Azzam 2016.

Study characteristics
Methods	Study design: prospective randomised intra‐individual (split‐scar) controlled trial conducted in Egypt. Scar segment as the unit of randomisation. Duration of the study: not reported Follow‐up time: 3 months (intermediate‐term follow‐up) Protocol was published before recruitment of participants: participants were recruited from the outpatient clinic of Dermatology Department, Kasr Alainy, Cairo University, after approval of the study by the local ethical committee Details of trial registration: not reported Funding sources: no funding sources were used to support this work
Participants	Number of participants assigned: 30 participants (with a total of 30 scars treated ‐ divided into 2 halves = 60 segments) Keloid Group: 18 participants (total of 36 segments enrolled) Segment 1A: a total of 18 segments treated Segment 2A: a total of 18 segments not treated (control) Hypertrophic scar Group: 12 participants (total of 24 segments enrolled) Segment 1B: a total of 12 segments treated Segment 2B: a total of 12 segments not treated (control) Loss: 11 Keloid group: 6 participants (3 dropped after the 3rd laser session, 2 did not come for the 3rd month follow‐up, and 1 did not come for the 6‐month follow‐up visit). Hypertrophic scar group: 5 participants (3 dropped after the 2nd and 2 after the 3rd laser session). Number of participants assessed: 19 individuals Keloid Group: 12 individuals (total of 24 segments) Hypertrophic scar Group: 7 individuals (total of 14 segments) Inclusion criteria: presence of hypertrophic scars and keloids of any size age above 16 years of either sex participants’ skin type ranging between II and VI Exclusion criteria: pregnancy; history of malignancy or radiation therapy, infections or viral skin diseases immunosuppression or long‐term systemic corticosteroid therapy; history of any treatment for the scar 4 weeks prior to the beginning of laser therapy. Age (years): (keloid group) 31.4 ± 11.1 (mean); (hypertrophic scar group) 24.5 ± 9.4 (mean) Gender: (keloid group) male: 11; 61 (number; %); female: 7; 39 (number; %); (hypertrophic scar group) male: 4, 33.3 (number; %); female: 8, 66.7 (number; %) Duration of scars (years): (both groups) 4.62; 0.167‐20 (mean; range) Skin phototypes: (both groups) II‐VI Scar Location: (both groups) head and neck, and upper limbs (most common sites of lesion)
Interventions	Keloid group: Segment 1A: 1 half of the keloid scar was treated with a fractional CO2 laser (smart stack, 30 W, stack 4, 1000‐μs dwelling time, and 800‐μm spacing) Segment 2A: 1 half of the scar was not treated, serving as an internal control Hypertrophic scar group: Segment 1B: 1 half of the hypertrophic scar was treated with a fractional CO2 laser (smart stack, 25 W, stack 3, 600‐μs dwelling time, 700‐μm spacing for skin type III and 800 μm for skin type IV) Segment 2B: 1 half of the scar was not treated, serving as an internal control Obs: in both 1A and 1B groups, the equipment used was the fractional CO2 laser, DEKA, SMARTXIDE DOT, Italy. Topical anaesthetic cream (lidocaine 25 % and prilocaine 25 % ‐ Pridocaine®) was applied under occlusion 60 minutes prior to the laser session and wiped off just before. Four laser sessions, 6 weeks apart, were performed. The follow‐up was done at 1 month, 3 months, and 6 months after the last treatment.
Outcomes	Primary outcomes: Patient Satisfaction: Assessed at the end of the study, and graded according to the following: excellent (more than 75 % improvement), good (50 to 75 % improvement), moderate (25% to 50 % improvement), and poor (less than 25 % improvement) Vancouver Burn Scar Assessment Scale (VBS): Treatment outcome was evaluated by the Vancouver Burn Scar (VBS) before and 1, 3, and 6 months after the last laser session by a blinded observer. Four components were considered, such as pigmentation, vascularity, pliability and height. Severity of scar was determined by numeric value from a minimum of 0 to 13 as the most severe form on this scale. Digital photographs were taken using a Sony Cyber shot DSC‐H10, Japan. Treatment‐related adverse effects: Were not assessed Secondary Outcomes: Change in scar pruritus: method not described Change in scar pain: method not described
Notes	Vancouver Burn Scar Assessment Scale (VBS) is cited along this study as Vancouver Scar Score (VSS). Histological and immunohistochemical results: Three biopsies (4 mm skin punch) were obtained from each patient's scar, before and 1, and 3 months after the last laser session, respectively. In addition, a 4th skin biopsy was obtained from normal skin in the same anatomical region before treatment as control. All skin biopsies were immediately fixed in 10 % formol saline and processed into paraffin blocks Paraffin sections of 5‐μm thickness were prepared and subjected to the following stains: hematoxylin and eosin for histological evaluation, Masson’s trichrome stain for collagen fibres, and anti‐matrix metalloproteinase (MMP9) immunohistochemistry. Skin biopsies obtained 3 months after the last laser session were not subjected to MMP‐9 immunohistochemistry. All stained paraffin sections were examined using an Olympus light microscope and photomicrographs were captured using a digital camera. The authors declared no funding sources were used and that no conflicts of interest were present.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was carried out by the participants drawing lots between sealed opaque envelopes, containing cards with treatment code of either laser treatment of test site "right" and no treatment of test site "left", and vice versa.
Allocation concealment (selection bias)	Low risk	The laser‐treated site was concealed from the evaluator throughout the study and was revealed only to the investigator who treated the participants.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and health professionals performing the treatment were not blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Scars were photographed and graded clinically by a blinded evaluator.
Incomplete outcome data (attrition bias) All outcomes	High risk	Eleven participants dropped out of the study (6 participants of keloid group and 5 of hypertrophic scars group) and the reasons were not described by the author.
Selective reporting (reporting bias)	High risk	No trial protocol is available. No skin biopsies were obtained from not treated areas of each participant's scar, in order to compare histological and immunohistochemical changes between treated and not treated scar areas.
Other bias	Low risk	No other sources of bias were found.