Publications by authors named "Steven J Shiff"
Background & Aims: Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from >8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for >4 years.
Methods: Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system.
Background: Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation. The objective of this trial was to evaluate the efficacy and safety of linaclotide in patients with chronic idiopathic constipation and concomitant moderate-to-severe abdominal bloating.
Methods: This Phase 3b, randomized, double-blind, placebo-controlled clinical trial randomized patients to oral linaclotide (145 or 290 μg) or placebo once daily for 12 weeks.
Article Synopsis
- The article investigates the effectiveness of "adequate relief" (AR) as a clinical trial endpoint for IBS-C and how it compares to other established endpoints like FDA and EMA criteria.
- It analyzes data from two phase 3 clinical trials involving linaclotide over 12 weeks to determine correlations between AR and abdominal symptoms, bowel symptoms, and global health assessments.
- The study concludes that AR serves as a consistent measure that aligns with FDA and EMA responder criteria, helping to standardize IBS-C trial outcomes and improve comparisons across studies.
Article Synopsis
- The study focuses on the need for effective clinical outcome assessments (COAs) in trials regarding pediatric chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C).
- A literature review including 1,105 abstracts identified a limited number of relevant studies and COAs that measure key symptoms such as bowel movement frequency, abdominal pain, and stool consistency in children.
- Although there is general agreement among experts on important symptoms to measure, the existing COAs fall short of regulatory standards for proper evaluation in clinical trials.
Article Synopsis
- Research highlights that chronic constipation (CC) not only involves bowel symptoms but also significant abdominal symptoms experienced by patients.
- A study involving literature reviews and patient interviews identified a range of symptoms important for clinical trials, discovering 62 distinct symptoms related to CC.
- Findings emphasize that both bowel and abdominal symptoms are crucial for understanding patient experiences and should be included in clinical trial assessments to evaluate treatment benefits effectively.
Background & Aims: Patients with irritable bowel syndrome with constipation (IBS-C) have abdominal symptoms that vary in severity. Linaclotide, a guanylate cyclase-C agonist, improves abdominal and bowel symptoms in these patients. We examined the prevalence of severe abdominal symptoms in patients with IBS-C and assessed the effects of linaclotide on abdominal symptoms, global measures, and quality of life (QOL).
View Article and Find Full Text PDFObjectives: The aims were: firstly, to review the definition and diagnosis of irritable bowel syndrome with constipation (IBS-C, a subtype of IBS); secondly, to critically assess current therapies for IBS-C with a focus on effectiveness for abdominal pain; and thirdly, to review clinical studies evaluating the efficacy of linaclotide, a therapy recently approved by the US Food and Drug Administration for the treatment of adults with IBS-C and chronic idiopathic constipation and the European Medicines Agency for the symptomatic treatment of moderate to severe IBS-C in adults, and in development for treatment of IBS-C worldwide.
Methods: A comprehensive literature review was performed to summarize IBS-C and current treatments. MEDLINE and gastrointestinal society congress proceedings were searched to identify data from linaclotide clinical studies in adults with IBS-C published between January 2010 and August 2012.
Objectives: Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C).
Methods: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μ g oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period.
Objectives: Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide treatment in patients with irritable bowel syndrome with constipation (IBS-C) over 26 weeks.
Methods: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μg of oral linaclotide once daily for a 26-week treatment period.
Background: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. In two trials, we aimed to determine the efficacy and safety of linaclotide in patients with chronic constipation.
Methods: We conducted two randomized, 12-week, multicenter, double-blind, parallel-group, placebo-controlled, dual-dose trials (Trials 303 and 01) involving 1276 patients with chronic constipation.
Topical delivery of non-steroidal anti-inflammatory drugs through the oral mucosa has been used for oral cancer chemoprevention. Local permeation of these agents has been one of the major concerns. Here we propose an approach to predict the permeability of topically applied agents for oral cancer chemoprevention.
View Article and Find Full Text PDFEvidence that chronic intake of non-steroidal anti-inflammatory drugs, especially aspirin, prevents cancer development continues to accumulate. The data are particularly convincing for colorectal cancer; however, because of well-known side effects, they cannot routinely be recommended for this purpose. An appreciation of the mechanisms that underlie their anti-cancer effects might permit the development of safer agents.
View Article and Find Full Text PDFTo assess the mechanism of action of 5-fluorouracil (5-FU) apoptosis (AI) and proliferation (PI) indices were determined histochemically in colon carcinoma and normal colon tissue of 7 patients treated preoperatively with 5-FU (300 mg/m2/day for 5 days) and 11 controls. 5-Fluorouracil induced apoptosis selectively in malignant colonocytes (AI in 5-FU-group: 0.126 +/- 0.
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