Summary Background Clinical information on 24-h spirometric efficacy of combining tiotropium and salmeterol compared to single-agent therapy is lacking in patients with COPD. Methods A randomized, ...double-blind, four-way crossover study of 6-week treatment periods comparing combination therapy of tiotropium 18 μg plus qd or bid salmeterol 50 μg versus single-agent therapy. Serial 24-h spirometry (FEV1 , FVC), effects on dyspnea (TDI focal score) and rescue salbutamol use were evaluated in 95 patients. Results Tiotropium plus qd salmeterol was superior to tiotropium or salmeterol alone in average FEV1 (0–24 h) by 72 mL and 97 mL ( p < 0.0001), respectively. Compared to this qd regimen, combination therapy including bid salmeterol provided comparable daytime (0–12 h: 12 mL, p = 0.38) bronchodilator effects, but significantly more bronchodilation during the night-time (12–24 h: 73 mL, p < 0.0001). Clinically relevant improvements in TDI focal score were achieved with bronchodilator combinations including salmeterol qd or bid (2.56 and 2.71; p < 0.005 versus components). Symptom benefit of combination therapies was also reflected in less need for reliever medication. All treatments were well tolerated. Conclusion Compared to single-agent therapy, combination therapy of tiotropium plus salmeterol in COPD provided clinically meaningful improvements in airflow obstruction and dyspnea as well as a reduction in reliever medication.
An Economic Index of Riskiness Aumann, Robert J.; Serrano, Roberto
The Journal of political economy,
10/2008, Letnik:
116, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Define theriskinessof a gamble as the reciprocal of the absolute risk aversion (ARA) of an individual with constant ARA who is indifferent between taking and not taking that gamble. We characterize ...this index by axioms, chief among them a “duality” axiom that, roughly speaking, asserts that less risk‐averse individuals accept riskier gambles. The index is positively homogeneous, continuous, and subadditive; respects first‐ and second‐order stochastic dominance; and for normally distributed gambles is half of variance/mean. Examples are calculated, additional properties are derived, and the index is compared with others.
This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume ...in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 microg q.d., formoterol 12 microg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0-12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12-24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs.day(-1), tiotropium 2.41 puffs x day(-1), formoterol 2.37 puffs x day(-1)). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.
Why consciousness? Aumann, Robert J.
Neuropsychologia,
04/2024, Letnik:
196
Journal Article
Recenzirano
Conscious emotions drive all we do, except for automatic tasks like breathing. Specifically, they enable the operation of incentives—like hunger for eating—that motivate us to perform tasks that are ...vital to our lives. Indeed, we act because we want to act, and desire is an emotion. Next, we want to act because we expect the action to lead to some positive emotion such as pleasure, enjoyment, satisfaction, comfort, fulfillment, …. Finally, to feel this emotion, we must perceive—consciously experience—the outer world. Conscious emotions also operate indirectly, as when driving an automobile: Though most driving is nonconscious, each particular journey is consciously undertaken for some specific reason; also, emotions operated consciously during the period in which driving was being learned, and for some time afterwards. In short, we suggest that the adaptive function of consciousness is to enable conscious emotions to operate.
Summary Background Tiotropium, a once daily inhaled anticholinergic delivered via HandiHaler® , provides bronchodilation for >24 h and improves patient-centred outcomes. The Respimat® Soft Mist™ ...Inhaler (SMI), a novel, propellant-free inhaler, has been developed and proposed as an alternative delivery device for use with tiotropium. Methods In a pre-specified, pooled analysis of two 30-week, double-blind, double-dummy, crossover studies, 207 patients with Chronic Obstructive Pulmonary Disease (COPD) were randomised to receive once daily tiotropium 5 μg or 10 μg (aqueous solution delivered via Respimat SMI), tiotropium 18 μg (inhalation powder via HandiHaler) or placebo. The primary endpoint was trough forced expiratory volume in 1 s (FEV1 ) response. Forced vital capacity (FVC), peak expiratory flow rate (PEFR), rescue medication use, safety and pharmacokinetics (in a subgroup of patients) were also assessed. Results Both tiotropium doses delivered by Respimat SMI were significantly superior to placebo and non-inferior to tiotropium 18 μg HandiHaler on the primary endpoint (all p < 0.0001). All active treatments were significantly superior to placebo (all p < 0.0001) and both doses of tiotropium Respimat SMI were non-inferior to tiotropium 18 μg HandiHaler on the secondary spirometry variables and rescue medication use. The systemic exposure was similar between tiotropium 5 μg Respimat SMI and tiotropium 18 μg HandiHaler but was higher for tiotropium 10 μg Respimat SMI. All active treatments were well tolerated. Conclusions Tiotropium 5 μg Respimat SMI is comparable with tiotropium 18 μg HandiHaler in terms of efficacy, pharmacokinetics and safety. Respimat SMI is an effective alternative, multi-dose delivery device for tiotropium.
Ceci est le texte de l’intervention de l’auteur au colloque organisé en son honneur le 11 octobre 2021 à l’Université Paris-Panthéon-Assas, à l’occasion de la réception le lendemain d’un doctorat ...honoris causa décerné par cette même université. Après avoir remercié les initiateurs et les organisateurs de l’événement, et rendu hommage aux grandes figures disparues de la théorie des jeux, l’auteur décrit son « parcours personnel » dans la science. Le leitmotiv, mis en lumière par ses études universitaires, sa thèse de doctorat et ses travaux ultérieurs en théorie des jeux, est que la science pure et la science appliquée ne sont finalement qu’une seule et même chose. Cela est illustré, entre autres, par la relation entre la théorie des jeux (GT) et l’économie comportementale (BE) : l’idée défendue ici est que les heuristiques et les biais supposés irrationnels par la seconde (BE) conduisent presque toujours à définir un comportement qui s’accorde bien avec l’analyse rationnelle proposée par la première (GT).
The "Shapley value" of a finite multi- person game associates to each player the amount he should be willing to pay to participate. This book extends the value concept to certain classes ofnon-atomic ...games, which are infinite-person games in which no individual player has significance. It is primarily a book of mathematics-a study of non-additive set functions and associated linear operators.
Originally published in 1974.
ThePrinceton Legacy Libraryuses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.
Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently ...controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.
In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices). The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.
A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001). IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01). TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05). The incidence of adverse events was similar for the two treatment groups.
In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.
Text of the author’s talk at the colloquium held in his honor on October 11, 2021, at the University Paris–Panthéon–Assas, to mark his receipt on the next day of a doctorate honoris causa granted by ...the same university. After thanking the initiators and organizers of the event, and paying homage to the great figures of game theory who have passed away, the author describes his “personal journey” in Science. The leitmotif, illustrated by his undergraduate studies, his doctoral dissertation, and his subsequent work in game theory, is that pure and applied science are ultimately one and the same. This is illustrated, inter alia, by the relationship between game theory (GT) and behavioral economics (BE): it is argued that BE’s supposedly irrational heuristics and biases almost always lead to behavior that accords well with GT’s rational analysis.
Ceci est le texte de l’intervention de l’auteur au colloque organisé en son honneur le 11 octobre 2021 à l’Université Paris-Panthéon-Assas, à l’occasion de la réception le lendemain d’un doctorat honoris causa décerné par cette même université. Après avoir remercié les initiateurs et les organisateurs de l’événement, et rendu hommage aux grandes figures disparues de la théorie des jeux, l’auteur décrit son « parcours personnel » dans la science. Le leitmotiv, mis en lumière par ses études universitaires, sa thèse de doctorat et ses travaux ultérieurs en théorie des jeux, est que la science pure et la science appliquée ne sont finalement qu’une seule et même chose. Cela est illustré, entre autres, par la relation entre la théorie des jeux (GT) et l’économie comportementale (BE): l’idée défendue ici est que les heuristiques et les biais supposés irrationnels par la seconde (BE) conduisent presque toujours à définir un comportement qui s’accorde bien avec l’analyse rationnelle proposée par la première (GT).
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