Every year, millions of people from around the world grapple with the European Union's emerging migration management apparatus. Through border controls, biometric information technology, and circular ...migration programs, this amorphous system combines a whirlwind of disparate policies. The Migration Apparatus examines the daily practices of migration policy officials as they attempt to harmonize legal channels for labor migrants while simultaneously cracking down on illegal migration. Working in the crosshairs of debates surrounding national security and labor, officials have limited individual influence, few ties to each other, and no serious contact with the people whose movements they regulate. As Feldman reveals, this complex construction creates a world of indirect human relations that enables the violence of social indifference as much as the targeted brutality of collective hatred. Employing an innovative "nonlocal" ethnographic methodology, Feldman illuminates the danger of allowing indifference to govern how we regulate population—and people's lives—in the world today.
Abstract
Background
Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting
β
2
-agonist in development for chronic obstructive pulmonary disease (COPD). This 12-week, double-blind study ...compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD.
Methods
Efficacy variables included 24-h trough FEV
1
(mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms). Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs.
Results
Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150
μ
g o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study. Trough FEV
1
(LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p < 0.001). Trough FEV
1
after one dose was significantly higher with indacaterol than placebo (p < 0.001). Indacaterol demonstrated significantly higher peak FEV
1
than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p < 0.001) and 160 ± 28 mL (p < 0.001), respectively. Standardised AUC measurements for FEV
1
(between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose) at Week 12 were all significantly greater with indacaterol than placebo (p < 0.001), with LSM (± SEM) differences of 170 ± 24, 180 ± 24, and 170 ± 24 mL, respectively. Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p < 0.001) and was also associated with significantly reduced use of rescue medication (p < 0.001). The overall rates of AEs were comparable between the groups (indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%). One patient died in the placebo group. Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms.
Conclusions
Indacaterol 150
μ
g o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo.
Trial registration
NCT00624286
The defining feature of chronic obstructive pulmonary disease (COPD) is progressive airflow limitation that causes air trapping and hyperinflation. The increasing hyperinflation results in dyspnea ...along with associated inability to engage in the activities of daily living. The American Thoracic Society (ATS), European Respiratory Society (ERS) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines all place bronchodilators as the foundation of pharmacological management of COPD. In patients with moderate-to-very-severe respiratory impairment, adding regular treatment with one or more long-acting bronchodilators is recommended long-acting β2-agonists (LABAs) or long-acting muscarinic antagonists (LAMAs). A growing body of evidence shows that LAMA and LABA co-administration is more effective than either drug class alone in managing stable COPD to improve lung function, symptoms and health status. Recently, new drug applications (NDAs) for a fixed-dose combination (FDC) of umeclidinium (UMEC), a LAMA, and vilanterol (VI), a LABA, at UMEC/VI doses of 125/25 and 62.5/25 µg have been submitted by sponsors to the US Food and Drug Administration (FDA) and to the European Medicines Agency (EMA). Thus, UMEC/VI has become the first FDC LAMA/LABA product that has reached a regulatory approval stage. Other LAMA/LABA once-daily combinations coming through development include FDCs of tiotropium and olodaterol, glycopyrronium and indacaterol, and twice-daily aclidinium and formoterol. The aim of this review is to explore currently available data for once-daily UMEC/VI in the context of the evolving standards of COPD management.
Efforts to theorize globalization remain limited by an ethnographic data set obtained primarily through direct sensory experience. This article argues that such empiricism persists because the ...difference between connections and relations as methodological constructs remains blurred. Their conflation precludes a fuller view of how apparatuses organize global processes. Apparatuses decompose direct social connections and replace them with shifting constellations of indirect social relations. Unlike connections, relations are mediated by abstract third agents and have an arbitrary relationship in/to space and time. This weakens participant-observation’s ability to capture an apparatus’s operations. As a remedy, the article suggests ‘nonlocal’ ethnography, which examines how disconnected actors utilize an apparatus’s mediating agents – e.g. statistical calculations, probabilities estimates, high-scale moral narratives, and interpretative paradigms – to channel the global circulation of migrants. The argument for the apparatus’s theoretical value and nonlocal ethnography’s methodological value is illustrated through an illegal migration journey from Senegal to Italy.
Trial registry
ClinicalTrials.gov;
NCT00931385
and
NCT00932646
.
These studies evaluated the 24-h forced expiratory volume in 1 sec (FEV
1
) profile of once-daily (QD) olodaterol compared to placebo ...and twice-daily (BID) formoterol in patients with moderate to very severe chronic obstructive pulmonary disease. In two replicate, randomized, double-blind, double-dummy, four-way crossover studies, patients received olodaterol 5 and 10 μg QD, formoterol 12 μg BID, or placebo for 6 weeks in addition to usual-care background maintenance therapy. Co-primary end points were FEV
1
area under the curve from 0–12 h (AUC
0–12
) response (change from baseline) and FEV
1
AUC from 12–24 h (AUC
12–24
) response after 6 weeks, with FEV
1
AUC from 0–24 h response identified as a key secondary end point. Other secondary end points included FEV
1
AUC from 0–3 h and trough FEV
1
responses, as well as corresponding forced vital capacity responses. With both olodaterol doses, FEV
1
increased to near-maximal 30 min post-morning dose, which was sustained over 24 h. FEV
1
also increased within 30 min post-morning dose of formoterol and was sustained over 12 h; the second formoterol dose resulted in a further increase, sustained for an additional 12 h. FEV
1
AUC
0–12
and AUC
12–24
responses with both QD olodaterol doses and BID formoterol were significantly greater than placebo at 6 weeks (
P
< .0001). Secondary end-point outcomes were consistent with those of the co-primary end points. These data, together with those from the wider phase III clinical program, provide evidence for the 24-h bronchodilator efficacy of olodaterol QD in this patient population.
Batefenterol is a novel bifunctional muscarinic antagonist β
-agonist in development for COPD. The primary objective of this randomized, double-blind, placebo-controlled, active comparator, Phase IIb ...study was to model the dose-response of batefenterol and select a dose for Phase III development.
Patients aged ≥40 years with COPD and FEV
≥30% and ≤70% predicted normal were randomized equally to batefenterol 37.5, 75, 150, 300, or 600 µg, placebo, or umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg once daily. The primary and secondary endpoints were weighted-mean FEV
over 0-6 hours post-dose and trough FEV
, analyzed by Bayesian and maximum likelihood estimation E
of dose-response modeling, respectively, on day 42.
In the intent-to-treat population (N=323), all batefenterol doses demonstrated statistically and clinically significant improvements from baseline vs placebo in the primary and secondary endpoints (191.1-292.8 and 182.2-244.8 mL, respectively), with a relatively flat dose-response. In the subgroup reversible to salbutamol, there were greater differences between batefenterol doses. Lung function improvements with batefenterol ≥150 µg were comparable with those with UMEC/VI. Batefenterol was well tolerated and no new safety signals were observed.
Batefenterol 300 µg may represent the optimal dose for Phase III studies.
Based on intensive ethnographic fieldwork among an undercover police investigative team in a southern European Union member state, I argue that moments arise when this team acts “ethically” in spite ...of the legal and policy mandates surrounding their work. I understand ethical action to include action that people undertake because they refuse to bear any responsibility (active or passive) for events that they deem to be “evil,” lest such events become constitutive of their own personhood. This situation would preclude individuals from living in agreement with themselves. To this end, the article details some basic conditions in which this team works when operating outside of the law. This ethnographic analysis points to a form of political sovereignty that depends squarely upon particular speaking subjects rather than transcends and homogenizes those subjects as made evident in Agamben's “state of exception” argument. Those conditions include their particular place in the investigative process; egalitarianism among particular subjects; deep familiarity with each other; and an understanding of similarities between themselves and the targets of their investigations. Though fleeting in its appearance, the impetus to political action and a sovereign form premised upon particular speaking subjects can be well understood by developing certain implications in phenomenological anthropology and the anthropology of ethics. Most important among them is the need for mutual recognition among particular speaking subjects as political equals.
Correct use and ease of use of a placebo dry powder inhaler was evaluated in two single-arm, United States-multicenter, phase-IV studies in adults with asthma (n = 259) or chronic obstructive ...pulmonary disease (COPD; n = 278) who were receiving maintenance inhaler therapy. Subjects demonstrating correct placebo inhaler use within three attempts at screening were instructed to take once-daily inhalations from the inhaler for 28 ± 2 days (continuing usual maintenance), followed by randomization to complete one of two versions of an ease-of-use questionnaire and reassessment for correct inhaler use. At study end, 96% asthma/93% COPD subjects rated the placebo inhaler as “easy” or “very easy” to use while demonstrating correct use. Furthermore, 99% asthma/99% COPD subjects indicated it was “easy” or “very easy” to determine number of doses remaining, and 81%/84%, respectively, indicated they would be “likely” or “very likely” to request their current medication in the inhaler, if available. Adverse event (AE) rates were 12% asthma/15% COPD, most frequently headache (3%/3%). Treatment-related AEs were reported in one subject with asthma (cough) and four subjects with COPD (cough, n = 3; back pain, n = 1). At study end, most subjects with asthma or COPD operated the placebo inhaler correctly and found it easy to use.
This is a short essay stimulated by Why Anthropologists Don't Reach the Public: A Rumination on Books of Thomas Hylland Eriksen, by Gordon Mathews (DOI:
https://doi.org/10.1080/00664677.2018.1502074
...).
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