Descripción de la terapia cognitivo-conductual para la ansiedad en pacientes con cáncer terminal

The aim of this study was to describe the major components and features of cognitive behavioral therapy when used to treat anxiety in patients with terminal cancer. Specifically, four components of cognitive behavioral therapy for terminal cancer patients are described: 1) principles of cognitive behavioral therapy 2) relaxation techniques 3) identification and restructuring negative thoughts 4) planning activities. Similarly, the average duration of cognitive behavioral therapy, number of sessions, application intervals and major problems reported when therapy is applied are described. Finally, recommendations for the implementation of therapy and for the development of future research in this field are described.El objetivo de este trabajo es describir los principales componentes y características de la terapia cognitivo conductual cuando se utiliza para tratar problemas de ansiedad en pacientes con cáncer terminal. A lo largo del escrito se describen los cuatro componentes que más se han utilizados en las investigaciones en este área: 1) principios de la terapia cognitivo conductual 2) técnicas de relajación 3) identificación y reestructuración de pensamientos negativos 4) planeación de actividades. De igual forma, se describe el promedio de duración de la terapia cognitivo conductual, número de sesiones, intervalos de aplicación y los principales problemas reportados cuando se aplica la terapia. Finalmente, se especifican recomendaciones para la aplicación de la terapia y para el desarrollo de líneas futuras de investigación en el área

Descripción de la terapia cognitivo-conductual para la ansiedad en pacientes con cáncer terminal

El objetivo de este trabajo es describir los principales componentes y características de la terapia cognitivo conductual cuando se utiliza para tratar problemas de ansiedad en pacientes con cáncer terminal. A lo largo del escrito se describen los cuatro componentes que más se han utilizados en las investigaciones en este área: 1) principios de la terapia cognitivo conductual 2) técnicas de relajación 3) identificación y reestructuración de pensamientos negativos 4) planeación de actividades. De igual forma, se describe el promedio de duración de la terapia cognitivo conductual, número de sesiones, intervalos de aplicación y los principales problemas reportados cuando se aplica la terapia. Finalmente, se especifican recomendaciones para la aplicación de la terapia y para el desarrollo de líneas futuras de investigación en el área

Genitourinary quality-of-life comparison between urethral sparing prostate stereotactic body radiation therapy monotherapy and virtual high-dose-rate brachytherapy boost

Purpose: Although radiation dose escalation improves prostate cancer disease control, it can cause increased toxicity. Genitourinary (GU) symptoms after prostate radiation therapy affect patient health-related quality of life (QoL). We compared patient-reported GU QoL outcomes following 2 alternative urethral sparing stereotactic body radiation therapy regimens. Methods and Materials: Expanded Prostate Cancer Index Composite (EPIC)–26 GU scores were compared between 2 urethral sparing stereotactic body radiation therapy trials. The SPARK trial prescribed a “Monotherapy” dose of 36.25 Gy in 5 fractions to the prostate. The PROMETHEUS trial prescribed 2 phases: a 19- to 21-Gy in 2 fractions “Boost” to the prostate, followed by 46 Gy in 23 fractions or 36 Gy in 12 fractions. The biological effective dose (BED) for urethral toxicity was 123.9 Gy for Monotherapy and 155.8 to 171.2 Gy for Boost. Mixed effects logistic regression models were utilized to estimate the difference in the odds of a minimal clinically important change from baseline EPIC-26 GU score between regimens at each follow-up. Results: 46 Monotherapy and 149 Boost patients completed baseline EPIC-26 scoring. Mean EPIC-26 GU scores revealed statistically superior urinary incontinence outcomes for Monotherapy at 12 months (mean difference, 6.9; 95% confidence interval [CI], 1.6-12.1; P = .01) and 36 months (mean difference, 9.6; 95% CI, 4.1-15.1; P < .01). Monotherapy also revealed superior mean urinary irritative/obstructive outcomes at 12 months (mean difference, 6.9; 95% CI, 2.0-12.9; P < .01) and 36 months (mean difference, 6.3; 95% CI, 1.9-10.8; P < .01). For both domains and at all time points, the absolute differences were <10%. There were no significant differences in the odds of reporting a minimal clinically important change between regimens at any time point. Conclusions: Even in the presence of urethral sparing, the higher BED delivered in the Boost schedule may have a small adverse effect on GU QoL compared with Monotherapy. However, this did not translate to statistically significant differences in minimal clinically important changes. Whether the higher BED of the boost arm offers an efficacy advantage is being investigated in the Trans Tasman Radiation Oncology Group 18.01 NINJA randomized trial

Observation of Binding and Rotation of Methane and Hydrogen within a Functional Metal-Organic Framework

The key requirement for a portable store of natural gas is to maximize the amount of gas within the smallest possible space. The packing of methane (CH₄) in a given storage medium at the highest possible density is, therefore, a highly desirable but challenging target. We report a microporous hydroxyl-decorated material, MFM-300­(In) (MFM = Manchester Framework Material, replacing the NOTT designation), which displays a high volumetric uptake of 202 v/v at 298 K and 35 bar for CH₄ and 488 v/v at 77 K and 20 bar for H₂. Direct observation and quantification of the location, binding, and rotational modes of adsorbed CH₄ and H₂ molecules within this host have been achieved, using neutron diffraction and inelastic neutron scattering experiments, coupled with density functional theory (DFT) modeling. These complementary techniques reveal a very efficient packing of H₂ and CH₄ molecules within MFM-300­(In), reminiscent of the condensed gas in pure component crystalline solids. We also report here, for the first time, the experimental observation of a direct binding interaction between adsorbed CH₄ molecules and the hydroxyl groups within the pore of a material. This is different from the arrangement found in CH₄/water clathrates, the CH₄ store of nature

The incidence of ventilator-associated pneumonia using the PneuX System with or without elective endotracheal tube exchange: A pilot study

<p>Abstract</p> <p>Background</p> <p>The PneuX System is a novel endotracheal tube and tracheal seal monitor, which has been designed to minimise the aspiration of oropharyngeal secretions. We aimed to determine the incidence of ventilator-associated pneumonia (VAP) in patients who were intubated with the PneuX System and to establish whether intermittent subglottic secretion drainage could be performed reliably and safely using the PneuX System.</p> <p>Findings</p> <p>In this retrospective observational study, data was collected from 53 sequential patients. Nine (17%) patients were initially intubated with the PneuX System and 44 (83%) patients underwent elective exchange to the PneuX System. There were no episodes of VAP while the PneuX System was <it>in situ</it>. On an intention to treat basis, the incidence VAP was 1.8%. There were no complications from, or failure of, subglottic secretion drainage during the study.</p> <p>Conclusions</p> <p>Our study demonstrates that a low incidence of VAP is possible using the PneuX System. Our study also demonstrates that elective exchange and intermittent subglottic secretion drainage can be performed reliably and safely using the PneuX System.</p

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes