Summary Background We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. Methods We did a ...randomised trial in 15 countries worldwide during the 2008–09 (year 1) and 2009–10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an internet-based system, with a blocking scheme and stratification by age (65–74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov , number NCT00753272. Findings We enrolled 43 802 participants, of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 1·27%, 95% CI 1·12–1·43 of 21 573 vs 310 1·44%, 1·29–1·61 of 21 482; relative efficacy 12·11%, 95% CI −3·40 to 25·29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 1·04%, 95% CI 0·91–1·18 vs 270 1·26, 1·11–1·41; relative efficacy 17·53%, 95% CI 1·55–30·92) and influenza A H3N2 (170 0·79, 0·67–0·92 vs 205 0·95, 0·83–1·09; post-hoc analysis relative efficacy 22·0%, 95% CI 5·68–35·49). Interpretation AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints. Funding GlaxoSmithKline Biologicals SA.
Postpanopticism and the “mobility turn” within the social sciences provide important challenges to territorial constructs, such as Foucauldian panopticism and James Scott’s notion of the synoptic. ...According to these critiques, migration and mobility exemplify social practice that cannot easily be grasped through grid-like technologies of governing. In this paper, I take issue with these arguments by illuminating notable static and territorial ways in which migration governance is enacted. By examining anti-trafficking programs along the Lao-Thai border, I highlight how such programs make trafficking legible through static means. I argue that such grid-making practices are central to the reproduction of these programs. Furthermore, empirical specificity is central in theorizing migration governance, because it shows us how sedentary attempts at making migration legible for policy interventions must be understood in their specific context.
This article offers an anthropological perspective on international relations by studying ‘macro-structures’ as the effects of elite-conducted contingent practices. It draws on Der Derian’s ...genealogical explanation of diplomacy as a second-order mediation among ‘estranged states’. This view sets up the argument that national minorities are constructed as international security concerns within diplomatic discourse because they obstruct nation-states from mutually securing themselves through diplomacy. Thus, each state has a vested interest in supporting other states as stable actors with established national identities. As Others in the nation-state, national minorities threaten the inter-state system as they destabilize any given nation-state’s identity as a diplomatic actor. This situation ostensibly obstructs diplomacy whereby European nation-states seek mutual security by approximating the putative pre-Westphalian unity from which they emerged after Christendom’s collapse. The argument is demonstrated through a critical analysis of post-Second World War international agreements and ethnographic research among western diplomats working on Estonia’s minority integration policy.
The cardiovascular safety of revefenacin, an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive lung disease (COPD), was evaluated in phase 3 trials in ...patients with moderate to very severe COPD. No clinically meaningful changes in 12-lead electrocardiogram recordings were observed with up to 52 weeks of once-daily revefenacin 88 or 175 μg. In a pooled analysis of Studies 0126 and 0127, the incidence of prolonged QT interval corrected for heart rate using the Fridericia correction formula (QTcF; >450 msec) for revefenacin 88 μg (n = 23, 5.6%) and revefenacin 175 μg (n = 23, 5.9%) was similar to that for placebo (n = 22, 5.3%). In Study 0128, the incidence of prolonged QTcF was similar in the revefenacin 175 μg (n = 25, 7.7%) and tiotropium (n = 26, 7.3%) groups and lower in the revefenacin 88 μg (n = 15, 4.2%) group. There were four major adverse cardiac events (MACEs) in Study 0126 (one, two, and one in the placebo, revefenacin 88 μg, and revefenacin 175 μg groups, respectively), no MACEs in Study 0127 and 26 MACEs in Study 0128 (9, 10 and 7 in the revefenacin 88 μg, revefenacin 175 μg and tiotropium groups, respectively). In Study 0128, only one MACE was considered possibly/probably related to revefenacin (atrial fibrillation in the revefenacin 175 μg group). Thus, revefenacin may provide beneficial nebulized therapy for patients with COPD without further elevating their risk of cardiovascular events.
The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD. This study investigated the efficacy and safety of UMEC versus ...TIO in COPD.
This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study. Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo. The primary end point was trough forced expiratory volume in 1 second (FEV1) at day 85 (non-inferiority margin -50 mL; per-protocol PP population). Other end points included weighted mean FEV1 over 0-24 and 12-24 hours post-dose. Patient-reported outcomes comprised Transition Dyspnea Index score, St George's Respiratory Questionnaire total score, and COPD Assessment Test score. Adverse events were also assessed.
In total, 1,017 patients were randomized to treatment. In the PP population, 489 and 487 patients received UMEC and TIO, respectively. In the PP population, change from baseline in trough FEV1 was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval CI: 29-88; P<0.001). Similar results were observed in the intent-to-treat analysis of trough FEV1 at day 85 (53 mL, 95% CI: 25-81; P<0.001). Improvements in weighted mean FEV1 over 0-24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12-24 hours post-dose (70 mL; P=0.015). Clinically meaningful improvements in Transition Dyspnea Index and St George's Respiratory Questionnaire were observed with both treatments at all time points. No differences were observed between UMEC and TIO in patient-reported outcomes. Overall incidences of adverse events were similar for UMEC and TIO.
UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV1 at day 85. Safety profiles were similar for both treatments.
Focusing on the Estonian government's policy to integrate Soviet-era Russian-speaking immigrants, this article historically examines how public officials have come to constitute Estonian state space ...as a particular national place through the re-constitution of these immigrants in public policy. Drawing on Lefebvre's The Production of Space, the analysis describes place as a combined result of three types of space mobilized in social practice: spatial practices, representational spaces, and representations of space. Conceived through the third type, successful statecraft produces an abstract space thai traps target populations through subject-making. The article's deeper project is two-fold. First, it aims to theorize the spatial interplay between deterrito. rialization and the state's efforts to reterritorialize the nation through citizenship and integration policy. Second, it aims to compensate for ethnographic tendencies that privilege data obtained through direct sensory experience to better capture how the deployment of spatial abstractions in public policy marginalize immigrants and minority groups.
Abstract Background Umeclidinium (UMEC; GSK573719) is a new long-acting muscarinic antagonist (LAMA) currently in development in combination with vilanterol (VI), an inhaled, long-acting beta2 ...agonist for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to evaluate the safety and tolerability of repeat dosing of UMEC and VI in combination once daily for 28 days in patients with COPD. Methods This was a multicenter, double-blind, placebo-controlled, parallel group study. Patients aged ≥40 years with post-bronchodilator FEV1 ≤80% of predicted normal values and FEV1 /FVC ratio ≤0.70, and a smoking history of ≥10 pack-years, were randomized 4:1 to once-daily UMEC/VI (500/25 mcg; n = 42) or placebo ( n = 9). Results UMEC/VI was non-inferior to placebo in weighted mean pulse rate over 0–6 h at Day 28 (primary endpoint: difference of −0.5 bpm, 95% CI: −5.5 to 4.5). There was no evidence of a difference between UMEC/VI compared with placebo in blood pressure, minimum and maximum pulse rate, or QTcF assessments. Adverse events (AEs) were reported by 11 (26%) patients in the UMEC/VI group and one (11%) patient in the placebo group. No serious AEs were reported. Both UMEC and VI showed rapid absorption (median tmax ∼6 min for both drugs) with no evidence of accumulation for AUC or Cmax on Day 28 compared with Day 1 for UMEC or VI. There was no correlation between individual steady-state Cmax and pulse rate on Day 28. Change from baseline in trough FEV1 on Day 29 showed numerically greater improvements with UMEC/VI compared with placebo. Conclusion Once-daily dosing with UMEC in combination with VI in patients with moderate-to-very-severe COPD was well tolerated over 28 days.
This article uses historical research and ethnographic fieldwork to ask how policymakers interpret historical, political, and economic factors to construct inter-ethnic communities that would bring ...security and economic growth to an enlarged European Union (EU). Focusing on post-Soviet Estonia's ethnic integration policy, the article argues that 'flexibility' applies not only to post-Fordist, individualized subjects, but also to relations between subjects of different nationalities that policymakers want to form organically in service sector employment. The article explains how this policy construction emerged in light of Estonia's historical trajectory from 1991 to 2001 and demonstrates how it conceptually resolved the fundamental tension between the territorialized nation-state and deterritorialized global capitalism. A visual media campaign entitled 'Many Nice People: Integrating Estonia' captured the essence of this construction, which obscured how the Estonian nation-state marginalized minorities while integrating into the EU.
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