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This large trial involving children with asthma examined whether the addition of a long-acting beta-agonist to current therapy with inhaled glucocorticoids affected asthma control in children. The primary safety end point was within the prespecified noninferiority margin. The safety of inhaled beta-agonists in patients with asthma has been debated since the 1960s. 1 – 5 After the introduction of long-acting beta-agonists (LABAs) in the 1990s and the findings of two studies involving adults, attention focused on a potential association of LABAs with an increased risk of asthma-related death. 6 , 7 A 2008 meta-analysis conducted by the Food and Drug Administration (FDA) showed a higher risk of asthma-related events (death, intubation, or hospitalization) among patients receiving LABAs than among patients not receiving these medications. 8 In a subsequent meta-analysis, a higher risk of serious asthma-related events was observed with salmeterol than with . . .

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.

Patients with COPD were randomly assigned to triple inhaled therapy with either a 160-μg or 320-μg dose of budesonide or to one of two dual therapies. Both triple regimens were superior to the dual regimens with respect to the rate of moderate or severe exacerbations; no difference was observed between the triple regimens.

In this trial, patients with mild asthma used albuterol alone as needed, inhaled budesonide maintenance therapy plus albuterol as needed, or an inhaler containing both budesonide and formoterol as needed for asthma symptoms. There were fewer exacerbations in both groups in which treatment included budesonide.

Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802. Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.

Purpose The aim of this proof-of-concept study was to characterize the pharmacokinetics and pharmacodynamics of intranasal dexmedetomidine compared with its intravenous administration in a small number of healthy volunteers. Methods Single doses of 84 μg of dexmedetomidine were given once intravenously and once intranasally to seven healthy men. Plasma dexmedetomidine concentrations were measured for 10 h, and pharmacokinetic variables were calculated with standard noncompartmental methods. Heart rate, blood pressure, concentrations of adrenaline and noradrenaline in plasma, and central nervous system drug effects (with the Maddox wing, Bispectral Index, and three visual analog scales) were monitored to assess the pharmacological effects of dexmedetomidine. Results Six individuals were included in the analyses. Following intranasal administration, peak plasma concentrations of dexmedetomidine were reached in 38 (15–60) min and its absolute bioavailability was 65% (35–93%) (medians and ranges). Pharmacological effects were similar with both routes of administration, but their onset was more rapid after intravenous administration. Conclusions Dexmedetomidine is rather rapidly and efficiently absorbed after intranasal administration. Compared with intravenous administration, intranasal administration may be a feasible alternative in patients requiring light sedation.

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.

In this trial, clonidine, an α2-adrenergic agonist, did not reduce the rate of death or MI among patients undergoing noncardiac surgery. Clonidine did increase the risk of perioperative hypotension, bradycardia, and nonfatal cardiac arrest. Myocardial infarction is the most common major vascular complication of surgery and is associated with substantial mortality. 1 During and after noncardiac surgery, there is marked activation of the sympathetic nervous system, which can lead to a mismatch between the supply of and demand for myocardial oxygen and to subsequent myocardial infarction. 2 – 4 We previously reported that perioperative administration of a high-dose, long-acting beta-blocker (initiated 2 to 4 hours before surgery and continued after surgery) reduced the risk of myocardial infarction but increased the risk of death, stroke, and clinically important hypotension. 5 Clonidine, an α 2 -adrenergic agonist, blunts central sympathetic . . .

In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS. We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged ≥16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 μg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO 2/F IO 2) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86. We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03–2·08). Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of β-2 agonist treatment in ventilated patients with this disorder cannot be recommended. UK Medical Research Council, UK Department of Health, UK Intensive Care Foundation.