Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2).

BACKGROUND: Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM. METHODS: Data were pooled from two double-blind, placebo-controlled phase 3 trials; EVOLVE-1 and EVOLVE-2. Patients were 18-65 years old, experienced 4-14 monthly migraine headache days (MHDs) for ≥1 year prior, with onset at \u3c 50 years of age. Migraine headaches were tracked via electronic patient-reported outcome system and randomization was stratified by low (LFEM; 4-7 monthly MHDs) or high (HFEM; 8-14 monthly MHDs) frequency. Subgroup analysis compared the HFEM and LFEM subgroups with a linear or generalized linear mixed model repeated measures approach. RESULTS: The intent-to-treat patients (N = 1773) had a mean age of 41.3 years, were mostly white (75%), female (85%), and 66% of patients had HFEM. In both the LFEM and HFEM subgroups, the overall (Months 1-6) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medication use compared with placebo were statistically significantly reduced for galcanezumab 120-mg and 240-mg. Galcanezumab (120-mg and 240-mg) significantly decreased the overall and monthly MHDs with nausea and/or vomiting, and with photophobia and phonophobia versus placebo in patients with LFEM or HFEM. In both subgroups, the mean overall (Months 1-6) and monthly percentages of patients with ≥50%, ≥75%, and 100% reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcanezumab versus placebo. Galcanezumab (120-mg and 240-mg) significantly improved the Migraine-Specific Quality of Life Questionnaire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM. There were no significant subgroup-by-treatment interactions. CONCLUSIONS: Galcanezumab was as effective in patients with HFEM as in those with LFEM. Associated symptoms, quality of life, and disability were similarly improved in patients with HFEM or LFEM. TRIAL REGISTRATION: NCT02614183 , NCT02614196

Validation of the geriatric anxiety inventory in a duloxetine clinical trial for elderly adults with generalized anxiety disorder

Background: The Generalized Anxiety Inventory (GAI) has been developed for use in the assessment of anxiety symptoms in older adults (≥ 65 years), but previous validation work has not examined the psychometric qualities of the instrument in relation to treatment. The objective of this study was to examine the performance of the GAI for its internal reliability, convergent and divergent validity, and its sensitivity to treatment. Methods: Elderly patients with generalized anxiety disorder (GAD) participated in a 10-week double-blind study of duloxetine treatment for patients with GAD. Anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale (HAMA), the Hospital Anxiety and Depression Scale (HADS) anxiety and depression subscales, and the GAI. Internal reliability of the GAI was assessed with Cronbach's α. Correlations among the HAMA, HADS, and GAI scores were analyzed to determine convergent and divergent validity. Patients were also compared on remission status using recommended cut-off scores for the GAI. Results: Patients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140) for 10 weeks acute therapy. The mean change on the GAI was significantly greater with duloxetine compared with placebo treatment (−8.36 vs. −4.96, respectively, p ≤ 0.001). The GAI demonstrated good internal consistency, good convergent and divergent validity, but suggested cut-off values for caseness with the GAI did not correspond to remission status as measured by the HAMA. Conclusions: Within an elderly patient population with GAD, the GAI demonstrated sound psychometric qualities and sensitivity to change with treatment

Labor Market Concentration Does Not Explain the Falling Labor Share and Other Essays in Economics

This dissertation is comprised of three essays. The first and third chapter explore possible causes of the falling U.S. labor share. They show, first, that labor-market concentration is an implausible driver of the falling labor share and, second, that within-industry wages are not keeping up with output. The second chapter ins concerned with private equity and the financialization of the U.S. economy. Using U.S. administrative data, Chapter 1 shows that the employment-weighted average labor market concentration has been declining since 1980 -- the opposite of the change needed to explain the falling labor share. The relationship between wages and labor market concentration has also weakened (become less negative) over that time. Together, these results make labor market concentration an implausible driver of the falling labor share despite a strong, negative relationship between labor market concentration and wages. Chapter 2, work with Steven J. Davis, John Haltiwanger, Kyle Handley, Josh Lerner, and Javier Miranda, studies the impact of U.S. private equity buyouts on firm-level employment, job reallocation, wages, and labor productivity. Our sample covers thousands of buyouts from 1980 to 2013, which we link to Census micro data on the target firms, their establishments, and millions of comparable firms and establishments that serve as controls. Our results uncover striking differences in the real effects of buyouts, depending on the nature of the target firm, GDP growth, and credit market conditions. Employment at target firms shrinks by nearly 13% relative to controls over two years in buyouts of publicly listed firms but expands by 11% in buyouts of privately held firms. Slower GDP growth after the buyout brings lower employment growth at targets (relative to controls), as does a widening of credit spreads. Buyouts lead to productivity gains at target firms relative to controls – nine percentage points, on average, over two years post buyout. Tighter credit conditions at the time of the buyout are associated with much larger post-buyout productivity gains in target firms. A post-buyout widening of credit spreads or slowdown in GDP growth sharply curtails or reverses productivity gains in public-to-private deals. Chapter 3 documents that the falling labor share comes entirely from decreases of within-sector labor shares while industrial-output reallocation and changes in self-employed output have counteracted some of the effect. Additionally, the decline in Manufacturing's contribution to the aggregate labor share is almost exactly offset by the increase in Services'.PHDEconomicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/153467/1/blipsius_1.pd

Modellierung der raum-zeitlichen Dynamik von Pflanzenpopulationen

Modelle für die raum-zeitliche Dynamik von Pflanzenpopulationen werden auf so unterschiedlichen Gebieten wie die Ausbreitung von herbizidresistenten Biotypen in der Landwirtschaft, die Abschätzung von Risiken der Ausbreitung genetischer Informationen von genetisch veränderten Kulturpflanzen oder die Migration von Pflanzen unter Klimaänderungen angewendet. In dieser Arbeit werden Modellansätze für die lokale Populationsdynamik, die Ausbreitung innerhalb kleiner Landschaftsausschnitte, die Ausbreitung von Pollen und die großmaßstäbige Ausbreitung von Populationen dargestellt. Modellansätze sind zelluläre Automaten, atmosphärische Transportmodelle für die Pollenausbreitung und ein neuartiger aggregierter Ansatz in Form von partiellen Differentialgleichungen für die Dynamik im Landschaftsmaßstab

[De amphitheatro liber]

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Iusti Lipsi Poliorcetic[omega]n siue De machinis tormentis telis libri quinque ...

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 2009Marca tip. de imp. en port. y colofón (éste en p. [6])Sign.: *-2*\p4\s, A-Z\p4\s, a-k\p4\s, l\p6\sLas il. son grabs. cal

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Los seys libros de las politicas o doctrina ciuil de Iusto Lipsio : que siruen para el gouierno del Reyno, o Principado...

Copia digital. España : Ministerio de Cultura y Deporte. Subdirección General de Coordinación bibliotecaria, 2018Mención de imp. consta en colofónSign.: ¶8, A-Q8, R4, ¶4Port. con esc. xil. rea