This Guide was written to support educators interested in building a competency-based workplace curriculum. It aims to provide an up-to-date overview of the literature on Entrustable Professional Activities (EPAs), supplemented with suggestions for practical application to curriculum construction, assessment and educational technology. The Guide first introduces concepts and definitions related to EPAs and then guidance for their identification, elaboration and validation, while clarifying common misunderstandings about EPAs. A matrix-mapping approach of combining EPAs with competencies is discussed, and related to existing concepts such as competency milestones. A specific section is devoted to entrustment decision-making as an inextricable part of working with EPAs. In using EPAs, assessment in the workplace is translated to entrustment decision-making for designated levels of permitted autonomy, ranging from acting under full supervision to providing supervision to a junior learner. A final section is devoted to the use of technology, including mobile devices and electronic portfolios to support feedback to trainees about their progress and to support entrustment decision-making by programme directors or clinical teams.

The data suggest that these therapies act through very similar pathways and that, in order to more effectively treat renal fibrosis, these drugs must be combined with other drugs that act by different mechanisms.

Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25 ml/min per 1.73 m2, and a urine protein to creatinine ratio over 1.8 mg/mg were eligible. All 16 patients completed the study in which each received one of four single-dose levels of fresolimumab (up to 4 mg/kg) and was followed for 112 days. Fresolimumab was well tolerated with pustular rash the only adverse event in two patients. One patient was diagnosed with a histologically confirmed primitive neuroectodermal tumor 2 years after fresolimumab treatment. Consistent with treatment-resistant FSGS, there was a slight decline in eGFR (median decline baseline to final of 5.85 ml/min per 1.73 m2). Proteinuria fluctuated during the study with the median decline from baseline to final in urine protein to creatinine ratio of 1.2 mg/mg with all three Black patients having a mean decline of 3.6 mg/mg. The half-life of fresolimumab was ∼14 days, and the mean dose-normalized Cmax and area under the curve were independent of dose. Thus, single-dose fresolimumab was well tolerated in patients with primary resistant FSGS. Additional evaluation in a larger dose-ranging study is necessary.

We provide a safe and an easy-to-handle citrate anticoagulation protocol that allows an excellent acid-base and electrolyte control in critically ill patients with acute renal failure. The protocol can be adapted to patients' need, allowing a wide spectrum of treatment doses.