Assessment of the cardiac safety and pharmacokinetics of a short course, twice daily dose of orally-administered mifepristone in healthy male subjects

Background: Mifepristone is approved to control hyperglycemia in adults with endogenousCushing’s syndrome and is described as a mildly QTc prolonging drug, based on a TQT study.The aim of the present study was to assess the effect of mifepristone on the QTc interval at plasmamifepristone concentrations exceeding those observed in the TQT study.Methods: Twenty healthy, male volunteers were given three doses of 1200 mg mifepristoneevery 12 h with a high-fat meal in a randomized, placebo-controlled 2-period crossover study.Holter ECG recordings were made on Day 1 and 2.Results: Eighteen subjects completed the study. Mean peak plasma mifepristone concentrationswere 4.01 μg/mL (CV: 31%) on the fi rst dose and 5.77 μg/mL (CV: 29%) on the thirddose. Mifepristone did not have a meaningful QTc effect. The placebo-corrected, change-from--baseline QTcF (ΔΔQTcF) was between –1.6 and 0.7 ms on the fi rst dose (upper bound of 90%CI 3.8 ms) and the largest ΔΔQTcF on the third dose was 4.9 ms (upper bound of 90% CI: 8.4 ms).Concentration effect modeling showed a slightly negative slope of –0.01 ms/ng/mL.Conclusions: Mifepristone did not cause a clinically meaningful QTc prolongation in healthyvolunteers at plasma concent rations of mifepristone and its main metabolites that clearlyexceeded those seen in a previous TQT study

The National Teaching Repository − Sharing effective interventions: Learning from each other so that we can continue to enhance and improve what we do

The National Teaching Repository (NTR) is a widely recognised Open Educational Resource (OER) that has made a significant impact on the global higher education community. Recently, the UNESCO Secretariat invited the NTR team to present reports on the repository’s reach and impact (Wooff and Irving-Bell, 2022), which has prompted this article. In it, we provide an overview of the NTR’s origins, values, and vision, and we also extend an invitation for you to join us in this exciting initiative

Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m2per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF

Corporatised Identities ≠ Digital Identities: Algorithmic Filtering on Social Media and the Commercialisation of Presentations of Self

Goffman’s (1959) dramaturgical identity theory requires modification when theorising about presentations of self on social media. This chapter contributes to these efforts, refining a conception of digital identities by differentiating them from ‘corporatised identities’. Armed with this new distinction, I ultimately argue that social media platforms’ production of corporatised identities undermines their users’ autonomy and digital well-being. This follows from the disentanglement of several commonly conflated concepts. Firstly, I distinguish two kinds of presentation of self that I collectively refer to as ‘expressions of digital identity’. These digital performances (boyd 2007) and digital artefacts (Hogan 2010) are distinct, but often confused. Secondly, I contend this confusion results in the subsequent conflation of corporatised identities – poor approximations of actual digital identities, inferred and extrapolated by algorithms from individuals’ expressions of digital identity – with digital identities proper. Finally, and to demonstrate the normative implications of these clarifications, I utilise MacKenzie’s (2014, 2019) interpretation of relational autonomy to propose that designing social media sites around the production of corporatised identities, at the expense of encouraging genuine performances of digital identities, has undermined multiple dimensions of this vital liberal value. In particular, the pluralistic range of authentic preferences that should structure flourishing human lives are being flattened and replaced by commercial, consumerist preferences. For these reasons, amongst others, I contend that digital identities should once again come to drive individuals’ actions on social media sites. Only upon doing so can individuals’ autonomy, and control over their digital identities, be rendered compatible with social media