AIM:To study the clinical efficacy and safety of Fecal microbiota transplantation(FMT).We systematically reviewed FMT used as clinical therapy.METHODS:We searched MEDLINE,EMBASE,the Cochrane Library and Conference pro...AIM:To study the clinical efficacy and safety of Fecal microbiota transplantation(FMT).We systematically reviewed FMT used as clinical therapy.METHODS:We searched MEDLINE,EMBASE,the Cochrane Library and Conference proceedings from inception to July,2013.Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category,on an intention-to-treat basis.RESULTS:We included 45 studies;34 on Clostridium difficile-infection(CDI),7 on inflammatory bowel disease,1 on metabolic syndrome,1 on constipation,1 on pouchitis and 1 on irritable bowel syndrome(IBS).In CDI 90% resolution of diarrhea in 33 case series(n = 867) was reported,and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial(RCT)(n = 16).In ulcerative colitis(UC) remission rates of 0% to 68% were found(n = 106).In Crohn's disease(CD)(n = 6),no benefit was observed.In IBS,70% improvement of symptoms was found(n = 13).100% Reversal of symptoms was observed in constipation(n = 3).In pouchitis,none of the patients(n = 8) achieved remission.One RCT showed significant improvement of insulin sensitivity in metabolic syndrome(n = 10).Serious adverse events were rare.CONCLUSION:FMT is highly effective in CDI,and holds promise in UC.As for CD,chronic constipation,pouchitis and IBS data are too limited to draw conclusions.FMT increases insulin sensitivity in metabolic syndrome.展开更多
Effect sizes are estimated from several study designs when the subjects are individually sampled. When the samples are the aggregate cluster of individuals, the within cluster correlation must be accounted for to cons...Effect sizes are estimated from several study designs when the subjects are individually sampled. When the samples are the aggregate cluster of individuals, the within cluster correlation must be accounted for to construct correct confidence intervals, and to conduct valid statistical inference. The purpose of this article is to propose and evaluate statistical procedures for the estimation of the variance of the estimated attributable risk in parallel groups of clusters, and in a design dividing each of k clusters into two segments creating multiple sub-clusters. The estimated variance is the first order approximation and is obtained by the delta method. We apply the methodology and propose a Wald type confidence interval on the difference between two correlated attributable risks. We also construct a test on the hypothesis of equality of two correlated attributable risks. We evaluate the power of the proposed test via Monte-Carlo simulations.展开更多
BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, doub...BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the α 4β 7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as com-pared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1∶ 125 developed, incomplete saturation of the α 4β 7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.展开更多
文摘AIM:To study the clinical efficacy and safety of Fecal microbiota transplantation(FMT).We systematically reviewed FMT used as clinical therapy.METHODS:We searched MEDLINE,EMBASE,the Cochrane Library and Conference proceedings from inception to July,2013.Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category,on an intention-to-treat basis.RESULTS:We included 45 studies;34 on Clostridium difficile-infection(CDI),7 on inflammatory bowel disease,1 on metabolic syndrome,1 on constipation,1 on pouchitis and 1 on irritable bowel syndrome(IBS).In CDI 90% resolution of diarrhea in 33 case series(n = 867) was reported,and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial(RCT)(n = 16).In ulcerative colitis(UC) remission rates of 0% to 68% were found(n = 106).In Crohn's disease(CD)(n = 6),no benefit was observed.In IBS,70% improvement of symptoms was found(n = 13).100% Reversal of symptoms was observed in constipation(n = 3).In pouchitis,none of the patients(n = 8) achieved remission.One RCT showed significant improvement of insulin sensitivity in metabolic syndrome(n = 10).Serious adverse events were rare.CONCLUSION:FMT is highly effective in CDI,and holds promise in UC.As for CD,chronic constipation,pouchitis and IBS data are too limited to draw conclusions.FMT increases insulin sensitivity in metabolic syndrome.
文摘Effect sizes are estimated from several study designs when the subjects are individually sampled. When the samples are the aggregate cluster of individuals, the within cluster correlation must be accounted for to construct correct confidence intervals, and to conduct valid statistical inference. The purpose of this article is to propose and evaluate statistical procedures for the estimation of the variance of the estimated attributable risk in parallel groups of clusters, and in a design dividing each of k clusters into two segments creating multiple sub-clusters. The estimated variance is the first order approximation and is obtained by the delta method. We apply the methodology and propose a Wald type confidence interval on the difference between two correlated attributable risks. We also construct a test on the hypothesis of equality of two correlated attributable risks. We evaluate the power of the proposed test via Monte-Carlo simulations.
文摘BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the α 4β 7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as com-pared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1∶ 125 developed, incomplete saturation of the α 4β 7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.
