81 Review Inflammatory Mediators in Animal Burn Models for the uninjured animal group. In case of missing data, such as the number of animals or SD, we contacted corresponding authors by email and ResearchGate, including a reminder after 2 weeks. Synthesis of results and meta-analysis Meta-analyses were performed on overall outcome measures from which at least 5 studies were available. Data were analyzed using Comprehensive Meta-Analysis software (version 4; Biostat, Englewood, NJ), and the effect sizes were expressed as standardized mean difference (Hegdes’s g) of inflammatory mediator levels in blood or wound tissue from burn-injured animals compared to levels in blood or skin from uninjured animals (baseline or uninjured controls) with 95% confidence interval. A random-effects model was used in the analyses and the I2 statistic was used as a measure for statistical heterogeneity. Inflammatory mediators that were considered as the same entity were pooled (Supplementary Table 1 and Supplementary Table 2). Remaining wound area was calculated using outcome data on wound closure, re-epithelization and contraction. Possible publication bias was explored using Duval and Tweedie’s trim and fill methodology for overall outcomes with at least 10 studies [83]. Data was visualized using GraphPad version 5.01 (PRISM, Ja Jolla, USA). Subgroup analyses Predefined subgroup meta-analyses were performed on subgroups that consisted of at least 10 studies. Comprehensive Meta-Analysis software was used to determine differences based on time interval after burn (PBD 0-1, 2-4, 5-9, 10-14, 15-21, 22-28, or >29), percentage of total body surface area (≤5, 5-25, or >25), burn depth (superficial, partial-thickness, deep dermal, or full-thickness), injury site (abdominal, dorsal, both sides or paw), burn agent (water, contact, flame, or air), animal species (mouse, rat, or pig), animal sex, animal age (young or adult), and detection method (mRNA or protein analysis). In addition, differences between baseline-controlled studies and studies that used a separate control group were assessed. Common among-study variance across subgroups (pool within-group estimates of tau-squared) was assumed and subgroups were combined using fixed effects model. Effect was compared at different levels of the subgroups. Reported SMDs are based on the random effects model. P-values were based on the 95% confidence interval of the difference between subgroups. Bonferroni correction was applied, that is, the P-values were multiplied by the number of comparisons within each subgroup analysis. In the case of repeated measures of an experimental group within a time interval, the maximum effect size within that time interval was selected. When required, total body surface area was calculated using the reported area of the burn, weight (W) of 3
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