Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Global Regulations for a Digital Economy: Between New and Old Challenges

© 2020 Durham University and John Wiley & Sons, Ltd Digital technologies are often described as posing unique challenges for public regulators worldwide. Their fast-pace and technical nature are viewed as being incompatible with the relatively slow and territorially bounded public regulatory processes. In this paper, we argue that not all digital technologies pose the same challenges for public regulators. We more precisely maintain that the digital technologies’ label can be quite misleading as it actually represents a wide variety of technical artifacts. Based on two dimensions, the level of centralization and (im)material nature, we provide a typology of digital technologies that importantly highlights how different technical artifacts affect differently local, national, regional and global distributions of power. While some empower transnational businesses, others can notably reinforce states’ power. By emphasizing this, our typology contributes to ongoing discussions about the global regulation of a digital economy and helps us identify the various challenges that it might present for public regulators globally. At the same time, it allows us to reinforce previous claims that these are importantly, not all new and that they often require us to solve traditional cooperation problems

Why blockchains need the law: Secondary rules as the missing piece of blockchain governance

Governance issues limit blockchains’ ability to evolve and face unforeseen challenges. It seems possible to argue that this impasse is because most blockchains lack meta-rules. This work considers blockchains as a socio-technical system of rules, in order to draw a comparison with legal systems. Following the comparison, one finds that most blockchains lack what, in legal theory, are considered secondary rules. That is, the meta-rule of the system. This works examines the relevant concepts and provides their definitions, then proceeds to outline concrete example of the failure of governance among popular blockchains before drawing the parallelism with legal systems and argue that secondary rules might solve some of the issues of the governance of blockchains. Secondary rules are the necessary infrastructure for building sound governance structures and a necessary condition for blockchains to succeed as a new mode of governance. The conclusion provides future research directions

Multicomponent click synthesis of 1,2,3-triazoles from epoxides in water catalyzed by Copper nanoparticles on activated carbon

Copper nanoparticles on activated carbon have been found to effectively catalyze the multicomponent synthesis of β-hydroxy-1,2,3-triazoles from a variety of epoxides and alkynes in water. The catalyst is easy to prepare, reusable at a low copper loading (0.5 mol %), and exhibits higher catalytic activity than some commercially available copper sources. The regio- and stereochemistry of the reaction has been revised and unequivocally established on the basis of X-ray crystallographic analyses. An NMR experiment has been implemented for the rapid and unmistakable determination of the regiochemistry of the process. Some mechanistic aspects of the reaction have been also undertaken which unveil the participation of copper(I) acetylides.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (MICINN; CTQ2007-65218 and Consolider Ingenio 2010-CSD2007-00006), the Generalitat Valenciana (GV; PROMETEO/2009/039), and FEDER. Y.M. acknowledges the ISO of the Universidad de Alicante for a grant

Blockchain ventures and international business

© 2019 by Emerald Publishing Limited All rights of reproduction in any form reserved. This chapter examines the implications of blockchain ventures for international business. The author highlights the advantages blockchain technologies can create for firms seeking to access international markets for investors, customers, employees, and suppliers. Overall, the international character of initial coin offerings and their business models suggest several advantages over traditional internationalization methods

Bioorthogonal labelling of biomolecules: new functional handles and ligation methods

Contains fulltext : 112899.pdf (preprint version ) (Open Access)21 augustus 201