**2.3. Exclusion criteria**

Patients who are bedridden, have ischemic or malignant ulcers, or osteomyelitis in the treated limb were primarily excluded. Patients with ischemic diabetic ulcers were excluded; however, it should be noted that diabetes in isolation was not considered an exclusion criterion. A prior study has shown that the AOTI Hyper‐Box (AOTI Ltd., Galway, Ireland) is not sufficient in ischemic diabetic ulcers. It may induce iatrogenic deterioration of the affected diabetic limb due to the cyclic pressure of the Hyper‐Box [46, 47].

## **2.4. Statistical analysis**

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 comparison.

### **2.5. Quality-Adjusted Time Spent Without Symptoms of disease and Toxicity of treatment (Q-TWiST)**

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

### **2.6. Techniques**

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