Effect of footbath protocols for prevention and treatment of digital dermatitis in dairy cattle: A systematic review and network meta-analysis.

Digital dermatitis (DD) is an infectious bacterial disease affecting cattle feet. Footbaths are a common herd-level control method for DD; however, variations in product, concentration, and frequency of use complicate comparisons between protocols. The objective of this systematic review was to evaluate all walk-through footbath protocols reported that determined efficacy for prevention and treatment of DD lesions in dairy cattle. An extensive literature search was conducted, including electronic databases and gray literature updated until March 2018. Studies identified included all liquid walk-through footbath protocols that were compared to other footbath protocols or no footbath. Only studies with treatment or prevention of DD lesions as an outcome were included. Literature search and subsequent screening identified 14 publications with 24 treatment comparisons and 24 prevention comparisons. Studies included mostly had low and/or unclear risks of bias. Descriptive analyses were performed according to prevention and treatment outcomes, with case and success definitions summarized as odds ratios (OR). A subsequent network meta-analysis was conducted of 11 studies, comparing 17 protocol comparisons for the prevention outcome and 10 studies comparing 19 protocol comparisons for the treatment outcome, using semi-informative priors in a Bayesian statistical framework. Results of a random effects Bayesian network meta-analysis indicated only 5% copper sulfate used at least 4 times/wk was superior to both no footbath (OR: 5.26; 95% CrI: 1.27-28.8) and a water placebo (OR: 9.47; 95% CrI: 1.03-85.8) in treatment of DD. No other protocol was associated with a reduction in DD, and there were no differences in pair-wise comparisons between any active treatments. Unfortunately, for both outcomes (treatment and prevention), small sample sizes (adjusted for clustering) limited the power to detect substantial differences between protocol effects. Thus, despite widespread use of footbaths, limited strength of evidence for use remains and standardized protocols with large sample sizes are needed to further investigate effectiveness of footbath protocols for control of DD. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.

BACKGROUND: Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. AIM: To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. RESULTS: A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. CONCLUSIONS: Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.

Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis.

INTRODUCTION: Crohn's disease (CD) and ulcerative colitis (UC) have a progressive course leading to hospitalisation and surgery. The ability of existing therapies to alter disease course is not clearly defined. AIM: To investigate the comparative efficacy of currently available inflammatory bowel disease (IBD) therapies to reduce hospitalisation and surgery. METHODS: We conducted a systematic review in MEDLINE/PubMed for randomised controlled trials (RCT) published between January 1980 and May 2016 examining efficacy of biological or immunomodulator therapy in IBD. We performed direct comparisons of pooled proportions of hospitalisation and surgery. Pair-wise comparisons using a random-effects Bayesian network meta-analysis were performed to assess comparative efficacy of different treatments. RESULTS: We identified seven randomised controlled trials (5 CD; 2 UC) comparing three biologics and one immunomodulator with placebo. In CD, anti-TNF biologics significantly reduced hospitalisation [Odds ratio (OR) 0.46, 95% confidence interval (CI) 0.36-0.60] and surgery (OR 0.23, 95% CI 0.13-0.42) compared to placebo. No statistically significant reduction was noted with azathioprine or vedolizumab. Azathioprine was inferior to both infliximab and adalimumab in preventing CD-related hospitalisation (>97.5% probability). Anti-TNF biologics significantly reduced hospitalisation (OR 0.48, 95% CI 0.29-0.80) and surgery (OR 0.67, 95% CI 0.46-0.97) in UC. There were no statistically significant differences in the pair-wise comparisons between active treatments. CONCLUSIONS: In CD and UC, anti-TNF biologics are efficacious in reducing the odds of hospitalisation by half and surgery by 33-77%. Azathioprine and vedolizumab were not associated with a similar improvement, but robust conclusions may be limited due to paucity of RCTs.