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A universal anti-Xa assay for the determination of rivaroxaban, apixaban and edoxaban drug concentrations would simplify laboratory procedures and facilitate widespread implementation. Following two pilot studies analysing spiked samples and material from 698 patients, we conducted a prospective multicentre cross-sectional study, including 867 patients treated with rivaroxaban, apixaban or edoxaban in clinical practice to comprehensively evaluate a simple, readily available anti-Xa assay that would accurately measure drug concentrations and correctly predict relevant levels in clinical practice. Anti-Xa activity was measured by an assay calibrated with low-molecular-weight heparin (LMWH) in addition to ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). As an external validation, LMWH-calibrated anti-Xa activity was also determined in nine external laboratories. The LMWH-calibrated anti-Xa activity correlated strongly with rivaroxaban, apixaban or edoxaban drug levels [r s = 0·98, 95% confidence interval (CI) 0·98-0·98]. The sensitivity for the clinically relevant cut-off levels of 30, 50 and 100 µg/l was 96·2% (95% CI 94·4-97·4), 96·4% (95% CI 94·4-97·7) and 96·7% (95% CI 94·3-98·1) respectively. Concordant results were obtained in the external validation study. In conclusion, a universal, LMWH-calibrated anti-Xa assay accurately measured rivaroxaban, apixaban and edoxaban concentrations and correctly predicted relevant drug concentrations in clinical practice.

An initial coin offering (ICO) has become a popular venue for crowdfunding at an early stage in a blockchain project. In the ICO process, a whitepaper may serve as an effective marketing tool to influence investor perception and investor trading behaviour. In this paper, we investigate whether management sentiment, as captured by the disclosure tone of the ICO whitepaper, is seen as a credible signal and capable of affecting price behaviour of the ICO on its first trading day. We document a positive association between management's net positive tone in the whitepaper and ICO first-day return, indicating that management sentiment has a significant impact on investor behaviour. Our findings show, however, that such association is contingent on the presence of causal argument, suggesting that disclosure tone needs a significant extent of causal reasoning support to back up its credibility and make it persuasive. These findings provide incremental evidence on the relationship between management tone and relative asset returns during an ICO process in the cryptocurrency markets. While management may benefit from soft information disclosure in the whitepaper, investors and regulators should be aware of self-serving incentives in whitepaper disclosures.

Aim This paper discusses the risk factors and management of paediatric irritable bowel syndrome (IBS), with a focus on the role of the gastrointestinal microbiome. Methods English articles of interest published in PubMed and Google Scholar were searched using subject heading and keywords of interest. Results Only few randomised controlled trials on the management of IBS in children have been published. The vast majority of these intervention trials target to change the composition of the gastrointestinal microbiome. Most studies are underpowered. Major heterogeneities in study designs such as differences in inclusion criteria, including patients with different pain-related functional gastrointestinal disorders and differences in primary outcomes, make it impossible to formulate recommendations. Overall, few adverse events are reported what could indicate safety or point to suboptimal conduction of clinical trials and safety reporting. However, it can also not be excluded that some interventions such as the administration of selected probiotic products may result in benefit. Conclusion There is insufficient evidence to recommend any therapeutic intervention in paediatric IBS, including manipulation of the gastrointestinal tract microbiome, despite the evidence that dysbiosis seems an associated pathophysiologic factor. More designed prospective trials are needed since IBS is not a rare condition during childhood.

The COVID‐19 pandemic has dramatically impacted the lives of consumers across the globe. What guidance can consumer researchers and policymakers provide consumers to elicit adaptive responses that contribute to their life‐satisfaction under these adverse conditions? To this end, we develop and test an adaptive response model and demonstrate its impact on the life‐satisfaction of the consumers experiencing the pandemic in Turkey. Our model suggests that amidst COVID‐19, seeking emotional help triggers the positivity in people, which in turn increases life‐satisfaction. Moreover, turning to religion to deal with the challenges of the pandemic leads to positivity and hope, which in turn positively affect life‐satisfaction. Importantly, “escape” behaviors (such as excessive work or time spent in online shows/games) reduce positivity and hope in consumers, thus negatively impacting life‐satisfaction. The paper discusses the conceptual and public policy implications of the results and offers recommendations for future research., Special issue on Pandemics and Consumer Well‐being

Leishmaniasis corresponds to a group of neglected tropical diseases caused by flagellated protozoa belonging to the Leishmania genus. This widely spread illness is found in over 90 countries in the tropic and sub-tropic regions and also in southern Europe. As parasites exclusively infect the highly phagocytic cells (macrophages), this aspect can be exploited for targeted delivery making use of nanoparticles. Drug-loaded nanoparticles have been proposed to improve the bioavailability of classical drugs commonly in use as standard leishmania therapy, to overcome parasitic resistance and side effects and improve the treatment efficacy. Infected macrophages are expected to recognize drug-loaded nanoparticles which undergo phagocytosis releasing the drug inside macrophages. This approach can further be exploited for the development of nanovaccines. This paper provides an overview of the current disease status worldwide, its classical pharmacological treatments and how these can be improved by the use of featured nanoparticles specific tailored for such a complex disease. Several types of nanoparticles have been proposed while others have already reached clinical trials. This article is protected by copyright., This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017–2100 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq no. 01/2019) and the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund)., info:eu-repo/semantics/publishedVersion

Background Although heart failure (HF) patients often consider sexual activity as an essential aspect of their quality of life (QoL) and are usually uncertain if it is safe to perform sexual activity, this topic is overall poorly addressed in clinical practice. Aims The aim of this study was to explore the perceptions and practices of Flemish caregivers. Methods Healthcare providers were recruited through convenience sampling and filled in an adapted version of the UNITE Sexual Counselling Instrument. Several relevant network structures in Flanders were used to distribute the questionnaires-online as well as on paper-to healthcare workers being involved in the care to HF patients. Results Results of 180 participants indicated that 51.5% of the healthcare providers have never provided sexual counselling in HF patients. Being male, having a masters' degree, having more than 10 years of experience in cardiovascular disease, working in an ambulatory care department and having more positive attitudes were independently associated with a higher provision of sexual counselling in practice. Conclusion Although healthcare providers perceive it as their responsibility to discuss patients' sexual concerns, these issues are not often addressed in daily practice. Increasing knowledge in healthcare providers and specific practical training in providing information on sexual activity in HF patients are recommended. Further studies are needed to investigate how sexual counselling can be provided in agreement with HF patients' expectations and needs.