*2.6.1. TWO2 therapy*

Sixty‐seven ulcers were treated with TWO2 therapy. The limb was placed in the Hyper‐Box for twice daily for a duration of 180 min and under pressure of 50 mbar. Oxygen supplied at 10 L/min with continuous humidification. Between each session, wounds were washed and left exposed with no dressings or compression. Wounds were cleaned, debrided and re‐ measured twice weekly [42, 46, 47].

### *2.6.2. Compression therapy*

ischemic diabetic ulcers. It may induce iatrogenic deterioration of the affected diabetic limb

Data was collected and analysed using SPSS 18 software (SPSS Inc., Chicago, IL). An inde‐ pendent sample *t*‐test was used for continuous variables, while the Mann‐Whitney *U* test was used to compare unpaired, non‐parametric data. Categorical proportions were examined using the chi‐squared test. Time for healing was examined using Kaplan‐Meier with log‐rank

**2.5. Quality-Adjusted Time Spent Without Symptoms of disease and Toxicity of treatment**

The survival time for patients was divided into three separate phases: the time spent with toxicity of the disease or severe adverse events prior to disease progression known as Toxicity (TOX); the time spent without any symptoms of disease progression or toxicity of treatment known as TWiST; and finally the time spent with progression of the disease known as Progression (PROG). Ulcer recurrence in fully healed ulcers or an increase of size in ulcers that had not fully healed was defined as progression of disease. The Kaplan Meier method was used to determine the mean time spent in each of the TOX, TWiST and PROG periods for each

The anatomical location and duration of the ulcer, signs of infection, slough, and cellulitis, as well as any other vascular risk factors were observed in each patient. The leg ulcers were swabbed for culture as well as for level of sensitivity. Prior to therapy, a numerical rating scale in regards to pain was used. This was then repeated every three days. To record surface area, maximum length and maximum width of the ulcer, the ulcers were cleaned, debrided and digitally photographed using a Visitrak system (Smith & Nephew Ltd., Hull, United King‐ dom). For all patients, ABI with big toe digital pressure measurement and punch biopsy were performed, as well as venous duplex ultrasound scan for full CEAP assessment [44, 45]. Venous

Sixty‐seven ulcers were treated with TWO2 therapy. The limb was placed in the Hyper‐Box for twice daily for a duration of 180 min and under pressure of 50 mbar. Oxygen supplied at 10 L/min with continuous humidification. Between each session, wounds were washed and left exposed with no dressings or compression. Wounds were cleaned, debrided and re‐

treatment group. Mean Q‐TWiST was calculated for each treatment.

Clinical Severity Score was recorded for each patient [48, 49].

due to the cyclic pressure of the Hyper‐Box [46, 47].

312 Wound Healing - New insights into Ancient Challenges

**2.4. Statistical analysis**

comparison.

**(Q-TWiST)**

**2.6. Techniques**

*2.6.1. TWO2 therapy*

measured twice weekly [42, 46, 47].

Sixty-five ulcers were treated with compression therapy. Full compression was performed using Profore ◊ multilayer compression bandage system with underlying non-adherent Profore◊ wound contact layer dressings (Profore◊ , Smith & Nephew plc., London, United Kingdom). Dressings were applied by a wound care specialist nurse and changed as required, one to three times per week, depending on the amount of exudates.

Treatment was continued for 12 weeks or until complete healing of the ulcer or whichever can be first. As soon as the ulcer is healed, the leg was fitted with a class 3, closed toe, below knee elastic stocking during the day [50]. Patients were advised to revitalise the skin by soaking the leg with tap water, baby oil or olive oil to prevent itching and dry cracked skin. Patients were followed up at 3 monthly intervals following the end of the therapy. Patients without full healing of their ulcer by 12 weeks were considered failures of treatment. They were managed with CCD and continued to be seen on a weekly basis.
