Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease.

BACKGROUND: Minimising placebo response is essential for drug development. AIM: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. RESULTS: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. CONCLUSIONS: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.

[Management of liver diseases during pregnancy]. / Maladies hépatiques liées à la grossesse.

Liver tests abnormalities during pregnancy should encourage the clinician to seek liver diseases of pregnancy. The liver diseases of pregnancy are those proper to pregnancy including hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, all the "hypertensive" related diseases and acute fatty liver of pregnancy. These pathologies can involve the vital prognosis of the mother and the child. An adequate management reduces maternal-fetal complications. Close monitoring of pregnancy with sometimes induction of labour and verification of the normalization of liver tests after childbirth are essential.

Severe starvation-induced hepatocyte autophagy as a cause of acute liver injury in anorexia nervosa: a case report.

Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common causes of liver injury, the patient was carefully refed. As liver tests remained abnormal, liver biopsy was performed. At histology and electron microscopy, numerous signs suggestive of starvation-induced hepatocyte autophagy were found. Discussion. Severe starvation can be associated with acute liver injury that is slowly reversible with careful enteral nutrition. In this clinical situation, profound hepatic glycogen depletion in association with autophagy appears as the leading cause of liver injury.

Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: There exists considerable practice variation and little evidence to guide red blood cell (RBC) transfusion in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). Studies in other critically ill cohorts suggest associations between transfusions and adverse patient outcomes. AIM: To characterise any possible clinically-relevant association between RBC transfusion following NVUGIB with rebleeding and mortality. METHODS: Observational study utilising the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE). Multivariable logistic regression models were used to examine and quantify independent associations between RBC transfusion and clinical outcomes. RESULTS: Overall, 1677 patients were included (66.2 ± 16.8 years, 61.7% male, 2.5 ± 1.7 comorbid conditions, initial haemoglobin, 96.8 ± 27.2 g/L); 53.7% received RBC transfusions (2.9 ± 1.6 units of blood), 31.6% had haemodynamic instability, 5.1% fresh blood on rectal examination and 8.6% in the nasogastric tube aspirate. Endoscopic haemostasis was performed in 35.2%. Overall rebleeding (defined as continuous bleeding, rebleeding or surgery) and mortality rates were 17.9% and 5.4%, respectively. After adjusting for potential confounders, transfusion of RBC within 24 h of presentation was significantly and independently associated with an increased risk of rebleeding (OR: 1.0, 95% CI: 0.6-1.8), but not death (OR: 1.5, 95% CI: 0.94-2.23). CONCLUSIONS: This study suggests an association between RBC transfusion following NVUGIB and subsequent rebleeding, after appropriate and extensive adjustment for confounding. Prospective randomised trial evidence is needed to identify the most efficacious and cost-effective transfusional strategies in these patients.

[Can antiplatelet therapy be continued in upper gastrointestinal bleeding?]. / Peut-on poursuivre un traitement antiagrégant en cas d'hémorragie digestive haute?

During a gastro-intestinal bleeding, treatment options regarding antiplatelet agents depend on the indication. In primary prevention, treatment can reasonably be stopped regarding the low expected benefit. In secondary prevention, experts recommend resuming treatment after a five-day interruption. In patients with a coronary stent, the decision is made on a case by case basis and requires close multidisciplinary collaboration between internists, cardiologists and gastroenterologists.

[Antibiotic prophylaxis in liver cirrhosis]. / Antibioprophylaxie de la péritonite bactérienne spontanée.

Bacterial infections are frequent and severe complications in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is the most common infection in such patients. The risk of recurrence at one year after a first episode of SBP is higher than 70% and hospital mortality is estimated between 30-50%. Therefore, there is growing interest in antibiotic prophylaxis (ATP) in these patients. Risk factors for the occurrence of SBP include low protein level in ascitis, a history of previous SBP and an episode of gastrointestinal bleeding. In all three situations, the indication of ATP, reviewed in this paper, is recognized and improves survival.