Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer

BACKGROUND AND OBJECTIVE: Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone.METHODS: A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.RESULTS: Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC 0-8 h and C max of oxycodone with, respectively, 44.7% (p &lt; 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC 0-8 h and C max of the active metabolite oxymorphone were 74.2% (p &lt; 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC 0-8 h and C max of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide. CONCLUSION: Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.</p

Economic considerations and patients’ preferences affect treatment selection for rheumatoid arthritis patients : A discrete choice experiment among European rheumatologists

Peer reviewedPostprin

Intermediated Social Preferences: Altruism in an Algorithmic Era

What are the consequences of intermediating moral responsibility through complex organizations or transactions? This paper examines individual decision-making when choices are known to be obfuscated under randomization. It reports the results of a data entry experiment in an online labor market. Individuals enter data, grade another individual’s work, and decide to split a bonus. However, before they report their decision, they are randomized into settings with different degrees of intermediation. The key finding is that less generosity results when graders are told the split might be implemented by a new procurement algorithm. Those whose decisions are averaged or randomly selected among a set of graders are more generous relative to the asocial treatment. These findings relate to “the great transformation” whereby moral mentalities are shaped by modes of (a)social interaction

Organization Culture as an Explanation for Employee Discipline Practices

Most supervisors dread employee discipline and often employ strategies not officially sanctioned by the organization. Poorly designed discipline systems cause this variation in discipline practices. Inconsistent discipline can cause losses in productivity and reduce employee morale. Extant literature offers little in the form of guidance for improving this important human resource activity. This article explore where normative literature on organizational culture may have explanatory value for understanding variation in discipline practices. The article suggests two groups of factors that have causal effects on discipline practices. The tangible factors are those describing the formal practices the organization wishes its employees to follow. The intangible factors provide cues for explaining why informal strategies emerge as successful practices for getting things done. Using this conception of organization culture, the article proposes hypotheses for future testing to validate the suspected influence of culture on decisions regarding employee discipline.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Reversing the Extraverted Leadership Advantage: The Role of Employee Proactivity

Extraversion predicts leadership emergence and effectiveness, but do groups perform more effectively under extraverted leadership? Drawing on dominance complementarity theory, we propose that although extraverted leadership enhances group performance when employees are passive, this effect reverses when employees are proactive, because extraverted leaders are less receptive to proactivity. In Study 1, pizza stores with leaders rated high (low) in extraversion achieved higher profits when employees were passive (proactive). Study 2 constructively replicates these findings in the laboratory: passive (proactive) groups achieved higher performance when leaders acted high (low) in extraversion. We discuss theoretical and practical implications for leadership and proactivity

An Integrative Approach to Understanding Counterproductive Work Behavior: The Roles of Stressors, Negative Emotions, and Moral Disengagement

Several scholars have highlighted the importance of examining moral disengagement (MD) in understanding aggression and deviant conduct across different contexts. The present study investigates the role of MD as a specific social-cognitive construct that, in the organizational context, may intervene in the process leading from stressors to counterproductive work behavior (CWB). Assuming the theoretical framework of the stressor-emotion model of CWB, we hypothesized that MD mediates, at least partially, the relation between negative emotions in reaction to perceived stressors and CWB by promoting or justifying aggressive responses to frustrating situations or events. In a sample of 1,147 Italian workers, we tested a structural equations model. The results support our hypothesis: the more workers experienced negative emotions in response to stressors, the more they morally disengaged and, in turn, enacted CW

On ethically solvent leaders : the roles of pride and moral identity in predicting leader ethical behavior.

The popular media has repeatedly pointed to pride as one of the key factors motivating leaders to behave unethically. However, given the devastating consequences that leader unethical behavior may have, a more scientific account of the role of pride is warranted. The present study differentiates between authentic and hubristic pride and assesses its impact on leader ethical behavior, while taking into consideration the extent to which leaders find it important to their self-concept to be a moral person. In two experiments we found that with higher levels of moral identity, authentically proud leaders are more likely to engage in ethical behavior than hubristically proud leaders, and that this effect is mediated by leaders’ motivation to act selflessly. A field survey among organizational leaders corroborated that moral identity may bring the positive effect of authentic pride and the negative effect of hubristic pride on leader ethical behavior to the forefront

How does ethical leadership trickle down? Test of an integrative dual-process model

Although the trickle-down effect of ethical leadership has been documented in the literature, its underlying mechanism still remains largely unclear. To address this gap, we develop a cross-level dual-process model to explain how the effect occurs. Drawing on social learning theory, we hypothesize that the ethical leadership of high-level managers could cascade to middle-level supervisors via its impact on middle-level supervisors’ two ethical expectations. Using a sample of 69 middle-level supervisors and 381 subordinates across 69 sub-branches from a large banking firm in China, we found that middle-level supervisors’ ethical efficacy expectation and unethical behavior–punishment expectation (as one form of ethical outcome expectations) accounted for the trickle-down effect. The explanatory role of middle-level supervisors’ ethical behavior–reward expectation (as the other form of ethical outcome expectations), however, was not supported. The theoretical and practical implications are discussed