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.

Epidemiology and clinical features of patients with hepatocellular carcinoma at a tertiary hospital in Jeddah.

BACKGROUND: This study describes the epidemiology and clinical features of hepatocellular carcinoma (HCC), and it investigates any association between Child-Pugh's classification and HCC. MATERIALS AND METHODS: A retrospective chart review was performed for HCC cases diagnosed between 2008 and 2014 at King Abdulaziz University Hospital. We documented the age at cancer diagnosis, gender, occupation, ethnic origin, HCC etiology, Child-Pugh scores, tumor characteristics, alpha-fetoprotein (AFP), and alkaline phosphatase (ALP) levels at diagnosis, and treatment administered. The Chi-square test was used to determine differences between categorical variables. RESULTS: We included 128 patients. Hepatitis B and C viral infections were documented in 24.2% and 33.6% of the patients, respectively. Patients with tumors >5 cm were more likely to have Child's Class C disease, whereas those with tumors ≤2 cm were more likely to have Child's Class A (P < 0.001). Similarly, patients with bilobular or metastatic tumors were more likely to have Child's Class C disease (P = 0.001 and 0.002, respectively). No difference in Child-Pugh score was found between patients with single or multiple tumors (P = 0.480). Furthermore, patients who were both hepatitis B and C positive were more likely to have Child's Class C disease (P = 0.018). Likewise, those who had abnormal AFP and ALP levels ≥1000 ng/mL were more likely to have Child-Pugh's Class C liver disease (P = 0.021 in both cases). CONCLUSION: Hepatitis C and B infections were the main risk factors associated with HCC.