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Therapeutic ultrasound for carpal tunnel syndrome

  1. Matthew J Page1,*,
  2. Denise O'Connor1,
  3. Veronica Pitt2,
  4. Nicola Massy-Westropp3

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 27 NOV 2012

DOI: 10.1002/14651858.CD009601.pub2

How to Cite

Page MJ, O'Connor D, Pitt V, Massy-Westropp N. Therapeutic ultrasound for carpal tunnel syndrome. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD009601. DOI: 10.1002/14651858.CD009601.pub2.

Author Information

  1. 1

    Monash University, School of Public Health & Preventive Medicine, Melbourne, Victoria, Australia

  2. 2

    National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia

  3. 3

    University of South Australia, Health Sciences, Adelaide, South Australia, Australia

*Matthew J Page, School of Public Health & Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Road, Melbourne, Victoria, 3004, Australia. matthew.page@monash.edu.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 MAR 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

 
Summary of findings for the main comparison. Therapeutic ultrasound compared with placebo for carpal tunnel syndrome (CTS)

Therapeutic ultrasound compared with placebo for carpal tunnel syndrome

Patient or population: patients with CTS
Settings: outpatient clinic of university department of physical medicine and rehabilitation, Vienna, Austria
Intervention: therapeutic ultrasound
Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboTherapeutic ultrasound

Short-term overall improvement (three months or less)Study populationRR 2.36
(1.4 to 3.98)
68
(1 study)
⊕⊕⊝⊝
low2,3

324 per 10001765 per 1000
(454 to 1000)

Adverse effectsSee commentSee commentNot estimable68
(1 study)
⊕⊕⊝⊝
low2,3
No adverse effects were reported in the intervention or control groups

Short-term improvement in pain and/or paraesthesia (after seven weeks of treatment)

Scale from: zero to 10
The mean improvement in pain and/or paraesthesia (after seven weeks of treatment) in the control groups was
2.68
The mean improvement in pain and/or paraesthesia (after seven weeks of treatment) in the intervention groups was
0.99 lower
(1.77 to 0.21 lower)
68
(1 study)
⊕⊕⊝⊝
low2,3

Short-term improvement in hand grip strength (change from baseline to seven weeks)The mean improvement in hand grip strength (change from baseline to seven weeks) in the control groups was
-0.09 kilograms
The mean improvement in hand grip strength (change from baseline to seven weeks) in the intervention groups was
3.96 higher
(1.31 to 6.61 higher)
90
(1 study)
⊕⊕⊝⊝
low2,3

Long-term improvement in CTS symptoms (number of participants with complete remission of subjective symptoms) (six months follow-up)Study populationRR 3.67
(1.74 to 7.74)
60
(1 study)
⊕⊕⊝⊝
low2,3

200 per 10001734 per 1000
(348 to 1000)

Long-term improvement in pain and/or paraesthesia (six months follow-up)

Scale from: zero to 10
The mean improvement in pain and/or paraesthesia (six months follow-up) in the control group was 2.92The mean improvement in pain and/or paraesthesia (six months follow-up) in the intervention groups was
1.86 lower
(2.67 to 1.05 lower)
60
(1 study)
⊕⊕⊝⊝
low2,3

Long-term improvement in hand grip strength (six months follow-up)The mean improvement in hand grip strength (six months follow-up) in the control groups was 18.1 kilogramsThe mean improvement in hand grip strength (six months follow-up) in the intervention groups was
4.16 higher
(0.88 lower to 9.2 higher)
60
(1 study)
⊕⊕⊝⊝
low2,3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Assumed risk is based on the risk in the control group in the one study comparing therapeutic ultrasound to placebo (Ebenbichler 1998).
2 Unit of analysis error committed.
3 Reasons for loss-to-follow-up not reported; not clear if participants were inappropriately excluded from the analyses.

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
 

Description of the condition

Carpal tunnel syndrome (CTS) is a neuromuscular condition in which the median nerve at the level of the wrist undergoes irritation which is often attributed to increased pressure within the carpal tunnel (Keith 2009; Kerwin 1996). The most commonly reported symptoms of CTS include pain in the wrist and hand which can radiate to the arm (Rempel 1998) and paraesthesiae (numbness) in the thumb, index, middle and radial half of the ring finger (Szabo 1994). In advanced stages of the condition, thenar muscle weakness can occur (Szabo 1994).

Results of a Swedish study suggest that the prevalence of CTS in the general population is 3.8% for clinically diagnosed cases and 2.7% for electrophysiologically confirmed cases (Atroshi 1999). Recent evidence indicates that between 1981 to1985 the adjusted annual incidence of CTS was 258 per 100,000 person-years, compared with 424 per 100,000 person-years between 2000 to 2005 in Minnesota, USA, though it is not clear whether this apparent increase in incidence is due to increased diagnostic practice and awareness of CTS (Gelfman 2009). Age and gender are associated with the incidence of CTS. People aged less than 25 years accounted for only 2.4% of patients presenting to Australian general practices between 2000 and 2009 with the condition, compared with people aged 45 to 64 years who accounted for 45.5% of these cases (Charles 2009). As for gender, 67% of CTS encounters at Australian general practices were attributable to females (Charles 2009). Females in their fourth and fifth decades have been found to suffer CTS four times more commonly than males (Atroshi 1999). An association between obesity and an increased incidence of CTS has also been identified (Atroshi 1999; Bland 2005; Stallings 1997; Werner 1994).

 

Description of the intervention

CTS can be treated using surgery or non-surgical interventions, or a combination of both (for example carpal tunnel release followed by rehabilitation exercises). Surgical treatment is usually offered to individuals who have persistent CTS symptoms, severe sensory disturbance or thenar motor weakness. By contrast, non-surgical treatments are offered to those who experience intermittent symptoms of mild to moderate CTS, and sometimes temporarily to those awaiting carpal tunnel release. Surgical treatment options for patients with CTS have been examined in other Cochrane reviews: surgical treatment options for CTS (Scholten 2007), and the effect of surgical versus non-surgical treatment (Verdugo 2008).

Many different non-surgical options for the treatment of CTS exist, such as therapeutic ultrasound, splinting, exercises or mobilisation, ergonomic modification (equipment or positioning), oral medication, vitamins and complementary therapies. Therapeutic ultrasound is a physical therapy which involves application of a round-headed instrument to the skin of the painful area to deliver sound waves that are absorbed by the underlying connective tissue, such as ligaments and tendons (Watson 2008) The intervention can vary in its intensity and frequency of sound waves, and the duration of treatment can range from a few days to months. Ultrasound can be administered by a range of trained health professionals (for example physiotherapists and chiropractors). Therapeutic ultrasound is also used to treat a number of musculoskeletal conditions, such as osteoarthritis (Rutjes 2010) and acute ankle sprain (Van den Bekerom 2011)

 

How the intervention might work

Early experimental studies suggest that therapeutic ultrasound can have an anti-inflammatory and tissue stimulating effect, by enhancing blood flow, increasing membrane permeability, and altering connective tissue extensibility and nerve conduction, due to its thermal effect (Binder 1985; Hong 1988; Lehmann 1974). However, Yildiz 2011 highlights other research which suggests that ultrasound does not have an anti-inflammatory effect but rather accelerates the process of formation and resolution of pressure in the carpal tunnel canal (Young 2002). Despite these alternative theories, therapeutic ultrasound has not always been associated with a beneficial effect in clinical settings, so the underlying mechanism of action remains unclear.

 

Why it is important to do this review

Following the publication of the original version of this review (Page 2012a), which was based on searches conducted up to February 2011, the evidence base for all non-surgical interventions for CTS has grown. Given the personal and financial impact of CTS, there is a need to synthesise the most up-to-date evidence on the efficacy of therapeutic ultrasound for the treatment of CTS.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

The objective of this review was to compare the efficacy of therapeutic ultrasound for carpal tunnel syndrome (CTS) with no treatment, placebo or another non-surgical treatment for improving clinical outcome.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

All published and unpublished studies using or attempting to use a randomised methodology were eligible for inclusion. We included studies comparing therapeutic ultrasound with no treatment, placebo, or other non-surgical treatments . We excluded studies comparing therapeutic ultrasound to surgical treatment, as these studies are the focus of another Cochrane systematic review (Verdugo 2008). There were no language restrictions for the inclusion of studies.

 

Types of participants

All participants with a diagnosis of CTS, as defined by the authors of each study. Participants who had previous surgery for CTS were excluded.

 

Types of interventions

All therapeutic ultrasound interventions (that is of any frequency, intensity, and duration). Comparison interventions included no treatment, placebo, or other non-surgical interventions; surgical interventions were excluded as comparisons. Trials where therapeutic ultrasound was used as an adjunct to another treatment were included only if the comparison provided information on the additional effect of the therapeutic ultrasound intervention.

 

Types of outcome measures

We modified the outcomes reported in this review from the original review (O'Connor 2003) to be consistent with other Cochrane reviews on carpal tunnel syndrome (Marshall 2007; Scholten 2007; Verdugo 2008).

 

Primary outcomes

  1. Short-term overall improvement (any measure in which patients indicate the intensity of their complaints compared with baseline, for example global rating of improvement, satisfaction with treatment) (dichotomous outcome; three months or less)

 

Secondary outcomes

  1. Adverse effects
  2. Short-term improvement in CTS symptoms (for example, pain, paraesthesia, nocturnal paraesthesia) (three months or less).
  3. Short-term improvement in functional ability or health-related quality of life (three months or less).
  4. Short-term improvement in neurophysiologic parameters (three months or less).
  5. Long-term improvement in CTS symptoms (greater than three months).
  6. Long-term improvement in functional ability or health-related quality of life (greater than three months).

 

Search methods for identification of studies

 

Electronic searches

On 27 November, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012 , Issue 11 in The Cochrane Library), MEDLINE (January 1966 to November 2012), EMBASE (January 1980 to November 2012), CINAHL Plus (January 1937 to November 2012), and AMED (January 1985 to November 2012).

The detailed search strategies are in the appendices: CENTRAL, Appendix 1, MEDLINE Appendix 2, EMBASE Appendix 3, CINAHL Plus Appendix 4 and AMED Appendix 5.

 

Searching other resources

We searched protocols of trials on the clinical trials register that is maintained by the US National Institute of Health at http://clinicaltrials.gov, and searched protocols of trials published after July 1st 2005 using the Clinical Trial Register at the International Clinical Trials Registry Platform of the World Health Organisation (http://www.who.int/ictrp/en/). We also reviewed the reference lists of randomised or quasi-randomised trials identified from the electronic searches.

 

Data collection and analysis

The review authors followed the recommended strategies for data collection and analysis as documented in Chapter 7 and 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a).

 

Selection of studies

At least two review authors independently selected trials for possible inclusion against a predetermined checklist of inclusion criteria (see Criteria for considering studies for this review). We screened titles and abstracts and initially categorised studies into the following groups.

  • Possibly relevant - studies that met the inclusion criteria and studies from which it was not possible to determine whether they met the criteria either from their title or abstract.
  • Excluded - those clearly not meeting the inclusion criteria.

If a title, or abstract, appeared to meet the eligibility criteria for inclusion of the review, or we could not tell, we obtained a full text version of the article and two review authors independently assessed it in order to determine whether it met the inclusion criteria. The review authors resolved discrepancies through discussion.

 

Data extraction and management

Two authors independently extracted data using a standard data extraction form developed for this review. The authors resolved any discrepancies through discussion until consensus was reached. We pilot tested the data extraction form and modified it accordingly before use. In addition to items for assessing risk of bias and study results, we also recorded the following study characteristics:

  • participant details, including demographic data and inclusion/exclusion criteria;
  • types of interventions used in the intervention and comparison groups;
  • outcomes reported, including the tools and timing for outcome measures.

One author compiled all comparisons and entered outcome data into Review Manager 5.1. At least one author cross-checked data. For trials where the required data were not reported, one author requested further information. When unsuccessful, we included the study in the review and fully described it, but did not include it in any meta-analysis. An entry of this process was made in the notes section of the Characteristics of included studies tables.

 

Assessment of risk of bias in included studies

Two review authors independently assessed the risk of bias in included studies using The Cochrane Collaboration's tool for assessing risk of bias, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). The following items were assessed for risk of bias based on information extracted from reports of the included studies:

  • random sequence generation;
  • allocation concealment;
  • blinding of participants and personnel;
  • blinding of outcome assessment;
  • incomplete outcome data (defined separately for data measured at 12 weeks or less, and after 12 weeks);
  • selective reporting;
  • other sources of bias (for example inappropriate unit of analysis).

Each item was rated as being at 'Low risk', 'Unclear risk' or 'High risk' of bias. We resolved any discrepancies through discussion.

 

Measures of treatment effect

We used the Cochrane statistical software Review Manager 5.1 to perform data analysis. We expressed results as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and (unstandardised) mean differences (MD) with 95% CI for continuous outcomes if the same measurement tool was used to measure the same outcome across separate studies. Alternatively, we summarised continuous outcomes using the standardised mean difference (SMD) when studies measured the same outcome but employed different measurement tools.

 

Unit of analysis issues

We sought information about the unit of randomisation used (that is, wrists or participants) where participants with bilateral CTS receive the same intervention for both wrists). In studies that randomised wrists, we sought information about whether wrists of each participant were allocated to different treatments, or whether there was no constraint that the two wrists be allocated to different treatments. Given that results for different wrists in participants with bilateral CTS are unlikely to be independent, we assessed how the investigators of studies which included participants with bilateral CTS took account of this dependence in their analyses (for example, use of paired or matched analyses, generalised estimating equations). If this information was not reported, we contacted trialists for clarification. We also requested individual wrist outcome data from trialists to re-analyse the data. If we were unable to obtain individual wrist outcome data, we had planned to estimate parameters (such as an intra-class correlation coefficient) from studies that reported sufficient information to calculate this, and to use these estimates to adjust the results in other studies, following the advice provided in sections 16.3 and 16.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c). If unable to adjust the outcome data, we included the data as reported by the trialists, and commented on the validity of such analyses.

 

Dealing with missing data

We sought relevant missing information from the authors of included studies about study design, outcome data, or attrition rates such as drop-outs, losses to follow-up and withdrawn study participants, where possible.

 

Assessment of heterogeneity

We assessed clinical heterogeneity by determining whether the characteristics of participants, interventions, outcome measures and timing of outcome measurement were similar across studies. We assessed statistical heterogeneity using the Chi2 statistic and the I2 test (Higgins 2002). We interpreted the I2 statistic using the following as an approximate guide:

  • 0% to 40% might not be important heterogeneity;
  • 30% to 60% may represent moderate heterogeneity;
  • 50% to 90% may represent substantial heterogeneity;
  • 75% to 100% may represent considerable heterogeneity (Deeks 2011).

 

Assessment of reporting biases

To assess publication bias, we would have generated funnel plots if at least 10 studies examining the same treatment comparison were included in the review (Sterne 2011). To assess outcome reporting bias, we planned to compare the outcomes specified in trial protocols with the outcomes reported in the corresponding study publications; if trial protocols were unavailable, we compared the outcomes reported in the methods and results sections of the study publications (Dwan 2011).

 

Data synthesis

We pooled results of studies with similar characteristics (participants, interventions, outcome measures and timing of outcome measurement) to provide estimates of the efficacy of therapeutic ultrasound for CTS. Where we could not combine data, we presented a narrative synthesis of results. We meta-analysed pooled results using either a fixed-effect or random-effects model (depending on the level of clinical and methodological heterogeneity). We set statistical significance at P < 0.05 for primary and secondary outcome measures.

 

Subgroup analysis and investigation of heterogeneity

We planned to conduct subgroup analyses according to severity of CTS symptoms and sex, since these factors may cause variations in outcomes. We defined subgroups as follows:

  • severity of CTS symptoms: early (E), intermediate (I) and advanced (A) symptoms (Szabo 1992);
  • sex: male, female.

 

Sensitivity analysis

We conducted sensitivity analyses for each item in the 'Risk of bias' table by excluding studies judged as 'High risk of bias'. We also conducted sensitivity analyses using the following filter.

  • Quality of diagnostic criteria: high (A), moderate (B) and low (C) quality (Rempel 1998).

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.

 

Results of the search

The search conducted up until 27 November 2012 identified a total of 221 records. Table 1 reports the number of hits retrieved by each search strategy. The number of records after removal of duplicates was 128. From these, we retrieved 26 full text papers for further examination. After screening the full text of the selected papers for eligibility, 11 studies (Bakhtiary 2004; Baysal 2006; Bilgici 2010; Dincer 2009; Duymaz 2012; Ebenbichler 1998; Ekim 2008; Koyuncu 1995; Oztas 1998; Piravej 2004; Yildiz 2011) fulfilled the inclusion criteria. The only new study included in this review update was Duymaz 2012. A flow diagram of the study selection process is presented in Figure 1. Searches of clinical trials registries resulted in the identification of one ongoing placebo-controlled RCT of therapeutic ultrasound (NCT01590745).

 FigureFigure 1. Study flow diagram.

Table 1


DatabasePeriod searchedDate searchedNumber of hits

Cochrane Neuromuscular Disease Group Specialized Registerto 27 November 201227 November 201220

CENTRALto Issue 11, 201227 November 201223

MEDLINEJanuary 1966 to November 201227 November 201255

EMBASEJanuary 1980 to November 201227 November 201270

CINAHL PlusJanuary 1937 to November 201227 November 201240

AMEDJanuary 1985 to November 201227 November 201213



 

Included studies

Eleven studies allocated adults with CTS to a therapeutic ultrasound regimen (delivered alone or with another non-surgical intervention) or to placebo ("sham" ultrasound) or another non-surgical intervention. A total of 414 participants with 664 CTS-affected wrists were included. The sex of participants was unclear in the studies by Bakhtiary 2004 and Ebenbichler 1998; in the remaining studies there were 287 females and 29 males included. The ultrasound interventions varied in intensity and frequency, and duration of treatment across the studies.

Bakhtiary 2004 compared the effects of 15 sessions performed once a day, five times a week for three weeks of pulsed ultrasound treatment administered for 15 minutes per session to the area over the carpal tunnel at a frequency of 1 MHz and an intensity of 1.0 W/cm2, compared with low-level laser therapy, on the outcomes pain, pinch strength, hand grip strength and neurophysiologic parameters in 50 participants with 90 CTS-affected wrists.

Baysal 2006 compared three different treatment groups in 36 participants with 72 affected wrists. One group received therapeutic ultrasound plus a neutral volar wrist splint worn at day and night. The second group received therapeutic ultrasound plus splint plus nerve and tendon gliding exercises. The third group received splint plus nerve and tendon gliding exercises. Treatment duration was for three weeks, and outcome measurements included symptoms, pain, Tinel and Phalen sign, two-point discrimination, hand function, grip strength, pinch strength, neurophysiologic parameters, and patient satisfaction. The ultrasound component was delivered pulsed at a frequency of 1 MHz and an intensity of 1.0 W/cm2, for 15 minutes once a day, five times a week, for three weeks.

In the study conducted by Bilgici 2010, 34 participants with 49 CTS-affected wrists were randomly allocated to receive either therapeutic ultrasound at a frequency of 3 MHz and intensity of 1.5 W/cm2 for five minutes, five times a week for four weeks, or to local corticosteroid injection plus neutral-positioned wrist splint worn as much as possible during the day and night for four weeks. Outcomes were symptoms, pain, hand function, grip strength, neurophysiologic parameters, and adverse effects.

In the study conducted by Dincer 2009, 60 female participants with bilateral CTS were randomly allocated to wearing a splint worn at night and during aggravating daytime activities for three months, or wearing a splint for three months and receiving continuous ultrasound at a frequency of 3 MHz and intensity of 1.0 W/cm2 for three minutes per session, with 10 sessions performed once a day, five times a week for two weeks, or wearing a splint for three months and receiving low-level laser therapy administered at 10 sessions performed once a day, five times a week for two weeks. Outcomes assessed were pain, symptoms, function, neurophysiologic parameters, and patient satisfaction.

Duymaz 2012 compared therapeutic ultrasound (for five minutes per session, once a day five times a week for three weeks; intensity was 0.8 W/cm2 and frequency was 1 MHz) to dexamethasone iontophoresis and to placebo iontophoresis in 58 participants with 58 CTS-affected wrists. All groups also received nerve and tendon gliding exercises plus a neutral wrist splint worn every night plus activity modification training. Outcomes assessed were symptoms, pain, Tinel's test, Phalen's test, Reverse Phalen's test, hand function, grip strength, pinch strength, and neurophysiologic parameters.

In the study conducted by Ebenbichler 1998, pulsed ultrasound therapy at 1.0 W/cm2 intensity and 1 MHz frequency was compared with placebo ("sham") ultrasound for seven weeks duration in 45 participants with 90 CTS-affected wrists. Outcomes assessed were CTS symptoms, sensation, grip strength, pinch strength, neurophysiologic parameters, medication use, adverse effects and return to work.

Ekim 2008 randomly allocated 28 participants with 28 CTS-affected wrists to either continuous ultrasound at 1.5 W/cm2 intensity and 3 MHz frequency plus splint worn at night, or placebo ultrasound at 0.0 W/cm2 intensity plus splint worn at night. Both the active and placebo ultrasound regimens were delivered for five minutes, five days a week for two weeks. Outcomes assessed were symptoms, pain, Tinel's test, Phalen's test, hand function, grip strength, and neurophysiologic parameters.

Koyuncu 1995 compared the delivery of circular ultrasound at two different frequencies (1 and 3 MHz), both at 1.0 W/cm2 intensity and delivered for eight minutes per session, five days per week, for four weeks in 16 participants with 21 CTS-affected wrists. Outcomes assessed were pain, paraesthesiae, superficial touch sensation, large and small object grasping, sensory and motor nerve transmission delay and Tinel and Phalen sign.

In the study conducted by Oztas 1998, the use of continuous ultrasound at different intensities (1.5, 0.8 and 0.0W/cm2), all at 3 MHz frequency for five minutes a day, five days a week for two weeks were compared in 18 females with 30 CTS-affected wrists. Outcomes assessed were pain, CTS symptoms, nocturnal wakening and neurophysiologic parameters.

In the study conducted by Piravej 2004, 18 participants with 30 CTS-affected wrists were randomly allocated to either continuous ultrasound therapy performed at an intensity of 0.5 W/cm2 and frequency of 1 MHz for 10 minutes per session, five days a week for four weeks, plus placebo drug taken each day, or to "sham" ultrasound plus diclofenac 75 mg/day (a nonsteroidal anti-inflammatory drug) taken in a divided dose each day for four weeks. Outcomes assessed were pain (measured using a visual analogue scale (VAS)), presence of nocturnal and/or diurnal pain and/or paraesthesia , frequency of awakening at night, and neurophysiologic parameters.

Yildiz 2011 investigated the effects of "sham" ultrasound for two weeks compared with ultrasound delivered at a frequency of 1 MHz and intensity of 1 W/cm2 for 15-minute sessions, once a day, five times a week for two weeks, or to ultrasound with 2.5% ketoprofen gel (a nonsteroidal anti-inflammatory drug) delivered at a frequency of 1 MHz and intensity of 1 W/cm2 for 15-minute sessions, once a day, five times a week for two weeks. The 51 participants (76 CTS-affected wrists) in all groups wore a splint at night and during the day for eight weeks, and the outcomes were pain, symptoms, function, adverse effects (complications) and neurophysiologic parameters.

The primary outcome, short-term overall improvement using any measure where patients indicate the intensity of their complaints compared with baseline (over three months or less) was measured in only two of the 11 studies (Dincer 2009; Ebenbichler 1998). Adverse effects were only measured in three studies (Bilgici 2010; Ebenbichler 1998; Yildiz 2011).

In nine studies (Bakhtiary 2004; Baysal 2006; Bilgici 2010; Dincer 2009; Ebenbichler 1998; Koyuncu 1995; Oztas 1998; Piravej 2004; Yildiz 2011) some or all participants had bilateral CTS, where both wrists contributed to the analysis. In three of these nine studies (Baysal 2006; Dincer 2009; Piravej 2004), randomisation occurred at the level of participants, where the same intervention was delivered to both wrists in participants with bilateral CTS. In two studies (Bakhtiary 2004; Ebenbichler 1998), randomisation of wrists occurred, where all participants with bilateral CTS received a different intervention to each wrist. In two studies (Oztas 1998; Yildiz 2011), randomisation of wrists occurred, where there was no constraint that participants' wrists be allocated to the same or different treatments. It was unclear in Bilgici 2010 or Koyuncu 1995 whether participants with bilateral CTS received the same or different interventions to each wrist. All outcomes of interest to the review were analysed at the wrist level in these nine studies. In seven of these studies (Baysal 2006; Bilgici 2010; Dincer 2009; Koyuncu 1995; Oztas 1998; Piravej 2004; Yildiz 2011), the trialists did not report how the analysis accounted for correlation between wrists in bilateral CTS and attempts to obtain this information from the trialists were unsuccessful (so it is not clear whether a unit of analysis error occurred in these studies). However, personal communication with Bakhtiary 2004 and Ebenbichler 1998 confirmed that the correlation between wrists was not accounted for in the analysis (therefore a unit of analysis error occurred in these studies).

 

Excluded studies

We excluded a total of 15 studies after review of the full text publication. Reasons for exclusion of studies are provided in the Characteristics of excluded studies table. The main reasons for exclusion were that a non-randomised study design had been employed and that therapeutic ultrasound plus another intervention was compared to a different intervention for CTS (so the additional effect of ultrasound could not be determined).

 

Risk of bias in included studies

Full details of our assessment of risk of bias in included studies are available in the 'Risk of bias' tables, and a summary is presented in Figure 2. In cases where risk of bias was rated as 'Unclear risk of bias', attempts to contact the trial authors for further information were made, and unless otherwise specified, these were unsuccessful.

 FigureFigure 2. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

 

Allocation

Generation of the randomisation sequence was judged to have been adequate and at 'Low risk of bias' in six studies (Bakhtiary 2004; Baysal 2006; Duymaz 2012; Ebenbichler 1998; Piravej 2004; Yildiz 2011), as all used computer-generated randomisation sequences; in the remaining studies (Bilgici 2010; Dincer 2009; Ekim 2008; Koyuncu 1995; Oztas 1998), the method used to generate this sequence was unclear. Only two studies were judged to be at low risk of bias for the domain allocation concealment (Bilgici 2010; Ebenbichler 1998), as these studies reported using sealed, opaque, sequentially numbered envelopes to conceal the allocation sequence. The remaining nine studies were rated as being at 'Unclear risk of bias' on this domain, as they either did not report any method for concealing the allocation sequence (Ekim 2008; Koyuncu 1995; Oztas 1998; Piravej 2004), or reported only some components of an effective method (for example they reported that sealed, sequentially numbered envelopes were used, but did not report whether these were opaque) (Bakhtiary 2004; Baysal 2006; Dincer 2009; Duymaz 2012; Yildiz 2011).

 

Blinding

Participants in six studies were reported as being blinded to the intervention they received (Ebenbichler 1998; Ekim 2008; Koyuncu 1995; Oztas 1998; Piravej 2004; Yildiz 2011). Blinding in these studies was possible because they involved either a "sham" ultrasound regimen (Ebenbichler 1998; Ekim 2008; Oztas 1998; Piravej 2004; Yildiz 2011) or two different types of ultrasound that could not be differentiated by the participants (Koyuncu 1995; Oztas 1998). These studies were therefore rated at 'Low risk' of performance bias. Because of the nature of the interventions delivered in the studies conducted by Baysal 2006, Bilgici 2010, Dincer 2009, and Duymaz 2012, patients were not blinded in these studies. The study conducted by Bakhtiary 2004 was rated as being at 'Unclear risk of bias' for this performance bias domain. Three studies (Duymaz 2012; Ekim 2008; Oztas 1998) reported that blinding of assessors of all subjective and some objective outcomes was not done, while in Bilgici 2010 and Koyuncu 1995 it was unclear whether outcome assessors were blinded; all remaining studies were rated at low risk of detection bias.

 

Incomplete outcome data

Nine studies were judged as being at low risk of bias for completeness of outcome data at three months or less (Bakhtiary 2004; Baysal 2006; Bilgici 2010; Dincer 2009; Duymaz 2012; Ekim 2008; Koyuncu 1995; Piravej 2004; Yildiz 2011). Two studies were rated as 'Unclear risk of bias' for this domain (Ebenbichler 1998; Oztas 1998). Only two studies could be assessed for completeness of outcome data collected three months or more after treatment ended, with one study rated as 'High risk of bias' (Baysal 2006) and the other rated as 'Unclear risk of bias' (Ebenbichler 1998).

 

Selective reporting

Five studies were judged as being at 'Low risk of bias' for selective outcome reporting (Bakhtiary 2004; Baysal 2006; Bilgici 2010; Ekim 2008; Yildiz 2011). Judgements were based on comparing outcomes specified in the methods section with those reported in the results section of the publication, and the finding that the majority of effect estimates for the reported outcomes in these studies were not statistically significant. Two studies were rated as being at 'Unclear risk of bias' (Oztas 1998; Piravej 2004) because they did not report on function as an outcome (whereas all other included studies did), and a protocol for these studies was not available to confirm that this outcome was not measured. Four studies were rated as being at 'High risk' of reporting bias (Dincer 2009; Duymaz 2012; Ebenbichler 1998; Koyuncu 1995). Dincer 2009 introduced a new outcome in the results section which was not pre-specified in the methods section of the publication. The authors reported the "number of completely normal hands based on electroneuromyography at three months", but did describe this outcome or define "completely normal" in the methods section. Duymaz 2012 fully reported means and standard deviations for some outcomes, but partially reported (that is, only specified whether differences between groups were statistically significant or not) or did not report any data at all for other outcomes. In the study conducted by Ebenbichler 1998, it was reported that nerve conduction studies assessing median motor nerve conduction and sensory nerve action potentials were conducted but results were not reported. The same study reported that three participants were off work; however, work status was not stated as an outcome measure in the methods section of the publication. The study conducted by Koyuncu 1995 was rated as being at a 'High risk' of reporting bias because outcomes were assessed every week throughout the four-week treatment period but only results at baseline and at the end of treatment were reported. Further, results for motor nerve distal transmission delay and sensory nerve transmission delay were only partially reported as median endpoint values and mean change scores (without measures of variation). No protocols or trial registry entries for any of the included studies were identified, which limits our assessment of selective reporting.

 

Other potential sources of bias

All studies were judged to be at low risk of other potential sources of bias.

 

Effects of interventions

See:  Summary of findings for the main comparison Therapeutic ultrasound compared with placebo for carpal tunnel syndrome (CTS)

 

Therapeutic ultrasound versus placebo

Two trials compared a regimen of therapeutic ultrasound with placebo ("sham" ultrasound) (Ebenbichler 1998 and Oztas 1998). Ebenbichler 1998 compared pulsed ultrasound therapy (1.0 W/cm2 intensity and 1 MHz frequency) with placebo ultrasound (0.0 W/cm2 intensity) for a duration of seven weeks, while Oztas 1998 compared different intensities of continuous ultrasound: 1.5 W/cm2 versus 0.8 W/cm2 versus 0.0 W/cm2 (placebo), all at 3 MHz frequency, for a duration of two weeks. In Ebenbichler 1998, the correlation between wrists in participants with bilateral CTS was not accounted for in the analysis. Whether this correlation was accounted for in the analysis in Oztas 1998 is unclear. Therefore, all outcome data reported in these two studies may be invalid due to a unit of analysis error. Attempts to retrieve individual wrist outcome data from the trialists were unsuccessful. Without access to the individual wrist data, and without being able to estimate parameters such as the intraclass correlation coefficient from other studies included in the review, we did not attempt to adjust the results of these two studies. We have included the outcome data as reported by the trialists, but emphasise that results of these studies should be interpreted with caution, as the lack of adjustment may have produced overly narrow 95% CIs with artificially smaller P values (Higgins 2011c). Both Ebenbichler 1998 and Oztas 1998 assessed some of the same outcomes, but owing to the potential unit of analysis errors, we did not pooldata.

 

Primary outcomes

 
1) Short-term overall improvement (three months or less)

Reported as an outcome in Ebenbichler 1998 but not Oztas 1998.

In the study conducted by Ebenbichler 1998, participants were dichotomised into those who rated improvement in their wrists as 'good to excellent overall improvement' and those who did not. By the end of seven weeks of treatment, the chance of rating 'good to excellent overall improvement' was 136% higher for wrists receiving ultrasound compared with wrists receiving placebo (RR 2.36; 95% CI 1.40 to 3.98). However this outcome should be interpreted with caution, as 11 participants were not included in the analysis of outcomes measured at seven weeks because of non-compliance in keeping appointments (eight participants) and excessive pain requiring additional therapeutic measures (three participants). While these losses were balanced evenly across groups, it is unclear whether it was still possible to assess and include some, or all, of the outcome data for these individuals or whether they had been inappropriately excluded from the analysis; therefore, the direction of potential bias is unclear.

 

Secondary outcomes

 
1) Adverse effects

Reported as an outcome in Ebenbichler 1998 but not Oztas 1998.

No side effects due to ultrasound treatment were reported by participants (Ebenbichler 1998).

 
2) Short-term improvement in CTS symptoms (three months or less)

Reported as an outcome in Ebenbichler 1998 and Oztas 1998.

Ebenbichler 1998 found that wrists receiving ultrasound had pain or paraesthesia that was 0.33 points lower on an 11-point scale after two weeks (MD -0.33; 95% CI -1.31 to 0.65) and 0.99 points lower at the end of seven weeks of treatment (endpoint MD -0.99; 95% CI -1.77 to -0.21) than wrists receiving placebo. Further, using a five-point scale measuring subjective pain or paraesthesia, the authors dichotomised wrists into those that experienced 'satisfactory improvement or complete remission of symptoms' and those that did not, and found that therapeutic ultrasound increased the likelihood of reporting complete remission of symptoms by 77% (RR 1.77; 95% CI 1.09 to 2.88). Ebenbichler 1998 also found the mean change from baseline to two weeks in sensory loss was larger for the therapeutic ultrasound group compared with placebo (MD -1.24; 95% CI -2.36 to -0.12). The difference between groups in mean change from baseline to seven weeks for this outcome was also larger for the therapeutic ultrasound group, but the low precision of the effect estimate suggests a positive effect of placebo is also possible (MD -1.07; 95% CI -2.23 to 0.09).

After two weeks and five days of treatment, Oztas 1998 found that the VAS pain score (scale 0 to 10, with lower scores denoting less pain) was 1.10 points lower in wrists receiving ultrasound 1.5 W/cm2 intensity compared with placebo (MD -1.10; 95% CI -2.92 to 0.72), and was 0.40 points lower in wrists receiving ultrasound 0.8 W/cm2 intensity compared with placebo (MD -0.40; 95% CI -2.30 to 1.50). VAS pain or paraesthesia was no different between wrists receiving ultrasound 1.5 W/cm2 intensity compared with placebo (MD 0.00; 95% CI -0.68 to 0.68) and 0.30 points higher in wrists receiving ultrasound 0.8 W/cm2 intensity compared with placebo (MD 0.30; 95% CI -0.49 to 1.09). Further, there was no difference in frequency of nocturnal awakening at this time point between wrists receiving ultrasound 1.5 W/cm2 intensity and those receiving placebo (MD 0.00; 95% CI -0.92 to 0.92), and a small difference on this outcome between wrists receiving ultrasound 0.8 W/cm2 intensity and those receiving placebo (MD -0.40; 95% CI -1.36 to 0.56). None of the 95% CIs of these effect estimates rule out the possibility of negative effects of ultrasound on these outcomes.

 
3) Short-term improvement in functional ability or health-related quality of life (three months or less)

Reported as an outcome in Ebenbichler 1998 but not Oztas 1998.

Ebenbichler 1998 measured grip strength (kg) and pinch strength (kg) at two weeks and seven weeks post-treatment, and reported mean change from baseline. The authors reported improvement from baseline to two weeks for hand grip strength was 1.32 kg higher for wrists receiving therapeutic ultrasound (MD 1.32; 95% CI -1.10 to 3.74); however, the 95% CI incorporates both positive and negative changes in hand grip strength compared with placebo. In contrast, the difference between wrists in improvement from baseline to seven weeks was greater, and favoured those receiving ultrasound (MD 3.96; 95% CI 1.31 to 6.61). The difference between groups in pinch strength at two weeks was 0.19 points higher for the ultrasound group (MD 0.19; 95% CI 0.05 to 0.33), and while the effect estimate at seven weeks indicates pinch strength was 0.27 points higher for the ultrasound group (MD 0.27; 95% CI -0.09 to 0.63), the 95% CI incorporates both increases and decreases in pinch strength compared with placebo.

 
4) Short-term improvement in neurophysiologic parameters (three months or less)

Reported as an outcome in Ebenbichler 1998 and Oztas 1998.

Ebenbichler 1998 found that therapeutic ultrasound resulted in a greater improvement in both motor distal latency at two weeks (MD -0.27; 95% CI -0.45 to -0.09) and at the end of seven weeks of treatment (MD -0.61; 95% CI -0.83 to -0.39), and in sensory nerve conduction velocity at two weeks (MD 5.34; 95% CI 5.06 to 5.62) and at the end of seven weeks of treatment (MD 8.24; 95% CI 7.96 to 8.52) compared with placebo.

After two weeks and five days of treatment, Oztas 1998 found median sensory distal latency was 0.15 ms slower in wrists receiving ultrasound with 1.5 W/cm2 intensity compared with wrists receiving placebo (MD 0.15; 95% CI -0.93 to 1.23) but 0.13 ms faster in wrists receiving ultrasound with 0.8 W/cm2 intensity when compared with wrists receiving placebo (MD -0.13; 95% CI -0.95 to 0.69); and motor distal latency was 0.64 ms slower in wrists receiving ultrasound with 1.5 W/cm2 intensity compared with wrists receiving placebo (MD 0.64; 95% CI -0.88 to 2.16) and 0.74 ms faster in wrists receiving ultrasound with 0.8 W/cm2 intensity when compared with wrists receiving placebo (MD 0.74; 95% CI -0.55 to 2.03). Further, antidromic sensory nerve conduction velocity was 2.10 m/s better for wrists receiving placebo when compared with wrists receiving ultrasound at 1.5 W/cm2 intensity (MD -2.10; 95% CI -11.87 to 7.67) and 6.4 m/s better for wrists receiving ultrasound with 0.8 W/cm2 intensity when compared with wrists receiving placebo (MD 6.40; 95% CI -4.05 to 16.85); and median motor forearm conduction velocity was 0.20 m/s better for wrists receiving placebo when compared with wrists receiving ultrasound at 1.5 W/cm2 intensity (MD -0.20; 95% CI -6.13 to 5.73), and 0.20 m/s better for wrists receiving ultrasound with 0.8 W/cm2 intensity when compared with wrists receiving placebo (MD 0.20; 95% CI -4.57 to 4.97). However, the 95%CIs for these effect estimates all incorporate effects that are positive or negative for ultrasound compared with placebo.

 
5) Long-term improvement in CTS symptoms (more than three months)

Reported as an outcome in Ebenbichler 1998 but not Oztas 1998.

Ebenbichler 1998 dichotomised wrists into those rated by participants as experiencing an 'overall unsatisfactory outcome' or not. Six months after the seven-week treatment period ended, ultrasound increased the likelihood of not experiencing an overall unsatisfactory outcome by 91% compared with placebo (RR 1.91; 95% CI 1.13 to 3.23). Also, wrists receiving ultrasound were reported as having pain or paraesthesia 1.86 points lower on an 11-point scale (MD -1.86; 95% CI -2.67 to -1.05) and sensory loss 1.18 points lower on an 11-point scale (MD -1.18; 95% CI -2.02 to -0.34) at this time point. Using a five-point scale on subjective pain and/or paraesthesia, wrists were dichotomised into those who experienced 'satisfactory improvement or complete remission of symptoms' or not, and more wrists in the therapeutic ultrasound group (73% compared with 20%) were reported as having experienced complete remission of symptoms at six months follow-up (RR 3.67; 95% CI 1.74 to 7.74).

 
6) Long-term improvement in functional ability or health-related quality of life (more than three months)

Reported as an outcome in Ebenbichler 1998 but not Oztas 1998.

Ebenbichler 1998 measured functional outcomes using grip strength (kg) and pinch strength (kg) at six months follow-up. Wrists receiving ultrasound had 4.16 kg better grip strength than wrists receiving placebo (MD 4.16; 95% CI -0.88 to 9.20) and 0.74 kg better pinch strength than the wrists receiving placebo (MD 0.74; 95% CI -0.17 to 1.65); however, both effect estimates have 95% CI that do not exclude the possibility of no difference between groups, or a negative effect of ultrasound.

 

Therapeutic ultrasound: different frequencies

One trial compared the efficacy of therapeutic ultrasound delivered at different frequencies (Koyuncu 1995). In this study, circular ultrasound delivered at frequency 1 MHz was compared with ultrasound delivered at frequency 3 MHz, over a duration of four weeks. It was unclear whether the correlation between wrists in participants with bilateral CTS was accounted for in the analysis. Therefore, all outcome data reported in this study may be invalid due to a unit of analysis error. Attempts to retrieve individual wrist outcome data from the trialists were unsuccessful. Without access to the individual wrist data, and without being able to estimate parameters such as the intraclass correlation coefficient from other studies included in the review, we did not attempt to adjust the results of this study. We have included the outcome data as reported by the trialists, but emphasise that results should be interpreted with caution, as the possible lack of adjustment may have produced overly narrow 95% CIs with artificially smaller P values (Higgins 2011c).

 

Primary outcomes

 
1) Short-term overall improvement (three months or less)

Not reported as an outcome.

 

Secondary outcomes

 
1) Adverse effects

Not reported as an outcome.

 
2) Short-term improvement in CTS symptoms (three months or less)

From baseline to the end of four weeks of treatment, Koyuncu 1995 found that when compared with ultrasound at 1 MHz frequency, ultrasound at 3 MHz frequency reduced the risk of pain by 37% (RR 0.63; 95% CI 0.26 to 1.52), paraesthesia by 63% (RR 0.37; 95% CI 0.09 to 1.42), superficial sensation by 45% (RR 0.55; 95% CI 0.06 to 5.18), and positive Tinel sign by 44% (RR 0.66; 95% CI 0.21 to 2.08). In contrast, ultrasound at 1 MHz frequency increased the risk of positive Phalen sign by 10% when compared with ultrasound at 3 MHz frequency (RR 1.10; 95% CI 0.37 to 3.27). For all these outcomes, the low precision of the 95% CIs means that positive and negative effects of both treatment regimens are possible.

 
3) Short-term improvement in functional ability or health-related quality of life (three months or less)

By the end of four weeks of treatment, the authors found that ultrasound at 1 MHz frequency increased the chances of having improvement in the grasping of large, and small, objects, both by 227% when compared with ultrasound at 3 MHz frequency (RR 3.27; 95% CI 0.15 to 72.23). However, the 95% CIs are very wide, making it difficult to make any firm conclusions about these outcomes.

 
4) Short-term improvement in neurophysiologic parameters (three months or less)

Koyuncu 1995 assesses motor nerve distal transmission delay and sensory nerve transmission delay, but only median values for these neurophysiologic endpoints were reported. Attempts to obtain summary data for inclusion in a meta-analysis (for example, means and SDs) from the authors were unsuccessful.

 
5) Long-term improvement in CTS symptoms (more than three months)

Not reported as an outcome.

 
6) Long-term improvement in functional ability or health-related quality of life (more than three months)

Not reported as an outcome.

 

Therapeutic ultrasound: different intensity

One trial compared regimens of therapeutic ultrasound delivered at different intensities (Oztas 1998). This study examined any differences between continuous ultrasound delivered at intensity 1.5 W/cm2, compared with intensity 0.8 W/cm2. It was unclear whether the correlation between wrists in participants with bilateral CTS was accounted for in the analysis. Therefore, all outcome data reported in this study may be invalid due to a unit of analysis error. Attempts to retrieve individual wrist outcome data from the trialists were unsuccessful. Without access to the individual wrist data, and without being able to estimate parameters such as the intraclass correlation coefficient from other studies included in the review, we did not attempt to adjust the results of this study. We have included the outcome data as reported by the trialists, but emphasise that results should be interpreted with caution, as the possible lack of adjustment may have produced overly narrow 95% CIs with artificially smaller P values (Higgins 2011c).

 

Primary outcomes

 
1) Short-term overall improvement (three months or less)

Not reported as an outcome.

 

Secondary outcomes

 
1) Adverse effects

Not reported as an outcome.

 
2) Short-term improvement in CTS symptoms (three months or less)

At the end of two weeks and five days of treatment, Oztas 1998 reported that pain intensity for wrists receiving ultrasound at 1.5 W/cm2 intensity was 0.70 points lower on an 11-point scale (MD -0.70; 95% CI -2.28 with 0.88), and night pain/paraesthesia was 0.30 points lower on an 11-point scale (MD -0.30; 95% CI -0.90 to 0.30) compared with wrists receiving ultrasound at 0.8 W/cm2 intensity. The group receiving ultrasound at 0.8 W/cm2 intensity awoke on average 0.40 fewer times at night per week than the group receiving ultrasound at 1.5 W/cm2 intensity (MD 0.40; 95% CI -0.41 to 1.21). However, none of the 95% CIs of these effect estimates exclude the possibility of effects in either direction for these two ultrasound intensities.

 
3) Short-term improvement in functional ability or health-related quality of life (three months or less)

Not reported as an outcome.

 
4) Short-term improvement in neurophysiologic parameters (three months or less)

After two weeks and five days of treatment, median motor distal latency was 0.10 ms faster for wrists receiving ultrasound at 1.5 W/cm2 intensity compared with wrists receiving ultrasound at 0.8 W/cm2 intensity (MD -0.10; 95% CI -1.61 to 1.41). In contrast, wrists receiving ultrasound at 0.8 W/cm2 intensity had 0.28 ms faster median sensory distal latency (MD 0.28; 95% CI -0.72 to 1.28), 0.40 m/s better median motor forearm conduction velocity (MD -0.40; 95% CI -5.90 to 5.10), and 8.50 m/s better sensory nerve conduction velocity (MD -8.50; 95% CI -18.91 to 1.91) compared with wrists receiving ultrasound at 1.5 W/cm2 intensity. It must be cautioned that the precision of these effect estimates is low and the 95% CIs incorporate changes in either direction for both of the ultrasound intensities.

 
5) Long-term improvement in CTS symptoms (more than three months)

Not reported as an outcome.

 
6) Long-term improvement in functional ability or health-related quality of life (more than three months)

Not reported as an outcome.

 

Therapeutic ultrasound (single intervention) versus other non-surgical intervention

Two trials compared therapeutic ultrasound delivered as a single intervention versus another non-surgical intervention. One trial compared therapeutic ultrasound with low-level laser therapy delivered for three weeks (Bakhtiary 2004), while Bilgici 2010 compared therapeutic ultrasound with local corticosteroid injection plus splint for four weeks. In Bakhtiary 2004, the correlation between wrists in participants with bilateral CTS was not accounted for in the analysis. Whether this correlation was accounted for in the analysis in Bilgici 2010 is unclear. Therefore, all outcome data reported in these two studies may be invalid due to a unit of analysis error. Attempts to retrieve individual wrist outcome data from the trialists were unsuccessful. Without access to the individual wrist data, and without being able to estimate parameters such as the intraclass correlation coefficient from other studies included in the review, we did not attempt to adjust the results of these two studies. We have included the outcome data as reported by the trialists, but emphasise that results of these studies should be interpreted with caution, as the lack of adjustment may have produced overly narrow 95% CIs with artificially smaller P values (Higgins 2011c).

 

Primary outcomes

 
1) Short-term overall improvement (three months or less)

Not reported as an outcome in Bakhtiary 2004 or Bilgici 2010.

 

Secondary outcomes

 
1) Adverse effects

Reported as an outcome in Bilgici 2010 but not Bakhtiary 2004.

Bilgici 2010 found no side effects due to ultrasound treatment were reported by participants, whereas some participants receiving local corticosteroid injection plus splint reported transient local injection pain (however the number of participants reporting this were not reported).

 
2) Short-term improvement in CTS symptoms (three months or less)

Reported as an outcome in Bakhtiary 2004 and Bilgici 2010.

Bakhtiary 2004 assessed pain using a 0 to 10 VAS, and found a greater improvement in pain in the ultrasound group compared with the low-level laser therapy group in terms of mean change from baseline with the end of three weeks of treatment (MD -3.20; 95% CI -3.76 to -2.64) and mean change from baseline to seven weeks follow-up (MD -4.30; 95% CI -4.90 to -3.70). Given that it is not clear whether patients were blinded, this outcome should be interpreted with caution, as it is possible that participants' expectations of ultrasound or low-level laser therapy may have biased their self-reported assessment for pain.

Bilgici 2010 reported that wrists receiving ultrasound had a symptom severity score (measured using a Turkish-validated version of the Levine questionnaire (Levine 1993)) that was 0.66 points lower at the end of four weeks of treatment (MD -0.66; 95% CI -1.89 to 0.57), but 0.18 points higher at four weeks post-treatment (MD 0.18; 95% CI -0.45 to 0.81), and pain (measured using a visual analogue scale; scale units not reported) that was 0.55 points lower at the end of four weeks of treatment (MD -0.55; 95% CI -2.17 to 1.07) and 0.12 points lower at four weeks post-treatment (MD -0.12; 95% CI -1.39 to 1.15), compared with wrists receiving local corticosteroid injection plus splint. The precision of each of these effect estimates was low, and opposite effects of treatment are possible.

 
3) Short-term improvement in functional ability or health-related quality of life (three months or less)

Reported as an outcome in Bakhtiary 2004 and Bilgici 2010.

Bakhtiary 2004 found a greater improvement in hand grip strength in wrists receiving ultrasound compared with wrists receiving low-level laser therapy in terms of mean change from baseline to the end of three weeks of treatment (MD 17.20; 95% CI 10.05 to 24.35) and mean change from baseline to seven weeks follow-up (MD 18.10; 95% CI 9.83 to 26.37). Further, a difference in pinch strength favoured the ultrasound group at the end of three weeks of treatment (MD 6.50; 95% CI 5.27 to 7.73) and at seven weeks follow-up (MD 7.00; 95% CI 5.33 to 8.67).

Bilgici 2010 reported that wrists receiving ultrasound had a functional status score (measured using a Turkish-validated version of the Levine questionnaire (Levine 1993)) that was 0.81 points lower at the end of four weeks of treatment (MD -0.81; 95% CI -1.70 to 0.08) and 0.24 points lower at four weeks post-treatment (MD -0.24; 95% CI -1.01 to 0.53), and grip strength that was 2.80 mmHg better at the end of four weeks of treatment (MD 2.80; 95% CI 1.01 to 4.59) and 3.43 mmHg better at four weeks post-treatment (MD 3.43; 95% CI 1.71 to 5.15) compared with wrists receiving local corticosteroid injection plus splint. Of all these effect estimates, only the grip strength results had 95% CIs that ruled out a null or alternative effect of treatment.

 
4) Short-term improvement in neurophysiologic parameters (three months or less)

Reported as an outcome in Bakhtiary 2004 and Bilgici 2010.

In Bakhtiary 2004, wrists receiving ultrasound had a greater change from baseline than wrists receiving low level laser therapy in: motor distal latency after three weeks of treatment (MD -0.70; 95% CI -0.90 to -0.50) and at seven weeks follow-up (MD -0.90; 95% CI -1.06 to -0.74); in compound muscle action potential (CMAP) amplitude after three weeks of treatment (MD 2.00; 95% CI 1.03 to 2.97) and at seven weeks follow-up (MD 2.50; 95% CI 1.55 to 3.45); in thumb sensory latency after three weeks of treatment (MD -0.50; 95% CI -0.75 to -0.25) and at seven weeks follow-up (MD -0.50; 95% CI -0.73 to -0.27); in thumb sensory action potential (SAP) amplitude after three weeks of treatment (MD 5.00; 95% CI 1.92 to 8.08) and at seven weeks follow-up (MD 5.70; 95% CI 2.74 to 8.66); in index sensory latency after three weeks of treatment (MD -0.90; 95% CI -1.36 to -0.44) and at seven weeks follow-up (MD -0.90; 95% CI -1.33 to -0.47); and in index sensory action potential (SAP) amplitude after three weeks of treatment (MD 9.10; 95% CI 2.76 to 15.44) and at seven weeks follow-up (MD 10.30; 95% CI 4.66 to 15.94).

Bilgici 2010 reported that wrists receiving ultrasound had a median nerve motor distal latency that was 0.05 msec faster at the end of four weeks of treatment (MD -0.05; 95% CI -0.55 to 0.45) and 0.11 msec slower at four weeks post-treatment (MD 0.11; 95% CI -0.66 to 0.88), and a sensory nerve conduction velocity that was 3.71 m/sec higher at the end of four weeks of treatment (MD 3.71; 95% CI -0.45 to 7.87) and 2.32 m/sec higher at four weeks post-treatment (MD 2.32; 95% CI -1.89 to 6.53), compared with wrists receiving local corticosteroid injection plus splint. The 95% CIs of all these effect estimate were wide and incorporate both null and opposite effects of treatment.

 
5) Long-term improvement in CTS symptoms (more than three months)

Not reported as an outcome in Bakhtiary 2004 or Bilgici 2010.

 
6) Long-term improvement in functional ability or health-related quality of life (more than three months)

Not reported as an outcome in Bakhtiary 2004 or Bilgici 2010.

 

Therapeutic ultrasound (as part of multiple interventions) versus other non-surgical interventions

Six trials compared therapeutic ultrasound delivered as part of a multi-component intervention with another non-surgical intervention (Baysal 2006; Dincer 2009; Duymaz 2012; Ekim 2008; Piravej 2004; Yildiz 2011). In the study conducted by Baysal 2006, therapeutic ultrasound plus splint was compared with therapeutic ultrasound plus nerve and tendon gliding exercises plus splint and with nerve and tendon gliding exercises plus splint. While there are three possible comparisons in the study by Baysal 2006, only the two comparisons where therapeutic ultrasound was delivered to one of the groups were compared (that is we did not include data on the comparison between therapeutic ultrasound plus nerve and tendon gliding exercises plus splint versus therapeutic ultrasound plus splint). Dincer 2009 compared splint worn at night and during aggravating daytime activities, with splint and continuous ultrasound, or splint and low-level laser therapy. Duymaz 2012 compared therapeutic ultrasound with dexamethasone iontophoresis and with placebo iontophoresis (all groups also received nerve and tendon gliding exercises plus night splint plus activity modification). Ekim 2008 compared ultrasound plus splint with placebo ultrasound plus splint. Piravej 2004 compared continuous ultrasound therapy plus placebo drug, with "sham" ultrasound plus diclofenac 75 mg/day. Yildiz 2011 compared "sham ultrasound" plus splint with either ultrasound plus splint or to ultrasound with 2.5% ketoprofen gel plus splint. In Baysal 2006, Dincer 2009, Piravej 2004, and Yildiz 2011 it was unclear whether the correlation between wrists in participants with bilateral CTS was accounted for in the analysis. Therefore, all outcome data reported in these four studies may be invalid due to a unit of analysis error. Attempts to retrieve individual wrist outcome data from the trialists were unsuccessful. Without access to the individual wrist data, and without being able to estimate parameters such as the intraclass correlation coefficient from other studies included in the review, we did not attempt to adjust the results of these four studies. We have included the outcome data as reported by the trialists, but emphasise that results should be interpreted with caution, as the possible lack of adjustment may have produced overly narrow 95% CIs with artificially smaller P values (Higgins 2011c). Only two of these studies were deemed to be relatively similar (Ekim 2008 and Yildiz 2011), but were not combined because of heterogeneity of intensity, frequency, and duration of ultrasound treatment. We have provided a narrative synthesis of the results.

 

Primary outcomes

 
1) Short-term overall improvement (three months or less)

Reported as an outcome in Dincer 2009 but not Baysal 2006, Duymaz 2012, Ekim 2008, Piravej 2004 or Yildiz 2011.

Dincer 2009 found that ultrasound and splint increased the chance of being satisfied with treatment (RR 3.02; 95% CI 1.36 to 6.72), and of having completely normal hands based on electroneuromyography (RR 3.17; 95% CI 1.30 to 7.77) compared with splint alone, at three months after treatment ended. Compared with low-level laser therapy plus splint, the ultrasound plus splint group had slightly fewer participants who were satisfied with treatment (RR 0.87; 95% CI 0.57 to 1.33), and fewer completely normal hands based on electroneuromyography (RR 0.88; 95% CI 0.54 to 1.45), though the precision of these effect estimates was low. The results regarding the number of people with completely normal hands based on electroneuromyography should be interpreted with caution as they are associated with a high risk of selective reporting bias, as the authors did not pre-specify this outcome or define "completely normal hands" in the Methods section of the publication.

 

Secondary outcomes

 
1) Adverse effects

Reported as an outcome in Yildiz 2011 but not Baysal 2006, Dincer 2009, Duymaz 2012, Ekim 2008 or Piravej 2004.

None of the participants in the study by Yildiz 2011 reported complications or side effects of treatment during the study period.

 
2) Short-term improvement in CTS symptoms (three months or less)

Reported as an outcome in Baysal 2006, Dincer 2009, Duymaz 2012, Ekim 2008, Piravej 2004 and Yildiz 2011.

In the study conducted by Baysal 2006, wrists receiving ultrasound and splint had lower mean VAS pain scores (on a zero to 10 scale) at the end of three weeks of treatment (MD -1.10; 95% CI -2.59 to 0.39) and eight weeks post-treatment (MD -0.10; 95% CI -1.87 to 1.67), and lower mean symptom severity scores (assessed using the Levine questionnaire (Levine 1993)) at the end of three weeks of treatment (MD -2.60; 95% CI -7.81 to 2.61) and eight weeks post-treatment (MD -1.10; 95% CI -7.31 to 5.11), than wrists receiving exercise and splint. The low precision of these effect estimates does not rule out beneficial effects of exercise and splint only. Wrists receiving ultrasound and exercises and splint also had a lower mean VAS pain scores at the end of three weeks treatment (MD -2.00; 95% CI -3.46 to -0.54) and at eight weeks post-treatment (MD -1.80; 95% CI -3.00 to -0.60), and lower mean symptom severity scores at the end of treatment (MD -3.60; 95% CI -7.80 to 0.60) and at eight weeks post-treatment (MD -4.60; 95% CI -9.36 to 0.16) compared with exercises and splint only. However, the 95% CIs do not exclude the possibility of a small beneficial effect of exercise and splint alone, and the risk of bias associated with non-blinding of patients for these self-reported outcomes is high. Ultrasound and splint reduced the risk of having a positive Phalen's sign by 18% at the end of three weeks of treatment (RR 0.82; 95% CI 0.38 to 1.76) and by 32% at eight weeks post-treatment (RR 0.68; 95% CI 0.29 to 1.59), compared with exercises and splint only. Ultrasound and splint also reduced the risk of having a positive Tinel's sign by 37% at the end of three weeks of treatment (RR 0.63; 95% CI 0.27 to 1.43), but increased the risk by 7% at eight weeks post-treatment (RR 1.07; 95% CI 0.41 to 2.79), compared with exercises and splint only. In comparison to the exercises and splint group, receiving ultrasound and exercises and splint reduced the risk of having a positive Phalen's sign at the end of three weeks of treatment by 5% (RR 0.95; 95% CI 0.47 to 1.93) and by 32% at eight weeks post-treatment (RR 0.68; 95% CI 0.29 to 1.59), and reduced the risk of having a positive Tinel's sign by 37% at the end of three weeks of treatment (RR 0.63; 95% CI 0.27 to 1.43) and by 79% at eight weeks post-treatment (RR 0.21; 95% CI 0.03 to 1.58). None of the 95% CIs of these effect estimates rule out a negative effect of the interventions comprising ultrasound.

In the study by Dincer 2009, wrists receiving ultrasound and splint had less symptom severity at one month (MD -0.34; 95% CI -0.53 to -0.15) and three months after treatment ended (MD -0.70; 95% CI -1.06 to -0.34), and less pain (VAS) at one month (MD -2.60; 95% CI -3.46 to -1.74) and three months after treatment ended (MD -2.53; 95% CI -3.52 to -1.54), compared with wrists receiving splint alone. In contrast, wrists receiving low-level laser therapy and splint had less symptom severity (as assessed using the Levine questionnaire (Levine 1993)) at one month (MD 0.45; 95% CI 0.15 to 0.75) and three months after treatment ended (MD 0.71; 95% CI 0.29 to 1.13), and less pain (VAS) at one month (MD 0.61; 95% CI -0.30 to 1.52) and three months after treatment ended (MD 1.25; 95% CI 0.22 to 2.28), compared with wrists receiving ultrasound and splint (however, the low precision of the VAS pain effect estimate at one month follow-up means an opposite effect of treatment is possible). The possible lack of allocation concealment and lack of patient blinding may have biased these results in favour of low-level laser therapy and should therefore be interpreted with caution.

Duymaz 2012 reported that wrists receiving ultrasound plus exercises, night splint and activity modification had a symptom severity score (as assessed using the Levine questionnaire (Levine 1993)) that was 4.25 points higher (worse) at the end of treatment (MD 4.25; 95% CI -1.12 to 9.62) and 5.2 points higher at three months follow-up (MD 5.20; 95% CI 0.27 to 10.13) compared with wrists receiving dexamethasone iontophoresis plus exercises, night splint and activity modification, and that was 0.45 points higher at the end of treatment (MD 0.45; 95% CI -5.88 to 6.78) and 1.10 points lower (better) at three months follow-up (MD -1.10; 95% CI -7.11 to 4.91) compared with wrists receiving placebo iontophoresis plus exercises, night splint and activity modification. Compared with the ultrasound group, the change from baseline to the end of treatment in: (i) VAS pain on movement was 1.45 points larger (better) in the dexamethasone iontophoresis group (MD -1.45; 95% CI -2.55 to -0.35) and 0.64 points smaller (worse) in the placebo iontophoresis group (MD 0.64; 95% CI -0.32 to 1.60); (ii) VAS pain at rest was 1.35 points larger in the dexamethasone iontophoresis group (MD -1.35; 95% CI -2.43 to -0.27) and 0.70 points smaller in the placebo iontophoresis group (MD 0.70; 95% CI -0.14 to 1.54); and (iii) VAS pain at night was 0.10 points larger in the dexamethasone iontophoresis group (MD -0.10; 95% CI -1.49 to 1.29) and 0.64 points smaller in the placebo iontophoresis group (MD 0.64; 95% CI -0.67 to 1.95). For all these self-reported outcomes, results should be interpreted with caution due to the lack of participant blinding. Trialists also reported measuring Phalen's test, Reverse Phalen's test, Tinel's test and carpal compression test, but only reported whether differences between groups on these outcomes were statistically significant (therefore no useable data for these outcomes have been included in the review).

Ekim 2008 found that wrists receiving therapeutic ultrasound plus splint worn at night reduced the risk of having a positive Tinel's test by 13% (RR 0.87; 95% CI 0.46 to 1.64), reduced the risk of having a positive Phalen's test by 26% (RR 0.74; 95% CI 0.33 to 1.65), and reduced symptom severity score (as assessed using Turkish translated version of the Levine questionnaire (Levine 1993)) by 6.4 points (MD -6.40; 95% CI -8.40 to -4.40) at the end of two weeks of treatment when compared with wrists receiving placebo ultrasound plus splint worn at night (only the result for symptom severity score was statistically significant). Ekim 2008 also measured pain using a 100 mm VAS but reported medians and interquartile ranges (IQR) only as the data were skewed, and therefore could not be entered into RevMan. The ultrasound plus splint group had a median VAS pain of 30 (IQR 25 to 39.25) and the placebo ultrasound plus splint group had a higher median VAS pain of 50 (IQR 40 to 65) at the end of two weeks of treatment. All these results should be interpreted with caution because it was not clear whether the random allocation sequence was adequately concealed.

When comparing wrists receiving ultrasound plus placebo to wrists receiving "sham" ultrasound plus NSAID, Piravej 2004 found small differences in the following outcomes at the end of four weeks of treatment: VAS pain score (MD -0.20; 95% CI -1.53 to 1.13), pain/paraesthesia (MD -0.07; 95% CI -0.52 to 0.38) and frequency of awakening at night (MD 0.07; 95% CI -0.42 to 0.56). The low precision of effect estimates means the results cannot be interpreted as one intervention being of greater benefit than the other. The above effect estimates are based on endpoint scores; results based on change from baseline scores were also reported in the publication, and were similar in terms of direction, magnitude and statistical significance of effect for all outcomes except for VAS pain score and frequency of awakening, where the direction of effect changed.

Yildiz 2011 found small differences between wrists receiving ultrasound and splint and wrists receiving "sham" ultrasound and splint on the following outcomes: VAS pain score at the end of two weeks of treatment (MD -0.31; 95% CI -1.55 to 0.93) and six weeks after treatment ended (MD -0.51; 95% CI -2.01 to 0.99), and symptom severity score (as assessed using the Levine questionnaire (Levine 1993)) at the end of two weeks of treatment (MD 0.10; 95% CI -0.22 to 0.42) and six weeks after treatment ended (MD -0.11; 95% CI -0.52 to 0.30). The precision of all these effect estimates was low, and opposite effects of interventions cannot be ruled out. Small, nonsignificant differences between wrists receiving ultrasound with 2.5% ketoprofen gel plus splint and wrists receiving ultrasound plus splint were also shown for VAS pain score at the end of two weeks of treatment (MD -0.62; 95% CI -1.83 to 0.59), and symptom severity score at the end of two weeks of treatment (MD 0.26; 95% CI -0.12 to 0.64) and six weeks after treatment ended (MD 0.34; 95% CI -0.04 to 0.72). However, at six weeks after treatment ended, the VAS pain score was lower in the wrists receiving ultrasound with 2.5% ketoprofen gel and splint, (MD 1.79; 95% CI 0.55 to 3.03). All the above effect estimates are based on an intention-to-treat (ITT) analysis; results based on a per-protocol analysis were also reported in the publication, and were similar in terms of direction, magnitude, and statistical significance of effect.

 
3) Short-term improvement in functional ability or health-related quality of life (three months or less)

Reported as an outcome in Baysal 2006, Dincer 2009, Duymaz 2012, Ekim 2008, and Yildiz 2011, but not Piravej 2004.

Baysal 2006 found that wrists receiving ultrasound and splint had a mean self-reported functional status that was 1.30 points lower on a 40-point scale at the end of three weeks of treatment (MD 1.30; 95% CI -3.83 to 6.43) and 1.20 points lower at eight weeks post-treatment (MD 1.20; 95% CI -3.81 to 6.21) compared with wrists receiving exercises and splint. The ultrasound and splint group wrists had hand grip strength that was 0.70 kg better at the end of three weeks of treatment (MD 0.70; 95% CI -4.82 to 6.22) and 0.80 kg better at eight weeks post-treatment (MD 0.80; 95% CI -2.42 to 4.02) when compared with the exercises and splint wrists, but had pinch strength which was 0.60 kg worse at the end of three weeks of treatment (MD -0.60; 95% CI -1.98 to 0.78) and at eight weeks post-treatment (MD -0.60; 95% CI -1.92 to 0.72) compared with exercises and splint group wrists. Further, wrists receiving ultrasound and exercises and splint had a mean self-reported functional status that was 3.10 points lower (better) on a 40-point scale at the end of three weeks of treatment (MD -3.10; 95% CI -6.58 to 0.38) and 2.30 points lower at eight weeks post-treatment (MD -2.30; 95% CI -5.42 to 0.82) compared with wrists receiving exercises and splint, and hand grip strength was 0.60 kg better at the end of treatment (MD 0.60; 95% CI -3.09 to 4.29), but 0.40 kg worse at eight weeks post-treatment (MD -0.40; 95% CI -4.27 to 3.47). Pinch strength was 0.70 kg better at the end treatment (MD 0.70; 95% CI -0.56 to 1.96) and at eight weeks post-treatment (MD 0.70; 95% CI -0.57 to 1.97) compared with wrists receiving exercises and splint only. All of these effect estimates have 95% CIs that do no exclude the possibility of no difference between groups or effects that favour either treatment group.

Wrists in the study by Dincer 2009 that received ultrasound and splint had better self-reported functional ability than wrists receiving splint only at one month (MD -0.13; 95% CI -0.28 to 0.02), and three months (MD -0.65; 95% CI -0.82 to -0.48) after treatment ended. Alternatively, wrists receiving low-level laser therapy and splint had better self-reported functional ability than wrists receiving ultrasound and splint at one month (MD 0.32; 95% CI 0.07 to 0.57), and three months after treatment ended (MD 0.18; 95% CI -0.10 to 0.46). However, the lack of patient blinding means this self-reported outcome could be biased based on participant expectations of the benefits offered by low-level laser therapy as being greater than ultrasound and either of these interventions being greater than splint alone.

Duymaz 2012 reported that wrists receiving ultrasound plus exercises, night splint and activity modification had a functional status score (as assessed using the Levine questionnaire (Levine 1993)) that was 3.20 points higher (worse) at the end of treatment (MD 3.20; 95% CI -0.76 to 7.16) and 3.5 points higher at three months follow-up (MD 3.50; 95% CI -0.53 to 7.53) compared with wrists receiving dexamethasone iontophoresis plus exercises, night splint and activity modification, and that was 2.94 points higher at the end of treatment (MD 2.94; 95% CI -1.73 to 7.61) and 1.85 points higher at three months follow-up (MD 1.85; 95% CI -2.74 to 6.44) compared to wrists receiving placebo iontophoresis plus exercises, night splint and activity modification. Compared to the ultrasound group, Health Assessment Questionnaire scores were 0.24 points lower (better) at the end of treatment (MD 0.24; 95% CI -0.12 to 0.60) and 0.07 points lower at three months follow-up (MD 0.07; 95% CI -0.26 to 0.40) in the dexamethasone iontophoresis group, and 0.07 points lower at the end of treatment (MD 0.07; 95% CI -0.31 to 0.45) and 0.02 points higher (worse) at three months follow-up (MD -0.02; 95% CI -0.36 to 0.32) in the placebo iontophoresis group. For all these outcomes, results should be interpreted with caution due to the lack of participant and outcome assessor blinding. Trialists also reported measuring grip and pinch strength, but only reported whether differences between groups on these outcomes were statistically significant (therefore no data for these outcomes have been included in the review).

Ekim 2008 found that wrists receiving therapeutic ultrasound plus splint worn at night had a functional status score (as assessed using Turkish translated version of the Levine questionnaire (Levine 1993)) that was 1.00 points lower (better) (MD -1.00; 95% CI -4.45 to 2.45), and grip strength that was better (MD 0.04; 95% CI -0.02 to 0.10) (units of measurement not specified) at the end of two weeks of treatment when compared with wrists receiving placebo ultrasound plus splint worn at night. However, the wide 95% CIs incorporate effects in either direction.

Yildiz 2011 found small differences favouring wrists that received ultrasound plus splint over wrists receiving "sham" ultrasound plus splint on self-reported functional status at the end of two weeks of treatment (MD -0.15; 95% CI -0.52 to 0.22) and six weeks after treatment ended (MD -0.21; 95% CI -0.67 to 0.25), though the precision of effect estimates was low. Differences in self-reported functional status between wrists receiving ultrasound with 2.5% ketoprofen gel plus splint compared with wrists receiving ultrasound plus splint were also small and imprecise at the end of two weeks of treatment (MD -0.23; 95% CI -0.61 to 0.15) and six weeks after treatment ended (MD 0.19; 95% CI -0.24 to 0.62). All the above effect estimates are based on an ITT analysis; results based on a per-protocol analysis were also reported in the publication, and were similar in terms of direction, magnitude, and statistical significance of effect.

 
4) Short-term improvement in neurophysiologic parameters (three months or less)

Reported as an outcome in Baysal 2006, Dincer 2009, Duymaz 2012, Ekim 2008, Piravej 2004 and Yildiz 2011.

In the study by Baysal 2006, wrists receiving ultrasound and splint had a mean motor distal latency that was 0.20 ms faster at the end of treatment (MD -0.20; 95% CI -0.95 to 0.55) and 0.30 ms faster at eight weeks post-treatment (MD -0.30; 95% CI -0.91 to 0.31), and a mean sensory distal latency that was 0.10 ms slower at the end of treatment (MD 0.10; 95% CI -0.28 to 0.48) and no different at eight weeks post-treatment (MD 0.00; 95% CI -0.36 to 0.36), compared with wrists receiving exercises and splint only. Comparisons between wrists receiving ultrasound plus exercises plus splint and wrists receiving exercises plus splint alone indicate that mean motor distal latency was 0.20 ms faster at the end of treatment (MD -0.20; 95% CI -1.37 to 0.97) and 0.20 ms faster at eight weeks post-treatment (MD -0.20; 95% CI -1.46 to 1.06), and mean sensory distal latency was 0.20 ms slower at the end of treatment (MD 0.20; 95% CI -0.13 to 0.53) and 0.20 ms slower at eight post-treatment (MD 0.20; 95% CI -0.12 to 0.52) when compared with wrists receiving exercises and splint only. None of these effect estimates had high precision though as indicated by the 95% CI that incorporates effects of the intervention in either direction.

Dincer 2009 found that wrists receiving ultrasound and splint had better median nerve motor distal latency at one month (MD -0.15; 95% CI -0.26 to -0.04) and three months (MD -0.29; 95% CI -0.46 to -0.12) after treatment ended, and better second digit-wrist median nerve sensory velocity at one month (MD 3.09; 95% CI 1.42 to 4.76) and three months (MD 3.29; 95% CI -0.35 to 6.93) after treatment ended, compared with wrists receiving splint only. Further, wrists receiving low-level laser therapy had slightly better median nerve motor distal latency at one month (MD 0.05; 95% CI -0.07 to 0.17) and three months (MD 0.07; 95% CI -0.10 to 0.24) after treatment ended, and better second digit-wrist median nerve sensory velocity at one month (MD -2.69; 95% CI -4.80 to -0.58) and three months (MD -2.67; 95% CI -6.38 to 1.04) after treatment ended, compared with wrists receiving ultrasound and splint. However, the precision of the effect estimates was low and in a number of cases, opposite effects cannot be ruled out.

Duymaz 2012 reported means and SDs for sensory nerve distal latency, sensory nerve amplitude, sensory nerve conduction velocity, motor nerve distal latency, motor nerve amplitude, motor nerve conduction velocity, compound muscle action potential (CMAP) of the abductor pollicis brevis muscle, but it is not clear whether the data are endpoint values at end of treatment, endpoint values at three months follow-up, change from baseline to end of treatment values, or change from baseline to three months follow-up values. For this reason, we did not extract the mean (SD) outcome data reported for any these six neurophysiologic parameters.

Ekim 2008 found that at the end of two weeks of treatment, wrists receiving ultrasound plus splint worn at night had motor distal latency that was 0.10 msec slower (MD 0.10; 95% CI -0.46 to 0.66), motor nerve conduction velocity that was 2.70 m/sec higher (MD 2.70; 95% CI -1.08 to 6.48), sensory distal latency that was 0.10 msec faster (MD -0.10; 95% CI -0.32 to 0.12), and palm-wrist conduction velocity that was 0.90 m/sec lower (MD -0.90; 95% CI -4.31 to 2.51) compared with wrists receiving placebo ultrasound plus splint worn at night. The low precision of these effect estimates suggests that null or alternative effects are possible though.

At the end of four weeks of treatment, Piravej 2004 found small differences between wrists receiving ultrasound plus placebo and wrists receiving "sham" ultrasound plus NSAID for median nerve sensory distal latency (endpoint scores: MD -0.35; 95% CI -0.74 to 0.04), sensory nerve action potential (SNAP) (endpoint scores: MD 13.11; 95% CI -7.12 to 33.34), median nerve motor distal latency (change from baseline scores: MD -0.32; 95% CI -0.73 to 0.09), and CMAP (endpoint scores: MD 1.37; 95% CI -0.87 to 3.61). However, the low precision of effect estimates means that results cannot be interpreted as one intervention having clear benefit over another. The change from baseline score for the outcome, median nerve motor distal latency, is reported here because the standard deviation for the endpoint score was reported incorrectly in the trial publication. While the direction, magnitude and statistical significance of the outcomes, median nerve sensory distal latency and CMAP were similar when comparing endpoint to change from baseline scores, the endpoint score for sensory nerve action potential revealed no statistically significant difference between groups, whereas the change from baseline score for this outcome revealed a statistically significant difference favouring the ultrasound plus placebo group (MD -19.27; 95% CI -34.36 to -4.18). Twelve participants had bilateral CTS and six had unilateral CTS and the authors did not report controlling for inter-correlation between the outcomes of both hands per participant with bilateral CTS. It is possible that unit of analysis error may have occurred, which may have artificially narrowed the 95% CIs, so these results should be interpreted with caution.

When comparing wrists receiving ultrasound plus splint to wrists receiving "sham" ultrasound plus splint, Yildiz 2011 found small differences in the outcomes, median nerve motor distal latency at the end of two weeks of treatment (MD 0.15; 95% CI -0.19 to 0.49) and six weeks after treatment ended (MD 0.11; 95% CI -0.21 to 0.43), and median nerve sensory distal latency at the end of two weeks of treatment (MD -0.04; 95% CI -0.24 to 0.16) and six weeks after treatment ended (MD -0.07; 95% CI -0.29 to 0.15). Further, when comparing wrists that received ultrasound with 2.5% ketoprofen gel and wrists that received ultrasound plus splint, small differences were found in the outcomes, median nerve motor distal latency at the end of two weeks of treatment (MD 0.20; 95% CI -0.07 to 0.47) and six weeks after treatment ended (MD 0.28; 95% CI 0.03 to 0.53), and median nerve sensory distal latency at the end of two weeks of treatment (MD 0.08; 95% CI -0.10 to 0.26) and six weeks after treatment ended (MD 0.08; 95% CI -0.09 to 0.25). The low precision of all these effect estimates makes it is impossible to conclude that one intervention is more beneficial than the other. All the above effect estimates are based on an ITT analysis; results based on a per-protocol analysis were also reported in the publication, and were similar in terms of direction, magnitude, and statistical significance of effect for all outcomes, except for the outcome median nerve motor distal latency at six weeks after treatment ended when comparing ultrasound plus splint to "sham" ultrasound plus splint, which found a non-significant effect (MD 0.28; 95% CI -0.00 to 0.56).

 
5) Long-term improvement in CTS symptoms (more than three months)

Reported as an outcome in Baysal 2006 but not Dincer 2009, Duymaz 2012, Ekim 2008, Piravej 2004 and Yildiz 2011.

Baysal 2006 asked participants to report their satisfaction with treatment for each wrist at an average of 11 ± 4.5 months after the end of treatment. The authors reported the number of participants rated as 'excellent/good' (asymptomatic or rarely symptomatic), 'fair' (symptomatic only during compelling activity), and 'poor' (continuing symptoms without relief following treatment). In the therapeutic ultrasound and splint group, 25% of participants had 'excellent/good' satisfaction compared with 0% of participants receiving exercises and splint only (RR 9.69; 95% CI 0.55 to 171.98). Further, 61% of participants receiving ultrasound plus exercises plus splint had 'excellent/good' satisfaction compared with 0% of participants receiving exercises and splint only (RR 21.86; 95% CI 1.38 to 347.18). However, the precision of both effect estimates was very low, and the lack of patient blinding and unclear reasons for incomplete data for these outcomes suggests these results should be interpreted with caution.

 
6) Long-term improvement in functional ability or health-related quality of life (more than three months)

Not reported as an outcome in Baysal 2006, Dincer 2009, Duymaz 2012, Ekim 2008, Piravej 2004 or Yildiz 2011.

 

Subgroup and sensitivity analyses

We could not perform the planned subgroup and sensitivity analyses given the small number of studies that could be pooled. This may be possible in future updates of the review.

 

Assessment of reporting bias

The recommended number of studies required to generate a funnel plot (Sterne 2011) is 10, and in the absence of meta-analyses, we could not assess publication bias. We did not locate protocols or trial registry entries for any of the studies included in the review, so our assessment of selective reporting was limited to comparing outcomes reported in the methods and results sections of publications.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
 

Summary of main results

We set out to determine the effectiveness of therapeutic ultrasound compared with no treatment, a placebo, or other non-surgical treatments for improving clinical outcome in people with CTS. Eleven studies randomising 414 participants were included; two studies compared ultrasound with placebo, two studies compared different frequencies or intensities of ultrasound, and eight studies compared ultrasound with other non-surgical interventions. No studies comparing ultrasound with 'no treatment' were found.

Overall there is insufficient evidence to recommend one therapeutic ultrasound regimen over another, or to recommend therapeutic ultrasound over other non-surgical interventions for CTS. There is low quality evidence that therapeutic ultrasound may result in greater short-term overall improvement and greater improvement in pain or paraesthesia compared with placebo at the end of seven weeks of treatment, and at six months follow-up (Ebenbichler 1998). These results must be interpreted with caution given the unclear reasons for loss to follow-up and failure to adjust for the correlation between wrists in participants with bilateral CTS in Ebenbichler 1998. However, differences between ultrasound and placebo for symptoms of pain or paraesthesia and neurophysiologic parameters after two weeks treatment, when pooled in a meta-analysis, were small and not statistically significant (Ebenbichler 1998; Oztas 1998). This suggests that any beneficial effects of ultrasound may take more than a couple of weeks to become apparent. Studies comparing different frequencies (Koyuncu 1995) and different intensities of ultrasound (Oztas 1998) both had small study samples and results indicate there is limited evidence to recommend one type of ultrasound frequency or intensity over others, particularly in relation to short-term overall improvement, symptoms, function and neurophysiologic parameters. We also found evidence that therapeutic ultrasound may be more effective than low-level laser therapy for short-term symptoms, function (hand grip strength and pinch strength) and neurophysiologic parameters (Bakhtiary 2004), but the investigators of this trial did not adjust for the correlation between wrists in participants with bilateral CTS so these results must be interpreted with caution. There is no high quality evidence that therapeutic ultrasound, when delivered as part of a multi-component intervention, is any more effective than other non-surgical interventions for CTS in terms of short-term overall improvement, CTS symptoms, function and neurophysiological parameters (Baysal 2006; Dincer 2009; Duymaz 2012; Ekim 2008; Piravej 2004; Yildiz 2011). No studies reported any adverse effects of therapeutic ultrasound, but this outcome was only measured in three studies (Bilgici 2010; Ebenbichler 1998; Yildiz 2011). More adverse effects data are required before any firm conclusions on the safety of therapeutic ultrasound can be made.

 

Overall completeness and applicability of evidence

The evidence included in this review is limited in its completeness and applicability. There were a number of important pieces of information about study conduct and data that were not provided by the authors of the included studies (either in the publication or when requested). For example, the authors of nine studies did not report sufficient information to determine whether an adequate method of allocation concealment was used (Bakhtiary 2004; Baysal 2006; Dincer 2009; Duymaz 2012; Ekim 2008; Koyuncu 1995; Oztas 1998, Piravej 2004; Yildiz 2011). This is an important component of study design, given the meta-epidemiological evidence to suggest that inadequate allocation concealment can result in biased treatment effects (Savović 2012). The included studies were also limited in the timing of outcome assessment, in that only two studies assessed outcomes more than three months post-treatment cessation (Baysal 2006; Ebenbichler 1998), and the majority only assessed outcomes at the end of treatment. As a result there is limited evidence about the long-term effects of therapeutic ultrasound for people with CTS. Further, of the 414 participants recruited in total, only 29 were reported as being male (note that two studies did not report the sex distribution of patients (Bakhtiary 2004, Ebenbichler 1998)). While there is a higher prevalence of CTS in females in the general population (Atroshi 1999, Charles 2009), the few males included in these studies limits the extent to which the results of the studies can be applied to men. In addition, only two small studies compared different regimens of therapeutic ultrasound (Koyuncu 1995; Oztas 1998), which limits any conclusions about the most effective ultrasound regimen. Finally, no studies provided a head-to-head comparison of therapeutic ultrasound delivered over different durations (for example sessions delivered over two weeks versus 10 weeks). Therefore, there is insufficient evidence regarding the most efficacious duration of therapeutic ultrasound delivery.

 

Quality of the evidence

The methodological quality varied across the studies. All of the studies were small (the largest included 60 participants with 120 CTS-affected wrists (Dincer 2009)). Two of the studies reported using a random allocation sequence that was adequately concealed (Bilgici 2010; Ebenbichler 1998), six reported blinding of participants (Ebenbichler 1998; Ekim 2008; Koyuncu 1995; Oztas 1998; Piravej 2004; Yildiz 2011), and all but five of the studies (Bilgici 2010; Duymaz 2012; Ekim 2008; Koyuncu 1995; Oztas 1998) reported blinded assessment of objective outcomes. The lack of participant blinding in four studies is of concern given that many outcomes were self-reported, and empirical evidence indicates that trials with self-reported outcomes show exaggerated treatment effects (Savović 2012). Further, unit of analysis errors clearly occurred in two studies (Bakhtiary 2004; Ebenbichler 1998) and possibly occurred in another seven studies (Baysal 2006; Bilgici 2010; Dincer 2009; Koyuncu 1995; Oztas 1998; Piravej 2004; Yildiz 2011). Some type of selective outcome reporting was present in four studies (Dincer 2009; Duymaz 2012; Ebenbichler 1998; Koyuncu 1995), and suspected (though unclear) in another two (Oztas 1998; Piravej 2004). The latter finding is concerning given the results of a recent study which suggests that selective outcome reporting of "positive" or statistically significant trial results can bias the results and conclusions of a systematic review (Kirkham 2010).

 

Potential biases in the review process

While our described methods attempted to minimise bias in the selection of studies, collection of published data, and analysis for the review, our searches were limited to electronic databases, and as a result we have only included published studies. In future updates of this review, we will attempt to identify grey literature, given that empirical evidence suggests that published studies tend to have exaggerated treatment effects compared with unpublished studies (Hopewell 2007). It was also difficult to obtain relevant unpublished data from the authors of included studies. Further, it was difficult to assess selective outcome reporting as no protocols or trial registry entries for the included studies were identified.

 

Agreements and disagreements with other studies or reviews

To our knowledge, no other systematic reviews specifically focusing on therapeutic ultrasound for CTS exist. However, the findings of this review are generally consistent with those of other systematic reviews of non-surgical interventions for CTS, which conclude there is limited or insufficient evidence for the effectiveness of therapeutic ultrasound for CTS (Ashworth 2010; Gerritsen 2002; Goodyear-Smith 2004; Huisstede 2010; Muller 2004; Ono 2010; Piazzini 2007; Robertson 2001). In comparison to this review, the most recent systematic review of all non-surgical interventions for CTS by Huisstede 2010 also included the studies conducted by Bakhtiary 2004, Baysal 2006, Koyuncu 1995, Ebenbichler 1998 and Oztas 1998; however, it did not include the studies conducted by Bilgici 2010, Dincer 2009, Duymaz 2012, Ekim 2008, Piravej 2004 or Yildiz 2011. Based on the date we conducted our searches, to our knowledge the current review is the most comprehensive and up-to-date review of randomised trials assessing the efficacy of therapeutic ultrasound for CTS.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

 

Implications for practice

There is only poor quality evidence from very limited data to suggest that therapeutic ultrasound may be more effective than placebo for either short- or long-term symptom improvement in people with carpal tunnel syndrome. There is insufficient evidence to support the greater benefit of one type of therapeutic ultrasound regimen over another or to support the use of therapeutic ultrasound as a treatment with greater efficacy compared with other non-surgical interventions for CTS, such as splinting, exercises, and oral drugs. The preferences of both clinicians and patients should be taken into consideration when deciding whether to offer therapeutic ultrasound to people with CTS.

 
Implications for research

Large scale, methodologically rigorous randomised trials are needed to assess the safety and efficacy of different therapeutic ultrasound regimens as compared with other non-surgical interventions for CTS. More randomised trials are needed to ascertain the most effective frequency and intensity of therapeutic ultrasound to use. Trials should blind participants, personnel and outcome assessors where possible, and test the success of blinding (for example by asking participants to indicate which intervention they believe they received). Trialists should consider collecting data on overall improvement, adverse effects CTS symptoms, function, and neurophysiologic parameters. Finally, the long-term effects of CTS need to be determined (that is outcomes should be assessed at least three months post-treatment cessation).

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

We thank Ruth Brassington, Louisa Dunn, Kate Jewitt, Carolyn Reid, Angela Gunn and Rachel Barton from the Cochrane Neuromuscular Disease Group for their assistance in devising the search strategy, helping to locate people to translate the non-English trials and ongoing support for this review. We thank Shawn Marshall for his substantial contribution to the original version of this review. We thank Katherine Beringer from the Monash Institute of Health Services Research for her assistance in retrieving studies relevant to the review. We thank the trialist Gerold Ebenbichler who corresponded with the principal reviewer to clarify additional information and/or provided additional data for the review. We thank the translators, in particular Murat Zinnuroglu, for their assistance in translating abstracts and papers for the review. We thank the peer reviewers for their helpful comments.

We thank the following institutions for their support during the review:

  • School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia;
  • School of Occupational Therapy, University of South Australia, Adelaide, Australia.

Editorial support from the Cochrane Neuromuscular Disease Group is funded by the MRC Centre for Neuromuscular Diseases.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
Download statistical data

 
Comparison 1. Therapeutic ultrasound versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term overall improvement (number of participants with good to excellent improvement) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 At 7 weeks (end of treatment)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (number of participants with complete remission of subjective symptoms) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 At 7 weeks (end of treatment)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (VAS pain score) (2 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 After 2 weeks of treatment (1.5 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 After 2 weeks of treatment (0.8 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (pain and/or paraesthesia) (3 months or less)2Mean Difference (IV, Random, 95% CI)Totals not selected

    4.1 After 2 weeks of treatment (endpoint values of Ebenbichler 1998)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    4.2 After 2 weeks of treatment (endpoint values of Oztas 1998 1.5 W/cm2 intensity)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    4.3 After 2 weeks of treatment (endpoint values of Oztas 1998 0.8 W/cm2 intensity)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    4.4 After 7 weeks of treatment (endpoint values in Ebenbichler 1998)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in CTS symptoms (sensory loss) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Change from baseline to two weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Change from baseline to seven weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in CTS symptoms (nocturnal waking) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 After 2 weeks of treatment (1.5 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 After 2 weeks of treatment (0.8 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in functional ability (hand grip strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 Change from baseline to two weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Change from baseline to seven weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Short-term improvement in functional ability (pinch strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 Change from baseline to two weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Change from baseline to seven weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Short-term improvement in motor distal latency (ms) (3 months or less)2Mean Difference (IV, Random, 95% CI)Totals not selected

    9.1 After 2 weeks treatment (change from baseline values in Ebenbichler 1998)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    9.2 After 2 weeks treatment (endpoint values in Oztas 1998 1.5 W/cm2 intensity)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    9.3 After 2 weeks treatment (endpoint values in Oztas 1998 0.8 W/cm2 intensity)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    9.4 Change from baseline to 7 weeks in Ebenbichler 1998
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 10 Short-term improvement in motor nerve conduction velocity (m/s) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    10.1 After 2 weeks 5 days treatment (1.5 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 After 2 weeks 5 days treatment (0.8 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 11 Short-term improvement in sensory distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    11.1 After 2 weeks 5 days treatment (1.5 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.2 After 2 weeks 5 days treatment (0.8 W/cm2 intensity) (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 12 Short-term improvement in sensory nerve conduction velocity (3 months or less)2Mean Difference (IV, Random, 95% CI)Totals not selected

    12.1 After 2 weeks treatment (change from baseline values in Ebenbichler 1998)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    12.2 After 2 weeks treatment (endpoint values in Oztas 1998 1.5 W/cm2 intensity)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    12.3 After 2 weeks treatment (endpoint values in Oztas 1998 0.8 W/cm2 intensity)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    12.4 Change from baseline to 7 weeks
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 13 Long-term improvement in CTS symptoms (>3 months) (number of participants who did not have an overall unsatisfactory outcome)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    13.1 At 7 months and 3 weeks (endpoint values)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 14 Long-term improvement in CTS symptoms (number of participants with complete remission of subjective symptoms) (>3 months)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    14.1 At 7 months and 3 weeks (endpoint values)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 15 Long-term improvement in CTS symptoms (pain and/or paraesthesia) (>3 months)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    15.1 At 7 months 3 weeks (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 16 Long-term improvement in CTS symptoms (sensory loss) (>3 months)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    16.1 At 7 months 3 weeks (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 17 Long-term improvement in functional ability (grip and pinch strength) (>3 months)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    17.1 Grip strength (kg) at 7 months and 3 weeks (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    17.2 Pinch strength (kg) at 7 months and 3 weeks (endpoint values)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Therapeutic ultrasound (varying frequency)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (pain) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 After 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (paraesthesia) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 After 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (superficial sensation) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 After 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (Tinel's sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 After 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in CTS symptoms (Phalen's sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    5.1 After 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in functional ability (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    6.1 Grasp of large objects after 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Grasp of small objects after 4 weeks of treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Therapeutic ultrasound (single intervention) versus low-level laser therapy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in functional ability (hand grip strength, N) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in functional ability (pinch strength, N) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in motor distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in compound muscle action potential (CMAP) amplitude (mV) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in thumb sensory latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in thumb sensory action potential (SAP) amplitude (µV) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Short-term improvement in index sensory latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Short-term improvement in index sensory action potential (SAP) amplitude (µV) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 Change from baseline to end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Change from baseline to 7 weeks follow-up
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Therapeutic ultrasound (varying intensity)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 After 2 weeks 5 days of treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (night pain / paraesthesia) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 After 2 weeks 5 days of treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (nocturnal awakening) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 After 2 weeks 5 days of treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in motor distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 After 2 weeks 5 days treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in motor nerve conduction velocity (m/s) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 After 2 weeks 5 days treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in sensory distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 After 2 weeks 5 days treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in sensory nerve conduction velocity (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 After 2 weeks 5 days treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 5. Therapeutic ultrasound (single intervention) versus local corticosteroid injection plus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (symptom severity score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 At the end of 4 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 4 weeks post-treatment cessation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 At the end of 4 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 4 weeks post-treatment cessation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in functional ability (functional status score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At the end of 4 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 4 weeks post-treatment cessation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in functional ability (grip strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At the end of 4 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 4 weeks post-treatment cessation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in median nerve motor distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At the end of 4 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 4 weeks post-treatment cessation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in median sensory nerve conduction velocity (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 At the end of 4 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 4 weeks post-treatment cessation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 6. Therapeutic ultrasound plus splint versus exercises plus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (Levine) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (Phalen sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 At end of treatment (3 weeks)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 At 11 weeks
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (Tinel sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 At end of treatment (3 weeks)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 At 11 weeks
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (Levine) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in functional ability (hand grip strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in functional ability (pinch strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Short-term improvement in motor distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Short-term improvement in sensory distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Long-term improvement in CTS symptoms (>3 months)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    10.1 At 11 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 7. Therapeutic ultrasound plus exercises plus splint versus exercises plus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (Levine) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (Phalen sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 At end of treatment (3 weeks)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 At 11 weeks
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (Tinel sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 At end of treatment (3 weeks)
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 At 11 weeks
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (Levine) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in functional ability (hand grip strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in functional ability (pinch strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Short-term improvement in motor distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Short-term improvement in sensory distal latency (ms) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 After end of 3 weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 At 11 weeks
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Long-term improvement in CTS symptom (>3 months)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    10.1 At 11 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 8. Therapeutic ultrasound plus splint versus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term overall improvement (completely normal hands based on electroneuromyography) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 2 Short-term overall improvement (patient satisfaction) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 3 Short-term improvement in CTS symptoms (symptom severity score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (functional status score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in median nerve motor distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in second digit-wrist median nerve sensory velocity (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 9. Therapeutic ultrasound plus splint versus low-level laser therapy plus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term overall improvement (completely normal hands based on electroneuromyography) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Short-term overall improvement (patient satisfaction) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Short-term improvement in CTS symptoms (symptom severity score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (functional status score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in median nerve motor distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in second digit-wrist median nerve sensory velocity (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 At 1 month after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 At 3 months after treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 10. Therapeutic ultrasound plus nerve and tendon gliding exercises plus night splint plus activity modification versus dexamethasone iontophoresis plus nerve and tendon gliding exercises plus night splint plus activity modification

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (BCTQ symptom severity score) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 End of treatment (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Three months post-treatment cessation (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (VAS pain on movement) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    2.1 Change from baseline to end of treatment
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (VAS pain at rest) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    3.1 Change from baseline to end of treatment
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (VAS pain at night) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    4.1 Change from baseline to end of treatment
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (BCTQ functional status score) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    5.1 End of treatment (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    5.2 Three months post-treatment cessation (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in functional ability (Health Assessment Questionnaire) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    6.1 End of treatment (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    6.2 Three months post-treatment cessation (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 11. Therapeutic ultrasound plus nerve and tendon gliding exercise plus night splint plus activity modification versus placebo iontophoresis plus nerve and tendon gliding exercises plus night splint plus activity modification

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (BCTQ symptom severity score) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    1.1 End of treatment (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Three months post-treatment cessation (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (VAS pain on movement) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    2.1 Change from baseline to end of treatment
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (VAS pain at rest) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    3.1 Change from baseline to end of treatment
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in CTS symptoms (VAS pain at night) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    4.1 Change from baseline to end of treatment
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (BCTQ functional status score) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    5.1 End of treatment (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    5.2 Three months post-treatment cessation (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in functional ability (Health Assessment Questionnaire) (3 months or less)1Mean Difference (IV, Random, 95% CI)Totals not selected

    6.1 End of treatment (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    6.2 Three months post-treatment cessation (endpoint values)
1Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 12. Therapeutic ultrasound plus splint versus placebo ultrasound plus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (Tinel's sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 At the end of two weeks treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (Phalen's sign) (3 months or less)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 At the end of two weeks treatment
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (symptom severity score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in functional ability (functional status score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in functional ability (grip strength) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in motor distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in motor nerve conduction velocity (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Short-term improvement in sensory distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Short-term improvement in palm-wrist conduction velocity (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 At the end of two weeks treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 13. Therapeutic ultrasound plus placebo versus sham ultrasound plus NSAID

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term improvement in CTS symptoms (pain and/or paraesthesia) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Endpoint scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (frequency of awakening) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Endpoint scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in median nerve sensory distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 Endpoint scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in sensory nerve action potential (SNAP) (endpoint) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Endpoint scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in sensory nerve action potential (SNAP) (change from baseline) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in median nerve motor distal latency (change from baseline) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Short-term improvement in compound muscle action potential (CMAP) (endpoint) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 Endpoint scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Short-term improvement in compound muscle action potential (CMAP) (change from baseline) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 Endpoint scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Change from baseline scores
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 14. Therapeutic ultrasound plus splint versus sham ultrasound plus splint

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 ITT analysis
151Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Per protocol analysis
145Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 At end of two weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (symptom severity score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 At end of two weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in functional ability (functional status score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 At end of two weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in median nerve motor distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 At end of two weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in median nerve sensory distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 At end of two weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 15. Therapeutic ultrasound plus splint versus therapeutic ultrasound plus splint plus ketoprofen phonophoresis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 ITT analysis
151Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Per protocol analysis
145Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Short-term improvement in CTS symptoms (VAS pain) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 At end of 2 weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Short-term improvement in CTS symptoms (symptom severity score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 At end of 2 weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Short-term improvement in functional ability (functional status score) (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 At end of 2 weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Short-term improvement in median nerve motor distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 At end of 2 weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Short-term improvement in median nerve sensory distal latency (3 months or less)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 At end of 2 weeks treatment (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 At end of 2 weeks treatment (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.3 6 weeks after treatment ended (ITT analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.4 6 weeks after treatment ended (per protocol analysis)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
 

Appendix 1. CENTRAL search strategy

#1"carpal tunnel syndrome"
#2(("nerve entrapment" or "nerve compression" or "entrapment neuropath*") and carpal)
#3(#1 OR #2)
#4ultrasound or ultrasonic*
#5(#3 AND #4)

 

Appendix 2. MEDLINE (OvidSP) search strategy

Database: Ovid MEDLINE(R) <1946 to November Week 3 2012>
Search Strategy:
--------------------------------------------------------------------------------
1 randomized controlled trial.pt. (342057)
2 controlled clinical trial.pt. (85675)
3 randomized.ab. (244680)
4 placebo.ab. (136464)
5 drug therapy.fs. (1586933)
6 randomly.ab. (175076)
7 trial.ab. (253559)
8 groups.ab. (1144975)
9 or/1-8 (2957994)
10 Carpal Tunnel Syndrome.tw. or Carpal Tunnel Syndrome/ (7533)
11 ((nerve entrapment or nerve compression or entrapment neuropath$) and carpal).mp. (1004)
12 10 or 11 (7637)
13 Ultrasonic Therapy/ (7786)
14 13 or (ultrasound or ultrasonic$).mp. (165487)
15 9 and 12 and 14 (55)
16 15 and 20110201:20121127.(ed). (14)

 

Appendix 3. EMBASE (OvidSP) search strategy

Database: Embase <1980 to 2012 Week 47>
Search Strategy:
--------------------------------------------------------------------------------
1 crossover-procedure/ (35555)
2 double-blind procedure/ (111920)
3 randomized controlled trial/ (332920)
4 single-blind procedure/ (16668)
5 (random$ or factorial$ or crossover$ or cross over$ or cross-over$ or placebo$ or (doubl$ adj blind$) or (singl$ adj blind$) or assign$ or allocat$ or volunteer$).tw. (1177991)
6 or/1-5 (1256891)
7 exp animals/ (17803412)
8 exp humans/ (13950314)
9 7 not (7 and 8) (3853098)
10 6 not 9 (1129193)
11 limit 10 to embase (875712)
12 carpal tunnel syndrome/ or carpal tunnel syndrome.tw. (10746)
13 ((nerve entrapment or nerve compression or entrapment neuropath$) and carpal).mp. (1717)
14 12 or 13 (10873)
15 ultrasound therapy/ (6848)
16 15 or (ultrasound or ultrasonic$).mp. (265491)
17 11 and 14 and 16 (70)
18 17 and 20110201:20121127.(dd). (20)

 

Appendix 4. CINAHL Plus (EBSCOhost) search strategy

Tuesday, November 27, 2012 12:24:44 PM

S33 S31 AND S32 14
S32 EM 20110201- 702,548
S31 s18 and s24 and s30 40
S30 s28 or s29 18,959
S29 ultrasound or ultrasonic* 18,959
S28 MM "Ultrasonic Therapy" 1,008
S27 "ultrasound therapy" 147
S26 ultrasound therapy 342
S25 s19 or s20 or s21 or s22 or s23 1,995
S24 s19 or s20 or s21 or s22 or s23 1,995
S23 entrapment neuropath* and carpal 45
S22 nerve compression and carpal 156
S21 nerve entrapment and carpal 58
S20 carpal tunnel syndrome 1,987
S19 (MH "Carpal Tunnel Syndrome") 1,769
S18 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14 or S15 or S16 or S17 574,889
S17 ABAB design* 78
S16 TI random* or AB random* 116,691
S15 ( TI (cross?over or placebo* or control* or factorial or sham? or dummy) ) or ( AB (cross?over or placebo* or control* or factorial or sham? or dummy) ) 239,937
S14 ( TI (clin* or intervention* or compar* or experiment* or preventive or therapeutic) or AB (clin* or intervention* or compar* or experiment* or preventive or therapeutic) ) and ( TI (trial*) or AB (trial*) ) 81,509
S13 ( TI (meta?analys* or systematic review*) ) or ( AB (meta?analys* or systematic review*) ) 24,425
S12 ( TI (single* or doubl* or tripl* or trebl*) or AB (single* or doubl* or tripl* or trebl*) ) and ( TI (blind* or mask*) or AB (blind* or mask*) ) 18,888
S11 PT ("clinical trial" or "systematic review") 106,933
S10 (MH "Factorial Design") 852
S9 (MH "Concurrent Prospective Studies") or (MH "Prospective Studies") 192,209
S8 (MH "Meta Analysis") 15,224
S7 (MH "Solomon Four-Group Design") or (MH "Static Group Comparison") 32
S6 (MH "Quasi-Experimental Studies") 5,714
S5 (MH "Placebos") 7,897
S4 (MH "Double-Blind Studies") or (MH "Triple-Blind Studies") 25,508
S3 (MH "Clinical Trials+") 151,619
S2 (MH "Crossover Design") 9,918
S1 (MH "Random Assignment") or (MH "Random Sample") or (MH "Simple Random Sample") or (MH "Stratified Random Sample") or (MH "Systematic Random Sample") 59,145

 

Appendix 5. AMED (OvidSP) search strategy

Database: AMED (Allied and Complementary Medicine) <1985 to November 2012>
Search Strategy:
--------------------------------------------------------------------------------
1 Randomized controlled trials/ (1560)
2 Random allocation/ (304)
3 Double blind method/ (454)
4 Single-Blind Method/ (33)
5 exp Clinical Trials/ (3227)
6 (clin$ adj25 trial$).tw. (5526)
7 ((singl$ or doubl$ or treb$ or trip$) adj25 (blind$ or mask$ or dummy)).tw. (2273)
8 placebos/ (524)
9 placebo$.tw. (2532)
10 random$.tw. (13034)
11 research design/ (1687)
12 Prospective Studies/ (522)
13 meta analysis/ (112)
14 (meta?analys$ or systematic review$).tw. (1931)
15 control$.tw. (28043)
16 (multicenter or multicentre).tw. (743)
17 ((study or studies or design$) adj25 (factorial or prospective or intervention or crossover or cross-over or quasi-experiment$)).tw. (9917)
18 or/1-17 (43215)
19 carpal tunnel syndrome/ or carpal tunnel syndrome.tw. (455)
20 ((nerve entrapment or nerve compression or entrapment neuropath$) and carpal).mp. (55)
21 19 or 20 (456)
22 ultrasonic therapy/ (235)
23 22 or (ultrasound or ultrasonic$).mp. (1427)
24 18 and 21 and 23 (13)
25 24 and 20110201:20121127.(up). (1)

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

Last assessed as up-to-date: 27 November 2012.


DateEventDescription

5 February 2013New citation required but conclusions have not changedSearches updated to November 2012 and results incorporated

8 January 2013New search has been performedOne new RCT identified from updated searches and included.

Davis 1998 was incorrectly included in the previous version of this review (Page 2012a) and has been excluded from the current version. Davis 1998 compared the effect of therapeutic ultrasound delivered along with manual thrusts, massage and wrist splints to ibuprofen and wrist splint, so the additional effect of therapeutic ultrasound cannot be determined in this study. Davis 1998 is currently included in the 'Exercise and mobilisation interventions for carpal tunnel syndrome' review (Page 2012b).

The meta-analyses reported in the previous version of this review (Page 2012a) under Comparison 1: Therapeutic ultrasound verus placebo have been removed. The reason for removal is that following publication of the review, we determined that the correlation between wrists in participants with bilateral carpal tunnel syndrome had not been accounted for in the analyses reported by Ebenbichler 1998 and it was unclear whether an appropriate analysis had been conducted by Oztas 1998. Based on the potentially inappropriate analyses reported in these trials, we decided it was inappropriate to pool results in a meta-analysis and have instead presented study-specific effect estimates per trial.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

MATTHEW PAGE (MP) was involved in the following stages of the review: design of the review (in collaboration with DOC); undertaking the search of studies; screening the search results (independently of, but in addition to DOC); organising retrieval of papers; screening retrieved papers against inclusion/exclusion criteria (independently of, but in addition to DOC); appraising the risk of bias of papers (independently of, but in addition to DOC and VP); extracting data from papers (independently of, but in addition to DOC, VP, and NMW); writing to study investigators for additional information; summarising the risk of bias of the studies (independently, but in addition to DOC and VP); compiling the summary of comparisons, tables of included, excluded, awaiting and ongoing studies; entering data into RevMan; performing analysis of data; interpreting the findings; writing of the review (in collaboration with DOC, VP and NMW); final approval of the version to be published.

DENISE O'CONNOR (DOC) was responsible for: design of the review (in collaboration with MP); developing the search strategy; screening the search results (independently of, but in addition to MP); screening retrieved papers against inclusion/exclusion criteria (independently of, but in addition to MP); appraising the risk of bias of papers (independently of, but in addition to MP and VP); extracting data from papers (independently of, but in addition to MP, VP and NMW); checking data entered into RevMan by MP (independently, but in addition to NMW) writing to study investigators for additional information; summarising the risk of bias of the studies (independently of, but in addition to MP and VP); writing the review (with contribution from MP, VP and NMW).

VERONICA PITT (VP) was involved in the following stages of the review: extracting data from papers (independently of, but in addition to MP, DOC and NMW); appraising the risk of bias of papers (independently of, but in addition to MP and DOC); summarising the risk of bias of papers (independently of, but in addition to MP and DOC) contributing to the writing of the review (in collaboration with MP, DOC and NMW).

NICOLA MASSY-WESTROPP (NMW) was involved in the following stages of the review: extracting data from papers (independently of, but in addition to MP, DOC and VP); checking data entered into RevMan (independently, but in addition to DOC); contributing to the writing of the review (in collaboration with MP, DOC, and VP).

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms
 

Internal sources

  • Australasian Cochrane Centre, Australia.

 

External sources

  • No sources of support supplied

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

This is a split review replacing the therapeutic ultrasound interventions included in the previous review titled 'Non-surgical treatment (other than steroid injection) for carpal tunnel syndrome' (O'Connor 2003).

In the review by O'Connor et al. (O'Connor 2003), types of outcome measures included in the review were as follows:

Primary outcome:

The primary outcome measure was improvement in clinical symptoms, such as pain and paraesthesiae, at least three months after the end of treatment.

Secondary outcome measures included:
1. improvement in functional status and/or health-related quality of life parameters at least three months after treatment;
2. improvement in objective physical examination measures, such as grip, pinch strength, and sensory perception at least three
months after treatment;
3. improvement in neurophysiological parameters after three months after treatment;
4. clinical improvement at less than three months of follow-up;
5. clinical improvement at one year after treatment;
6. need for surgical release of the flexor retinaculum during follow-up.

The outcomes reported in this review have been modified from the original review (O'Connor 2003) to make them as consistent as possible with other Cochrane reviews on carpal tunnel syndrome (O'Connor 2012; Page 2012b; Page 2012c; Marshall 2007; Scholten 2007; Verdugo 2008).

Assessment for study risk of bias has been performed using The Cochrane Collaboration's 'Risk of bias' tool in this update of the review. We have included a 'Summary of findings' table.

The 'Types of interventions' criteria for considering studies for this review has been modified to make it clearer that trials where therapeutic ultrasound was used as an adjunct to another treatment were included only if the comparison provided information on the additional effect of the therapeutic ultrasound intervention. This modification resulted in the exclusion of Davis 1998 which was incorrectly included in the previous version of this review (Page 2012a). Davis 1998 compared the effect of therapeutic ultrasound delivered along with manual thrusts, massage, and wrist splints, to ibuprofen and wrist splint, so the additional effect of therapeutic ultrasound cannot be determined in this study. Davis 1998 is currently included in the 'Exercise and mobilisation interventions for carpal tunnel syndrome' review (Page 2012b).

 

Notes

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Index terms

This is one of six reviews that will update the currently published review 'Non-surgical treatment (other than steroid injection) for carpal tunnel syndrome' (O'Connor 2003). Three, in addition to this title, have been published as new reviews (O'Connor 2012; Page 2012b; Page 2012c) and the scope of an existing review (Marshall 2007) is to be widened to include oral corticosteroids. When all six reviews are published we will withdraw the original review from publication. This review includes a new search, revised review question and selection criteria, updated methodology and an updated review team.

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Bakhtiary 2004 {published data only}
  • Bakhtiary AH, Rashidy-Pour A. Ultrasound and laser therapy in the treatment of carpal tunnel syndrome. Australian Journal of Physiotherapy 2004;50:147-51. [PUBMED: 15482245]
Baysal 2006 {published data only}
Bilgici 2010 {published data only}
  • Biligici A, Ulusoy H, Canturk F. The comparison of ultrasound treatment and local steroid injection plus splinting in the carpal tunnel syndrome: a randomized controlled trial. Bratislavske Lekarske Listy 2010;111(12):659-65. [PUBMED: 21384736]
Dincer 2009 {published data only}
  • Dincer U, Cakar E, Kiralp MZ, Kilac H, Dursun H. The effectiveness of conservative treatments of carpal tunnel syndrome: splinting, ultrasound, and low-level laser therapies. Photomedicine and Laser Surgery 2009;27(1):119-25. [PUBMED: 19196106]
Duymaz 2012 {published data only}
  • Duymaz T, Sindel D, Kesiktaş N, Müslümanoğlu L. Efficacy of some combined conservative methods in the treatment of carpal tunnel syndrome: a randomized controlled clinical and electrophysiological trial. Turkish Journal of Rheumatology 2012;27(1):38-46.
Ebenbichler 1998 {published data only}
  • Ebenbichler GR, Resch KL, Nicolakis P, Wiesinger GF, Uhl F, Ghanem A, et al. Ultrasound treatment for treating the carpal tunnel syndrome: randomised 'sham' controlled trial. BMJ 1998;316(7133):731-5. [PUBMED: 9529407]
Ekim 2008 {published data only}
  • Ekim A, Colak E. Ultrasound treatment in carpal tunnel syndrome: a placebo controlled study. Turkiye Fiziksel Tip ve Rehabilitasyon Dergisi 2008;54(3):96-101. [EMBASE: 2008610958]
Koyuncu 1995 {published data only}
  • Koyuncu H, Unver FN, Sahin U, Togay P. 1MHz - 3MHz ultrasound applications in carpal tunnel syndrome [Karpal tunel sendromunda 1MHz - 3MHz ultrason uygulamasi]. Fizik Tedavi ve Rehabilitasyon Dergisi 1995;19:141-5. [EMBASE: 1995350540]
Oztas 1998 {published data only}
Piravej 2004 {published data only}
  • Piravej K, Boonhong J. Effect of ultrasound thermotherapy in mild to moderate carpal tunnel syndrome. Journal of the Medical Association of Thailand 2004;87(Suppl 2):S100-6. [PUBMED: 16083171]
Yildiz 2011 {published data only}
  • Yildiz N, Atalay NS, Gungen GO, Sanal E, Akkaya N, Topuz O. Comparison of ultrasound and ketoprofen phonophoresis in the treatment of carpal tunnel syndrome. Journal of Back and Musculoskeletal Rehabilitation 2011;24(1):39-47. [PUBMED: 21248399]

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Avci 2004 {published data only}
  • Avci S, Günaydin R, Öztura I. Comparison of effectiveness of splint and splint with physical therapy in carpal tunnel syndrome [Karpal tunel sendromunda atel ve atel ile birlikte fizik tedavinin etkinliginin karsilastirilmasi]. Ftr Turkiye Fiziksel Tip Ve Rehabilitasyon Dergisi 2004;50(2):22-6.
Bakhtiary 2011 {published data only}
  • Bakhtiary AH, Fatemi E, Emami M, Malek M. Comparing the effects of iontophoresis and phonophoresis of dexamethasone on the treatment of carpal tunnel syndrome. Koomesh 2011;13(1):83-93.
Coskun 2011 {published data only}
  • Coskun G, Kirdi N, Can F. Effects of wrist traction on pain and hand function in the treatment of carpal tunnel syndrome [Karpal tünel sendromunun tedavisinde bilek traksiyonunun ağrı ve elin fonksiyonelliği üzerine etkisi]. Fizyoterapi Rehabilitasyon 2011;22(1):3-10.
Dakowicz 2005 {published data only}
  • Dakowicz A, Latosiewicz R. The value of iontophoresis combined with ultrasound in patients with the carpal tunnel syndrome. Roczniki Akademii Medycznej w Bialymstoku 2005;50(Suppl 1):196-8. [PUBMED: 16119664]
Davis 1998 {published data only}
  • Davis PT, Hulbert JR, Kassak KM, Meyer JJ. Comparative efficacy of conservative medical and chiropractic treatments for carpal tunnel syndrome: a randomized clinical trial. Journal of Manipulative & Physiological Therapeutics 1998;21(5):317-26. [PUBMED: 9627862]
Deliss 1998 {published data only}
  • Deliss L. Ultrasound treatment for carpal tunnel syndrome: emphasis must be on return of sensation and function. BMJ 1998;317(7158):601. [PUBMED: 9721127]
Gurcay 2012 {published data only}
  • Gurcay E, Unlu E, Gurcay AG, Tuncay R, Cakci A. Assessment of phonophoresis and iontophoresis in the treatment of carpal tunnel syndrome: a randomized controlled trial. Rheumatology International 2012;32(3):717-22.
Hui 2004 {published data only}
Jarvik 2009 {published data only}
  • Jarvik JG, Comstock BA, Kliot M, Turner JA, Chan L, Heagerty PJ, et al. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet 2009;374(9695):1074-81. [PUBMED: 19782873]
Lucas 2002 {published data only}
  • Lucas N. A critical appraisal of an article examining the efficacy of ultrasound treatment for carpal tunnel syndrome. Journal of Osteopathic Medicine 2002;5(1):28-30.
Robertson 2001 {published data only}
Sucher 1999 {published data only}
Taspinar 2007 {published data only}
  • Taspinar S, Sahin F, Ercalik C, Kuran B, Barkut K, Celik M, et al. Comparison of the efficacy of corticosteroid injection, night splint and physiotherapy in diabetic corpal tunnel syndrome. Turkiye Fiziksel Tip ve Rehabilitasyon Dergisi 2007;53(2):54-60.
Toro 1997 {published data only}
  • Toro JR, Rodriguez IG, Espinel JP, Caballero MLG, Rodriquez FA. Chronic idiopathic carpal tunnel syndrome: effectiveness of iontophoresis-corticoid treatment compared with iontophoresis-placebo (galvanization). Rehabilitacion 1997;31(2):118-26.
Walling 1998 {published data only}
  • Walling AD. Effects of ultrasound treatment in carpal tunnel syndrome. American Family Physician 1998;58(4):961-2.

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Ashworth 2010
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Atroshi 1999
Binder 1985
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Bland 2005
Charles 2009
Deeks 2011
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Dwan 2011
Gelfman 2009
Gerritsen 2002
  • Gerritsen AAM, De Krom MCTFM, Struijs MA, Scholten RJPM, De Vet HCW, Bouter LM. Conservative treatment options for carpal tunnel syndrome: a systematic review of randomised controlled trials. Journal of Neurology 2002;249(3):272-80. [PUBMED: 11993525]
Goodyear-Smith 2004
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Higgins 2011a
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Higgins 2011b
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Higgins 2011c
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Hong 1988
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Hopewell 2007
Huisstede 2010
  • Huisstede BM, Hoogvliet P, Randsdorp MS, Glerum S, Van Middelkoop M, Koes BW. Carpal tunnel syndrome. Part 1: Effectiveness of nonsurgical treatments - a systematic review. Archives of Physical Medicine and Rehabilitation 2010;91(7):981-1004. [PUBMED: 20599038]
Keith 2009
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Kerwin 1996
Kirkham 2010
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Lehmann 1974
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Levine 1993
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Marshall 2007
Muller 2004
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O'Connor 2012
Ono 2010
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Page 2012b
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Piazzini 2007
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Rutjes 2010
Savović 2012
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Scholten 2007
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References to other published versions of this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
O'Connor 2003
  • O'Connor D, Marshall S, Massy-Westropp N. Non-surgical treatment (other than steroid injection) for carpal tunnel syndrome. Cochrane Database of Systematic Reviews 2003, Issue 1. [DOI: 10.1002/14651858.CD003219]
Page 2012a
  • Page MJ, O'Connor D, Pitt V, Massy-Westropp N. Therapeutic ultrasound for carpal tunnel syndrome. Cochrane Database of Systematic Reviews 2012, Issue 1. [DOI: 10.1002/14651858.CD009601]