Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children (Review)

Background Traditionally inhaled treatment for asthma has been considered as preventer and reliever therapy. The combination of formoterol and budesonide in a single inhaler introduces the possibility of using a single inhaler for both prevention and relief of symptoms (single inhaler therapy). Objectives The aim of this review is to compare formoterol and corticosteroid in single inhaler for maintenance and relief of symptoms with inhaled corticosteroids for maintenance and a separate reliever inhaler. Search methods We last searched the Cochrane Airways Group trials register in September 2008. Selection criteria Randomised controlled trials in adults and children with chronic asthma. Data collection and analysis Two review authors independently assessed studies for inclusion and extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes. Main results Five studies on 5,378 adults compared single inhaler therapy with current best practice, and did not show a significant reduction in participants with exacerbations causing hospitalisation (Peto OR 0.59; 95% CI 0.24 to 1.45) or treated with oral steroids (OR 0.83; 95% CI 0.66 to 1.03). Three of these studies on 4281 adults did not show a significant reduction in time to first severe exacerbation needing medical intervention (HR 0.96; 95% CI 0.85 to 1.07). These trials demonstrated a reduction in the mean total daily dose of inhaled corticosteroids with single inhaler therapy (mean reduction ranged from 107 to 267 micrograms/day, but the trial results were not combined due to heterogeneity). The full results from four further studies on 4,600 adults comparing single inhaler therapy with current best practice are awaited. Three studies including 4,209 adults compared single inhaler therapy with higher dose budesonide maintenance and terbutaline for symptom relief. No significant reduction was found with single inhaler therapy in the risk of patients suffering an asthma exacerbation leading to hospitalisation (Peto OR 0.56; 95% CI 0.28 to 1.09), but fewer patients on single inhaler therapy needed a course of oral corticosteroids (OR 0.54; 95% CI 0.45 to 0.64). These results translate into an eleven month number needed to treat of 14 (95% CI 12 to 18), to prevent one patient being treated with oral corticosteroids for an exacerbation. The run-in for these studies involved withdrawal of long-acting beta2-agonists, and patients were recruited who were symptomatic during run-in. One study included children (N = 224), in which single inhaler therapy was compared to higher dose budesonide. There was a significant reduction in participants who needed an increase in their inhaled steroids with single inhaler therapy, but there were only two hospitalisations for asthma and no separate data on courses of oral corticosteroids. Less inhaled and oral corticosteroids were used in the single inhaler therapy group and the annual height gain was also 1 cm greater in the single inhaler therapy group, [95% CI 0.3 to 1.7 cm]. There was no significant difference found in fatal or non-fatal serious adverse events for any of the comparisons. Authors’ conclusions Single inhaler therapy can reduce the risk of asthma exacerbations needing oral corticosteroids in comparison with fixed dose maintenance inhaled corticosteroids. Guidelines and common best practice suggest the addition of regular long-acting beta2-agonist to inhaled corticosteroids for uncontrolled asthma, and single inhaler therapy has not been demonstrated to significantly reduce exacerbations in comparison with current best practice, although results of five large trials are awaiting full publication. Single inhaler therapy is not currently licensed for children under 18 years of age in the United Kingdom

Combination formoterol and inhaled steroid versus beta(2)-agonist as relief medication for chronic asthma in adults and children (Review)

Background Formoterol has a fast onset of action and can therefore be used to relieve symptoms of asthma. A combination inhaler can deliver formoterol with different doses of inhaled corticosteroid; when used as a reliever both drugs will be delivered more frequently when asthma symptoms increase. This has the potential to treat both bronchoconstriction and inflammation in the early stages of exacerbations. Objectives To assess the efficacy and safety of combined inhalers containing both formoterol and an inhaled corticosteroid when used for reliever therapy in adults and children with chronic asthma. Search methods We last searched the Cochrane Airways Group trials register in April 2009, and no new studies were found for inclusion in the review. Selection criteria Randomised trials in adults and children with chronic asthma, where a combination inhaler containing formoterol and inhaled corticosteroid is compared with fast-acting beta2-agonist alone for the relief of asthma symptoms. This should be the only planned difference between the trial arms. Data collection and analysis Two review authors independently extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes. Main results Three trials involving 5905 participants were included. In patients with mild asthma who do not need maintenance treatment, no clinically important advantages of budesonide/formoterol as reliever were found in comparison to formoterol as reliever. Two studies enrolled patients with more severe asthma who were not controlled on high doses of inhaled corticosteroids (around 700 mcg/day in adults), and had suffered a clinically important asthma exacerbation in the past year. Hospitalisations related to asthma in the two studies comparing budesonide/formoterol for maintenance and relief with the same dose of budesonide/formoterol for maintenance with terbutaline for relief yielded an odds ratio of 0.68 (95% CI 0.40 to 1.16), which was not a statistically significant reduction. In adults there was a reduction in exacerbations requiring oral corticosteroids compared to terbutaline, odds ratio 0.54 (95% CI 0.44 to 0.65), which translates into a number needed to treat over 12 months of 15 (95% CI 13 to 21). The study in children found less serious adverse events with budesonide/formoterol used for maintenance and relief. There was no significant difference in annual growth in children using budesonide/formoterol reliever in comparison to terbutaline. Authors’ conclusions In mild asthma it is not yet known whether patients who use a budesonide/formoterol inhaler for relief of asthma symptoms derive any clinically important benefits. In more severe asthma, two studies enrolled patients who were not controlled on inhaled corticosteroids, and had suffered an exacerbation in the previous year, and then had their maintenance inhaled corticosteroids reduced in both arms of the study. Under these conditions the studies demonstrated a reduction in the risk of exacerbations that require oral corticosteroids with budesonide/formoterol for maintenance and relief in comparison with budesonide/formoterol for maintenance and terbutaline or formoterol for relief. The incidence of serious adverse events in children was also less using budesonide/formoterol for maintenance and relief in one study, which similarly enrolled children who were not controlled on inhaled corticosteroids, and who had their maintenance inhaled corticosteroids reduced at the start of the study. This study also compared an explorative maintenance dose of budesonide/formoterol that is not approved for treatment

Perpetrators? Political civil servants in the Third Reich

Despite our ever-increasing interest in Nazi perpetrators, we still lack a precise definition of the term. Indeed, although much literature examines various persons and groups as perpetrators, few scholars have focused on what it is that makes them perpetrators. Instead, it is merely accepted that the subjects of perpetrator research – Täterforschung in German – are such, as scholars look to explain how and why they participate in acts of mass violence (Paul 2002). So in order to answer the question – whether state bureaucrats can be accurately described as perpetrators – we first need look at the dominant images that emerge in perpetrator research to see if they conform to what is there

Doctor of Philosophy

dissertationPeaceful Uprising grew out of civil disobedience actions taken in 2008 by Tim DeChristopher on behalf of the environment, when he illegally bid on Bureau of Land Management (BLM) land parcels to withhold them from businesses that would exploit that land. The resulting collective is the focus of this dissertation. The examination of the collective Peaceful Uprising reveals how collectivity is essential to social protest and how it is a rhetorical process that is essential to social movement rhetoric. This collectivity is defined as both a group that makes a whole and the qualities that make up and maintain that group, such as feelings of belonging, staying power, and an affect of hope. Additionally, these are the major rhetorical processes by which a social movement creates and maintains a sense of the collective. In understanding how collectivity is created and maintained within social movements, machines of mobilization-the active creation and deployment of a collectivist cultural assemblage focused on social protest and change-is a unique heuristic that allows social movement rhetoric scholars to better understand the rhetorical invention of collectivity. The rhetorical processes of collectivity and machines of mobilization are primarily examined through the participatory critical research (PCR) method, wherein I became part of the Peaceful Uprising movement in order to critically observe how they, as a machine of mobilization, interact with the state; how they use music/song rhetorically, particularly the utilization of citationality; and their use of place/space, especially in a post-9/11 world of restrictions

Networks and the Development of the Irish Biotechnology Sector

Biotechnology, an umbrella term describing combinations of engineering and scientific knowledge from an array of disciplines used to produce products and processes from living organisms, has been identified as a key sector for future economic developments among industrialised and industrialising nations as it blurs traditional boundaries between various industries. The Irish Government has introduced a series of initiatives to facilitate the development of an internationally competitive indigenous biotechnology sector since the late 1990s, yet no in-depth analysis of the sector relative to international sectoral characteristics, structures, or policy themes have informed their design or implementation. This thesis analyses the Irish sector in the context of global sectoral developments by studying the Post-Fordist organisational structure of the international sector, where biotechnology firms interact with various actors at different stages of the sectoral value chain in a variety of innovative networks determined by place specific actor and institution endowments that form local knowledge communities. Through qualitatively investigating the Irish sector's actors and collaborative network structure, the thesis analyses the implications of the nature and character of these elements for the sector's future sustainability and development, and appraises existing Government policies relating to sectoral developments. The thesis found that the on-going initiatives have facilitated significant advances, yet have not addressed the legacy of pre-initiative resource and skill capacity weaknesses, while the sectoral value chain is fragmented as actors have developed poor networking arrangements due to their conservative natures, and the relative absence of key sector actors, skills and resources. These issues demonstrate that a complex overarching policy framework is required so as to engender the long-term development of a regionally tailored, systems-based support ecosystem which addresses existing structural weaknesses, and which facilitates and drives entrepreneurial and innovative activities throughout the sector's value chain

"Even Now There Are Places Where a Thought Might Grow—"

The world is full of unattended nooks, places known to no one living, places hidden from all but a few, places unheard-of, not quite remembered, yet to be discovered or rediscovered, places vastly remote and others close to where we are right now. That is to say, the world is riddled with contingency. It is a condition of worldliness, merely the case, neither here nor there. But among those sites are places haunted by suffering, even cruelty, and our not knowing them is a cause for concern. Contingency is at work here too—the claim that emanates from such a place may or may not be heard—but now our failure to hear it is a question for us. The very universality of contingency turns out to be trivial, and dwelling on it turns out to be a way of ignoring the suffering that it not permitted to register. Once such a place—of unjust imprisonment, of industrial dying, of disposal—presents itself to consciousness, our not having seen it before is shocking. How can we not have known? What else have we failed to hear? Peer review process: Editoria

On the Economic Focus of Conciliar Trinitarianism

This article suggests that the shape of Conciliar Trinitarianism is rather different to what is often supposed in recent theological treatments of the Trinity. Conciliar Trinitarianism does support the claims of the consubstantiality of the Son and the full divinity of the Spirit, but is not directly concerned with a doctrine of One God in three persons in abstraction from the economy of salvation. The economy (οἰκονομία) is not taken as the starting point for knowledge of the “immanent Trinity”. Instead, claims about Trinity in itself ground claims about the economy of salvation. &nbsp