Chen 2017.

Study characteristics
Methods	Study design: randomised controlled, hospital‐based, parallel designed, and single‐blinded study, conducted in China. Participants as the unit of randomisation. Duration of the study: May 2014 to May 2015 Follow‐up time: 12 weeks (intermediate‐term follow‐up) Protocol was published before recruitment of participants: the study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Nanjing, China) Details of trial registration: not reported Funding sources: supported by grants from the National Natural Science Foundation of China (nos. 81573072 and 81371757) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (no. JX10231801)
Participants	Number of participants assigned: 69 participants (with a total of 69 scars treated ‐ 1 scar per participant) Group 1 (intralesional Diprospan ‐ betamethasone disodium phosphate and betamethasone dipropionate): 23 individuals Group 2 (intralesional Diprospan plus 5‐FU): 23 individuals Group 3 (intralesional Diprospan plus 5‐FU plus 1064‐nm Nd:YAG): 23 individuals Loss: 7 participants. Number of participants assessed: 62 participants Group 1: number of individuals not specified Group 2: number of individuals not specified Group 3: number of individuals not specified Inclusion criteria: presence of at least 1 keloid scar with a minimum of 10 mm in length (preferably on the trunk or proximal extremities). Exclusion criteria: people who were treated for keloids within the last 6 months; pregnant people or people considering pregnancy in the near future; lactating people; people with chronic renal failure; people showing any abnormalities of liver function or blood cell counts. Age (years): Group 1: 27.2 / 6.4 (mean /± SD) Group 2: 26.5 / 7.5 (mean /± SD) Group 3: 26.5 / 9.5 (mean /± SD) Gender: male: 42% female: 58% Scar Location: face and neck: 4.7%; trunk: 67.8%; proximal extremities: 22.5%; distal extremities: 5% Duration of scars (months): Group 1: 29.8 / 25.6 (mean / ± SD) Group 2: 29.2 / 33.6 (mean / ± SD) Group 3: 39.8 / 26.8 (mean / ± SD) Erythema score at baseline: Group 1: 3.5 / 0.8 (mean / ± SD) Group 2: 3.7 / 0.7 (mean / ± SD) Group 3: 3.6 / 0.8 (mean / ± SD) Pruritus score at baseline: Group 1: 3.4 / 0.6 (mean / ± SD) Group 2: 3.3 / 0.5 (mean / ± SD) Group 3: 3.5 / 0.7 (mean / ± SD) Pliability score at baseline: Group 1: 3.0 / 1.1 (mean / ± SD) Group 2: 2.9 / 1.0 (mean / ± SD) Group 3: 2.9 / 0.9 (mean / ± SD) No statistically significant differences were observed between the study groups regarding mean age (P = 0.872), duration (P = 0.557), erythema (P = 0.401), pruritus (P = 0.628) and pliability (P = 0.664) at baseline
Interventions	In all segment groups only 1 lesion (preferably on the trunk or proximal extremities) per participant was treated Group 1: keloids were treated once a month by intralesional injection of Diprospan (1 ml/ampoule contains 2 mg betamethasone disodium phosphate and 5 mg betamethasone dipropionate) for 3 months. Group 2: keloids received a combination of 0.5 ml 5‐FU (25 mg/ml; Jinyao Pharmaceutical Group, Tianjin, China) and 1 ml Diprospan, injected monthly for 3 months. Group 3: keloids were treated by a 1,064‑nm Nd:YAG (Lumenis One; Lumenis, Santa Clara, CA, USA) with a single 12‐msec pulse at an energy density of 90‐100 J/cm² with a 6 mm spot and a single pass of spots overlapping 5% to 10%, without cooling, for 3 sessions at a 1‐month interval. Each session consisted of 3 passes (without local anaesthesia), unless the participant felt intolerable pain at the 2nd pass. This way, the session was ceased. Intralesional injection of Diprospan plus 5‐FU was similar to that in group 2 and was given immediately after each Nd:YAG treatment for a total of 3 sessions.
Outcomes	Primary outcomes Overall Appearance (by Patient Self‐assessment): Assessed by participants 1 month after each session (at the 1st, 2nd, and 3rd months of the study), based on a 5‐point scale as, no improvement; poor improvement = up to 25%; fair improvement = 26% to 50%, good improvement = 51% to 75% improvement; and excellent improvement = 76% to 100%. Overall Appearance (Observer Assessment): Assessed by a blinded observer 1 month after each session (at the 1st, 2nd, and 3rd months of the study), by comparing the standardised photographs taken at the 4‐week intervals. The scales of overall appearance (improvement) were similar to those of the patient self‑assessment. Treatment‐related adverse effects: Treatment‐related adverse effects were reported according to the group in which they occurred. Secondary Outcomes: Change in scar erythema: erythema was graded by the observer on a 5‐point scale: 0 = no erythema; 1 = mild erythema; 2 = moderate erythema; 3 = severe erythema; and 4 = very severe erythema. The percentage of lesion improvement was defined as the percentage of erythema reduction compared with the erythema at baseline. Change in pliability: pliability was graded by the observer on a 5‐point scale: 0 = no induration; 1 = mild induration; 2 = moderate induration; 3 = severe induration; and 4 = very severe induration. The percentage of lesion malacia was defined as the percentage of reduction to the baseline pliability. Change in scar pruritus: severity of pruritus was graded by the participant on a 5‐point scale: 0 = no pruritus; 1 = mild pruritus; 2 = moderate pruritus; 3 = severe pruritus; and 4 = very severe pruritus. The percentage of itch reduction was defined as the percentage of pruritus reduction to the baseline pruritus.
Notes	Statistical analysis: The data were analysed using the SPSS 11.5 software package for Windows (SPSS Inc., Chicago, IL, USA). Standard 2‐tailed and paired Student's t‐tests were used to compare the differences between values at time‐points of assessment and at baseline. One‐way analysis of variance followed by post hoc and X² tests were used to compare the difference between baseline and 1, 2 and 3 months. All statistical tests were 2‑tailed. P < 0.05 was considered to indicate a significant difference. This work was supported by grants from the National Natural Science Foundation of China (nos. 81573072 and 81371757) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (no. JX10231801).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation was cited but the method was not described.
Allocation concealment (selection bias)	Unclear risk	Allocation process was not described.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Single‐blinded study. Participants and health professionals performing the treatment can't be blinded. Objective assessment of the results was made by a blinded observer.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Results were assessed by a blinded observer.
Incomplete outcome data (attrition bias) All outcomes	High risk	Seven participants did not complete the study. The reasons were not specified.
Selective reporting (reporting bias)	Low risk	No trial protocol is available, but all parameters listed in the methods to assess changes in the scars were described.
Other bias	Low risk	No other sources of bias were found.