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Therapeutic effects of low-level laser on lateral epicondylitis from differential interventions of chinese-western medicine: Systematic review

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Therapeutic Effects of Low-Level Laser on Lateral

Epicondylitis from Differential Interventions

of Chinese-Western Medicine: Systematic Review

AU3 c Wen-Dien Chang,1Jih-Huah Wu,2 Wen-Ju Yang,1and Joe-Air Jiang3

Abstract

Background: Low-level laser therapy (LLLT) is a conservative treatment for lateral epicondylitis (LE), but it is also an alternative intervention between the very different approaches of Chinese and Western medicine. Objective: The purpose of this study was to systematically review and meta-analyze the therapeutic effects of LLLT on LE. Methods: We searched several electronic databases, including Medline, PubMed, and CINAHL

AU4 c ,

and explored studies that were randomized controlled trials on the therapeutic effects of LLLT on LE from 1990 to February 2009. These studies were systematically reviewed for the difference in therapeutic effects among various LLLTs on acupuncture points and on tender and myofascial trigger points (MTrPs). The reviewed therapeutic effects included pain, grip strength, range of motion (ROM), and weight tests, and were compared by meta-analysis. Results: We selected ten articles, and in seven of them the irradiation was conducted on tender points or MTrPs in the experimental groups. In two other articles, the irradiation was conducted on acupuncture points, and the last one was conducted on both kinds of points. Only three articles provided sufficient data for meta-analysis. The results revealed that applying LLLT on tender points or MTrPs is an effective means to improve the effect size (ES) of pain release after treatment (pooled ES: 0.71, 95% CI: 0.82*0.60) and follow-up (pooled ES: 1.05, 95% CI: 1.16*0.94). LLLT application was also able to increase the grip force, ROM, and weight test ( p < 0.05). Conclusions: We suggest that using LLLT on tender points or MTrPs of LE could effec-tively improve therapeutic effects.

Introduction

L

ateral epicondylitis(LE), also known as tennis elbow, is a commonly seen musculoskeletal disease in the dom-inate hand stemming from overuse or repeated wrist move-ments. Clinical symptoms include tender points, myofascial trigger points (MTrPs), and pain induced in the lateral epi-condyle or muscles attached to forearm when using the arms, especially when grasping and lifting heavy objects.1The di-agnosis of LE is usually confirmed by provoking tests, in-cluding resistive contraction of wrist or finger extensors, to reproduce or aggravate clinical symptoms. These symptoms can affect functional movements and activities and can last for 3 to 6 years.2 Therefore, most patients receive treatments during the first 6 to 24 months.3Treatment strategies include steroid injections, non-steroidal anti-inflammatory drugs (NSAIDs), Chinese medicine, and physical therapy.1

A common suggestion among Chinese and Western prac-titioners for acute LE is to rest immediately, to stop all painful activities, and to reduce inflammation with an ice pack. In traditional Chinese medicine (TCM), dialectical thinking and approach would suggest using acupuncture and external ointments. An example is acupuncture at Shousanli (LI10) and Quchi (LI11) points, followed by an external plaster to alle-viate heat in order to release pain and to promote blood cir-culation and to remove blood-stasis.4In the Western physical therapy approach, hot packing, modality, orthosis, and ki-nesiotaping of the elbow are normally recommended.1 Mod-ality approaches include electrical stimulation, ultrasound, and low-level laser therapy (LLLT).5TCM therapy may also include local massage and acupuncture accompanied by herbs providing the effects of warming channels to dredge collaterals, promoting blood circulation to remove blood-stasis, and improving qi flow.4Based on the pain-relieving

1

Department of Rehabilitation Medicine, Da Chien General Hospital, Department of Bio-Industrial Mechatronics Engineering, National

Taiwan University,Taiwan. b AU2

2

Department of Biomedical Engineering, Ming Chuan University,Taiwan. b AU2

3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taiwan. b AU2

Photomedicine and Laser Surgery Volume 00, Number 00, 2009

ª Mary Ann Liebert, Inc.

Pp. 1–11

DOI: 10.1089=pho.2009.2558

1

PHO-2009-2558-Chang_1P Type: research-article

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theory of acupuncture, finding the appropriate treatment points on the channels could consequently bring about the release of endorphins and an increase in 5-hydroxy trypto-phan in the brain.4In addition, a TCM explanation for the effects of acupuncture is that qi or vital energy flows elicited by needling can remove energy-stagnation and then promote a balanced energy system to achieve pain-relieving effects.6 Symptoms of LE can bring about MTrPs in the wrist and finger extensors. Melzack et al. indicated that the correlation between MTrPs and the corresponding acupuncture points was 71%.6However, Hong and Simons7suggested that the etiology of MTrPs was related to sensitized nociceptors and dysfunctional endplates, and that the MTrPs were not the same as acupuncture points. Some ‘‘MTrPs’’ are actually ‘‘Ashi points’’ in acupuncture, but some ‘‘Ashi points’’ are not MTrPs.8 Moreover, tender points caused by LE were also found to be similar to Ashi points.9However, Simons et al.10

proposed that MTrPs were different from tender points. Pressing on tender points could induce local, but not referred, pain while pressing on MTrPs could cause referred pain and local twitch response. LLLT has been applied in laser acu-puncture, which has the benefits of being painless, sterile, safe, dose controllable, and easy to operate.11In summary, we examined three choices when applying LLLT on LE: emitting on acupuncture points, tender points, and MTrPs.

In LLLT, a low dose is usually used to induce photo-biochemical effects without causing significant changes in tissue level

AU5 c . Previous studies have shown that LLLT could promote the synthesis of prostaglandin and consequently reduce pain.12,13 Furthermore, arachidonic acid would be transported into endothelial and smooth muscle cells to en-hance dilation of blood vessels and reduce inflammation.14 Such laser irradiation would not burn or damage tissue, but would change tissue metabolism through a process called ‘‘Photobiomodulation’’.15 Some evidence derived from ani-mal studies showed that LLLT could promote collagen fiber formation and as a result facilitate tendon repair.16However, collagen fiber formation could be obviously affected by fac-tors such as dosage and wavelength of the laser.16 Some studies also found that a power density more than 100 mW=cm2might adversely inhibit the activity of fibrous tissue and the synthesis of collagen fiber.17,18In summary,

LLLT could cause changes in biochemistry in cells and tissue through photobiomodulation, and these changes could be affected by different dosage and wavelength of laser.

In the past, the most appropriate model explaining pho-tobiomodulation was the Arndt-Schultz law, which stated that a certain level of laser energy is required to reach the threshold and hence trigger biological stimulation.12

Differ-ent media of laser irradiation result in differDiffer-ent depths of penetration and various effects. Although in some systematic reviews, it had been substantially discussed that various clinical doses, methods, and modes of LLLT could bring about different treatment effects,19,20there are still very few papers investigating the different effects of Western and Chinese medicine. Therefore, the aim of this systematic re-view and meta-analysis study was to investigate the effec-tiveness of applying LLLT on LE in both traditions. The discussed effectiveness includes pain of elbow, grasp force, and other related measurements. These may in turn benefit both Western and Chinese medicine therapies.

Materials and Methods

This study searched papers published between January of 1990 and February of 2009 through Medline, PubMed and

CINAHL. Key words included low-level laser, lateral epi- b AU4 condylitis, tennis elbow, and laser acupuncture. The selected

articles were also utilized to assess other related studies. Because this systematic review and meta-analysis study was designed to understand the effectiveness of LLLT on LE, only studies of randomized controlled trials (RCTs) were in-cluded that met the following criteria: (1) the subjects were diagnosed as having LE of elbow with pain induced by re-sisted extension of the wrist, (2) LLLT was used on the in-flamed tendons, MTrPs, or acupuncture points as a treatment of LE, (3) the study must have involved randomized grouping with single- or double-blind design, and (4) the control group must have received a non-laser or placebo laser treatment with zero output. Based on these inclusions, 10 studies were selected.21–30 Their quality was rated according to Phy-siotherapy Evidence Database scale (PEDro) guidelines.31

Methods of evaluation used in related studies were chosen to assess pain, muscle power, function, and effectiveness after applying LLLT to LE.

(1) Pain measurement: This was to assess the effectiveness of treatment by observing subjects’ movements and ask-ing them to grade their pain under natural conditions or during press palpation. Based on past experience, sub-jects quantitatively expressed their present pain ac-cording to the most commonly used Visual Analogue Scale (VAS) with 0 for no pain and 10 for the worst possible pain. Another method was to rate pain by Five Point Verbal (FPV) scale, in which 0 represents no pain, 1 represents mild pain, 2 represents moderate pain, 3 represents severe pain, and 4 represents very severe pain.

(2) Grasp or finger grip force: This was measured by a grip dynamometer or a vigorimeter to assess the grip force of the hand. A pinch dynamometer was also used to measure the pinch force of the fingertips, to represent muscle strength during functional movements. (3) Muscle test: Subjects were given resistive tests of

fore-arm movements, such as pronation, supination, wrist extension and middle finger test, to see if any symp-tom was induced. The Mercy Wedge Pro (MWP) ex-ercise was also used to assess pain during wrist extension. Weight tests ranging from 1 to 4 kg served as a means of measurement to quantify the weight induced symptoms when straightening the wrist. An-other test to quantify muscle strength was the manual muscle testing (MMT) which rates muscle strength with six grades.

(4) Range of motion (ROM) of the wrist joint: The painless range of motion of wrist joint was measured by a go-niometer.

(5) Pain pressure threshold (PPT): Tender points were as-sessed quantitatively by applying a pressure algometer directly on muscles until the pain threshold is deter-mined.

(6) Questionnaire and treatment effects: Upper extremity function was assessed by the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), which

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cludes 30 questions with responses ranging from one point to five points. Subjects with higher scores may be more severely affected by LE. Follow-up assessments of the effectiveness of treatments were obtained by asking the subjects to subjectively report their general health status rated as excellent, good, improved, slightly improved, unchanged, or worse.

Statistical analysis

Data obtained from the selected literature were numbered, entered into datasheets, and divided into three parts. The first part, as shown inTable 1, summarizes the features of b T1 each study, including the representative author and publi-cation date, number and average age of subjects, sites of treatments, laser parameters, treatment dosages, and quality

of the study. The second part, as shown inTables 2 and 3,b T2b T3 includes periods and times of investment, assessable items b AU5 and time, and the results of the assessments. In the third part,

results in terms of effectiveness, expressed in average values and standard deviation, or the 95% confidence interval (CI) providing the standard deviation, were further selected to conduct an integrated comparison. Meta-analysis was then used to calculate the individual and total effect size (ES) for each variable.32

Pooled standard deviation (pooled SD) for each vari-able was calculated by the equation: pooled SD ¼

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi [(n1 1)s21þ (n2 1)s22]=(n1þ n2 2)

q

. In this equation, n1

and n2respectively represent the number of participants in

the experimental and the control groups, while s1 and s2

represent the SDs obtained from the experimental and the control groups, respectively. Afterwards, the ES for each variable was computed using the equation: ES ¼ (m1 m2)=

pooled SD, in which m1 and m2 respectively represent the

average values in the experimental and the control groups. The pooled ES for each variable was then calculated from all the ESs weighted by the number of total subjects. A positive pooled ES indicates a measured positive effect; whereas a negative value indicates that the treatment was ineffective.

The ESs of all assessable items were represented by using 95% CI, and analyzed statistically by distinguishing zero in the interval. A CI including zero represented that the null hypothesis could not be rejected and no statistically signifi-cant difference in effectiveness existed ( p > 0.05). A positive interval of CI, exclusive of 0, indicated a statistically signif-icant effectiveness ( p < 0.05).32

According to the criteria of ES proposed by Cohen’s d, an ES of 0.2 would be defined as small, 0.5 as medium, and 0.8 as large.32Finally, as shown inTable 4, the estimated values b T4 for effectiveness were analyzed and discussed based on the guidelines from the Philadelphia panel classification system,

and the grade of recommendation would be determined.33 b AU5 Results

This study aimed to investigate the effectiveness of ap-plying LLLT on LE in Western and Chinese medicine. Ten papers studying clinical effectiveness with quality assess-ment scores ranging from 3 to 8, as shown in Table 1, were selected through our search.21–30Seven of them were studies of comparisons between laser on tender points and laser on

Table 1. The Summaries of the Treatment Parameters and Quality Scale for Ten Studies Author (year) n Age Region Wavelength Dosage Laser instrument PEDro Stergioulas (2007) 21 50 45.6 Tender points 904 nm 2.4 J= cm 2 Ga As laser, P: 40 mW, F: 50 Hz 8 =11 Lam (2007) 22 39 47.4 Trigger points 904 nm 2.4 J= cm 2 Ga As laser, P: 25 mW, F: 5 kHz 8 =11 Basford (2000) 23 52 45.4 Tender points 1.06 m m 12.24 J= cm 2 Nd YAG laser, P: 1.6 W, continuous wave 7 =11 Papadopoulos (1996) 24 29 45.3 Tender points 820 nm 24 J= cm 2 Ga Al As laser, P: 50 mW, F: 5 kHz 5 =11 Krasheninnikoff (1994) 25 36 48.0 Tender points 830 nm 3.6 J= point Ga Al As laser, P: 30 mW 4 =11 Vasseljen (1992) 26 30 45.5 Tender points 904 nm 3.5 J= cm 2 Ga As laser, P: 18 mW, F: 880 Hz 6 =11 Haker (1991) 27 49 44.5 Tender points 904 nm 0.36 J= point Ga As laser, P: 12 mW, F: 70 Hz 5 =11 Haker (1991) 28 58 45.3 Tender points 904 nm 1.92 J= point Probe type: GaAs laser, P: 4 mW, F: 3800 Hz 5 =11 þ acupuncture points (LI11, LI12) þ 904 nm þ 0.9 J= point þ Penpoint type: GaAs laser Haker (1990) 29 49 46.7 Acupuncture points (LI10, LI11, LI12, Lu5, SJ5) 904 nm 0.36 J= point Ga As laser, P: 12 mW, F: 70 Hz 5 =11 Lundeberg (1987) 30 57 43.0 Acupuncture points (LI10, LI11, LI12, SJ5, SJ10, SI4, SI 8, H3, H4, P3) A:904 nm A: 0.004 J= point A: Ga As laser, P: 0.07 mW, F: 73 Hz 3 =11 B:632.8 nm B: 0.1 J= point B: He Ne laser, P: 1.56 mW, continuous wave Acu puncture points: LI1 0 (Sh ousanli), LI11 (Quchi), LI1 2 (Zhou liao), Lu5 (Ch ize), SJ5 (Wa iguan), SJ10 (Tia njing), SI4 (Wangu) , SI8 (Xiao hai), H3 (Shaohai), H4 (Lingdao), P3 (Quze) . n , num ber of patients; P, averag e powe r; F, freq uency; þ , to comb ine both types b AU5 .

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Table 2. Summaries of Investment b AU5 , Assessment, and Results for Ten Studies Author (year) Investment Assessable items Assessable times Results Stergioulas (2007) 21 30 sec at each point for 8 weeks (12 sessions) Resting =pressured =isometric wrist extension =middle finger extension = grasping VAS, painless ROM, grasp force, and weight test Before and after treatment, 8 weeks’ follow-up After treatment, pain was decreased, and grasp force and strength of wrist extensor were improved.* After follow-up, pain was decreased, and grasp force, ROM, and strength of wrist extensor were improved.* Lam (2007) 22 11 sec at each point, 3 times weekly for 3 weeks (9 sessions) PPT, VAS, grasp force, and DASH Before and after treatment, th 5 session, 3 weeks’ follow-up PPT was increased at 5 th session.* After treatment, PPT was increased, and VAS and DASH were decreased.* After follow-up, the same as the results after treatment added the increase of grasp force b AU5 .* Basford (2000) 23 60 sec at each point, 3 times weekly for 4 weeks (12 sessions) All day =pressured =grasping = finger griping VAS, grasp and finger grip force Before and after treatment, 6 th session, 1 week follow-up After treatment, pain was decreased, and grasp and finger grip force were increased. Papadopoulos (1996) 24 20 sec at each session (7 sessions) VAS, MWP Each session During treatment, MWP was decreased. Krasheninnikoff (1994) 25 120 sec at each point, 2 times weekly for 4 weeks (8 sessions) VAS, FPV, no. of patients with tender points, and MMT Each session, 10 weeks’ follow-up There were no differences in all items. VAS, Visual Analog ue Sca le; PPT, pai n pressure thr eshold; DASH, Disabilities of the Arm, Shoulder and Hand qu estionnai re; MW P, Marcy Wed ge Pro exerc ise; FPV, Five Point Ver bal scale; MMT, manual mus cle test ing; *, Signifi cant differences we re seen betw een grou ps (p < 0.05).

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Table 3. Summaries of Investment b AU5 , Assessment, and Results for Ten Studies Author (year) Investment Assessable items Assessable times Result Vasseljen (1992) 26 10 min at each session, 3 times weekly (8 sessions) Grasp force, weight test, painless ROM, all day VAS, satisfactory questionnaire Before and after treatment, 4 weeks’ follow-up After treatment, there were no differences in all items. After follow-up, pain was decreased, and grasp force was increased.* Haker (1991) 27 30 sec at each point, 2–3 times weekly (10 sessions) FPV for isometric wrist extension, forearm supination = pronation and middle finger extension, weight test, grasp force, and satisfactory questionnaire Before and after treatment, 3 and 12 months’ follow-up After treatment and 3 months’ follow-up, grasp force and strength of wrist extensor were improved.* Haker (1991) 28 Probe type: 8 min at each session Penpoint type: 2 min at each point. 3–4 times weekly (10 sessions) FPV for isometric forearm supination =pronation, weight test, grasp force, and satisfactory questionnaire Before and after treatment, 3, 6 and 12 weeks’ follow-up There were no differences in all items. Haker (1990) 29 30 sec at each point, 2–3 times weekly (10 sessions) FPV, weight test, grasp force Before treatment, 10th session, 3 and 12 months’ follow-up There were no differences in all items. Lundeberg (1987) 30 60 sec at each point, 2 times weekly for 5–6 weeks VAS, FPV for isometric wrist extension, weight test, grasp force 3 months’ follow-up There were no differences in all items. *, Significa nt diff erences were seen between groups (p < 0.05 ).

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the epicondyle of elbow, and all subjects were diagnosed according to Western medical criteria.21–27 In these studies,

the locations of irradiation were tender points of tendons or muscles. Only Lam and Cheing22utilized MTrPs as points of

irradiation. In two studies (Stergioulas,21Lam and Cheing22), the experimental and the control groups were both given therapeutic exercise. In two other papers, the points of irra-diation were acupuncture points of TCM, and the subjects were treated by laser acupuncture.29,30Among all selected

papers, only one had conducted laser on both tender points and acupuncture points.28

The wavelengths in these 10 papers were 904 nm in six of them,21,22,26–291.06 mm by Basford et al.,23 820 nm by Papa-dopoulos and Smith,24 and 830 nm by Krasheninnikoff et al.25 In addition, Lundeberg et al. tested lasers with wavelengths of 904 nm and 632.8 nm in the study group and compared the results with the control group.30Among these studies, the GaAs diode laser was mostly used with average power ranging from 0.07 to 50 mW. Only Basford et al.23and Lundeberg et al.30 used continuous wave irradiation, whereas other authors used pulsed lasers with frequencies between 50 Hz and 5000 Hz.

As for the dosage of treatment, some previous researches had provided laser treatment dose in terms of joules per point without describing the radius of the probe head and, therefore, joules per cm2could not be obtained.25,27–30Seven studies with Western medicine diagnosis and treatment had provided the treatment energy between 3.5 and 24 J=cm2and dose between 0.36 and 36 J.21–27 Another three studies uti-lizing laser acupuncture had LLLT with dose from 0.004 to 0.9 J per point.28–30

The period and times of investment that these ten papers had conducted LLLT

AU5 c were summarized in Tables 2 and

3.21–30 Tender points were irradiated for 20 seconds to 8

minutes,21,23–28and acupuncture points were irradiated for 30 seconds to 2 minutes.28–30The times of investment were

between

AU5 c 7 and 12 sessions.21–30 In most of the studies, the evaluations were conducted immediately after treatment and at follow-up from 3 weeks to 12 months.21–29One exception was the study by Lundeberg et al.,30in which only a 3 month follow-up evaluation was undertaken with no immediate evaluation after treatment.

All ten papers had assessed resting, motion-induced, and resisted pain. Regarding the pain assessments, seven papers utilized VAS,21–26,30 five papers used FPV,25,27–30 and two, Krasheninnikoff et al.25 and Lundeberg et al.,30 used both methods. Six papers included weight tests to assess the strength of wrist extensors.21,26–30Papadopoulos and Smith24 adopted MWP to assess wrist extensors, while

Krashenin-nikoff et al.25 utilized MMT to record the strength of wrist extensors. Stergioulas21 and Vasseljen et al.26 further

as-sessed painless range of motion of wrist joints.

Lam and Cheing22 included PPT and the DASH

ques-tionnaire. Vasseljen et al.26 and Haker and Lundeberg27,28 assessed effectiveness immediately after treatment and follow-up for a period ranging from 3 weeks to 12 months. Among all the assessment data, Stergioulas,21 Lam and Cheing,22and Vasseljen et al.26provided average values and

standard deviations after treatment and at follow-up. Since these three studies had four measurements in common, the pain scores of VAS, the measurements of grasp force, weight tests, and range of motion of wrist joints, these items were pooled into a meta-analysis. Other papers were individually reviewed and discussed.23–25, 27–30

The immediate effects of LLLT on pain relief after treatment

The lower the scores were, the better the effects were. Therefore, the ES values and the null hypothesis of all the pain scales were considered to be negative values. The effects of LLLT on pain relief for 119 subjects in three studies, as indicated inTable 5, were favorable.21,22,26Although the re- b T5 sults by Vasseljen et al.26did not show statistically significant

effects (95% CI: 0.63 * 0.08, p > 0.05), the pooled ES after being weighted was 0.71, which was considered to be a medium level effect (0.8 > jpooled ESj > 0.5). Furthermore, the 95% CI did not include zero (95% CI: 0.82 * 0.60) and indicated a statistically significant effect ( p < 0.05).

The effects of LLLT on pain relief after follow-up

The ESs of pain relief brought about by LLLT at follow-up, as indicated in Table 6, were obtained from the results of b T6 three papers including 119 subjects.21,22,26There was a trend showing that the favorable effect of pain relief still existed after follow-ups ranging from 3 to 8 weeks. After three weeks’ follow-up, the ES of 1.60 in Lam and Cheing’s study22was larger than the ES obtained by Vasseljen et al.26 The pooled ES after being weighted was 1.05, which was considered to be a large effect (jpooled ESj > 0.8). The 95% CI did not include zero (1.16 * 0.94) and indicated a statis-tically significant effect ( p < 0.05).

The effects of LLLT on grasp force

As shown inTable 7, the ESs of LLLT on grasp force were b T7 also obtained from the results of three studies with 119 sub-jects.21,22,26 Grasp force increased immediately after treat-Table4. Philadelphia Panel Classification System33

Grade Study design Clinical importance Statistical significance

A RCT (single or meta-analysis) Important þ

B CCT (single or meta-analysis) Important þ

Cþ RCT or CCT (single or meta-analysis) Important –

C Any study design Unimportant NA

D Well-designed RCT > 100 patients Unimportant –

RCT, randomized controlled trial; CCT, controlled clinical trial; þ, statistical significance; , not significant; NA, not applicable (clinical importance is not met, regardless of statistical significance).

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ments and follow-up. After being weighted, the pooled ES of 0.70 was considered to represent a medium effect (0.8 > jpooled ESj > 0.5). The 95% CI (0.52 * 0.88) did not in-clude zero, which indicated a statistically significant effect ( p < 0.05). As shown in

T8 c Table 8, there were significant effects

on grasp force after a period of follow-up ranging from 3 to 8 weeks. Furthermore, the pooled ES of the three studies was 1.09, which was considered to represent a large effect (jpooled ESj > 0.8). The 95% CI did not include zero (0.91 * 1.27), which indicated a statistically significant effect ( p < 0.05). The effects of LLLT on weight test

Lam and Cheing22 did not conduct measurements of

weight tests and ROM. Therefore, only the ESs of LLLT on the weight test for 80 subjects in two studies by Stergioulas21

and Vasseljen et al.26were included and are shown in Table 7. Although there was a trend showing a favorable effect of LLLT on weight tests, Stergioulas21did not find a statistically significant effect (95% CI: 0.14 * 0.42, p > 0.05). After being weighted, however, the pooled ES was 0.58, which was considered to represent a medium effect (0.8 > jpooled ESj > 0.5). The 95% CI (0.37 * 0.80) did not include zero, which indicated a statistically significant effect ( p < 0.05). After a period of follow-up ranging from 4 to 8 weeks, there were favorable and significant effects on the weight test in both studies,21,26as shown in Table 8. The pooled ES was 0.55, which was considered to represent a medium effect (0.8 > jpooled ESj > 0.5). The 95% CI did not include zero (0.33 * 0.76) and indicated a statistically significant effect ( p < 0.05).

The effects of LLLT on increasing ROM of the wrist For the 80 subjects in two studies,21,26there was a trend of

less favorable effect of LLLT on increasing ROM, as shown in Table 7, and the pooled ES was not statistically significant (pooled ES: 1.27, 95% CI: 0.37 * 0.81, p < 0.05). However, after a period of follow-up ranging from 4 to 8 weeks, there was a trend of favorable effect in terms of increasing ROM, as depicted in Table 8. The pooled ES was 0.72 and the 95% CI was 0.50 to 0.94, which both showed statistically signifi-cant effects ( p < 0.05).

Discussion

Low level laser used in clinical practice normally produces power less than 500 mW, and can be classified as 3B ac-cording to the guidelines from the American National Stan-dards Institute (ANSI).5 As LLLT is not based on thermal effects but on the principles of photobiomodulation, a 3B laser could reduce the dangers of burning skin, but still might harm eyes.21Review of the four papers revealed that

the application of LLLT to LE in TCM differed from appli-cation in Western medicine.27–30

The effectiveness of LLLT on acupuncture points in LE According to evidence provided in the series of studies by Haker and Lundeberg28,29 and Lundeberg et al.,30 the ap-plication of LLLT on acupuncture points was not effective (see Table 4). In 1991, Haker and Lundeberg28compared the study by Haker and Lundeberg29in 1990 with the study by

Lundeberg et al.30 in 1987. The former had utilized lasers Table5. Effect Sizes of Vas after Treatment

Author Assessable items n Pooled SD Wt ES 95% CI

Stergioulas21 VAS (resting) 50 6.98 0.16 0.19 0.47 * 0.09 b AU6

VAS (pressured) 50 17.43 0.16 0.92 1.20 * 0.64*

VAS (wrist extension) 50 15.64 0.16 0.79 1.07 * 0.51*

VAS (middle finger extension) 50 15.01 0.16 0.99 1.27 * 0.72*

VAS (grasping) 50 9.95 0.16 0.53 0.81 * 0.25*

Lam22 VAS 39 1.94 0.12 1.21 1.52 * 0.89*

Vasseljen26 VAS 30 0.68 0.08 0.28 0.63 * 0.08

Pooled 0.71 0.82 * 0.60*

VAS, visual analogue scale; n, numbers of patients; SD, standard deviation; Wt, weight value; ES, effect size; CI, confidence interval; *, There was a statistically significant difference.

Table6. Effect Sizes of Vas after Follow-Up

Author Assessable items n Pooled SD Wt ES 95% CI

Stergioulas21(8 wks) VAS (resting) 50 3.21 0.16 0.41 0.69 * 0.13*

VAS (pressured) 50 15.34 0.16 0.87 1.15 * 0.60*

VAS (wrist extension) 50 12.74 0.16 1.27 1.54 * 0.99*

VAS (middle finger extension) 50 18.69 0.16 0.72 1.00 * 0.44*

VAS (grasping) 50 8.56 0.16 1.57 1.85 * 1.30*

Lam22(3wks) VAS 39 1.75 0.12 1.60 1.92 * 1.29*

Vasseljen26(3m) VAS 30 0.52 0.08 1.00 1.36 * 0.64*

Pooled 1.05 1.16 * 0.94*

*, There was a statistically significant difference.

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with an average power of 0.07 mW and energy of 0.004 J=point on five acupuncture points for 60 seconds per point. The latter had used lasers with an average power of 12 mW and energy of 0.36 J=point on ten acupuncture points for 30 seconds per point. Haker and Lundeberg28found that a dose of 0.36 J=point would be more suitable for laser acu-puncture, and that increasing the duration of laser irradia-tion would not guarantee better effects. Some other studies, with follow-up assessments, of subjects receiving laser acu-puncture revealed that painful symptoms were consistent or worse after the treatments.29 Given the nature of local in-flammation in LE, Haker and Lundeberg29thought that the anti-inflammatory mechanism of LLLT on acupuncture points was based on photobiomodulation, which followed the Arndt-Schultz law. During needling acupuncture, pulses of mechanical stimulation can penetrate through connective tissues and activate C fibers. In TCM theory, the pulses in-duced by stimulating the acupuncture points can regulate the flow of qi. In dialectical thinking of TCM

AU5 c , LE would be

diagnosed as a heat impediment or cold impediment, and approached by distinct acupuncture points. Haker and Lundeberg29 had proposed using a HeNe laser of 632.8 nm

and a GaAs laser of 904 nm, capable of penetratting 0.62 nm and 1.4 nm, respectively. Laser irradiance possesses a pho-toelectric effect and thus differs from needling acupuncture. Therefore, it remains questionable whether the depth of penetration or the physical effect of such laser irradiance is capable of attaining the effectiveness of needling acupunc-ture. Furthermore, the mechanical stimulation of LLLT may

not be as strong as acupuncture. Therefore, the ‘‘hyperstim-ulation analgesia’’ proposed as a possible mechanism of acupuncture may not apply to LLLT.34

In summary, the effects of laser acupuncture on LE were inconsistent with those of needling acupuncture, and im-provements after treatment were not obvious. Thus, based on the guidelines from the Philadelphia Panel Classification System,33the grade of recommendation with regard to ‘‘the

effectiveness of LLLT on acupuncture points in LE’’ was C. The effectiveness of LLLT on tender points

and MTrPs in LE

As Lam and Cheing22indicated that injured muscles and tendons were supposed to be the target tissues in managing LE of the elbow, laser irradiation applied to tender points and MTrPs should be a better treatment option. LLLT on acupuncture points did not irradiate the areas of injured tissues, and therefore the therapeutic effects were not found.29,30 Irradiating directly on areas of tendons could activate fibroblasts to enhance the repair of damaged tissues and was thus thought to be the most appropriate and effective method of irradiation.22Recent studies by Shah et al.35,36 found evidence of increased concentrations of

in-flammatory substances in the MTrPs region. Therefore, the anti-inflammatory effect of LLLT may be the major mech-anism for the relief of pain from MTrPs. After reviewing seven papers as shown in Table 2 and Table 3,21–27 we found that, in the studies by Sergioulas,21 Lam and

Che-Table7. Effect Sizes of Grasp Force, Weight Test, and Painless Rom after Treatment

Author Assessable items n Pooled SD Wt ES 95% CI

Stergioulas21 grasp force 50 8.93 0.42 0.88 0.60 * 1.16*

Lam22 grasp force 39 8.98 0.33 0.64 0.32 * 0.95*

Vasseljen26 grasp force 30 0.06 0.25 0.49 0.14 * 0.85*

Pooled 0.70 0.52 * 0.88*

Stergioulas21 weight test 50 0.86 0.63 0.14 0.14 * 0.42

Vasseljen weight test 30 0.23 0.37 1.33 0.97 * 1.68*

Pooled 0.58 0.37 * 0.80*

Stergioulas21 painless ROM 50 11.31 0.63 0.55 0.27 * 0.83*

Vasseljen26 painless ROM 30 1.20 0.37 2.50 2.14 * 2.86*

Pooled 1.27 0.37 * 0.81*

*, There was a statistically significant difference.

Table8. Effect Sizes of Grasp Force, Weight Test, and Painless Rom after Follow-up

Author Assessable items n Pooled SD Wt ES 95% CI

Stergioulas21(8 wks) grasp force 50 9.74 0.42 1.12 0.84 * 1.40*

Lam22(3 wks) grasp force 39 9.31 0.33 0.86 0.54 * 1.17*

Vasseljen26(3m) grasp force 30 0.06 0.25 1.33 0.97 * 1.69*

Pooled 1.09 0.91 * 1.27*

Stergioulas21(8 wks) weight test 50 1.18 0.63 0.35 0.07 * 0.62*

Vasseljen26(3m) weight test 30 0.57 0.37 0.88 0.52 * 1.24*

Pooled 0.55 0.33 * 0.76*

Stergioulas21(8 wks) painless ROM 50 11.93 0.63 0.66 0.38 * 0.93*

Vasseljen26(3 m) painless ROM 30 1.20 0.37 0.83 0.48 * 1.19*

Pooled 0.72 0.50 * 0.94*

*, There was a statistically significant difference.

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ing,22 and Vasseljen et al.,26 not only was pain reduced

statistically ( p < 0.05) after LLLT, but also grasp force and performance during functional movements were improved statistically ( p < 0.05). Lam and Cheing22proposed that pain relief was related to the increased metabolism of adenosine triphosphate (ATP) in mitochondria, which resulted in the increased metabolism of MTrPs.22 Hence, the focus on MTrPs for the treatment of LE could be more effective through induced local hypoxia and improvement of blood circulation. Even so, Krasheninnikoff et al.25 had found no

statistically significant effectiveness of LLLT on tender points in LE ( p > 0.05). Because appropriate parameters and doses of laser were unclear, they also proposed that ap-plying LLLT to musculoskeletal diseases might also be in-effective.

To summarize, the treatment mechanisms were consistent and the effectiveness of different treatments was statisti-cally significant in some studies ( p < 0.05),21,22,26 but other studies did not find statistically significant improvement ( p > 0.05).23–25,27Therefore, based on the guidelines from the Philadelphia Panel Classification System,33the grade of rec-ommendation with regard to ‘‘the effectiveness of LLLT on tender points and MTrPs in LE in Western medicine’’was Cþ to B.

Appropriate treatment parameters of LLLT for LE

The photobiomodulation of LLLT was related to three parameters: wavelength, energy density, and power, all three of which were crucial in determining the effectiveness of LLLT.21Energy density was the energy absorbed by

su-perficial tissues, usually in terms of J=cm2, and was referred to as treatment dosage. Sergioulas21suggested that using a

laser of 904 nm wavelength with an average power of 40 mW should be appropriate for musculoskeletal diseases. Lam and Cheing22indicated that the depth of penetration was another important factor, and a laser with a wavelength of 920 nm, which is almost the wavelength of visible red light, had better penetration ability. They also reported that laser with pulsed output could produce better penetration effects than continuous wave laser. This was due to lowered impedance across the skin, by which 37% of the laser energy would otherwise be blocked.29In a series of studies by Haker and Lundeberg27–29 and Lundeberg et al.30 in 1987, a double wavelength laser combining 940 nm and 632.8 nm was uti-lized as a tool of laser acupuncture.30 In 1991, Haker and Lundeberg29used a 940 nm probe laser to treat tender points

combined with a pen-point laser to irradiate on acupuncture points.28 However, the effects seen in these studies did not

reach statistical significance ( p > 0.05). Sergioulas21inferred that the different doses and types of LLLT used in this series of studies had led to the ineffectiveness. Lam and Cheing22 also thought that the doses used in this series of studies were insufficient. Addressing the issue of lower energy used in those studies, Krasheninnikoff et al.25decided on utilizing a laser with more energy (3.6 J=point) than the 0.004 J=point used in the Lundeberg et al. study30and the 0.36 J=point in the Haker and Lundeberg study.27,29Two of the studies used

laser on tender points,25,27 while the others used laser on acupuncture points.29,30 Krasheninnikoff et al.,25 however, observed no statistically significant differences ( p > 0.05), and instead found results that were similar to those of the

others. It seems that the energy density of LLLT must be

accentuated and canvassed. We found a lack of evidence that b AU5 could be used to ascertain the appropriate treatment dose for

laser acupuncture. Regarding treatment dose on MTrPs, Lam and Cheing22showed that energy density ranging from 0.3 to 3 J=cm2 was thought to be appropriate for LE. Basford et al.23had tried a longer wavelength (1.06 mm) with stronger treatment dosage (12.24 J=cm2) on tender points, and a larger

probe (radius: 5 cm) to increase the irradiance. No statisti-cally significant effectiveness, however, was observed in the parameters of pain and grasp force ( p > 0.05). Sergioulas21 indicated that LLLT with wavelength of 904 nm, average power of 40 nm, frequency of 60 Hz, and dosage of 2.4 J=cm2 on tender points was most effective for LE ( p < 0.05). These parameters were also suggested for the treatment of other musculotendinous diseases.21 Therefore, an energy density of 2.4 J=cm2 on tender points was presumed to be an

ap-propriate treatment dose, and energy that was stronger would be ineffective. More studies with RCT are required to provide stronger evidence for the effectiveness of this dose. Improvement in pain relief, grasp force,

ROM, and weight test

The results of our meta-analysis showed that using LLLT for LE exerted statistically significant effects in the areas of pain relief, increasing grasp force, increasing ROM of wrist joints, and improving weight tests, regardless of whether the testing was conducted after the treatments or after the follow-up visits ( p < 0.05). After separately reviewing the results of Sergioulas21and Lam and Cheing,22we concluded

that‘‘using LLLT in LE can reduce pain significantly’’, and the grade of recommendation would be A. Lam and Che-ing22 thought that the analgesia mechanism for LLLT was dependent on an immediate decrease in the synthesis of prostaglandins and the conduction velocities of Ad and C fibers. They also suggested that the absorption of LLLT could be accumulated during the treatment sessions. As a result, they conducted LLLT three times per week, and did not find any obvious improvement in PPT ( p > 0.05) until the fifth treatment ( p < 0.05). However, these effects remained for only three weeks after treatment. Vasseljen et al.26also found

that 47% of subjects had improvement in symptoms after four weeks’ follow-up.

Measures of grasp force, ROM of wrist joints, and weight tests can illustrate functional improvement in symptoms and recovery of muscle strength. According to the analyses of Sergioulas,21Lam and Cheing,22and Vasseljen et al.,26there was statistically significant improvement after treatment and follow-up ( p < 0.05). To review separately the results of these studies,21,22,26 the grade of recommendation for the

state-ment ‘‘using LLLT in LE could improve muscle strength significantly’’ would be A. The study by Sergioulas21 in-volved plyometrics training for both experimental and con-trol groups. The training program included pain-free wrist extension movements which progressed from active to re-sistant, to be done twice a week for 16 weeks. Lam and Cheing22 also conducted a 3-week exercise program that

included stretching and strengthening exercises of the fore-arm for both experimental and control groups. These exer-cises were considered to have positive effects for clinical application.

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Our suggestions and limitations

Many assessment measurements have been used to man-age LE, but some of the assessment tools were considered to be inappropriate after reviewing some studies.25, 27, 30Haker and Lundeberg27 and Lundeberg et al.30thought that FPV

could not be utilized to detect and assess minor changes in pain reduction, and that the MMT rating system for muscle strength, with six grades, also had this problem.25 Highly sensitive measurement tools were necessary. Vasseljen et al.26 suggested that the VAS, grip dynamometer, and

weight tests were better assessment tools for LE. Due to the lower number of RCTs in laser acupuncture, we were unable to further explore the effectiveness of LLLT on acupuncture points for LE. Moreover, we suggest that more stringent RCTs of TCM are needed to compare its therapeutic effects with Western medicine.

This study had some limitations in understanding the ef-fectiveness of applying LLLT for LE. Only three papers could be used for the meta-analysis21,22,26 because there were no

unified standards for various assessment tools in the papers we had collected. There were no detailed values for the as-sessments after treatment and follow-up which could have been used for further meta-analysis.

Conclusion and Summary

Few articles in the literature address the use of LLLT on acupuncture points in TCM-based treatment. Tender points in LE were diagnosed as part of the Western medicine treatment process, but Ashi points were not. Therefore, the current evidence justifying the therapeutic effects of LLLT on LE in Western medicine was better than that for TCM. More exact diagnosis of Ashi points and clinical RCTs will be needed to prove the effects of LLLT in TCM. LLLT on tender points and MTrPs would be more appropriate. There were no consistent conclusion as to the appropriate parameters of LLLT, and more studies will be needed.

Acknowledgments

The authors are grateful to the National Science Council of the Republic of China for financially supporting this research under contracts no. NSC 96-2218-E-002-015, NSC 97-2218-E-002-006, and NSC 96-2628-E-002-252-MY3.

Disclosure Statement AU1 c

References

1. Calfee, R.P., Patel, A., DaSilva, M.F., and Akelman, E. (2008). Management of lateral epicondylitis: current concepts. J. Am. Acad. Orthop. Surg. 16, 19–29.

2. Shiri, R., Viikari-Juntura, E., Varonen, H., and Helio¨vaara, M. (2006). Prevalence and determinants of lateral and medial epicondylitis: a population study. Am. J. Epidemiol. 164, 1065–1074.

3. Smidt, N., Lewis, M., van der Windt, D.A., Hay, E.M., Bouter, L.M., and Croft, P. (2006). Lateral epicondylitis in general practice: course and prognostic indicators of out-come. J. Rheumatol. 33, 2053–2059.

4. Trinh, K.V., Phillips, S.D., Ho, E., and Damsma, K. (2004). Acupuncture for the alleviation of lateral epicondyle pain: a systematic review. Rheumatology 43, 1085–1090.

5. Viola, L. (1998). A critical review of the current conservative therapies for tennis elbow (lateral epicondylitis). Australas. Chiropr. Osteopathy 7, 53–67.

6. Melzack, R., Stillwell, D.M., and Fox, E.J. (1997). Trigger points and acupuncture points for pain: correlations and implications. Pain 3, 3–23.

7. Hong, C.Z., and Simons, D.G. (1998). Pathophysiologic and electrophysiologic mechanisms of myofascial trigger points. Arch. Phys. Med. Rehabil. 79, 863–872.

8. Hong, C.Z. (2000). Myofascial trigger points: pathophysi-ology and correlation with acupuncture points. Acup. Med. 18, 41–47.

9. Xu, R.D., and Li, H. (2005). Conception of Ashi points. Zhongguo Zhen Jiu 25, 281–283.

10. Simons, D.G., Travell, J.G., and Simons, L.S. (1999). Travell & Simons’s Myofascial Pain and Dysfunction: The Trigger Point Manual. 2nd ed. Baltimore (MD): Williams & Wilkins, pp. 94–173.

11. Schjelderup, V. (1984). The use of laser therapy in acu-puncture. Acupunct. Med. 2, 22–27.

12. Hecox, B., Andemicael Mehreteab, T., and Weisberg, J. (1994). Physical Agents: A Comprehensive Text for Physical Therapists. Norwalk (CT): Appleton & Lange, pp. 391–396. 13. Chang, W.D., Wu, J.H., Jiang, J.A., Yeh, C.Y., and Tsai, C.T. (2008). Carpal tunnel syndrome treated with a diode laser: a controlled treatment of the transverse carpal ligament. Photomed. Laser Surg. 26, 551–557.

14. Tam, G. (1999). Low power laser therapy and analgesic ac-tion. J. Clin. Laser Med. Surg. 17, 29–33.

15. Ohshiro, T. (1988). Low Level Laser Therapy. Avon (U.K.): Wiley and Sons, pp. 16–30.

16. Ghamsari, S.M., Acorda, J.A., Taguchi, K., Abe, N., and Ya-mada, H. (1996). Evaluation of wound healing of the teat with and without low level laser therapy in dairy cattle by laser Doppler flowmetry in comparison with histopathology, ten-siometry and hydroxyproline analysis. Br. Vet. J. 152, 583–592. 17. Houreld, N.N., and Abrahamse, H. (2008). Laser light influences cellular viability and proliferation in diabetic-wounded fibroblast cells in a dose- and wavelength-dependent manner. Lasers Med. Sci. 23, 11–18.

18. van Breugel, H.H., and Ba¨r, P.R. (1992). Power density and exposure time of He-Ne laser irradiation are more important than total energy dose in photo-biomodulation of human fibroblasts in vitro. Lasers Surg. Med. 12, 528–537.

19. Bjordal, J.M., Lopes-Martins, R.A., Joensen, J., et al. (2008). A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendi-nopathy (tennis elbow). B.M.C. Musculoskelet. Disord. 9, 75. 20. Stasinopoulos, D.I., and Johnson, M.I. (2005). Effectiveness of low-level laser therapy for lateral elbow tendinopathy. Photomed. Laser Surg. 23, 425–430.

21. Stergioulas, A. (2007). Effects of low-level laser and plyo-metric exercises in the treatment of lateral epicondylitis. Photomed. Laser Surg. 25, 205–213.

22. Lam, L.K., and Cheing, G.L. (2007). Effects of 904-nm low-level laser therapy in the management of lateral epicondylitis: a randomized controlled trial. Photomed. Laser Surg. 25, 65–71. 23. Basford, J.R., Sheffield, C.G., and Cieslak, K.R. (2000). Laser therapy: a randomized, controlled trial of the effects of low intensity Nd:YAG laser irradiation on lateral epicondylitis. Arch. Phys. Med. Rehabil. 81, 1504–1510.

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24. Papadopoulos, E.S., and Smith, R.W. (1996). Low-level laser therapy does not aid the management of tennis elbow. Clin. Rehabil. 10, 9–11.

25. Krasheninnikoff, M., Ellitsgaard, N., Rogvi-Hansen, B., et al. (1994). No effect of low power laser in lateral epicondylitis. Scand. J. Rheumatol. 23, 260–263.

26. Vasseljen, O. Jr., Høeg, N., Kjeldstad, B., Johnsson, A., and Larsen S. (1992). Low level laser versus placebo in the treatment of tennis elbow. Scand. J. Rehabil. Med. 24, 37–42. 27. Haker, E., and Lundeberg, T. (1991). Is low-energy laser treatment effective in lateral epicondylalgia? J. Pain Symp-tom Manage. 6:241–246.

28. Haker, E., and Lundeberg, T. (1991). Lateral epicondylalgia: report of noneffective midlaser treatment. Arch. Phys. Med. Rehabil. 72, 984–988.

29. Haker, E., and Lundeberg, T. (1990). Laser treatment applied to acupuncture points in lateral humeral epicondylalgia: A double-blind study. Pain 43, 243–247.

30. Lundeberg, T., Haker, E., and Thomas, M. (1987). Effect of laser versus placebo in tennis elbow. Scand. J. Rehabil. Med. 19, 135–138.

31. Moseley, A.M., Herbert, R.D., Sherrington, C., and Maher, C.G. (2002). Evidence for physiotherapy practice: a survey of the Physiotherapy Evidence Database (PEDro). Aust. J. Physiother. 48, 43–49.

32. Egger, M., and Smith, G.D. (1997). Meta-Analysis. Potentials and promise. B.M.J. 315, 1371–1374.

33. Harris, G.R., and Susman, J.L. (2002). Managing musculo-skeletal complaints with rehabilitation therapy: summary of the Philadelphia Panel evidence-based clinical practice guidelines on musculoskeletal rehabilitation interventions. J. Fam. Pract. 51, 1042–1046.

34. Melzack, R. (1981). Myofascial trigger points: relation to acupuncture and mechanism of pain. Arch. Phys. Med. Re-habil. 62, 114–117.

35. Shah, J.P., Danoff, J.V., Desai, M.J., et al. (2008). Biochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points. Arch. Phys. Med. Rehabil. 89, 16–23.

36. Shah, J.P. (2008). Uncovering the biochemical milieu of myofascial trigger points. Using in vivo microdialysis. J. Musculoske. Pain 16, 17–20.

Address correspondence to: Joe-Air Jiang, Ph.D., P.Eng. Department of Bio-Industrial Mechatronics Engineering National Taiwan University No. 1, Sec. 4, Roosevelt Road Taipei 10617 Taiwan E-mail: jajiang@ntu.edu.tw

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數據

Table 6. Effect Sizes of Vas after Follow-Up
Table 8. Effect Sizes of Grasp Force, Weight Test, and Painless Rom after Follow-up

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