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Hospital de Órbigo, Spain

Nava S.,University of Bologna | Ferrer M.,Thorax Institute | Esquinas A.,Intensive Care Unit | Scala R.,Respiratory Ward and Respiratory Intermediate Care Unit | And 8 more authors.
The Lancet Oncology | Year: 2013

Background: Despite best-possible medical management, many patients with end-stage cancer experience breathlessness, especially towards the end of their lives. We assessed the acceptability and effectiveness of non-invasive mechanical ventilation (NIV) versus oxygen therapy in decreasing dyspnoea and the amount of opiates needed. Methods: In this randomised feasibility study, we recruited patients from seven centres in Italy, Spain, and Taiwan, who had solid tumours and acute respiratory failure and had a life expectancy of less than 6 months. We randomly allocated patients to receive either NIV (using the Pressure Support mode and scheduled on patients' request and mask comfort) or oxygen therapy (using a Venturi or a reservoir mask). We used a computer-generated sequence for randomisation, stratified on the basis of patients' hypercapnic status (PaCO2 >45 mm Hg or PaCO2 ≤45 mm Hg), and assigned treatment allocation using opaque, sealed envelopes. Patients in both groups were given sufficient subcutaneous morphine to reduce their dyspnoea score by at least one point on the Borg scale. Our primary endpoints were to assess the acceptability of NIV used solely as a palliative measure and to assess its effectiveness in reducing dyspnoea and the amount of opiates needed compared with oxygen therapy. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00533143. Findings: We recruited patients between Jan 15, 2008, and March 9, 2011. Of 234 patients eligible for recruitment, we randomly allocated 200 (85%) to treatment: 99 to NIV and 101 to oxygen. 11 (11%) patients in the NIV group discontinued treatment; no patients in the oxygen group discontinued treatment. Dyspnoea decreased more rapidly in the NIV group compared with the oxygen group (average change in Borg scale -0·58, 95% CI -0·92 to -0·23, p=0·0012), with most benefit seen after the first hour of treatment and in hypercapnic patients. The total dose of morphine during the first 48 h was lower in the NIV group than it was in the oxygen group (26·9 mg [37·3] for NIV vs 59·4 mg [SD 67·1] for oxygen; mean difference -32·4 mg, 95% CI -47·5 to -17·4). Adverse events leading to NIV discontinuation were mainly related to mask intolerance and anxiety. Morphine was suspended because of severe vomiting and nausea (one patient in each group), sudden respiratory arrest (one patient in the NIV group), and myocardial infarction (one patient in the oxygen group). Interpretation: Our findings suggest that NIV is more effective compared with oxygen in reducing dyspnoea and decreasing the doses of morphine needed in patients with end-stage cancer. Further studies are needed to confirm our findings and to assess the effectiveness of NIV on other outcomes such as survival. The use of NIV is, however, restricted to centres with NIV equipment, our findings are not generalisable to all cancer or palliative care units. Funding: None. © 2013 Elsevier Ltd. Source

Niccoli G.,Catholic University of the Sacred Heart | Scalone G.,Catholic University of the Sacred Heart | Scalone G.,Thorax Institute | Crea F.,Catholic University of the Sacred Heart
European Heart Journal | Year: 2015

Myocardial infarction (MI) with no obstructive coronary atherosclerosis (MINOCA) is a syndrome with different causes. Its prevalence ranges between 5 and 25% of all MIs. The prognosis is extremely variable, depending on the causes of MINOCA. Clinical history, echocardiography, coronary angiography, and left ventriculography represent the first-level diagnostic investigations. Nevertheless, additional tests are required in order to establish its specific cause, thus allowing an appropriate risk stratification and treatment. We review pathogenesis, diagnosis, prognosis, and therapy of MINOCA and propose an algorithm for its management. © Crown copyright 2014. Source

Stevens G.R.,Yeshiva University | Garcia-Alvarez A.,Mount Sinai School of Medicine | Garcia-Alvarez A.,Japan National Cardiovascular Center Research Institute | Garcia-Alvarez A.,Thorax Institute | And 5 more authors.
JACC: Cardiovascular Imaging | Year: 2012

Objectives: This study investigated whether right ventricular (RV) adaptation to chronic pressure overload is associated with pulmonary artery (PA) stiffness beyond the degree of severity of pulmonary hypertension (PH). Background: Increased PA stiffness has been associated with reduced survival in PH. The mechanisms for this association remain unclear. Methods: Right heart catheterization and cardiac magnetic resonance were performed within 1 week in 124 patients with known or suspected chronic PH. Pulmonary vascular resistance index (PVRI) and PA pressures were quantified from right heart catheterization. Cardiac magnetic resonance included standard biventricular cine sequences and main PA flow quantification with phase-contrast imaging. Indexes of PA stiffness (elasticity, distensibility, capacitance, stiffness index beta, and pulse pressure) were quantified combining right heart catheterization and cardiac magnetic resonance data. RV performance and adaptation were measured by RV ejection fraction, right ventricular mass index (RVMI), RV end-systolic volume index, and right ventricular stroke work index (RVSWI). Results: All indexes of PA stiffness were significantly correlated with measures of RV performance (Spearman rho coefficients ranging from -0.20 to 0.61, p < 0.05). Using multivariate regression analysis, PA elasticity, distensibility, and index beta were independently associated with all measures of RV performance after adjusting PVRI (p ≤ 0.024). PA capacitance was independently associated with RV ejection fraction, RVMI, and RVSWI (p < 0.05), whereas PA pulse pressure was associated with RVMI and RVSWI (p ≤ 0.027). Compared with PVRI, PA elasticity, distensibility, capacitance, and index beta explained 15% to 68% of the variability in RV ejection fraction, RVMI, and RV end-systolic volume index. Relative contributions of PA stiffness for RVSWI were 1.2× to 18.0× higher than those of PVRI. Conclusions: PA stiffness is independently associated with the degree of RV dysfunction, dilation, and hypertrophy in PH. RV adaptation to chronic pressure overload is related not only to the levels of vascular resistance (steady afterload), but also to PA stiffness (pulsatile load). © 2012 American College of Cardiology Foundation. Source

Kerwin E.M.,Southern Research Institute | Scott-Wilson C.,Glaxosmithkline | Sanford L.,Glaxosmithkline | Rennard S.,University of Nebraska at Omaha | And 3 more authors.
Respiratory Medicine | Year: 2013

Background: Fluticasone furoate (FF)/vilanterol (VI) is a novel once-daily inhaled corticosteroid/long-acting β2-agonist combination therapy for COPD. We aimed to assess the efficacy and safety of two strengths of FF/VI (100/25 μg; 50/25 μg) vs. individual components (FF 100 μg, VI 25 μg) and placebo over 24 weeks. Methods: Multicentre, randomised, placebo-controlled, double-blind, parallel-group study of patients (N = 1030) with moderate-to-severe COPD. All medication was administered once daily in the morning. Co-primary efficacy endpoints were: (1) weighted mean (wm) FEV 1 (0-4 h post-dose on day 168) to assess acute lung function effects; and (2) trough FEV1 (23-24 h post-dose on day 169) to assess long-lasting effects. Symptom-related outcomes were analysed and adverse events (AEs) assessed. Results: Main findings were: (1) the combination of FF/VI at a strength of 100/25 μg significantly (p < 0.001) improved wm FEV 1 (173 ml) and trough FEV1 (115 ml) vs. placebo. Similar effects were observed with FF/VI 50/25 μg; (2) no significant difference was seen between FF/VI 100/25 μg and VI 25 μg for trough FEV1 (48 ml, p = 0.082), while an effect was observed between FF/VI 100/25 μg and FF 100 μg for wm FEV1 (120 ml, p < 0.001); (3) VI 25 μg over 24 weeks improved lung function vs. placebo significantly for wm FEV1 (103 ml, p < 0.001) and trough FEV1 (67 ml, p = 0.017); and (4) no safety signal was observed. Conclusions: In subjects with moderate-to-severe COPD, FF/VI 100/25 μg provides rapid and significant sustained bronchodilation at 24 weeks. Lung function is improved to a similar extent with FF/VI 50/25 μg and to a somewhat lesser extent with VI 25 μg. All treatments were well tolerated. GSK study number: HZC112206. ClinicalTrials.gov: NCT01053988.© 2012 Elsevier Ltd. All rights reserved. Source

Wan E.S.,Brigham and Womens Hospital | Qiu W.,Brigham and Womens Hospital | Baccarelli A.,Harvard University | Carey V.J.,Brigham and Womens Hospital | And 6 more authors.
Human Molecular Genetics | Year: 2012

The impact of cigarette smoking can persist for extended periods following smoking cessation and may involve epigenetic reprogramming. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to the latency between exposure and disease onset. Cross-sectional cohort data from subjects in the International COPD Genetics Network (n = 1085) and the Boston Early-Onset COPD study (n = 369) were analyzed as the discovery and replication cohorts, respectively. Genome-wide methylation data on 27 578 CpG sites in 14 475 genes were obtained on DNA from peripheral blood leukocytes using the Illumina HumanMethylation27K Beadchip in both cohorts. We identified 15 sites significantly associated with current smoking, 2 sites associated with cumulative smoke exposure, and, within the subset of former smokers, 3 sites associated with time since quitting cigarettes. Two loci, factor II receptor-like 3 (F2RL3) and G-protein-coupled receptor 15 (GPR15), were significantly associated in all three analyses and were validated by pyrosequencing. These findings (i) identify a novel locus (GPR15) associated with cigarette smoking and (ii) suggest the existence of dynamic, site-specific methylation changes in response to smoking which may contribute to the extended risks associated with cigarette smoking that persist after cessation. © The Author 2012. Published by Oxford University Press. All rights reserved. Source

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