Item response theory analysis of daytime sleepiness as a symptom of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a sleep disorder which is linked to many health risks. The gold standard to evaluate OSA in clinical trials is the Apnea-Hypopnea Index (AHI). However, it is time-consuming, costly, and disregards aspects such as quality of life.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity.

Topical Potassium Channel Blockage Improves Pharyngeal Collapsibility: A Translational, Placebo-Controlled Trial.

Background: Potassium (K) channel inhibition has been identified in animal models as a potential target to increase pharyngeal dilator muscle activity and to treat OSA. However, these findings have not yet been translated to humans.

Research Question: Does a novel, potent, tandem of P domains in a weak inward rectifying K channel (TWIK)-related acid-sensitive K (TASK) 1/3 channel antagonist, BAY2586116, improve pharyngeal collapsibility in pigs and humans, and secondarily, what is the optimal dose and method of topical application?

Study Design And Methods: In the preclinical study, pharyngeal muscle activity and upper-airway collapsibility via transient negative pressure application was quantified in 13 anesthetized pigs during administration of placebo, 0.

Inhaled mosliciguat (BAY 1237592): targeting pulmonary vasculature via activating apo-sGC.

Background: Oxidative stress associated with severe cardiopulmonary diseases leads to impairment in the nitric oxide/soluble guanylate cyclase signaling pathway, shifting native soluble guanylate cyclase toward heme-free apo-soluble guanylate cyclase. Here we describe a new inhaled soluble guanylate cyclase activator to target apo-soluble guanylate cyclase and outline its therapeutic potential.

Methods: We aimed to generate a novel soluble guanylate cyclase activator, specifically designed for local inhaled application in the lung.

BAY 2253651 for the treatment of obstructive sleep apnoea: a multicentre, double-blind, randomised controlled trial (SANDMAN).

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Riociguat for the Treatment of Raynaud's Phenomenon: A Single-Dose, Double-Blind, Randomized, Placebo-Controlled Cross-Over Pilot Study (DIGIT).

Background And Objective: Raynaud's phenomenon (RP) is characterized by transient digital ischemia and is commonly associated with connective tissue disease. Treatment remains unsatisfactory. Here we evaluate the efficacy, safety, and pharmacokinetics of a single dose of the soluble guanylate cyclase stimulator riociguat in RP.

Inhaled sGC Modulator Can Lower PH in Patients With COPD Without Deteriorating Oxygenation.

This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patients with COPD were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of an sGC modulator results in reduced partial pressure of oxygen (PaO ) and increased partial pressure of carbon dioxide (PaCO ) in arterial blood, if a drug-induced reduction of pulmonary vascular resistance (PVR) equal to that observed experimentally is assumed.

Pharmacokinetic interaction of riociguat with ketoconazole, clarithromycin, and midazolam.

Riociguat is a soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension that is principally metabolized via the cytochrome P450 (CYP) pathway. Three studies in healthy males investigated potential pharmacokinetic interactions between riociguat and CYP inhibitors (ketoconazole, clarithromycin, and midazolam). In two studies, subjects were pretreated with either once-daily ketoconazole 400 mg or twice-daily clarithromycin 500 mg for 4 days before cotreatment with either riociguat 0.

Effects of omeprazole and aluminum hydroxide/magnesium hydroxide on riociguat absorption.

Riociguat, a soluble guanylate cyclase stimulator, is a novel therapy for the treatment of pulmonary hypertension. Riociguat bioavailability is reduced in neutral versus acidic conditions and therefore may be affected by concomitant use of medications that increase gastric pH. The effect of coadministration of the proton pump inhibitor omeprazole or the antacid AlOH/MgOH on the pharmacokinetics, safety, and tolerability of riociguat 2.

Riociguat for pulmonary arterial hypertension associated with congenital heart disease.

Objective: The Pulmonary Arterial hyperTENsion sGC-stimulator Trial-1 (PATENT-1) was a randomised, double-blind, placebo-controlled phase III trial evaluating riociguat in patients with pulmonary arterial hypertension (PAH). PATENT-2 was an open-label long-term extension to PATENT-1. Here, we explore the efficacy and safety of riociguat in the subgroup of patients with persistent/recurrent PAH after correction of congenital heart disease (PAH-CHD) from the PATENT studies.

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.

Background: Riociguat, a member of a new class of compounds (soluble guanylate cyclase stimulators), has been shown in previous clinical studies to be beneficial in the treatment of chronic thromboembolic pulmonary hypertension.

Methods: In this phase 3, multicenter, randomized, double-blind, placebo-controlled study, we randomly assigned 261 patients with inoperable chronic thromboembolic pulmonary hypertension or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy to receive placebo or riociguat. The primary end point was the change from baseline to the end of week 16 in the distance walked in 6 minutes.

Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial.

We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0-2.

Riociguat (BAY 63-2521) and warfarin: a pharmacodynamic and pharmacokinetic interaction study.

Riociguat (BAY 63-2521) and warfarin are likely to be used concomitantly to treat pulmonary hypertension. The aim of this double-blind, crossover, clinical pharmacological study in 30 healthy volunteers was to investigate potential pharmacodynamic and pharmacokinetic interactions between the 2 drugs. Healthy volunteers took 2.

Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study.

We assessed the therapeutic potential of riociguat, a novel soluble guanylate cyclase stimulator, in adults with chronic thromboembolic pulmonary hypertension (CTEPH; n = 42) or pulmonary arterial hypertension (PAH; n = 33) in World Health Organization (WHO) functional class II/III. In this 12-week, multicentre, open-label, uncontrolled phase II study, patients received oral riociguat 1.0-2.

First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension.

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease).

Pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase activator cinaciguat (BAY 58-2667) in healthy male volunteers.

Preclinical data indicate that the nitric oxide-independent soluble guanylate cyclase activator cinaciguat (BAY 58-2667), which is a new drug in development for patients with heart failure, induces vasodilation preferentially in diseased vessels. This study aimed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinaciguat. Seventy-six healthy volunteers were included in this randomized, placebo-controlled study.

Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers.

The aim of the study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of BAY 63-2521, a new drug in development for pulmonary hypertension. Fifty-eight healthy male volunteers received a single oral dose of BAY 63-2521 (0.25-5 mg) or placebo.

[Cancer in Israel: mass mediated reality vs. real reality].

Background: Cancer, being a terminal and often incurable disease, is a source of fear and concern for human beings. One of the most important sources of medical information in general, and cancer specifically, is the mass media. The media can shape beliefs regarding health and influence people's decision-making.

Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.

Objective: To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT).

Background: HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4.