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Examine the evidence for a relationship between pregabalin effect on pain and baseline anxiety and depressive symptoms in patients with fibromyalgia (FM).
Chronic pain and concomitant anxiety and depressive symptoms are common in patients with FM, as well as in other chronic pain disorders. Pregabalin was effective for treating pain in FM patients in three parallel group RCTs (105, 1056, 1077) where data for anxiety and depressive symptom levels were collected.
Patients meeting ACR criteria for FM with a pain VAS score ≥40 mm were followed for 8-14 weeks in 3 randomized, double-blind, placebo-controlled trials. Patients (N=2022) received 150, 300, 450 or 600mg/d pregabalin or placebo. The primary efficacy parameter was change in endpoint Mean Pain Score (MPS) (range 0 [no pain]-10[worst possible pain]). Regression analyses evaluated whether changes in pain bore any relation to the baseline Hospital Anxiety and Depression Scales (HADS-A) and (HADS-D) levels.
Pregabalin 300, 450, and 600 mg/d, but not 150 mg/d, showed statistically significant improvements in pain compared with placebo (p<0.0001). For each pregabalin treatment group, improvements in pain at endpoint were not found to have a statistically significant association with baseline levels of anxiety or depressive symptoms. Adverse events (AEs) were consistent with known side effects of pregabalin; dizziness and somnolence, mild to moderate in intensity, were the most frequently reported AEs for pregabalin patients.
Pregabalin treatment demonstrated significant improvements in pain regardless of baseline anxiety or depressive symptom levels for patients with FM.
For forty years, successive editions of Ethical Theory and Business have helped to define the field of business ethics. The 10th edition reflects the current, multidisciplinary nature of the field by explicitly embracing a variety of perspectives on business ethics, including philosophy, management, and legal studies. Chapters integrate theoretical readings, case studies, and summaries of key legal cases to guide students to a rich understanding of business ethics, corporate responsibility, and sustainability. The 10th edition has been entirely updated, ensuring that students are exposed to key ethical questions in the current business environment. New chapters cover the ethics of IT, ethical markets, and ethical management and leadership. Coverage includes climate change, sustainability, international business ethics, sexual harassment, diversity, and LGBTQ discrimination. New case studies draw students directly into recent business ethics controversies, such as sexual harassment at Fox News, consumer fraud at Wells Fargo, and business practices at Uber.
We used two sunflower genotypes displaying pericarp-imposed dormancy at high incubation temperatures (i.e. 30°C) to investigate the role of the pericarp as a limitation to oxygen availability to the embryo (hypoxia), and its impact on embryo abscisic acid (ABA) content and sensitivity to ABA. Results showed that both genotypes displayed very different oxygen threshold values for inhibition of embryo germination when incubation was performed at 30°C. Expression of dormancy in one genotype was therefore related to exacerbated embryo sensitivity to hypoxia, whereas in the other genotype, the pericarp appeared to act as a more severe restraint to oxygen entry. Increased sensitivity to hypoxia was, in part, related to increased sensitivity to ABA, but not to alterations in ABA metabolism. The activity of pericarp-microbial communities (bacteria and fungi) at high temperatures was also assessed as a potential determinant of hypoxia to the embryo. Oxygen consumption in pericarps incubated at 30°C was attenuated with antibiotics, which concomitantly promoted achene germination. In agreement with the observed more severe oxygen deprivation to the embryo exerted by the pericarp, the bacterial load in the pericarp was significantly higher in the commercial hybrid than in the inbred line; however, the application of antibiotics strongly reduced the bacterial colony counts for each genotype. Different bacterial and fungal communities, assessed through their profiles of carbon-source utilization, were determined between genotypes and after treatment with antibiotics. This work highlights the relationship between enhancement of sensitivity to hypoxia with incubation temperature and seed dormancy expression, and suggests that microbial activity might be part of the mechanism through which hypoxia is imposed.