Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been declared a global pandemic and urgent treatment and prevention strategies are needed. Nitazoxanide, an anthelmintic drug has been shown to exhibit in vitro activity against SARS‐CoV‐2. The present study used physiologically‐based pharmacokinetic (PBPK) modelling to inform optimal doses of nitazoxanide capable of maintaining plasma and lung tizoxanide exposures above the reported SARS‐CoV‐2 EC90. Methods A whole‐body PBPK model was validated against available pharmacokinetic data for healthy individuals receiving single and multiple doses between 500–4000 mg with and without food. The validated model was used to predict doses expected to maintain tizoxanide plasma and lung concentrations above the EC90 in >90% of the simulated population. PopDes was used to estimate an optimal sparse sampling strategy for future clinical trials. Results The PBPK model was successfully validated against the reported human pharmacokinetics. The model predicted optimal doses of 1200 mg QID, 1600 mg TID, 2900 mg BID in the fasted state and 700 mg QID, 900 mg TID and 1400 mg BID when given with food. For BID regimens an optimal sparse sampling strategy of 0.25, 1, 3 and 12h post dose was estimated. Conclusion The PBPK model predicted tizoxanide concentrations within doses of nitazoxanide already given to humans previously. The reported dosing strategies provide a rational basis for design of clinical trials with nitazoxanide for the treatment or prevention of SARS‐CoV‐2 infection. A concordant higher dose of nitazoxanide is now planned for investigation in the seamless phase I/IIa AGILE trial (www.agiletrial.net)

ANIMAL HEALTH EFFECTS OF THE OCTOBER 2013 BLIZZARD: OBSERVATIONS

From Thursday, October 3, through Saturday, October 5, 2013, an unprecedented early season winter storm affected western South Dakota and portions of Wyoming, Montana, North Dakota, and Nebraska. This storm resulted in the deaths of an estimated 15,000 to 30,000 head of cattle, along with many sheep, horses, and other animals. The early occurrence of the storm as well as its severity contributed to direct losses of animals as well as subsequent health effects

Towards inclusive service delivery through social investment in the EU: The case of health services

This report aims at: (a) providing an overview of the European policy framework for health services; (b) providing a comparative analysis of this service market across the EU; and (c) performing a comparative analysis of the situations and trends in the health care sector in the eight RE-InVEST countries, so as to identify the approaches they take to health care. Finally, we provide some policy recommendations, in order to develop a rights-based/capability-oriented approach to health care.This report mixes qualitative and quantitative research methods. First, we analyse the scientific literature and policy documents (especially documents drafted by EU institutions). Second, we perform a quantitative analysis of relevant indicators from a variety of data sets

Budget impact of everolimus for the treatment of progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or lung origin that are advanced or metastatic

<p><b>Background:</b> Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic.</p> <p><b>Objective:</b> To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs.</p> <p><b>Methods</b> An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs.</p> <p><b>Results:</b> In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568–$0.1443 per member per month (PMPM) for GI NETs and from $0.0181–$0.0355 PMPM for lung NETs. The total budget impact was lower than the pharmacy budget impact because it included cost offsets from administration and AE management for everolimus compared with alternative therapies (e.g. chemotherapies).</p> <p><b>Limitations:</b> Because GI and lung NETs are rare diseases with limited published data, several assumptions were made that may influence interpretation of results.</p> <p><b>Conclusions:</b> The budget impact for everolimus was minimal in this rare disease area with a high unmet need, largely due to low disease prevalence. These results should be considered in the context of significant clinical benefits potentially provided by everolimus, including significantly longer progression-free survival (PFS) for advanced GI and lung NET patients.</p

Towards inclusive service delivery through social investment in England: An analysis of five sectors with a particular focus on mental health

This report examines trends in social investment in England following the financial crisis of 2007/8. The first section considers social investment in relation to four policy arenas: housing, financial services, early childhood education and care, and water. The second part of the report provides an overview of social investment and disinvestment trends in the healthcare system in England since the 1990s with a particular focus on mental health services. This section includes a detailed account of service users’ and professionals’ experiences of the impact of liberalisation and austerity measures on mental health service delivery drawing on qualitative data collection. Throughout the report we identify policy recommendations to address the effects and impacts of emergent trends towards social disinvestment and liberalisation of public services. This study is part of the wider pan-European RE-InVEST project to investigate the impact of the EU Social Investment package on marginalised groups since the 2007 crisis

Sexual and intimate citizenship in a Time of Pandemic.

This paper provides an overview of a transnational research project exploring the impact of the COVID-19 pandemic, and public health responses to it, on sexual and gendered politics. It sets out a framework for rethinking sexual and intimate citizenship during the COVID-19 pandemic, and draws on examples from India, Italy, Mexico and the UK to illustrate our analysis. We examine how the pandemic has impacted on the everyday negotiation of intimacy and highlighted material inequalities that impact on the lives of women and LGBTQ+ people. We argue that the pandemic has produced new faultlines between women and different groups of LGBTQ+ people, as well as amplifying existing tensions. In addition to identifying these faultlines, we explore the cracks opened by them which might reveal possibilities for new coalitions and alliances in relation to sexual and gendered politics

The Epistemologies of ‘Lockdown’: closets, vulnerability, and citizenship

Abstract: This paper reviews current concepts from the social sciences and humanities through which to understand and interpret the sexual and gendered politics of the COVID-19 pandemic. We revisit Sedgwick’s ‘epistemology of the closet’ to think about the ways in which sexuality and gender have become known and understood in new ways through a different form of containment, the experience of COVID-19 lockdowns. This paper sets out a framework for rethinking sexual and intimate citizenship during the COVID-19 pandemic. We examine how the pandemic has impacted on the everyday negotiation of intimacy and highlighted material inequalities that impact on the lives of women and LGBTQ+ people.Non-technical summary: This working paper provides an overview of concepts from the social sciences and humanities which might contribute to an analysis of the sexual and gendered politics of the COVID-19 pandemic. We draw parallels between the metaphor of ‘the closet’ to think about the ways in which sexuality and gender have become known and understood in new ways through a different form of containment, the experience of COVID-19 lockdowns. This paper sets out a framework for rethinking sexual and intimate citizenship during the COVID-19 pandemic. We examine how the pandemic has impacted on the everyday negotiation of intimacy and highlighted material inequalities that impact on the lives of women and LGBTQ+ people