Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 1

Primary outcomes

1. Within-session reliability of pitting test at the level of the foot, leg and midline region

   Time frame: baseline (within-session)

   intra and interrater reliability of pitting test at the level of the foot, leg and midline region;

   The grading of edema is determined by pit depth (measured visually) and recovery time from grade 0-3. The scale is used to rate the severity and the scores are as follows:

   • Grade 0: No clinical edema- Grade 1: Slight pitting (up to 2 mm depth) - Grade 2: Moderate pitting (2-5 mm) - Grade 3: Noticeably deep pit (>5 mm)

2. Within-session reliability of skinfold test at the level of the foot, leg and midline region

   Time frame: baseline (within-session)

   intra and interrater reliability of skinfold test at the level of the foot, leg and midline region Skin and subcutaneous tissue is lifted between thumb and index(and, if possible, compared to the contralateral side) Outcome:If skinfold is increased; yes(1), otherwise; no(0)

3. Within-session reliability of skin hardness test at the level of the foot, leg and midline region

   Time frame: baseline (within-session)

   intra and interrater reliability skin hardness test at the level of the foot, leg and midline region.

   Skin is palpated with thumb and index (and, if possible, compared to the contralateral side) Outcome: If skin is hardened; yes(1), otherwise; no(0)

4. Within-session reliability of measurement with MoistureMeterD at the level of the foot, leg and midline region

   Time frame: baseline (within-session)

   intra and interrater reliability of measurement with MoistureMeterD at the level of the foot, leg and midline region.

   This device can be applied to measure the percentage of water under the skin in terms of the Tissue Dielectric Constant value, making use of a probe with 300 MHz signal. Up to a depth of 2.5mm, this portable device allows measuring free and bounded water in the tissue through which the electromagnetic wave passes.

   Outcome: %PWC(% Percentage Water Content)

5. Within-session reliability of measurement with SkinFibroMeter at the level of the foot, leg and midline region

   Time frame: baseline (within-session)

   intra and interrater reliability of measurement with SkinFibroMeter at the level of the foot, leg and midline region.

   This device is a relatively recently developed device which consists of a 1-mm-long intender and records the resistance to 50 gram of pressure by using its reference plate and related built-in force sensors. Outcome: The resistance from the skin to deformation when an external force is applied, is expressed as a number in Newton (N) and represents the induration of the skin.

6. Within-session reliability of circumference measurements at the level of the leg and midline region

   Time frame: baseline (within-session)

   intra and interrater reliability of circumference measurements at the level of the leg and midline region; Outcome: in cm for each of the tapeline, but a total volume can be calculated (in ml) using a truncated cone formula

7. Within-session reliability of perometry at the level of the leg

   Time frame: baseline (within-session)

   intra and interrater reliability of perometry at the level of the leg; Optoelectronic volumetry (or perometry): a method that makes use of an optoelectronic infrared device to detect volume differences Outcome: in ml. The height of the measurement should be noted as well.

8. Within-session reliability of water displacement measurement at the level of the foot

   Time frame: baseline (within-session)

   intra and interrater reliability of water displacement measurement at the level of the foot

9. Within-session reliability of measurements with bio-impedance spectroscopy/analysis devices at the level of the lower limbs

   Time frame: baseline (within-session)

   intra and interrater reliability of measurements with bio-impedance spectroscopy/analysis devices at the level of the lower limbs

10. Within-session reliability of a questionnaire regarding skin integrity

    Time frame: baseline (within-session)

    intra and interrater reliability of a questionnaire regarding skin integrity (ICC compression questionnaire) that should be completed by the therapist The ICC-CQ is the first reliable and valid questionnaire evaluating different kinds of compression and the experience by patients with lymphedema or chronic venous disease.

11. Concurrent validity (only possible in case there are multiple measurement methods assessing the same lymphedema characteristic) of measurement methods for the assessment of LLL

    Time frame: baseline (within-session)

    the measurement methods assessing the same edema characteristic (for example: perometry and perimetry are two different methods that both evaluate lymphedema volume or swelling), will be correlated to each other

12. Clinical feasibility of measurement methods and questionnaires for the assessment of Lower lymb lymphoedema

    Time frame: baseline (within-session)

    Time efficiency will be examined for each method (timed), limitations regarding clinical feasibility will be listed and scored for each method (present or absent). Finally, an overall ranking regarding feasibility score will be determined based on the reliability (best -> worse reliability) and time-efficiency (fastest -> slowest measurement method).

13. Between-session reliability of pitting test at the level of the foot, leg and midline region

    Time frame: 2 weeks

    The grading of edema is determined by pit depth (measured visually) and recovery time from grade 0-3. The scale is used to rate the severity and the scores are as follows:

    • Grade 0: No clinical edema- Grade 1: Slight pitting (up to 2 mm depth) - Grade 2: Moderate pitting (2-5 mm) - Grade 3: Noticeably deep pit (>5 mm) A cohort of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

14. Between-session reliability of skinfold test at the level of the foot, leg and midline region

    Time frame: 2 weeks

    Skin and subcutaneous tissue is lifted between thumb and index(and, if possible, compared to the contralateral side) Outcome:If skinfold is increased; yes(1), otherwise; no(0)

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

15. Between-session reliability of skin hardness test at the level of the foot, leg and midline region

    Time frame: 2 weeks

    Skin is palpated with thumb and index (and, if possible, compared to the contralateral side) Outcome: If skin is hardened; yes(1), otherwise; no(0)

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

16. Between-session reliability of measurement with MoistureMeterD at the level of the foot, leg and midline region

    Time frame: 2 weeks

    This device can be applied to measure the percentage of water under the skin in terms of the Tissue Dielectric Constant value, making use of a probe with 300 MHz signal. Up to a depth of 2.5mm, this portable device allows measuring free and bounded water in the tissue through which the electromagnetic wave passes.

    Outcome: %PWC(% Percentage Water Content)

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

17. Between-session reliability of measurement with SkinFibroMeter at the level of the foot, leg and midline region

    Time frame: 2 weeks

    This device is a relatively recently developed device which consists of a 1-mm-long intender and records the resistance to 50 gram of pressure by using its reference plate and related built-in force sensors. Outcome: The resistance from the skin to deformation when an external force is applied, is expressed as a number in Newton (N) and represents the induration of the skin.

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

18. Between-session reliability of circumference measurements at the level of the leg and midline region

    Time frame: 2 weeks

    Circumference measurements (cm) with perimeter.

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

19. Between-session reliability of perometry at the level of the leg

    Time frame: 2 weeks

    Optoelectronic volumetry (or perometry): a method that makes use of an optoelectronic infrared device to detect volume differences Outcome: in ml. The height of the measurement should be noted as well.

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

20. Between-session reliability of water displacement measurement at the level of the foot

    Time frame: 2 weeks

    'Gold standard' in which the limb is immersed into a water tank and the weight of the limb is being weighted.

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

21. Between-session reliability of measurements with bio-impedance spectroscopy/analysis devices at the level of the lower limbs

    Time frame: 2 weeks

    Bio-impedance spectroscopy assesses the resistance (or impedance) to the flow of an electrical current that is primarily conducted by body fluid.

    A subgroup of patients with LLL (n= ±40) and healthy volunteers (±40) will be scheduled for a second visit, 2 weeks later for the same clinical evaluation (as at baseline), with only 1 assessor.

22. Between-session reliability of a questionnaire regarding skin integrity

    Time frame: 2 weeks

    Between-session reliability of a questionnaire regarding skin integrity: ICC compression questionnaire that should be completed by the therapist The ICC-CQ is the first reliable and valid questionnaire evaluating different kinds of compression and the experience by patients with lymphedema or chronic venous disease

23. Between-session reliability of a self-reported disease-specific quality of life questionnaire (Lymph-ICF-LL)

    Time frame: 2 weeks

    The Lymph-ICF-LL is a descriptive, evaluative tool containing 28 questions about impairments in function, activity limitations, and participation restrictions in patients with lower limb lymphedema. The questionnaire has 5 domains: physical function, mental function, general tasks/household activities, mobility activities, and life domains/social life.