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Isavuconazole is used to treat fungal infections. This study aims to describe isavuconazole pharmacokinetics in critically ill patients and evaluate their relationship with clinical efficacy and patient safety. We conducted a prospective, observational study in patients treated with intravenous isavuconazole. Samples were collected at predose (Cmin), 1 h (Cmax) and 12 h (C50) after the last dose. The plasma concentration was determined by high-performance liquid chromatography. The relationship between plasma concentration and clinical and microbiological outcomes and safety was evaluated. The influence of covariates (age, sex, weight, SAPS3, creatinine, liver enzymes and extracorporeal devices: continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO)) was analysed. Population pharmacokinetic modelling was performed using NONMEN®. A total of 71 isavuconazole samples from 24 patients were analysed. The mean Cmin was 1.76 (1.02) mg/L; 87.5% reached the optimal therapeutic target and 12.5% were below 1 mg/L. Population pharmacokinetics were best described by a one-compartment model with first-order elimination. No factor had a significant impact on the plasma concentration or pharmacokinetic parameters. Thus, isavuconazole could be safely used in a critically ill population, even in those treated with CRRT and ECMO, from a pharmacokinetic standpoint. Therefore, routine therapeutic drug monitoring may not be strictly necessary in daily clinical practice. [ABSTRACT FROM AUTHOR]

This study analyses the impact of political and regulatory pressures to increase the influence of women within the European board of directors' network. To accomplish this, we used a longitudinal approach, tracking two centrality measures of a European directors' network from 1999 to 2014. The network comprised publicly listed firms in 37 European countries, resulting in an extensive sample of 71,300 directors, of which around 10% were women. Governments promoting gender diversity in leadership positions have focused on two solutions: a slow track using voluntary approaches versus a fast track pushing for binding legislation. The panel data analysis shows how voluntary approaches to promote gender diversity, as implemented through corporate governance codes, have a positive and significant relationship with the 'closeness' of women to other directors in the network (i.e. their access to information). In contrast, binding legislation, such as gender quotas, increases women's role as unique 'bridges' between sub‐networks – a result that serves to heighten their 'betweenness' centrality (i.e. their control over information). [ABSTRACT FROM AUTHOR]

We analyze how the ECB's purchases of corporate bonds under its Corporate Sector Purchase Programme (CSPP) affected the financing of Spanish firms. We first document that the announcement of the CSPP in March 2016 raised firms' propensity to issue bonds. The flipside was a drop in the demand for bank loans by bond issuers. Around 75% of the drop in loans previously made to debt issuers was redirected to other, smaller nonbond issuing firms. This reallocation process was led by banks with weaker liquidity positions experiencing credit outflows, which extended credit to the same firms they were rationing prior to the CSPP. This positive credit supply shock raised the real investment of nonissuing firms. The concomitant ECB's Targeted Longer-Term Refinancing Operations (TLTRO-II) is estimated to have contributed to amplifying the credit-reallocation effect triggered by the CSPP. [ABSTRACT FROM AUTHOR]

In this empirical research, using a database of 41,107 directors from 38 European countries from 1999 to 2015, we analyze the topological features of the director's networks and observe that the degree distribution for both men and women follows a power law. The exponent of the power law is higher for women than the one for men, suggesting a milder role of interlocking for women that points to the absence of the "Golden Skirts" phenomenon at the European level (i.e., women who accumulate more directorships than men). This gender gap in power laws has faded away during the studied period, coinciding with two counteracting external forces. On one hand, the diffusion of corporate governance good practices in European companies, reducing the size of boards and discouraging the multiple directorships by a single person, democratizing the director's network. On the other, the political and regulatory pressure for more women on boards across Europe, creating a high demand for women in the network. [ABSTRACT FROM AUTHOR]