaments.
Intervention investigated
Amirjani et al1
Table 2 (continued)
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
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outcomes when treated with DEX iontophoresis, according to our review. Skin permeability may also influence the effectiveness of DEX iontophoresis.9 As a person ages, the stratum corneum decreases its permeability by drying, decreasing the microvascular blood supply in the epidermis, and becoming more resistant to hydrophilic compounds such as DEX. This decrease in permeability of the stratum corneum could limit the overall effectiveness of the drug. Of the 3 studies included in this review the mean age of the participants in years was 54 ± 10,1 45 to 50 median years,5 and 49.9 ± 10.3/50.9 ± 9.6.4 The most probable reason for this propensity to study older populations when dealing with these musculoskeletal conditions is their increased prevalence in an aging population compared with a younger population. However, this apparent research bias toward older population models could cause difficulties in adapting clinical protocols for younger patients with similar conditions.10 While we acknowledge the small samples sizes may be resulting in underpowered analyses, without all the necessary data in the published studies, a power analysis was not possible. The possibility of a type II error is a limitation, but without a power analysis it is only speculation. This lack of pertinent data highlights the paucity of high-quality published research results in this area. This manuscript is a preliminary review of the current literature and should be followed periodically with additional updates as more research becomes available. Future general research in this area would be needed to definitively determine if DEX iontophoresis, alone, is a viable modality for the treatment of musculoskeletal conditions. Research in this field should focus more specifically on inflammatory conditions as opposed to general musculoskeletal conditions. Another important aspect of future research would be the elimination of concurrent treatments, which may limit the ability of researchers and clinicians to determine a true efficacy of the modality. However, this may be difficult since the treatment norm for these conditions revolves around multiple treatment types. Future research should also compare younger populations with older populations to determine if differences in outcome variables exist. This CAT should be reviewed in 2 years to determine whether best evidence has been published that may change the clinical bottom line for this specific clinical question.
References 1. Amirjani N, Ashworth NL, Watt MJ, Gordon T, Chan KM. Corticosteroid iontophoresis to treat carpal tunnel syndrome: a double-blind randomized controlled trial. Muscle Nerve. 2009;39(5):627–633. PubMed doi:10.1002/ mus.21300 2. Gökoglu F, Fndkoglu G, Yorgancoglu ZR, Okumus M, Ceceli E, Kocaoglu S. Evaluation of iontophoresis and local corticosteroid injection in the treatment of carpal tunnel syndrome. Am J Phys Med Rehabil. 2005;84:92–96. 3. Karatay S, Aygul R, Melikoglu MA, et al. The comparison of phonophoresis, iontophoresis and local steroid injection in carpal tunnel syndrome treatment. Joint Bone Spine. 2009;76:719–721. PubMed doi:10.1016/j. jbspin.2009.02.008 4. Nirschl RP, Rodin DM, Ochiai DH, Maartmann-Moe C. Iontophoretic administration of dexamethasone sodium phosphate for acute epicondylitis: a randomized, doubleblinded, placebo-controlled study. Am J Sports Med. 2003;31:189–195. PubMed 5. Runeson L, Haker E. Iontophoresis with cortisone in the treatment of lateral epicondylalgia (tennis elbow)—a double-blind study. Scand J Med Sci Sports. 2002;12(3):136– 142. PubMed doi:10.1034/j.1600-0838.2002.02142.x 6. Colloca L, Lopiano L, Lanotte M, Benedetti F. Overt versus covert treatment for pain, anxiety, and Parkinson’s disease. Lancet Neurol. 2004;3(11):679–684. PubMed doi:10.1016/S1474-4422(04)00908-1 7. Brotzman SB, Wilk KE. Clinical Orthopedic Rehabilitation. 2nd ed. Philadelphia, PA: Mosby; 2003. 8. Ma CB, Zieve D, Black B, Slon S, Wang N. Carapal tunnel syndrome. 2013. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001469/. Accessed September 26, 2013. 9. Chopra P, Hao J, Li SK. Influence of drug lipophilicity on drug release from sclera after iontophoretic delivery of mixed micellar carrier system to human sclera. J Pharm Sci. 2013;102(2):480–488. PubMed doi:10.1002/ jps.23370 10. Brown CD, Lauber CA. Evidence-based practice guidelines for utilization of dexamethasone iontophoresis. Int J Athl Ther Train. 2011(16):33–36.
JSR Vol. 24, No. 3, 2015
Critically Appraised Topic
The Effect of Dexamethasone Iontophoresis on Decreasing Pain and Improving Function in Patients With Musculoskeletal Conditions Christopher D. Brown, Christine A. Lauber, and Thomas Cappaert Clinical Scenario: Iontophoresis is a method of local transfer of ionized medicated and nonmedicated substances through the skin and into the target tissues using magnetic polarization. The anti-inflammatory properties exhibited by dexamethasone sodium phosphate (DEX) combined with iontophoresis make it a potentially desirable treatment for clinicians wishing to administer a noninvasive localized drug concentration without having a large systemic concentration of that drug. Since concurrent treatments are commonly used in clinical practice, many of the published studies that included the use of DEX also used concurrent treatments. However, this may make it difficult for clinicians to determine the individual effectiveness of DEX iontophoresis in treating musculoskeletal conditions. Focused Clinical Question: Does DEX iontophoresis, alone, decrease pain and improve function in patients with musculoskeletal conditions when compared with placebo or control? Keywords: corticosteroid, transdermal drug delivery, therapeutic modalities
Clinical Scenario Iontophoresis is a method of local transfer of ionized medicated and nonmedicated substances through the skin and into the target tissues using magnetic polarization. The anti-inflammatory properties exhibited by dexamethasone sodium phosphate (DEX) combined with iontophoresis make it a potentially desirable treatment for clinicians wishing to administer a noninvasive localized drug concentration without having a large systemic concentration of that drug. Since concurrent treatments are commonly used in clinical practice, many of the published studies that included the use of DEX also used concurrent treatments. However, this may make it difficult for clinicians to determine the individual effectiveness of DEX iontophoresis in treating musculoskeletal conditions.
Focused Clinical Question Does DEX iontophoresis, alone, decrease pain and improve function in patients with musculoskeletal conditions when compared with placebo or control? Brown is with the Athletic Training Program, University of Southern Mississippi, Hattiesburg, MS. Lauber is with Athletic Training, University of Indianapolis, Indianapolis, IN. Cappaert is with Rocky Mountain University of Health Professions, Provo, UT. Direct correspondence to Christopher Brown at [email protected].
Summary of Search, “Best Evidence” Appraised, and Key Findings • The literature was searched for clinical trials that investigated the effect of dexamethasone iontophoresis on reducing pain and/or improving function in patients with musculoskeletal conditions. • Three high-quality randomized controlled trials were included. • Two of the 3 included studies did not note any difference in outcomes for DEX compared with a placebo or control. • Age bias was identified in the included studies, as the average age of study participants was 54 ± 10, 45 to 50 median years, and 49.9 ± 10.3/50.9 ± 9.6 years.
Clinical Bottom Line There is little evidence to support the use of dexamethasone iontophoresis to reduce pain and/or improve function in patients with musculoskeletal conditions. Strength of Recommendation: Level B evidence exists that dexamethasone iontophoresis is not effective in reducing pain or improving function when compared with a placebo in patients with musculoskeletal conditions.
327
328 Brown, Lauber, and Cappaert
Search Strategy Terms Used to Guide Search Strategy • Patient/Client group: musculoskeletal conditions • Intervention: dexamethasone and iontophoresis • Comparison: alternate treatments and placebo and control • Outcomes: reduce pain and improve function
Table 1 Summary of Study Designs of Articles Retrieved Level of evidence
Number Study design located Reference
2
Randomized controlled trial
5
Gökoglu et al2 Karatay et al3 Nirschl et al4 Runeson and Haker5
Sources of Evidence Searched
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
Amirjani et al1
• PubMed • PEDro • CINAHL (EBSCO) • SPORTDiscus • Additional resources obtained via review of reference lists and hand search
Inclusion and Exclusion Criteria Inclusion Criteria • The literature was searched for studies of level 2 evidence or higher investigating dexamethasone iontophoresis and its effect on pain and function in musculoskeletal conditions. • All ages and genders. • Musculoskeletal conditions in the extremities. • Limited to the English language. • Limited to humans. • PEDro score of at least 5/10.
Exclusion Criteria • Studies examining other drugs • Studies investigating iontophoresis in conjunction with other treatments • Studies examining the torso, head, neck, or face • Reviews practice acts or meta-analysis
Results of Search Five studies were located and categorized as shown in Table 1 (based on Levels of Evidence, Centre for Evidence Based Medicine, 2011).1–5 Two of these studies were excluded because of PEDro scores of less than 5/10.2,3
Best Evidence The following studies were identified as the “best” evidence and selected for inclusion in the CAT (Table 2). Reasons for selecting these studies were
• No concurrent treatments • Uniform treatment parameters • PEDro scores of at least 5/10
Implications for Practice, Education, and Future Research Two of the 3 studies demonstrated that DEX iontophoresis was not significantly more effective than a placebo.1,5 The third study demonstrated DEX was more effective than a placebo during a 2-day follow-up session but was not more effective 1 month later.4 This could have been influenced by the decision to allow participants the freedom to use other methods of treatment after the 2-day follow-up session. It could also have been influenced by the fact that all 3 studies used a placebo group in comparison with their DEX group. While placebo effects are still somewhat controversial in the medical fields, researchers have found that the simple awareness of being treated is potentially enough for an analgesic effect in some patients.6 Another factor that may have led to the results seen in the included studies could have been the type of conditions used to test DEX iontophoresis. The 3 included studies examined elbow epicondylitis,4 carpal tunnel syndrome, 1 and lateral epicondylalgia. 5 Of those conditions, only epicondylitis is commonly associated with inflammation, due to small tears that appear in muscle fibers over time.7 Carpal tunnel syndrome is by definition the entrapment of the median nerve. This condition can be caused by inflammation, but it also has many other possible causes including alcohol abuse, obesity, infections, fractures, cysts, tumors, or a congenitally small carpal tunnel.8 Since the authors did not report the cause of the carpal tunnel condition, it cannot be certain that that the condition was caused by inflammation. Lateral epicodylalgia is a musculoskeletal disorder characterized by pain and mechanical hyperalgesia at the lateral epicondyle. While inflammation may be present along with the condition, it is not a diagnostic criterion. An understanding of the cause of the condition to be treated is important to achieve positive patient outcomes with DEX iontophoresis. Conditions that are not inflammatory in nature do not result in positive patient
JSR Vol. 24, No. 3, 2015
JSR Vol. 24, No. 3, 2015
329
Subjects were eligible if they were between 18 and 75 y of age and had clinical signs leading to a diagnosis of medial or lateral humeral epicondylitis, if they had a duration of symptoms of 3 mo or less during the most recent episode before the screening evaluation, and if the investigator’s global evaluation of the severity of epicondylitis at screening and at the baseline evaluation was rated moderate or greater intensity.
Subjects were eligible if they presented with mild to moderately severe median nerve compression at the wrist that was confirmed by electrophysiological studies.
At least 85% of subjects were available for follow-up.
Groups were comparable at baseline
Subjects were eligible if they had pain with at least 2 tests (middle finger test, resisted wrist extension, hand grip test) and a history of pain of at least 1 mo.
Patients were randomized using sequentially numbered, opaque-sealed envelopes.
65 patients initially recruited. 1 patient dropped out—64 patients used for study (placebo group 45 y, experimental group 50 y).
Randomized controlled trial
Runeson and Haker5
At least 85% of subjects were available for follow-up.
Groups were comparable at baseline. (continued)
Subjects were excluded if they had any treatment during the last month for elbow Subjects were excluded if they had recurrent injury of the subject area, bilateral pain; had any demonstrated dysfunction of or multiple affected areas; had an injection of a steroid into the affected area shoulder, neck, and/or thoracic region; local within the past year, prior surgery to correct the problem; use of nonsteroidal or generalized arthritis, neurological deficit, anti-inflammatory medications, systemic and local corticosteroids, or analradial nerve entrapment, bilateral epicongesics within 3 d of study participation; involvement in a lawsuit or workers’ dylalgia, pregnancy, previous surgeries to compensation claim for any medical condition; or history of rheumatoid arthri- the elbow, or a pacemaker. tis, degenerative arthritis, polyarthritis, carpal tunnel syndrome, rotator-cuff Groups were comparable at baseline. tendinitis, neurologic abnormalities in the affected area, muscular dysfunction, 64.1% of subjects were available for 3-mo peripheral neuropathy, radial nerve entrapment, or fracture or tumor of the follow-up affected area.
Patients were randomized according to a computer-generated randomization schedule, and randomization was stratified according to initial disease severity so that equal numbers of patients with a disease severity of “very severe” at baseline would receive each treatment.
Patients were randomized according to a random-number-generator function of a commercially available software program.
Subjects were excluded if they had thenar atrophy, previous carpal tunnel decompression surgery, previous corticosteroid injection to the carpal tunnel, other neurological disorders contributing to symptoms, or a history of trauma to wrist or arm.
199 patients from 11 centers across the USA (experimental group 49.9 ± 10.3 y, placebo group 50.9 ± 9.6 y).
17 patients from a university teaching hospital (36–73 y, mean = 54 ± 10).
Randomized controlled trial
Randomized controlled trial
Participants
Nirschl et al4
Study design
Amirjani et al1
Table 2 Characteristics of Included Studies
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
330
JSR Vol. 24, No. 3, 2015
2
PEDro 10/10
Both groups had significant reduction in severity of symptoms throughout the trial but neither differed from the other. Nerve conduction did not change significantly throughout the study.
Level of evidence
Validity score
Conclusion
Semmes-Weinstein: no significant improvement in either group.
PEDro 7/10 There was no statistical difference between the placebo and iontophoresis groups throughout the study.
The results of a 2-d follow-up after the last treatment showed that patients who were treated with dexamethasone significantly improved their pain and global function compared with control group. These results were not applicable to a 1-mo follow-up.
2
Patients in both groups reported improvement throughout the study but not statistically significant.
No statistical significance between the 4 outcomes after treatment and at the followups.
PEDro 8/10
2
No significant difference in measures between groups at 1-mo follow-up.
Nerve-conduction studies: No significant Dexamethasone group significantly improved in investigator’s assessment of improvement in either group over course symptoms (P = .019) and investigator tenderness evaluation (P = .001) comof the study. pared with placebo during 2-d follow-up.
Levine Self-Assessment Questionnaire: no significant differences between groups at any time frame.
Dexamethasone group significantly improved in investigator’s global improvement (P = .013) and patient pain evaluation (P = .012) compared with placebo during 2-d follow-up.
Blinding of therapists, assessors, and subjects.
Treatments given at Mon/Wed/Fri/Mon or Wed/Fri/Mon/Wed schedule.
4 treatments were given over a 2-wk period.
Iontophoresis treatments were provided with the following parameters: 40 mA-min, 0.4% dexamethasone solution.
Main findings
investigator’s tenderness evaluation, and investigator’s assessment of disease severity.
Subjects could not begin concurrent treatments during their evaluative period.
Blinding of therapists, assessors, and subjects.
Treatments were spaced 1–3 d apart.
6 treatments given within 15 d.
Iontophoresis treatments were provided with the following parameters: 40 mA-min, 0.4% dexamethasone solution.
Runeson and Haker5
Primary Outcomes: Evaluation of global improvement by patient, evaluation of Primary Outcomes: Palpation at lateral epiglobal improvement by investigators, patient pain evaluations after treatment. condyle, resisted wrist extension, middlefinger test, handgrip strength. Secondary Outcomes: Evaluations of symptoms by patient and investigators,
Blinding of therapists, assessors, and subjects.
Treatments were given on alternate days.
6 treatments were given over a 2-wk period.
Iontophoresis treatments were provided with the following parameters: 80 mA-min, 0.4% dexamethasone solution.
Nirschl et al4
Outcome measures Primary Outcomes: Levine Self-assessment Questionnaire, nerve-conduction studies, Semmes-Weinstein monofilaments.
Intervention investigated
Amirjani et al1
Table 2 (continued)
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
Downloaded by Boston University on 09/17/16, Volume 24, Article Number 3
Dexamethasone Iontophoresis 331
outcomes when treated with DEX iontophoresis, according to our review. Skin permeability may also influence the effectiveness of DEX iontophoresis.9 As a person ages, the stratum corneum decreases its permeability by drying, decreasing the microvascular blood supply in the epidermis, and becoming more resistant to hydrophilic compounds such as DEX. This decrease in permeability of the stratum corneum could limit the overall effectiveness of the drug. Of the 3 studies included in this review the mean age of the participants in years was 54 ± 10,1 45 to 50 median years,5 and 49.9 ± 10.3/50.9 ± 9.6.4 The most probable reason for this propensity to study older populations when dealing with these musculoskeletal conditions is their increased prevalence in an aging population compared with a younger population. However, this apparent research bias toward older population models could cause difficulties in adapting clinical protocols for younger patients with similar conditions.10 While we acknowledge the small samples sizes may be resulting in underpowered analyses, without all the necessary data in the published studies, a power analysis was not possible. The possibility of a type II error is a limitation, but without a power analysis it is only speculation. This lack of pertinent data highlights the paucity of high-quality published research results in this area. This manuscript is a preliminary review of the current literature and should be followed periodically with additional updates as more research becomes available. Future general research in this area would be needed to definitively determine if DEX iontophoresis, alone, is a viable modality for the treatment of musculoskeletal conditions. Research in this field should focus more specifically on inflammatory conditions as opposed to general musculoskeletal conditions. Another important aspect of future research would be the elimination of concurrent treatments, which may limit the ability of researchers and clinicians to determine a true efficacy of the modality. However, this may be difficult since the treatment norm for these conditions revolves around multiple treatment types. Future research should also compare younger populations with older populations to determine if differences in outcome variables exist. This CAT should be reviewed in 2 years to determine whether best evidence has been published that may change the clinical bottom line for this specific clinical question.
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JSR Vol. 24, No. 3, 2015
