Effect of Manual Lymphatic Drainage After Total Knee Arthroplasty: A Randomized Controlled Trial

Effect of Manual Lymphatic Drainage After Total Knee Arthroplasty: A Randomized Controlled Trial

Accepted Manuscript The effect of manual lymphatic drainage following total knee arthroplasty: a randomized controlled trial Claude Pichonnaz, PT, MSc...

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Accepted Manuscript The effect of manual lymphatic drainage following total knee arthroplasty: a randomized controlled trial Claude Pichonnaz, PT, MSc, Doctoral student, Jean-Philippe Bassin, JP, PT, MSc, Estelle Lécureux, PhD, Statistician, Guillaume Christe, PT, Damien Currat, PT, Kamiar Aminian, PhD, Professor, Brigitte M. Jolles, MSc, Professor, Medical doctor PII:

S0003-9993(16)00041-1

DOI:

10.1016/j.apmr.2016.01.006

Reference:

YAPMR 56428

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 25 June 2015 Revised Date:

21 December 2015

Accepted Date: 2 January 2016

Please cite this article as: Pichonnaz C, Bassin J-P, Lécureux E, Christe G, Currat D, Aminian K, Jolles BM, The effect of manual lymphatic drainage following total knee arthroplasty: a randomized controlled trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2016), doi: 10.1016/ j.apmr.2016.01.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Manual lymphatic drainage following TKA

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The effect of manual lymphatic drainage following total knee arthroplasty: a

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randomized controlled trial.

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Claude Pichonnaz, PT, MSc, Doctoral student 1,2

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Jean-Philippe Bassin JP, PT, MSc 1

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Estelle Lécureux, Statistician, PhD 3

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Guillaume Christe, PT 1

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Damien Currat, PT 1

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Kamiar Aminian, Professor, PhD 4

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Brigitte M. Jolles, Professor, Medical doctor, MSc 2

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Physiotherapy Department, Haute Ecole de Santé Vaud (HESAV), HES-SO // University of Applied Sciences Western Switzerland, Lausanne, Switzerland.

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Orthopedics and Traumatology Department, CHUV-UNIL, Lausanne, Switzerland.

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Medical Direction, CHUV-UNIL, Lausanne, Switzerland.

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Laboratory of Movement Analysis and Measurement, EPFL STI CBT LMAM, Lausanne, Switzerland.

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Acknowledgement of presentation of the study material:

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Two congress presentations and one poster presentation have been made. Only congress abstracts

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have been published:

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Manual lymphatic drainage following TKA

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Pichonnaz C, Bassin J-P, Martin E, et al. Effets du drainage lymphatique manuel sur l'oedème et

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l'amplitude articulaire passive après prothèse totale de genou. Paper presented at: Physiocongress

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2012; 10 -11 May, 2012; Genève.

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Pichonnaz C, Bassin J-P, Martin E, et al. Outcome of manual lymphatic drainage on swelling, range of

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motion and pain following total knee arthroplasty. Paper presented at: Journées Francophones de

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Kinésithérapie, 7-9 February, 2013; Paris.

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Pichonnaz C., Bassin J.-P., Lecureux E., Christe G., Currat D., Jolles B.M. Effects of manual lymphatic

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drainage following total knee arthroplasty: a prospective randomised controlled trial. Poster

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presented at: World Confederation for Physical Therapy Congress, 1-4 May 2015, Singapore.

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Funding: Swiss National Science Foundation, n° 120298

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The study protocol was approved by the Ethics Commission of Clinical Research Biology and Medicine

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Faculty, University of Lausanne, Approval number: 224/06

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Conflicts of interest: none

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ClinicalTrials.gov identifier: NCT00711711

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Corresponding author:

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Claude Pichonnaz, Haute Ecole de Santé Vaud (HESAV), HES-SO // University of Applied Sciences

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Western Switzerland, Physiotherapy Department,

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Address: HESAV, Physiotherapy Department, Beaumont 21, 1011 Lausanne, Switzerland

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Phone: 0041/21 316 81 26, [email protected]

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Effect of manual lymphatic drainage

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THE EFFECTS OF MANUAL LYMPHATIC DRAINAGE FOLLOWING TOTAL

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KNEE ARTHROPLASTY: A RANDOMIZED CONTROLLED TRIAL

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The study protocol was approved by the Ethics Commission of Clinical Research

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Biology and Medicine Faculty, University of Lausanne, Approval number: 224/06

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The authors certify that they have no affiliations with or financial involvement in any

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organization or entity with a direct financial interest in the subject matter or materials

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discussed in the article.

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ClinicalTrials.gov identifier: NCT00711711

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Acknowledgements: The authors would like to thank, the physiotherapy team of the

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Orthopedics and Traumatology Department of the CHUV-UNIL for his contribution to

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the study organization and implementation, Pascal Morel from the laboratory of

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Movement Analysis and Measurements (EPFL) for his assistance in gait parameter

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analysis and Céline Ancey for her contribution to the manuscript revision and

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submission.

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Funding: Swiss National Science Foundation, n° 1202 98

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THE EFFECTS OF MANUAL LYMPHATIC DRAINAGE FOLLOWING TOTAL

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KNEE ARTHROPLASTY: A RANDOMIZED CONTROLLED TRIAL

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Abstract

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Objective: To evaluate the effects of manual lymph drainage (MLD) on knee swelling

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and the swelling’s assumed consequences following total knee arthroplasty (TKA).

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Design: Randomized controlled trial.

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Setting: Primary care hospital

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Participants: Two groups of 30 patients were randomized before TKA surgery (65%

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♀, age 70.7±8.8 y.o., weight 77.8±11.3 kg., size 1.64±0.08 m., BMI 29.9±4.1

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kg·m−2)

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Intervention: Participants received either five treatments of MLD or a placebo,

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added to rehabilitation, in between the second (D2) and the seventh (D7)

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postsurgical days.

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Outcome Measures: Swelling was measured by blinded evaluators before surgery,

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at D2, D7 and 3 months (3M) using bioimpedance spectroscopy and volume.

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Secondary outcomes were active and passive ROM, pain, knee function and gait

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parameters.

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Results: At D7 and 3M, no outcome was significantly different between groups,

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except for the knee passive flexion contracture at 3M which was smaller and less

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frequent in the MLD group (–2.6° [95%CI -5.0° to -0 .21], P=0.04; absolute risk

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reduction 26.6% [95% CI 0.9 to 52.3%]; NNT = 4). Pain decreased between 5.8 and

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8.2 mm on the VAS immediately after MLD, which was significant after four out of five

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MLD treatments.

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Conclusion: The MLD applied early following TKA surgery did not reduce swelling. It

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reduced pain immediately after treatment. Further studies, should investigate if the

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positive effect of MLD on knee extension is replicable.

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Key Words: edema, knee joint, replacement, rehabilitation, physical therapy

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specialty, treatment outcome

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Level of Evidence: Therapy, level 1b.

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List of abbreviations:

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MLD

Manual Lymph Drainage

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TKA

Total Knee Arthroplasty

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NNT

Number Needed To Treat

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D2

Second Day

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D7

Seventh Day

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3M

3 Months

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ROM

Range Of Motion

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RCT

Randomized Control Study

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BIS

Bioimpedance Spectroscopy

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BIS R0

BIS when a frequency theoretically equal to 0 is used

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CEAP

Clinical severity, Etiology, Anatomy, Pathophysiology

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WOMAC

Western Ontario and McMaster Universities Osteoarthritis Index

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KSS

Knee Society Score

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VAS

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AROM

Active Range Of Motion

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AAROM

Active-Assisted Range Of Motion

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BMI

Body Mass Index

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95% CI

95% Confidence Interval

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Visual Analog Scale

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The number of total knee arthroplasties (TKAs) spectacularly grew during the last

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decade due to population aging, the increasing prevalence of obesity and the impact

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of leisure activities1-3. Research to optimize the efficiency of rehabilitation

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interventions is thus essential.

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Standard rehabilitation is usually focused on pain control and the recovery of range

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of motion (ROM), strength, gait and functional activities4. Conversely, swelling

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reduction is rarely reported as an essential rehabilitation goal, although it is a

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determinant of TKA outcomes5, 6. Swelling after total knee arthroplasty (TKA) causes

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pain and range of motion (ROM) limitation7. It also induces gait alteration8,

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quadriceps inhibition9, and delays in functional recovery10.

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A therapy that would decrease swelling would possibly enhance postsurgical

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recovery. However, there is no established treatment standard for swelling following

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TKA. Cryotherapy and compression demonstrated no effect11, 12,13, 14, 15. The effect of

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knee positioning is controversial16, 17. Pulsed electromagnetic field was reported to

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influence the frequency of swelling but the effect on the magnitude of the swelling

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was not reported18, 19.

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Postsurgical joint swelling consists of soft-tissue edema, joint effusion and hematoma

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and is intrinsically related to the mechanisms of inflammation. Manual lymphatic

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drainage (MLD) might be an efficient method to decrease postsurgical TKA swelling.

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It has an effect on edema reduction as it increases lymphangion motricity, and

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stimulates collateral lymphatic vessels and anastomosis activity 20-22. MLD favors

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thus interstitial fluid, proteins and inflammation-related chemical mediators

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reabsorption23. Hence, it has been claimed to decrease postsurgical swelling after

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TKA24, 25.

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Two RCTs demonstrated a positive effect of MLD on swelling following distal radius

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fracture26, 27 and one following hindfoot surgery28. Conversely, a randomized control

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study (RCT) by Ebert et al found no effect on swelling, pain or function following

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TKA29. However, a significant effect was found on active knee flexion. Girth

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measurements were used to evaluate swelling in this study. Though reliable and

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currently used30, girth measurements are potentially biased by postsurgical

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amyotrophy and dressing29.

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Bioimpedance spectroscopy (BIS) is an alternative swelling measurement method

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that does not present these drawbacks. The BIS measurement is not altered by the

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metallic implant following TKA when a frequency theoretically equal to 0 (R0) is

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used31. The BIS R0 parameter is related to volume (R = 0.73) and knee girth (R =

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0.75). It demonstrates excellent intra- and inter-evaluator reliability (intraclass

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correlation (ICC) > 0.96 and > 0.97, respectively) and better responsiveness than

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volume32. A study using this measurement method would contribute to consolidating

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the evidence on the effect of MLD following TKA.

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The objective of this study was to evaluate the effects of MLD on swelling and on the

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consequences of swelling, i.e., pain, passive and active ranges of motion in the knee,

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function and gait. Swelling was considered as the main study outcome. It was

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hypothesized that MLD would have a significant effect on swelling measured using

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girth measurements and BIS, as well as on the consequences of swelling.

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METHODS

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A prospective RCT was conducted in the Department of Orthopedic and Traumatic

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Surgery of the University Hospital of [blinded for review]. Ethical approval was

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granted by the local ethics committee (Protocol # 224/06), and all subjects gave their

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written consent before enrollment. The MLD, added to the standard rehabilitation

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protocol of the department, was compared to a placebo. Five 30-minute sessions of

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MLD were undertaken in the treatment group on working days between the second

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day (D2) and the seventh day (D7) following surgery. Five 30-minutes of tape-

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recorded relaxation based on ericksonian hypnosis and autogenic training was used

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as a placebo.

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The treatments were applied by five physiotherapists with experience in MLD who

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completed two training sessions for standardization. The same therapist performed

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all of the study treatments for a given patient. The treatment was standardized

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according to the recommendations of Földi and Kubik33.

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The randomization was performed using a computer-generated random sequence of

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numbers. Study eligibility was determined based on inspection of the patient file. An

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independent collaborator performed the concealed allocation according to the order

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of appearance.

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The participants underwent primary TKA operations for osteoarthritis according to the

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standard procedures of the department from July 2008 to November 2010. All

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patients had a postero-stabilized mobile plate arthroplasty. The exclusion criteria

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were non-standard surgery, any lymphatic system pathology, concomitant lower limb

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pathology interfering with gait, high-dose anticoagulation, or chronic venous

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insufficiency at CEAP (Clinical severity, Etiology Anatomy Pathophysiology) stage C3

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or higher, as mentioned in the patient file. Patients with postsurgical complications

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(thrombosis, infection or any complication interfering with treatment or measurement)

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were excluded during the course of the study.

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All participants followed the standard rehabilitation program of the department twice

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daily until hospital discharge. Mean hospital stay was following surgery 10.4 +/- 3.0

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days. Controlled active mobilization, active-assisted mobilization, muscle

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strengthening and continuous passive motion started on the first post-operative day.

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Full weight-bearing gait was initiated on the second post-operative day. Ice was

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applied for 25 minutes 3 times a day. Patients who could walk safely and had

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sufficient social support returned home and were prescribed ambulatory

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rehabilitation, while those who did not meet these conditions pursued physiotherapy

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in a rehabilitation center.

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The sample size was calculated based on the effect found in the most comparable

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study existing at the time of this study design (6.4 +/- 6.3%)28. We used a

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conservative approach and calculated the sample size considering that a treatment

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effect smaller than 5% would have limited clinical significance. It was found that using

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a 5% difference between groups and a 6.3% SD, 25 participants per group were

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needed to reach a power of 0.80 power with a α < 0.05. Thirty patients per group

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were included to anticipate potential drop-outs.

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Measurement Protocol

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The participants were measured the day before surgery (baseline) and at D2 before

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beginning the study treatments. They were then measured at day seven (D7) and at

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3 months (3M) after surgery. The swelling (BIS and volume), active and passive

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ROM, pain and function using the Western Ontario and McMaster Universities

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Osteoarthritis Index (WOMAC), knee society score (KSS) and gait parameters were

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evaluated.

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The evaluations were performed by two evaluators who were blinded to the allocated

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treatment. One of them, who was randomly chosen by coin toss, performed all of the

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measurements, while the second evaluator supervised the procedures and noted the

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results. The evaluators completed two training sessions for standardization.

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The swelling measurement was performed on both of the lower limbs as described in

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Pichonnaz et al31.

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Swelling volume based on tape measurements was calculated using the truncated

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cone method34 as this method is considered valid and reliable35. Tape measurements

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were taken at 4-cm intervals starting from the patella + 1 cm level. The most proximal

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measurement was performed at the highest level of the thigh where it was possible

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not to skew the tape and the most distal point above the largest cross-sectional area

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of the ankle.

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Bioimpedance swelling measurements were performed using an Impedimed SFB7®

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device a). The BIS R0 of the healthy leg was measured first. One outer electrode was

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placed on the most distal girth measurement level of the leg and one on the most

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proximal girth measurement level of the thigh on the contralateral side. One inner

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electrode was placed 12 cm above the outer leg electrode and one on the most

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proximal girth measurement level of the measured thigh (FIGURE 1). Thus, the

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swelling between the two inner electrodes (between the proximal thigh to 12 cm

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above the malleoli) was evaluated. The same area was taken into consideration for

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the volume calculation. Then, the BIS R0 and volume lower limb percentage

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differences between the healthy side and the involved side were calculated.

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The pain at rest and when walking was evaluated using a visual analog scale

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(VAS)36. The pain was also evaluated by the treating physiotherapist before and after

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each treatment session to measure the immediate effect of MLD. The active range of

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motion (AROM) and active-assisted range of motion (AAROM) in flexion and in

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extension were evaluated using a hand held goniometer. This tool is valid and

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reliable for the evaluation of knee ROM37, 38.

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The knee function was evaluated using computerized gait analysis and two clinical

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questionnaires, namely the KSS39 and the WOMAC40. These approaches investigate

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complementary aspects of knee function41-43. Function evaluation was performed

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when applicable, i.e., at baseline, D7 and 3M for gait analysis and at baseline and

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3M for the clinical questionnaires.

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The gait analysis was performed using an inertial sensor-based movement analysis

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body-worn system b). This system is valid for the analysis of spatio-temporal

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parameters following TKA44-46. The sensors were placed on the anterior faces of the

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thighs and legs, at the junction of the proximal third and the distal two-thirds of the

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limb segment. The patients walked 30 meters both ways at their usual pace. The

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measurement at D7 was taken using crutches. The return trip was taken into

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consideration for analysis.

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The patient characteristics and potential confounding factors following discharge

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were documented to investigate their influence on treatment outcome (age, sex, size,

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weight, body mass index (BMI), stay in rehabilitation center, number of physiotherapy

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sessions after hospital discharge, and MLD during ambulatory physiotherapy

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sessions).

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Statistical Analysis

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The outcomes and control variables were compared between the treatment and

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control groups at each time point using the Wilcoxon rank sum test or the Chi-square

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test as applicable. The change in swelling from D2 to D7, i.e., during the treatment

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period, was compared using the Wilcoxon signed rank test. The significance level

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was set at p< 0.05.

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The number needed to treat to obtain a clinically significant improvement was also

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calculated for treatment outcomes when a significant difference between groups was

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found. Differences between groups had to be superior to the following threshold to be

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considered clinically significant:, ≥10% on measured volume35, ≥13 mm on the pain

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VAS 47, ≥5° for ROM 39, 48, and 15 points on the WOMAC49. The statistical analysis

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was performed using SPSS statistical software, version 18 (SPSS, Chicago, Illinois)

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and STATA 11 (StataCorp, College Station, Texas).

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RESULTS

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Sixty-five eligible patients were contacted, of whom 5 declined to participate. Two

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randomized groups of 30 patients were created. The CONSORT flow diagram

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detailing the recruitment process is presented in FIGURE 2. All exclusions were due

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to factors external to the study.

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The sample characteristics at baseline are presented in TABLE 1. No significant

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difference was found between the treatment and the control group. Similarly, no

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significant difference between groups was found for the gait parameters or their

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coefficients of variation.

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At D7, the treated group showed no significant difference compared with the control

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group for any of the measured outcomes (TABLE 2). At 3M, the mean knee passive

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flexion contracture was -2.6° lower in the treatmen t group (95% confidence interval

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(95%CI) -5.0° to -0.21°; P<0.05) (FIGURE 3). All other differences between groups

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were non-significant. The frequency of knee flexion contracture ≥5° was 27.6% in the

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MLD group vs. 54.2% in the control group. The absolute risk reduction of a 5° knee

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passive flexion contracture at 3M was 26.6% [95% CI 0.9 to 52.3%], and the NNT

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was 4.

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During the D2-D7 treatment period, the swelling volume increased by 1.9%±4.0 in the

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MLD group and 4.1%±7.9 in the control group. The change over time was not

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significantly different between groups (P=0.24). For the BIS R0, the increase was

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5.6%±6.2 in the MLD group and 7.7%±5.8 in the control group (P=0.19).

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No significant difference between groups was found at D7 and 3M for the gait

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parameters or any of their coefficients of variation. The gait parameters of the

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operated side are presented in TABLE 3.

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The mean pain level decrease ranged from 5.8 to 8.2 mm on the VAS immediately

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after treatment in the MLD group and from 2.7 to 8.7 in the control group (TABLE 4).

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The decrease was significant after four out of 5 MLD treatments, but no significant

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difference was found between groups.

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Controlling for potential confounding factors for the period from D7 – 3M showed no

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differences between the MLD and the control group for the stay in a rehabilitation

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center (14 stay/10 no stay vs. 14 stay/15 no stay, P = 0.47), the number of

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ambulatory physical therapy sessions (19.9±7.3 vs. 18.7±9.3, P=0.70) and the use of

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MLD by the treating therapist (10 MLD/14 no MLD vs. 16 MLD/13 no MLD, P=0.33).

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DISCUSSION

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Results interpretation

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This RCT aimed to evaluate the effects of MLD on knee swelling and the swelling’s

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consequences following TKA. No statistically significant difference between groups

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was found at baseline and D2.

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The primary outcome, swelling, was measured using two measurement methods to

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ensure the robustness of the results. No significant effect of MLD on postsurgical

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knee swelling was found at D7 and 3M, either using the limb volume or BIS R0

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measurement. The main study hypothesis was thus rejected.

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These findings using limb volume and bioimpedance spectroscopy (BIS R0) are

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concordant with those of Ebert et al29 who found no difference in limb girth

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measurement in a similar context. The limb volume and BIS measurements produced

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concordant results. However, this study confirmed the higher responsiveness of BIS

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R0.32

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The MLD had no significant effect on the swelling consequences except the knee

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AAROM flexion contracture at 3 months. The mean difference and frequency of

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flexion contracture were significantly lower in the MLD group. The mean difference

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between groups was slightly superior to the 2.3° st andard error of measurement of

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goniometry37. The mean control group flexion contracture increased 1.6° between D7

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and 3M, likely contributing to the significant findings. The MLD contributed thus to

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preserve rather than to improve knee extension between D7 and 3M. Ebert et al.29

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described the same evolution pattern and also found better extension in the MLD

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group but without reaching statistical significance (P = 0.07). The NNT highlighted

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that the MLD prevented a knee flexion contracture ≥ 5° each time 4 patients were

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treated.

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These results are of clinical importance, as knee flexion contracture is common,

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alters gait, increases joint constraints and requires supplementary medical

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interventions50. It is also related to decreased functional outcomes and

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dissatisfaction51.

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The improvement of knee extension in the absence of significant effect of MLD on

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swelling was unexpected, as knee contracture and swelling are theoretically related7.

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The mechanisms explaining this effect remain hypothetical. The slight effect of MLD

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on swelling observed in this study might have been sufficient to influence knee

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extension. MLD may also have mechanical effects on the soft tissues during popliteal

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maneuvers. It may also have prevented fibrosis by increasing protein reabsorption52.

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Finally, improved extension may result from muscular relaxation due to pain relief.

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The pain decreased immediately after the MLD treatments, reaching clinical

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significance for four out of five treatments. In a postsurgical context in which pain was

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controlled by pain medication, the immediate effect of MLD on pain was

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generalizable but transient and was of limited magnitude and not superior to

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relaxation. Despite these limitations, this effect might facilitate knee mobilization and

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gait training.

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No effect of MLD on knee function was found though complementary evaluation

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methods (KSS, WOMAC and gait analysis) were used41-43. This indicates that the

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lower knee flexion contracture in the MLD group did not translate into improved knee

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function at 3 months. The outcomes of both groups were comparable to those

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observed in a follow up study conducted in the department53.

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Study limitations

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The placebo treatment (relaxation) was chosen for its absence of an effect on

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swelling. Yet, it may also have had a superior effect on pain compared to a true

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placebo54. For practical reasons, the treating physiotherapist measured immediate

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post-treatment pain. The absence of blinding for this outcome may have influenced

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the results on both groups.

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Strength would have been an outcome of interest as swelling is related to quadriceps

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inhibition5, 9. This outcome was not measurable due to pain and range of motion

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limitations at the early stage following surgery. Further research should include such

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performance outcome measure to investigate deficiencies that are not captured by

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clinical questionnaires55.

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The rehabilitation program may have influenced the study outcomes but is not likely

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to have influenced the differences between groups. Exercise may for example have

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decreased swelling56 or increased inflammatory response57 in both groups. The

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patients’ environments and activities could not be fully controlled between D7 and

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3M. Importantly, no difference was found between groups for the measured

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confounding factors, i.e., staying in a rehabilitation center, the number of ambulatory

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physical therapy sessions and the use of MLD by the treating therapist.

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The study sample size calculation was based on the result of a previous study that

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found a medium to large effect size for MDL (Cohen’s d = 0.79)28. The statistical

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power of the present study was limited as a positive, but much lower effect, was

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found. A type one error cannot be excluded for significant results, as multiple

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outcomes were tested. However, the coherence of the effects on AROM and AAROM

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knee extension at different stages, and the results of Ebert’s et al study29, suggest

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that the effect found on flexion contractures at 3 months was valid. A Bonferroni

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adjustment was not used because it is overly conservative and based on

326

questionable foundations58, 59.

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Further research is needed to increase the evidence of the effect of MLD on knee

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extension following TKA. A study including only patients with flexion contracture

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would produce a more precise picture of the effect of MLD on knee flexion

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contracture in the target population.

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CONCLUSIONS

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This RCT compared the effect of MLD on swelling and the consequences of swelling

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to a placebo. MLD demonstrated no significant effect on swelling in the early phase

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following TKA surgery. This result reinforces the evidence against the use of MLD for

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swelling reduction in this context. Conversely, MLD decreased the frequency and

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magnitude of AAROM knee flexion contractures, a problematic deficiency following

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TKA. A transient effect on pain was also observed, which might be useful to facilitate

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knee mobilization and gait training in patients with pain.

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Further studies, should investigate if the positive effect of MLD on knee extension

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observed in this study is replicable. More research is also needed to develop and

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validate therapies for swelling reduction in this context.

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References

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20. Földi M, Kubik S. Treatment of the leg. Textbook of lymphology, for Physicians and lymphedema therapists. 3rd ed. München: Urban & Fischer; 2005. 21. Züther J, Norton S. Lymphedema management: The comprehensive guide for practitioners. 3nd ed. New york: Thieme; 2013. 22. Tan IC, Maus EA, Rasmussen JC, Marshall MV, Adams KE, Fife CE et al. Assessment of lymphatic contractile function after manual lymphatic drainage using nearinfrared fluorescence imaging. Arch Phys Med Rehabil 2011;92(5):756-64 e1. 23. Van den Berg F. Therapeutische Effekte des Massagetherapie. Angewandte Physiologie, Band 3: Therapie, Training, Tests. Stuttgart: Thieme; 2005. p 5-17. 24. Guigand O, Breton, G. . Rééducation et arthroplastie totale de genou. Encycl Méd Chir 2003;Kinésithérapie-Médecine Physique-Réadaptation:26-296-A-05. 25. Bonnin M, Westphal M, Jacquemard C, Biot V, Giroud A, Mathelin J et al. Rééducation après prothèse totale de genou. In: Bonnin M, Chambat P, editors. La gonarthrose: Traitement chirurgical: de l´ arthroscopie à la prothèse. Springer; 2007. p 31930. 26. Härén K, Backman C, Wiberg M. Effect of manual lymph drainage as described by Vodder on oedema of the hand after fracture of the distal radius: a prospective clinical study. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 2000;34(4):367-72. 27. Knygsand-Roenhoej K, Maribo T. A Randomized Clinical Controlled Study Comparing the Effect of Modified Manual Edema Mobilization Treatment with Traditional Edema Technique in Patients with a Fracture of the Distal Radius. Journal of Hand Therapy 2011;24(3):184-94. 28. Kessler T, de Bruin E, Brunner F, Vienne P, Kissling R. Effect of manual lymph drainage after hindfoot operations. Physiotherapy Research International 2003;8(2):101-10. 29. Ebert JR, Joss B, Jardine B, Wood DJ. Randomized trial investigating the efficacy of manual lymphatic drainage to improve early outcome after total knee arthroplasty. Arch Phys Med Rehabil 2013;94(11):2103-11. 30. Soderberg G, Ballantyne B, Kestel L. Reliability of lower extremity girth measurements after anterior cruciate ligament reconstruction. Physiotherapy Research International 1996;1(1). 31. Pichonnaz C, Bassin JP, Currat D, Martin E, Jolles BM. Bioimpedance for oedema evaluation after total knee arthroplasty. Physiother Res Int 2013;18(3):140-7. 32. Pichonnaz C, Bassin JP, Lecureux E, Currat D, Jolles BM. Bioimpedance spectroscopy for swelling evaluation following total knee arthroplasty: a validation study. BMC musculoskeletal disorders 2015;16:100. 33. Földi M, Kubik S. Treatment of the leg. In: Földi M, Földi E, editors. Textbook of lymphology for Physicians and lymphedema therapists. 3rd ed. München: Urban & Fischer; 2006. 34. Sitzia J. Volume measurement in lymphoedema treatment: examination of formulae. Eur J Cancer Care (Engl) 1995;4(1):11-6. 35. Badger C, Preston N, Seers K, Mortimer P. Physical therapies for reducing and controlling lymphoedema of the limbs. Cochrane Database Syst Rev 2004;4 Art. No.: CD003141. DOI: 10.1002/14651858.CD003141.pub2. 36. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care & Research 2011;63(S11):S240S52. 37. Piriyaprasarth P, Morris ME. Psychometric properties of measurement tools for quantifying knee joint position and movement: A systematic review. The Knee 2007;14(1):28.

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38. Jakobsen TL, Christensen M, Christensen SS, Olsen M, Bandholm T. Reliability of knee joint range of motion and circumference measurements after total knee arthroplasty: does tester experience matter? Physiotherapy Research International 2010;15(3):126-34. 39. Insall J, Dorr L, Scott R, Scott W. Rationale of the Knee Society clinical rating system. Clinical orthopaedics and related research 1989(248):13. 40. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15(12):1833-40. 41. Witvrouw E, Victor J, Bellemans J, Rock B, Van Lummel R, Van der Slikke R et al. A correlation study of objective functionality and WOMAC in total knee arthroplasty. Knee Surgery, Sports Traumatology, Arthroscopy 2002;10(6):347-51. 42. Lingard EA, Katz JN, Wright RJ, Wright EA, Sledge CB, Kinemax Outcomes G. Validity and responsiveness of the Knee Society Clinical Rating System in comparison with the SF-36 and WOMAC. J Bone Joint Surg Am 2001;83-A(12):1856-64. 43. Lindemann U, Becker C, Unnewehr I, Muche R, Aminin K, Dejnabadi H et al. Gait analysis and WOMAC are complementary in assessing functional outcome in total hip replacement. Clin Rehabil 2006;20(5):413-20. 44. Aminian K, Najafi B, Büla C, Leyvraz PF, Robert P. Spatio-temporal parameters of gait measured by an ambulatory system using miniature gyroscopes. Journal of biomechanics 2002;35(5):689-99. 45. Dejnabadi H. Analysis of gait and coordination for arthroplasty outcome evaluation using body-fixed sensors. Lausanne: Ecole Polytechnique Fédérale de Lausanne; 2006. 46. Jolles BM, Grzesiak A, Eudier A, Dejnabadi H, Voracek C, Pichonnaz C et al. A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up. J Bone Joint Surg Br 2012;94(5):648-55. 47. Tashjian RZ, Deloach J, Porucznik CA, Powell AP. Minimal clinically important differences (MCID) and patient acceptable symptomatic state (PASS) for visual analog scales (VAS) measuring pain in patients treated for rotator cuff disease. Journal of Shoulder and Elbow Surgery 2009;18(6):927-32. 48. Ritter MA, Lutgring JD, Davis KE, Berend ME, Pierson JL, Meneghini RM. The Role of Flexion Contracture on Outcomes in Primary Total Knee Arthroplasty. The Journal of Arthroplasty 2007;22(8):1092-6. 49. Escobar A, Quintana J, Bilbao A, Arostegui I, Lafuente I, Vidaurreta I. Responsiveness and clinically important differences for the WOMAC and SF-36 after total knee replacement. Osteoarthritis and Cartilage 2007;15(3):273-80. 50. Seyler TM, Marker DR, Bhave A, Plate JF, Marulanda GA, Bonutti PM et al. Functional problems and arthrofibrosis following total knee arthroplasty. J Bone Joint Surg Am 2007;89 Suppl 3:59-69. 51. Goudie S, Deakin A, Ahmad A, Maheshwari R, Picard F. Flexion contracture following primary total knee arthroplasty: risk factors and outcomes. Orthopedics 2011;34(12):e855. 52. Földi M, Földi E. The consequences of stagnating high-protein edema. In: Földi M, Földi E, editors. Földi's textbook of lymphology : for physicians and lymphedema therapists. 3rd ed. München: Urban & Fischer; 2006. p 217-9. 53. Jolles BM, Grzesiak A, Eudier A, Dejnabadi H, Voracek C, Pichonnaz C et al. A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up. Journal of Bone & Joint Surgery, British Volume 2012;94-B(5):648-55. 54. Jensen MP, Patterson DR. Hypnotic approaches for chronic pain management: clinical implications of recent research findings. Am Psychol 2014;69(2):167-77. 55. Stevens-Lapsley JE, Bade MJ, Shulman BC, Kohrt WM, Dayton MR. Minimally Invasive Total Knee Arthroplasty Improves Early Knee Strength But Not Functional Performance: A Randomized Controlled Trial. The Journal of Arthroplasty 2012;27(10):18129.e2.

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56. Uda S, Seo A, Yoshinaga F. Swell-preventing effect of intermittent exercise on lower leg during standing work. Ind Health 1997;35(1):36-40. 57. Beiter T, Hoene M, Prenzler F, Mooren FC, Steinacker JM, Weigert C et al. Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks. Exerc Immunol Rev 2015;21:42-57. 58. Perneger TV. What's wrong with Bonferroni adjustments. BMJ 1998;316(7139):12368. 59. Garcia LV. Escaping the Bonferroni iron claw in ecological studies. Oikos 2004;105(3):657-63.

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a) Impedimed SFB7® : Impedimed, 1/50 Parker Ct, Pinkenba QLD 4008, Australia

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b) Physilog®, Gait up, Avenue d’Ouchy, 17, 1006 Lausanne, Switzerland

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Suppliers

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Figure legend

518

FIGURE 1. The placement of the bioimpedance electrodes for the measurement of

519

the operated side

520 521

Legend: V1 and V2: outer electrodes I1 and I2: inner electrodes

523

From: [added]

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FIGURE 2. CONSORT Flow Diagram

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FIGURE 3. Evolution of knee flexion contractures over stages

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Abbreviation: AAROM, active assisted range of motion

527 528 529 530 531 532

* Significant difference P< 0.05 F line: MLD group Red line: control group Bars: ± 1 standard error

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ACCEPTED MANUSCRIPT TABLE 1. Patient characteristics before treatment

TABLE 1

Patients characteristics before treatment Total Mean (SD)

Control Mean (SD)

Treatment Mean (SD)

P value

Baseline

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D2

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Number of patients (n) Limbs volume difference (%) Limbs BIS R0 difference (%) Knee AROM flexion (deg.) Knee AAROM flexion (deg.) Knee AROM flexion contracture (deg.) Knee AAROM flexion contracture (deg.) VAS pain at rest (mm) VAS pain during gait (mm.)

60 13.3 34.2 108.6 115.7

(8.5) (8.5) (9.0) (14.1) (13.5)

30 62.1 71.3 76.5 1.65 28.2 0.2 2.5 118.7 125.1

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(9.12) (10.08) (0.08) (4.23) (5.0) (7.5) (12.1) (12.0)

SC

30 67.7 70.1 79.0 1.65 29.9 1.8 3.3 117.4 126.5

M AN U

Number of patients (n) 60 Women (%) 65.0 Age (years) 70.7 (8.8) Weight (kg.) 77.8 (11.3) Size (m) 1.64 (0.08) −2 Body mass index (kg·m ) 29.0 (4.1) Limb volume difference (%) 1.0 (4.8) Limb BIS R0 difference (%) 2.9 (9.6) Knee AROM flexion (deg.) 118.0 (16.5) Knee AAROM flexion (deg.) 125.8 (16.7) Knee AROM flexion contracture (deg.) 6.6 (6.3) Knee AAROM flexion 4.6 (5.9) contracture (deg.) VAS pain at rest (mm) 22.4 (23.5) VAS pain during gait (mm) 51.4 (25.7) KSS knee assessment (points) 48.9 (15.8) KSS function assessment (points) 66.0 (14.4) WOMAC total score (points) 46.1 (16.1) WOMAC pain score (points) 10.3 (3.0) WOMAC stiffness score (points) 4.1 (1.8) WOMAC function score (points) 31.7 (12.1)

6.8 (6.5)

(8.5) (12.5) (0.08) (3.9) (4.5) (11.5) (20.4) (20.7)

6.3 (6.2)

0.65 0.52 0.50 0.94 0.08 0.23 0.65 0.38 0.92 0.85

4.5 21.3 48.3 48.1

(5.9) (21.7) (25.5) (16.0)

4.6 23.6 54.5 49.7

(6.1) (25.7) (26.1) (15.8)

0.95 0.86 0.36 0.88

65.3 44.0 10.3 4.0 30.0

(13.7) (15.4) (2.71) (1.74) (11.9)

66.2 47.9 10.2 4.2 33.6

(15.4) (16.9) (3.3) (2.0) (12.3)

0.85 0.40 0.77 0.50 0.34

30 12.9 33.1 108.9 116.4

(9.7) (10.1) (16.2) (16.0)

30 13.7 35.5 108.4 115.1

(7.2) (7.7) (12.0) (10.8)

0.65 0.45 0.73 0.54

9.5 (7.0)

8.7 (5.7)

10.3 (8.1)

0.56

5.8 (5.2) 28.6 (25.2) 52.9 (25.8)

5.9 (4.8) 31.0 (28.4) 48.7 (28.7)

5.6 (5.7) 25.9 (21.5) 57.3 (21.8)

0.66 0.71 0.23

Abbreviations: BIS R0, bioimpedance spectroscopy using a frequency theoretically equal to 0; AROM active range of motion; AAROM active-assisted range of motion; VAS, visual analog scale; KSS, knee society score; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index

ACCEPTED MANUSCRIPT TABLE 2. Outcomes in the control and treatment groups after treatment

TABLE 2

Outcomes after treatment Total Mean (SD)

0.58 0.51 0.92 0.66

6.4 (5.5)

6.8 (4.9)

5.9 (6.1)

0.37

SC

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29 15.3 (6.5) 40.8 (6.6) 59.4 (12.1) 69.6 (13.3)

2.4 (3.8) 3.0 (4.1) 21.4 (19.3) 21.8 (22.1) 33.3 (20.9) 29.7 (18.8)

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P value

27 17.0 (10.7) 41.8 (6.5) 58.6 (11.2) 68.4 (11.5)

3 Months Number of patients (n) 53 24 Limb volume difference (%) 3.9 (5.5) 3.7 Limb BIS R0 difference (%) 17.9 (10.2) 16.6 Knee AROM flexion (deg.) 108.6 (14.1) 108.9 Knee AAROM flexion (deg.) 115.7 (13.5) 116.4 Knee AROM flexion contracture (deg.) 4.4 (5.3) 5.6 Knee AAROM flexion contracture (deg.) 3.2 (4.5) 4.6 VAS pain at rest (mm) 8.1 (11.6) 7.1 VAS pain during gait (mm) 12.8 (14.4) 8.4 KSS knee assessment (points) 74.2 (15.7) 74.9 KSS function assessment (points) 78.6 (16.0) 78.8 WOMAC total score (points) 24.6 (14.0) 22.2 WOMAC pain score (points) 5.1 (3.2) 4.5 WOMAC stiffness score (points) 2.6 (1.4) 2.6 WOMAC function score (points) 16.8 (10.3) 15.0

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Treatment Mean (SD)

56 16.2 (8.8) 41.3 (6.5) 59.0 (11.5) 69.0 (12.3)

M AN U

D7 Number of patients (n.) Limb volume difference (%) Limb BIS R0 difference (%) Knee AROM flexion (deg.) Knee AAROM flexion (deg.) Knee AROM flexion contracture (deg.) Knee AAROM flexion contracture (deg.) VAS pain at rest (mm) VAS pain during gait (mm)

Control Mean (SD)

(5.7) (9.3) (16.2) (16.0) (5.6) (5.2) (10.3) (9.7) (15.5) (16.7) (11.2) (2.4) (1.4) (8.4)

1.8 (3.4) 21.0 (16.5) 36.8 (22.5)

0.21 0.90 0.18

29 4.1 19.1 108.4 115.1

0.75 0.67 0.73 0.54

(5.4) (11.0) (12.0) (10.9)

3.2 (4.8) 2.0 9.0 16.7 73.5 78.3 26.7 5.6 2.7 18.3

0.11

(3.5) <0.05* (12.9) 0.52 (16.8) 0.06 (16.1) 0.81 (15.8) 0.90 (16.0) 0.43 (3.8) 0.38 (1.4) 0.83 (11.6) 0.50

Abbreviations: BIS R0, bioimpedance spectroscopy using a frequency theoretically equal to 0; AROM, active range of motion; AAROM, active-assisted range of motion; VAS, visual analog scale; KSS, knee society score; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index * Significant difference between groups

ACCEPTED MANUSCRIPT TABLE 3. Gait parameters in the control and treatment groups after treatment

Gait parameters after treatment

Mean (SD)

Mean (SD)

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EP

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3 Months Number of patients (n) 53 Gait speed (m/s) 1.03 (0.21) Stride length (m) 1.19 (0.17) Stride cadence (stride/min) 51.90 (5.30) Limp (%) 2.59 (1.58) Knee flexion during gait (deg.) 49.16 (7.93) Peak swing speed (deg./s) 297.94 (51.64) Stance time percentage (%) 60.23 (2.74) Swing time percentage (%) 39.77 (2.77) Double support time (%) 21.32 (4.39)

P

Mean (SD)

value

27 0.49 (0.17) 0.96 (0.21) 30.36 (6.13) 10.63 (9.03)

29 0.50 (0.22) 0.96 (0.21) 30.13 (8.94) 7.17 (5.08)

0.93 0.90 0.86 0.20

24.55 (10.67) 136.70 (45.24)

22.13 (8.36) 134.99 (46.84)

0.39 0.81

64.98 (7.43) 35.02 (7.43) 36.93 (12.13)

66.08 (7.38) 33.92 (7.38) 38.34 (13.19)

0.53 0.53 0.60

24 1.03 (0.23) 1.18 (0.20) 52.15 (5.02) 2.53 (1.71)

29 1.03 (0.18) 1.19 (0.13) 51.68 (5.63) 2.64 (1.46)

0.93 0.85 0.75 0.58

49.10 (7.91) 300.62 (55.24)

49.22 (8.10) 295.55 (49.16)

0.93 0.57

60.20 (3.05) 39.80 (3.05 20.78 (4.26)

60.30 (2.56) 39.74 (2.56 21.80 (4.52)

0.67 0.68 0.46

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D7 Number of patients (n) 56 Gait speed (m/s) 0.50 (0.20) Stride length (m) 0.96 (0.21) Stride cadence (stride/min) 30.24 (7.52) Limp (%) 8.97 (7.54) Knee flexion during gait (deg.) 23.39 (9.61) Peak swing speed (deg./s) 135.88 (45.56) Stance time percentage (%) 65.51 (7.35) Swing time percentage (%) 34.49 (7.35) Double support time (%) 37.61 (12.53)

Control (N= 24) Treatment (N= 29)

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Total (N= 53)

SC

TABLE 3

ACCEPTED MANUSCRIPT TABLE 4. Immediate effect on pain in the control and treatment groups

Treatment 1 Treatment 2 Treatment 3 Treatment 4 Treatment 5

Immediate effect on pain in the control and treatment groups (mm.) Control (N= 24)

Treatment (N= 29)

Mean (SD)

Mean (SD)

-6.3 -6.9 -3.7 -2.7 -8.7

(17.9) (12.5)* (8.8)* (15.8) (17.6)*

-5.8 -6.3 -8.2 -7.1 -5.7

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EP

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* Significant before/after differences within the group

(14.6)* (18.2) (13.8)* (11.5)* (11.7)*

P-value 0.39 0.76 0.11 0.20 0.65

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TABLE 4

AC C

EP

FIGURE 1.

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M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Assessed for eligibility (n= 520) Not meeting inclusion criteria (n= 464)

ALLOCATION Allocated to placebo (n=30) Received allocated intervention (n= 27) Did not receive allocated intervention (n= 3) (post-surgical complications)

SC

Allocated to MLD (n= 30) Received allocated intervention (n= 29) Did not receive allocated intervention (n= 1) (post-surgical complications)

D7 FOLLOW-UP

Lost to D7 follow-up (n=1) (post-surgical complications inducing measurement bias)

M AN U

Lost to D7 follow-up (n=3) (post-surgical complications precluding measurement or inducing bias

RI PT

Randomized (n= 60)

D7 ANALYSIS

Analysed (n= 29) Excluded from analysis (n=1) (no D7 measurement possible)

TE D

Analysed (n= 27) Excluded from analysis (n=3) (no D7 measurement possible)

3M FOLLOW-UP

EP

Lost to 3-month follow-up (n=3) (1 refused, 2x general health problem)

Lost to 3-month follow-up (n=0)

3M ANALYSIS

AC C

Analysed (n= 24) Excluded from analysis (n=2) (3-month measurement impossible)

FIGURE 2.

Analysed (n= 29) Excluded from analysis (n=2) (3-month measurement impossible)

ACCEPTED MANUSCRIPT

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Figure 3