Therapygenetics: using genetic markers to predict response to psychological treatment for mood and anxiety disorders

Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes with a primary focus on mood and anxiety disorders. Unlike most past work, which has considered prediction of response to pharmacotherapy, this article reviews recent work in the field of therapygenetics, namely the role of genes in predicting psychological treatment response. As this is a field in its infancy, methodological recommendations are made and opportunities for future research are identified

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

The INVENT COVID trial: a structured protocol for a randomized controlled trial investigating the efficacy and safety of intravenous imatinib mesylate (Impentri®) in subjects with acute respiratory distress syndrome induced by COVID-19

Background The coronavirus disease 2019 (COVID-19) pandemic has led to a disruptive increase in the number of intensive care unit (ICU) admissions with acute respiratory distress syndrome (ARDS). ARDS is a severe, life-threatening medical condition characterized by widespread inflammation and vascular leak in the lungs. Although there is no proven therapy to reduce pulmonary vascular leak in ARDS, recent studies demonstrated that the tyrosine kinase inhibitor imatinib reinforces the endothelial barrier and prevents vascular leak in inflammatory conditions, while leaving the immune response intact. Methods This is a randomized, double-blind, parallel-group, placebo-controlled, multicenter clinical trial of intravenous (IV) imatinib mesylate in 90 mechanically ventilated subjects with COVID-19-induced ARDS. Subjects are 18 years or older, admitted to the ICU for mechanical ventilation, meeting the Berlin criteria for moderate-severe ARDS with a positive polymerase chain reaction test for SARS-CoV2. Participants will be randomized in a 1:1 ratio to either imatinib (as mesylate) 200 mg bis in die (b.i.d.) or placebo IV infusion for 7 days, or until ICU discharge or death. The primary study outcome is the change in Extravascular Lung Water Index (EVLWi) between day 1 and day 4. Secondary outcome parameters include changes in oxygenation and ventilation parameters, duration of invasive mechanical ventilation, number of ventilator-free days during the 28-day study period, length of ICU stay, and mortality during 28 days after randomization. Additional secondary parameters include safety, tolerability, and pharmacokinetics. Discussion The current study aims to investigate the efficacy and safety of IV imatinib in mechanically ventilated subjects with COVID-19-related ARDS. We hypothesize that imatinib decreases pulmonary edema, as measured by extravascular lung water using a PiCCO catheter. The reduction in pulmonary edema may reverse hypoxemic respiratory failure and hasten recovery. As pulmonary edema is an important contributor to ARDS, we further hypothesize that imatinib reduces disease severity, reflected by a reduction in 28-day mortality, duration of mechanical ventilation, and ICU length of stay. Trial status Protocol version and date: V3.1, 16 April 2021. Recruitment started on 09 March 2021. Estimated recruitment period of approximately 40 weeks. Trial registration ClinicalTrials.govNCT04794088. Registered on 11 March 2021

Acción in vitro de la cafeína en anillos de arteria mamaria interna utilizada en cirugía de revascularización cardiaca

Introducción. El efecto vasodilatador de la cafeína en las arterias de modelos animales ya ha sido demostrado. Se desconocen estudios con la misma metodología in vitro utilizando arterias humanas. Objetivos. Evaluar los efectos vasoactivos in vitro de la cafeína en la arteria mamaria interna de humanos. Materiales y métodos. Se utilizaron 80 anillos de arteria mamaria interna (n=20 pacientes). La funcionalidad del endotelio se evaluó con acetilcolina a una concentración de 3,16x10-6M, de nitroglicerina con dosis acumulativas de 10 -11 M a 10 -4 M y de cafeína con concentraciones acumulativas de 10 -8 M a 10-4 M. Resultados. La nitroglicerina indujo un porcentaje máximo de relajación de 87,4±12,3%, la cafeína, de 86,9±21,0% en arterias con endotelio funcional y de 71,6±28,6% en arterias con disfunción endotelial. No se encontraron diferencias entre los tres grupos ( p=0,289). Tampoco se encontraron diferencias en la EC 50 en arterias con endotelio funcional (1,66x10 -5 ±1,57x10 -5 M) y arterias disfuncionales (7,75x10 -5 ±14,64x10 -5 M). La nitroglicerina resultó más potente que la cafeína (EC 50 = 4,30x10 -9 ±4,35x10 -9 M) ( p=0,013). Conclusiones. Aunque la nitroglicerina fue un vasodilatador más potente, la cafeína tuvo un fuerte efecto vasodilatador arterial in vitro independientemente de la funcionalidad del endotelio en arterias humanas