Prescribing Nirmatrelvir-Ritonavir: How to Recognize and Manage Drug-Drug Interactions

Nirmatrelvir-ritonavir (NMV/r) is now being used to treat high-risk patients with mild to moderate COVID-19. This article provides advice to clinicians regarding recognition of medications likely to interact with NMV/r and suggests approaches to managing such drug-drug interactions. An algorithm is provided to assist in decision making

Transdermal delivery with microneedle patches using in silico modelling

Design and qualification of a microneedle array patch PBPK model for transdermal delivery and prediction of ARV pharmacokinetics using this rout

Simulation of long-acting administration of antituberculosis agents using pharmacokinetic modelling

Design and qualify a PBPK model for existing oral anti-TB agents. Predict pharmacokinetics of long-acting nanoformulations of anti-TB agents in adults

In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents.

Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation. Physiologically-based pharmacokinetic modelling represents a valuable tool to inform dose finding prior to clinical trials. The objective of this study was to simulate potential dosing strategies for existing long-acting injectable depot formulations of cabotegravir and rilpivirine in children and adolescents (aged 3-18 years) using physiologically-based pharmacokinetic modelling.Whole-body physiologically-based pharmacokinetic models were developed to represent the anatomical, physiological and molecular processes and age-related changes in children and adolescents through allometric equations. Models were validated for long-acting injectable intramuscular cabotegravir and rilpivirine in adults. Subsequently, the anatomy and physiology of children and adolescents were validated against available literature. The optimal doses of monthly administration of cabotegravir and rilpivirine were identified in children and adolescents, to achieve trough concentrations over the target concentrations derived in a recent efficacy trial of the same formulations.Pharmacokinetic data generated through the physiologically-based pharmacokinetic simulations were similar to observed clinical data in adults. Optimal doses of long-acting injectable antiretrovirals cabotegravir and rilpivirine were predicted using the release rate observed for existing clinical formulations, for different weight groups of children and adolescents. The intramuscular loading dose and maintenance dose of cabotegravir ranged from 200 to 600 mg and from 100 to 250 mg, respectively, and for rilpivirine it ranged from 250 to 550 mg and from 150 to 500 mg, respectively, across various weight groups of children ranging from 15 to 70 kg.The reported findings represent a rational platform for the identification of suitable dosing strategies and can inform prospective clinical investigation of long-acting injectable formulations in children and adolescents

Long-acting injectable formulations for children and adolescents using PBPK modelling

Dose prediction of long-acting cabotegravir and rilpivirine in children and adolescents according to weight categorie

Educating a New Generation of Doctors to Improve the Health of Populations in Low- and Middle-Income Countries

Francesca Celletti and colleagues from WHO argue that a transformation in the scale-up of medical education in low- and middle-income countries is needed, and detail what this might look like

C Wright Mills, power and the power elites ? a reappraisal

This paper revisits and presents a critical appraisal of Mills's analysis of power and the power elite. There are signs of a revival of interest in Mills, but recent commentators have shown little interest in the intellectual, social or political context of his analysis. Setting Mills's thesis in its historical context, we consider an element of his project that has been particularly neglected in recent discussion: Mills's search for possible ways of redistributing power and his attempt to forge an ethico-political stance. Reflecting on recent discussion of contemporary elite formations, we comment on what critics might take from Mills in our own time in relation to the analysis of elites and the politics of critical management studies

Archaeology in 2022: Counter‐myths for hopeful futures

Archaeology in 2022 features more calls than ever for a socially and politically engaged, progressive discipline. Archaeologists increasingly respect and integrate decolonizing and Indigenous knowledge in theory and practice. They acknowledge and embrace the fluidity and diversity of sexes and genders, past and present. They document patterns of migration, ancient as well as contemporary, to combat retrograde and racist narratives that remain pervasive in the public sphere. At the same time, the field has a deep‐seated conservative bastion toward which many scholars retreat, arguing for an “objective” past that is free of political implications or interpretive ambiguity. As anarchist archaeologists, we see the myth of the objective past as one of many interconnected myths that have provided the basis for an archaeology that reifies and proliferates the current social order. We deconstruct myths relating to capitalist and colonialist ideologies of “human nature,” the assumed inevitability of the current order, and fatalistic commitment to dystopian or utopian futures. As alternatives, we present counter‐myths that emphasize the contingent and political nature of archaeological praxis, the creative and collaborative foundation of communities, the alternative orders that archaeology uncovers, and the role of a hopeful past for constructing the possibilities of different futures

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported