Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Page, 2012

Yes

Yes

Yes

Yes

Not applicable

Yes

No

No

Yes

Page, 2010_1

Yes

Yes

Yes

Yes

Not applicable

Yes

No

No

Yes

Page, 2012_2

Yes

Yes

Yes

Yes

Not applicable

Yes

No

No

Yes

Medina McKeon, 2008

Yes

Yes

No

Yes

Not applicable

Yes

No

No

No

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Jarvik, 2009

Computer generated random allocation stratified by site

Unlikely

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Gerritsen, 2002

“randomly allocated” stratified by center, poermuted blocks of 4

Unclear

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Unlikely

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Page, 2012

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs and quasi randomized studies

Literature search up to january 2012

Study design: RCTs and quasi randomized studies

Setting and Country: Australia

Source of funding:

Non-commercial

Inclusion criteria SR:

1) studies comparing any form of exercise or mobilisation with no treatment, placebo or other non-surgical intervention

2) participants: all had diagnosis CTS

Exclusion criteria SR:

1) studies comparing mobilisation to surgical treatment

16 studies included

Groups comparable at baseline? Unclear

Describe intervention:

A mobilisation intervention for the treatment of carpal tunnel syndrome (CTS)

Sometimes delivered as part of a multi-component intervention (in 9/16studies)

Describe control:

1) no treatment control (2 studies)

2) another mobilisation intervention (3 studies)

3) another non-surgical intervention such as splinting or ultrasound (11 studies)

End-point of follow-up:

10 days – 11 months

For how many participants were no complete outcome data available?

(intervention/control)

4 studies could be assessed for incomplete outcome of data

-in 2 of these studies the risk of bias due to incomplete outcome data was deemed Low

-in 2 other studies the risk of bias was deemed unclear

Outcome measure-1: short term overall imporvement:

1) exercise or mobilisation versus no treatment:

Improvement of symptoms was better in mobilisation group (2 very small studies, not randomised)

2) different mobilisation interventions

No difference in amount of improvement of symptoms between two different mobilisation interventions (2 studies)

3) Nerve mobilisation (as part of multiple interventions) versus control

Varying results, heterogenous studies and interventions, quality of studies very low, thus no clear conclusions can be drawn (9 studies)

Facultative:

Brief description of author’s conclusion:

There is limited and very low quality evidence of benefit for all of a diverse collection of exercise and mobilisation interventions for CTS.

Personal remarks on study quality, conclusions, and other issues (potentially) relevant to the research question:

16 small studies of low quality included, most studies were deemed to have a high overall risk of bias, also heterogeniety between studies was high

Page, 2012_1

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs and quasi randomized studies

Literature search up to january 2012

Study design: RCTs and quasi randomized studies

Setting and Country: Australia

Source of funding:

Non-commercial

Inclusion criteria SR:

1) studies comparing spliniting with no treatment (or placebo) or other non-surgical treatments

Exclusion criteria SR:

1) studies comparing splinting with surgical treatment

2) Patients who had previous surgery for CTS

19 studies included

Groups comparable at baseline? Unclear

Describe intervention:

Splinting

Or

Splint together with other non-surgical intervention (5/19 studies)

Describe control:

1) no treatment (2 studies)

2) different splint designs (5 studies)

3) different splint-wearing regiments (1 study)

4) other non-surgical intervention (12 studies)

End-point of follow-up:

4 weeks – 12 months

Most studies 4-8 weeks

For how many participants were no complete outcome data available?

Three studeis assessed risk of outcomes after 3 months post-treatment: 2 studies were rated as low risk and one study as high risk (attrition bias)

Outcome measure-1

Defined as short-term overall improvement

1) Splint versus no treatment

Higher overall improvement in splint group (RR 3.86, 95% CI: 2.29-6.61) (1 study, no blinding)

2)neutral splint versus extension splint

Likelier improvement in neutral splint goup (RR: 2.43 (95% CI: 1.12 – 5.28) ( 1 study, quasi-randomised)

Facultative:

Brief description of author’s conclusion:

Overall there is limited evidence that a splint worn at night is more effective than no treatment in the short term. But there is insufficient evidence regarding the effectiveness and safety of one splint design or wearing regimen over others, and of splint over other non-surgical interventions for CTS.

Personal remarks on study quality, conclusions, and other issues (potentially) relevant to the research question:

19 small studies of low quality included, most studies were deemed to have a high overall risk of bias, also heterogeniety between studies was high

Page, 2012_2

SR and meta-analysis of RCTs and quasi randomized studies

Literature search up to february 2011

Study design: RCTs and quasi randomized studies

Setting and Country: Australia

Source of funding:

Non-commercial

Inclusion criteria SR:

1) studies comparing therapeutic ultrasound with no treatment, placebo, or other non-surgical interventions

2) participants: diagnosis of CTS

Exclusion criteria SR:

1) studies comparing ultrasound to surgical interventions

2) participants who had previous surgery for CTS

11 studies included

Groups comparable at baseline? Unclear

Describe intervention:

Therapeutic ultrasound

Or therapeutic ultrasound as part of a multi-component intervention (6/11 studies)

Describe control:

1) placebo (2 studies)

2) another ultrasound regimen (1 study)

3) another non-surgical intervention (8 studies)

End-point of follow-up:

2 weeks – 6 months

(4-12 weeks in most studies)

For how many participants were no complete outcome data available?

8 studies rated as low risk of bias duet o incomplete outcome, 2 as unclear and one study as high risk of bias

Outcome measure:

Defined as short term overall improvement

1) ultrasound versus no treatment

therapeutic ultrasound may increase the chance of experiencing short-term overall improvement at the end of seven weeks

treatment (RR 2.36; 95% CI 1.40 to 3.98), (1 study, n=68, high loss to follow-up)

2) therapeutic ultrasound plus plint versus splint alone

at three months, post-treatment therapeutic ultrasound plus splint

increased the chance of short-termoverall improvement (patient satisfaction) when compared with splint alone (RR 3.02; 95%CI 1.36

to 6.72), but decreased the chance of short-term overall improvement when compared with low-level laser therapy plus splint (RR 0.87;

95% CI 0.57 to 1.33), (1 study, n=60, no random allocation)

Differences between groups receiving different frequencies and intensities of ultrasound, and between ultrasound

as part of a multi-component intervention versus other non-surgical interventions, were generally small and not statistically significant

for symptoms, function, and neurophysiologic parameters.

Only four studies measured adverse effects, none of which identified adverse

effects due to therapeutic ultrasound.

Facultative:

Brief description of author’s conclusion:

There is only poor quality 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 CTS. There is insufficient evidenc e to support the greater benfit of one ultrasound regimen over another or to support the use of ultrasound as a treatment with greater efficacy compared to other non-surgical interventions for CTS, such as splinitng, exercises and oral drugs.

Personal remarks on study quality, conclusions, and other issues (potentially) relevant to the research question:

11 small studies of low quality included, most studies were deemed to have a high overall risk of bias, also heterogeniety between studies was high.

Medina McKeon, 2008

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs / cohort / case-control studies

Literature search up to April 2008

Study design: RCT or cohort study

Setting and Country: United States of America

Source of funding:

Not reported

Inclusion criteria SR:

1) studies that compared neural gliding exercises to other forms of non-surgical treatment

2) at least one of the following outcome measures was reported:

-pain

-symptoms

-self-reported function

-Phalen and Tinel test

-two-point dicrimination

-grip strength and pinch strength

Exclusion criteria SR:

-

6 studies included

Groups comparable at baseline? Unclear

Describe intervention:

Neural gliding exercises

Describe control:

Other non-surgical intervention

End-point of follow-up:

Not reported

For how many participants were no complete outcome data available?

Not reported

Outcome measure

-pain

3 studies, effect size 95% CI: -0.3 to -2.1 (in favor of neural gliding)

-symptoms

4 studies, effect size 95% CI: -0.4 to 0.1 (in favor of neural gliding)

-self-reported function

4 studies, effect size 95% CI: -1.3 to 0.3 (in favor of neural gliding)

-Phalen test

4 studies, RR 95% CI: 0.3 to 3.9 (in favor of neural gliding)

-Tinel test

2 studies, RR 95% CI: 0.1 to 2.0 (in favor of neural gliding)

-two-point dicrimination

2 studies, effect size 95% CI: -1.1 to 0.8 (in favor of neural gliding)

-grip strength

5 studies, effect size 95% CI: -3.8 to 4.2 (in favor of neural gliding)

-pinch strength

9 studies, effect size 95% CI: -2 to 3.8 (in favor of neural gliding)

Facultative:

Brief description of author’s conclusion: The efficacy of neural gliding is unclear. More research is necessary to determine the population for which this intervention is effective.

Personal remarks:

-unclear whether included studies were RCTs or observational studies

-although studies were pooled, the studies were too heterogenuous for pooling, thus the conclusions are described very briefly

Level of evidence: GRADE Very low for all studies

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Jarvik, 2009

Type of study: randomised parallel group trial

Setting: outpatients from four academic and private practice parctice centers

Country: United States of America

Source of funding: non-commercial

Inclusion criteria:

1) symptoms for at least 2 weeks in at least two digits on one hand that include thumb, index or 1 ring finger

2) classical, probable or possible carpal tunnel syndrome on hand pain diagram

3) failure for at least two consecutive weeks of non-surgical treatment, including a trial of wrist splints

4) in the absence of electrodiagnostic criteria night pain that woke them and a positive flick test (shaking of wrist relieves symptoms)

5) able to complete English language questionnaires and telephone interviews

6) plan to stay in the region for 12 months

7) age ≥18 years

8) willing to undergo surgery under randomisation

Electrodiagnistic inclusion criteria (any one of the following)

1) median motor latency at the wirst ≥4.4ms

2) median ulnar sensory difference (14cm digit IV to wrist) >0.4ms

3) median ulnar sensory difference (8cm midpalm) >0.3ms

4) median radial sensory difference (10cm thumb to wrist) >0.5ms

5) combined sensory index ≥1.0ms

Exclusion criteria:

1) severe carpal tunnel syndrome (CTS)

2) previous CTS surgery on the study hand

3) any wirst or hand surgery within the previous 6 months

4) moderate-to severe arthritis involving the study hand of the wirst

5) known tumour mass or deformity of the study hand or wirst

6) history of severe trauma tot he study hand or wrist

7) current pregnancy or lactation

8) evidence of diffuse peripheral neuropathy or cervical radiculopathy

N total at baseline: 116

Intervention: 57

Control: 59

Important prognostic factors²:

For example

age ± SD:

I: 50 ± 10

C: 51 ± 9

Sex:

I: 51% M

C: 42% M

Groups comparable at baseline?

yes

Describe intervention (treatment/procedure/test):

Open or endoscopic carpal tunnel surgery

(depending on surgeon’s preference)

Describe control (treatment/procedure/test):

Non-surgical therapy

1) ibuprofen 200mg 3 times/day

2) customized hand therapy – 6 visits in 6 weeks

3) for individuals who did not improve: therapeutic ultrasound: 2-4 per week for 6 weeks

Length of follow-up:

12 months

Follow-up at 6 weeks, 3, 6, 9 and 12 months

Loss-to-follow-up:

Intervention:

8 (14%)

Reasons not reported

Control:

7 (12%)

Reasons not reported

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ):

Function score:

Δ-0.40 (95% CI: 0.11 – 0.70, p=0.08)

Symptoms score:

Δ0.34 (95% CI: 0.02 – 0.65, p=0.04)

No clincially important adverse events.

No surgical complications.

Power analysis adjusted mid-study to detect a greater treatment difference (from 0.40 to 0.50 on the CTSAQ function scale)

Gerritsen, 2002

Type of study: randomized controlled trial

Setting: 13 outpatient clinics

Country: the Netherlands

Source of funding: not reported

Inclusion criteria:

1) pain, paresthesia and/or hypesthesia in the are innervated by the median hand nerve

2) electrophysiological confirmation of the diagnosis

3) age ≥18 years

4) ability to complete written questionnaires (in Dutch)

Exclusion criteria:

1) previous treatment with splinting or surgery

2) a history of wrist trauma or surgery

3) a history suggesting underlying causes of CTS

4) clinical signs or symptoms or electrophysiological findings suggesting conditions that could mimic CTS or interfere with its validation

5) severe thenar muscle atrophy

N total at baseline: 176

Intervention: 89

Control: 87

Important prognostic factors²:

For example

age ± SD:

I: 49 ± 12

C: 49 ± 11

Sex:

I: 13% M

C: 24% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Wrist splinting during thenight for at least 6 weeks

Describe control (treatment/procedure/test):

Open carpal tunnel release

Length of follow-up:

18 months

Loss-to-follow-up:

Intervention:

10 (11%)

Reasons:

3 lack of time

1 not satisfied with treatment

1 unable to go to hospital at 12 months

4 did not return questionnaire

1 other

Control:

19 (22%)

Reasons:

8 refused surgery

1 lack of time

1 death (cancer)

2 unable to go to hospital at 12 months

5 did not return final questionnaire

2 other

Incomplete outcome data:

As above

Outcome measures and effect size (include 95%CI and p-value if available):

Improvement after 3 months:

62/78 (80%) in surgery group

46/86 (56%) in splinting group

Difference of 26% (95% CI: 12-40%, p<0.001)

Improvement after 18 months:

62/68 900%) in surgery group

59/79 (75%) in splinting group

Difference of 15% (95% CI: 3-27%, p=0.02)

However by that time 32/79 (41%) patients in the splint group had recieved surgery

By 18 months 32/79 (41%) patients in the splint group had recieved surgery