Definition of factor Xa inhibitor-related, life-threatening gastrointestinal bleeding and guidance on when to use reversal therapy: A Delphi panel.

Objective: To define and contextualize life-threatening gastrointestinal (GI) bleeding in the setting of factor Xa (FXa) inhibitor therapy and to derive a consensus-based, clinically oriented approach to the administration of FXa inhibitor reversal therapy.

Methods: We convened an expert panel of clinicians representing specialties in emergency medicine, gastroenterology, vascular medicine, and trauma surgery. Consensus was reached among the clinician panelists using the Delphi technique, which consisted of 2 survey questionnaires followed by virtual, real-time consensus-building exercises.

CNS sites controlling the gastric pyloric sphincter: Neuroanatomical and functional study in the rat.

The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher-order neurons and the nuclei that engage the DMV neurons controlling the pylorus. The purpose of the present study was twofold.

Development of a novel patient-reported outcome measure to assess signs and symptoms of COVID-19.

Background: Given the urgent need for vaccines and treatments for coronavirus disease 2019 (COVID-19), the Symptoms of Infection with Coronavirus-19 (SIC), a comprehensive, patient-reported outcome (PRO) measure of signs and symptoms associated with COVID-19, was developed in full alignment with current US regulatory guidance to support evaluations of vaccines and treatments in development.

Methods: An initial version of the SIC was developed to address concepts identified through a targeted literature review and consultation with experts in infectious diseases and clinicians routinely managing COVID-19 in a hospital setting. A qualitative study was conducted in sites in the United States among 31 participants aged ≥ 18 years who were English-speaking and willing and able to provide informed consent and a self-reported history by telephone or online method.

Cost-effectiveness analysis of universal noninvasive testing for post-treatment confirmation of Helicobacter pylori eradication and the impact of patient adherence.

Background: The treatment failure rate for Helicobacter pylori eradication therapy is ~20% due to poor patient compliance and increased antibiotic resistance. This analysis assessed the cost-effectiveness of universal post-treatment testing to confirm eradication of H. pylori infection in adults.

Impact of patient adherence on the cost-effectiveness of noninvasive tests for the initial diagnosis of Helicobacter pylori infection in the United States.

Objective: Previous US-based economic models of noninvasive tests for diagnosis of Helicobacter pylori infection did not consider patient adherence or downstream costs of continuing infection. This analysis evaluated the long-term cost-effectiveness of the urea breath test (UBT), fecal antigen test (FAT), and serology for diagnosis of H. pylori infection after incorporating information regarding test adherence.

Rhythmic Aortic Contractions Induced by Electrical Stimulation In Vivo in the Rat.

For over a century, the behavior of the aorta and other large arteries has been described as passive elastic tubes in which no active contraction occurs in the smooth muscle wall. In response to pulsatile pressure changes, the vessels undergo a 'passive' elastic dilatation-contraction cycle, described as a "Windkessel" effect. However, Mangel and colleagues have presented evidence that is contrary to this view.

From depolarization-dependent contractions in gastrointestinal smooth muscle to aortic pulse-synchronized contractions.

For decades, it was believed that the diameter of gastrointestinal smooth muscle cells is sufficiently narrow, and that the diffusion of calcium across the plasma membrane is sufficient, to support contractile activity. Thus, depolarization-triggered release of intracellular calcium was not believed to be operative in gastrointestinal smooth muscle. However, after the incubation of muscle segments in solutions devoid of calcium and containing the calcium chelator ethylene glycol tetraacetic acid, an alternative electrical event occurred that was distinct from normal slow waves and spikes.

Clinical trials in irritable bowel syndrome: a review.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and it is characterized by episodes of abdominal pain and altered bowel functions. The specific bowel disturbances of diarrhea, constipation or an alternation between the two defines the IBS subtypes of diarrhea-predominant, constipation-predominant, and mixed or alternating IBS. Because of the abnormalities in bowel states associated with each IBS subtype, it is not likely that one agent would successfully treat all three subtypes.

Asimadoline and its potential for the treatment of diarrhea-predominant irritable bowel syndrome: a review.

Irritable bowel syndrome (IBS) is a multifactorial condition with principal symptoms of pain and altered bowel function. The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS. Asimadoline, to date, has shown a good safety profile and the target Phase III population - diarrhea-predominant IBS patients with at least moderate pain - was iteratively determined in a prospective manner from a Phase II dose-ranging study.

Depolarization-stimulated contractility of gastrointestinal smooth muscle in calcium-free solution: a review.

The membrane of most gastrointestinal smooth muscles shows slow waves, slow rhythmic changes in membrane potential. Slow waves serve to bring the membrane potential of smooth muscle cells to a threshold level that elicits a second electrical event known as the spike or action potential. The inward current of the spike, in most gastrointestinal smooth muscle preparations, is carried, at least in part, by calcium.

Urgency as an Endpoint in Irritable Bowel Syndrome.

Background: The choice of endpoints is crucial for proper evaluation of agents in clinical trials of irritable bowel syndrome (IBS). In a recently published draft guidance for IBS from the United States Food and Drug Administration (FDA), urgency was not considered an appropriate primary endpoint. The FDA's position is that it is not clear how patients with diarrhea-predominant IBS (D-IBS) "define or describe urgency".

Does Timing of Colon Procedures Affect Outcomes in D-IBS Trials?

Background: Sigmoidoscopy/colonoscopy is usually performed prior to enrollment into clinical trials of irritable bowel syndrome (IBS). Two main reasons are to rule out alternative diagnoses and to ensure that colitis is not present. However, the possible impact of a recent versus remote colon procedure on symptoms in IBS trials has not been evaluated.

Asimadoline in the treatment of irritable bowel syndrome.

Importance Of The Field: Irritable bowel syndrome (IBS) represents one of the most common gastrointestinal disorders, with the diarrhea-predominant form (D-IBS) representing an area of high unmet medical need. One difficulty in identifying suitable treatments for IBS is that although there are animal models for the components of IBS, it is not clear whether animals are afflicted by the disease. In a recently completed Phase II study, the kappa-opioid agonist, asimadoline, was shown to be efficacious in a prospectively defined subgroup of D-IBS patients.

Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients.

Background: Crofelemer improves bowel function in several conditions characterized by states of prominent secretory diarrhea.

Aim: This double-blind, randomized, placebo-controlled trial evaluated the effects of 3 dose levels of crofelemer in patients with diarrhea-predominant irritable bowel syndrome (D-IBS).

Methods: Male and female patients were randomly assigned to receive crofelemer 125, 250 or 500 mg or placebo twice daily for 12 weeks.

Primary endpoints for irritable bowel syndrome trials: a review of performance of endpoints.

The choice of primary endpoint for a clinical trial is one of the most important determinants of the ability of a clinical trial to demonstrate efficacy of therapeutic agents. Although there are still no clear, universally accepted guidelines on the definition of clinical benefit for irritable bowel syndrome (IBS), consensus guidelines stress the importance of using validated endpoints. This article reviews the evidence available in the literature on the psychometric validation and performance of the 3 endpoints recommended by the Rome III Committee for use as primary endpoints in treatment trials of IBS.

Calcium-dependent, swelling-activated K+ conductance in human neuroblastoma cells.

In most mammalian cells, regulatory volume decrease (RVD) is mediated by swelling-activated Cl(-) and K(+) channels. Previous studies in the human neuroblastoma cell line CHP-100 have demonstrated that exposure to hypoosmotic solutions activates Cl(-) channels which are sensitive to Ca(2+). Whether a Ca(2+)-dependent K(+) conductance is activated after cell swelling was investigated in the present studies.