Safety of BI 1358894 in patients with major depressive disorder: Results and learnings from a phase II randomized decentralized clinical trial.

The feasibility of conducting a fully remote, interventional, phase II decentralized clinical trial (DCT) was investigated in major depressive disorder (MDD). Key learnings were collated to improve future DCTs. A double-blind, placebo-controlled, parallel-group, DCT enrolled adult MDD patients with inadequate response to first-line antidepressant monotherapy (ongoing ≥8 weeks) and a Montgomery-Åsberg Depression Rating Scale total score (MADRS) ≥22 at screening.

Artificial intelligence-adjudicated spatiotemporal dispersion: A patient-unique fingerprint of persistent atrial fibrillation.

Background: Spatiotemporal dispersion-guided ablation is a tailored approach for patients in persistent atrial fibrillation (PsAF). The characterization of dispersion extent and distribution and its association with common clinical descriptors of PsAF patients has not been studied.

Objectives: Artificial intelligence-adjudicated dispersion extent and distribution (AI-DED) was obtained with a machine/deep learning classifier (VX1 Software, Volta Medical) in PsAF patients undergoing ablation.

Reliability of a simple fluoroscopic image to assess leg length discrepancy during direct anterior approach total hip arthroplasty.

Background: Direct anterior approach (DAA) total hip arthroplasty (THA) in a supine position provides a unique opportunity to assess leg length discrepancy (LLD) intra-operatively with fluoroscopy. Reported fluoroscopic techniques are useful but are generally complicated or costly. Despite the use of multiple techniques for leg length assessment, LLD continues to be a major post-operative source of patient dissatisfaction further emphasizing the importance of near-anatomic restoration.

Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans.

Background: In randomized trials, prazosin, an α-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans.

Methods: We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women.

Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease.

Background: Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.

A new probabilistic method for quantifying n-dimensional ecological niches and niche overlap.

Considerable progress has been made in the development of statistical tools to quantify trophic relationships using stable isotope ratios, including tools that address size and overlap of isotopic niches. We build upon recent progress and propose a new probabilistic method for determining niche region and pairwise niche overlap that can be extended beyond two dimensions, provides directional estimates of niche overlap, accounts for species-specific distributions in niche space, and, unlike geometric methods, produces consistent and unique bivariate projections of multivariate data. We define the niche region (NR) as a given 95% (or user-defined a) probability region in multivariate space.

Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

Background: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.

Methods: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.

Heparin-associated anti-Xa activity and platelet-derived prothrombotic and proinflammatory biomarkers in moderate to high-risk patients with acute coronary syndrome.

Heparin compounds, to include fractionated and unfractionated preparations, exert both antithrombotic and antiinflammatory effects through combined inhibition of factor Xa and thrombin. The contribution of modulated platelet activity in vivo is less clearly defined. The SYNERGY library was a prospectively designed repository for candidate clinical, hemostatic, platelet, and molecular biomarkers from patients participating in SYNERGY--a large-scale, randomized clinical trial evaluating the comparative benefits of unfractionated heparin (UFH) and enoxaparin in high-risk patients with acute coronary syndrome (ACS).

CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concentrationin patients with schizophrenia.

Clozapine is an atypical antipsychotic drug and displays efficacy in 30% to 60% of patients with schizophrenia who do not respond to traditional antipsychotics. A clozapine concentration greater than 1,150 nmol/L increases the probability of antipsychotic efficacy. However, plasma clozapine concentration can vary more than 45-fold during long-term treatment.

Very slow chiral inversion of clopidogrel in rats: a pharmacokinetic and mechanistic investigation.

Clopidogrel hydrogen sulfate, a thienopyridine derivative, is an ADP receptor antagonist that inhibits platelet aggregation. Clopidogrel is an enantiopure carboxylic ester of S-configuration. The R-enantiomer is devoid of antithrombotic activity and can provoke convulsions at high doses in animals.

Cerebral 6-[18F]fluoro-L-DOPA uptake in rhesus monkey: pharmacological influence of aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) inhibition.

FDOPA/PET scans were performed in one rhesus monkey to study the influence of three catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on FDOPA pharmacokinetics. COMT inhibitors were administered in combination with carbidopa, a peripherally acting inhibitor of the aromatic amino acid decarboxylase (AAAD). FDOPA was administered intravenously and its metabolic fate in plasma was determined using an HPLC system with an on-line gamma-gamma coincidence detector.

Potent anti-murine cytomegalovirus activity and reduced nephrotoxicity of ganciclovir cyclic phosphonate.

Ganciclovir cyclic phosphonate (SR3775) is a derivative of the R enantiomer (SR3773) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine), both of which are potent inhibitors of human ctyomegalovirus and murine cytomegalovirus (MCMV). Against wild-type and four drug-resistant strains of MCMV, SR3773 was 2.3- to 3-fold more potent than SR3775.

Antidepressant responses and changes in visual adaptation after sleep deprivation.

The effects of 1 night of total sleep deprivation on mood state and visual light-dark adaptation were studied in 15 patients with major depression and nine normal comparison subjects. Mood improvements were evident in all but one patient, although responders (n = 9) could be easily distinguished from nonresponders (n = 6). No significant group differences were found in ocular responses before treatment.

Nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in BALB/c and severe combined immunodeficient mice.

Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S enantiomer (SR3772), R enantiomer (SR3773), and R,S enantiomeric mixture (SR3745A) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities against murine cytomegalovirus. In severe combined immunodeficient mice infected with murine cytomegalovirus, SR3773 and SR3745A (12.5, 25, and 50 mg/kg of body weight per day) were superior to ganciclovir in extending the mean time to death, whereas SR3722 and SR3772 was less potent than ganciclovir.

Platelet MAO activity in personality disorders and normal controls.

Platelet monoamine oxidase (MAO) activity has been related to several psychiatric disorders and personality dimensions. The purpose of this study was to measure platelet MAO activity in personality disorders and determine its relationship to symptoms analogous to sensation seeking. Twenty-eight males admitted to a psychiatric unit with a DSM-III-R diagnosis of personality disorder were compared to normal controls.