Explore the vast range of titles available.

The frequency of COPD exacerbations during treatment with a triple inhaler — delivering a long-acting beta-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled glucocorticoid — was compared with that with a LABA–LAMA or LABA–inhaled glucocorticoid.

Treatment with tezepelumab, a human monoclonal antibody specific for thymic stromal lymphopoietin, reduced exacerbation frequency among patients whose asthma remained uncontrolled with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.

Patients with cardiogenic shock were assigned to receive milrinone or dobutamine for inotropic support. There was no significant difference between the two groups in the composite primary outcome of in-hospital death from any cause or cardiovascular or renal events.

Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat-evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, μg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 μg isoproterenol infusion, the GAD group (n = 24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the healthy comparison (HC) group (n = 24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than the HC group during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 μg isoproterenol infusion. Using analyzable blood oxygenation level-dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing in prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level-dependent responses during peripheral adrenergic stimulation.

Abstract Asthma control is improved by combining inhaled corticosteroids with long-acting β2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting β2-agonist (SABA) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy, thereby reducing exacerbations. In this double-blind, randomized, parallel-group study, 2,760 patients with asthma aged 4–80 years (FEV1 60–100% predicted) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 μg twice a day (bud/form + SABA) or bud 320 μg twice a day (bud + SABA) or bud/form 80/4.5 μg twice a day with 80/4.5 μg as-needed (bud/form maintenance + relief). Children used a once-nocte maintenance dose. Bud/form maintenance + relief prolonged time to first severe exacerbation (p < 0.001; primary endpoint), resulting in a 45–47% lower exacerbation risk versus bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form maintenance + relief also prolonged the time to the first, second, and third exacerbation requiring medical intervention (p < 0.001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.

This trial involving more than 6000 patients with chronic obstructive pulmonary disease (COPD) compared the effects on all-cause mortality of treatment with an inhaler containing both salmeterol and fluticasone, salmeterol or fluticasone alone, or placebo. After 3 years, the study showed a reduction of 2.6 percentage points in the mortality rate; this fell short of the study's prespecified goals. There were improved clinical outcomes among patients treated with the combination regimen. This trial involving more than 6000 patients with COPD compared the effects on all-cause mortality of treatment with an inhaler containing both salmeterol and fluticasone, salmeterol or fluticasone alone, or placebo. After 3 years, the study showed a reduction of 2.6 percentage points in the mortality rate, which fell short of the prespecified goal. Chronic obstructive pulmonary disease (COPD) is a major cause of illness, death, and the use of health care resources globally. 1 – 3 The disease causes approximately 2.75 million deaths annually, and the number is projected to increase. 2 Treatment for COPD is focused on minimizing risk factors, improving symptoms, and preventing exacerbations. 3 With the exception of smoking-cessation programs for patients with early disease, 4 home oxygen treatment for persistent hypoxemia, 5 , 6 and lung-reduction surgery for selected patients with emphysema, 7 no treatment has been shown to reduce mortality. Pulmonary inflammation is prominent in COPD. 8 Antiinflammatory drugs such as inhaled corticosteroids have little or no . . .

BackgroundPrevious studies in adults with asthma incorporating the control of sputum eosinophils into management strategies have shown significant reductions in exacerbations. A study was undertaken to investigate whether this strategy would be successful in children with severe asthma.Methods55 children (7–17 years) with severe asthma were randomised to either a conventional symptom-based management strategy or to an inflammation-based strategy (principally sputum eosinophils). Children were seen 3-monthly over a 1-year period.ResultsThe annual rate of total and major exacerbations (courses of oral corticosteroids) was non-significantly lower in the inflammatory management group compared with the symptom management group (3.6 vs 4.8, incident rate ratio (IRR) 0.75, 95% CI 0.54 to 1.04, p=0.082; and 1.9 vs 2.7 IRR 0.73, 95% CI 0.42 to 1.28, p=0.274 for total and major exacerbations, respectively). Significantly fewer subjects in the inflammatory management group experienced an exacerbation within 28 days of a study visit. There were small non-significant differences in measures of asthma control (symptom-free days and short-acting β agonist use) favouring the inflammatory management group. There was no significant difference in the inhaled corticosteroid dose prescribed over the course of the study.ConclusionIncorporating the control of sputum eosinophils into the management algorithm did not significantly reduce overall exacerbations or improve asthma control. Exacerbations were reduced in the short term, suggesting that more frequent measurements would be needed for a clinically useful effect and that controlling inflammation may have a role to play in subgroups of children with severe asthma.

Abstract Rationale Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits. Objectives To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting β2-agonist combination therapy. Methods In this 12-week, randomized, double-blind, parallel-group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV1, 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 μg once daily) plus either budesonide/formoterol (320/9 μg) (n = 329) or placebo (n = 331) twice daily. Measurements and Main Results Clinic predose (primary outcome) and postdose FEV1, predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV1 and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide/formoterol plus tiotropium significantly increased predose FEV1 by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P < 0.001). Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25–0.57; P < 0.001). Both treatments were well tolerated. Conclusions In patients with chronic obstructive pulmonary disease, budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00496470).

To compare the safety of salmeterol xinafoate or placebo added to usual asthma care. A 28-week, randomized, double-blind, placebo-controlled, observational study. Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks. Subjects (> 12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting beta2-agonist use were excluded. Salmeterol, 42 mug bid via metered-dose inhaler (MDI), and placebo bid via MDI. Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo. For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.

Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7 days (interquartile range 6-15), and the median dose was 0.08 μg/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60 days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.