Citations

AbstractBackgroundLangerhans cell histiocytosis (LCH) is a clonal neoplasm characterized by widely varied clinical presentations, including multisystem involvement and systemic inflammatory symptoms. The AKT pathway is relevant to survival and proliferation of dendritic cells, and is also often upregulated in hematopoietic malignancies. A clinical response in an adult patient with LCH participating in the first‐in‐human trial of afuresertib prompted this prospective trial.ProcedureThe population in the current study included treatment‐naïve (n = 7) and recurrent/refractory patients with LCH (n = 10), who received oral afuresertib (125 mg). The majority of patients were treated for > 24 weeks, with four patients receiving treatment for > 48 weeks.ResultsPharmacokinetic analysis showed similar exposures in previously reported patients with other hematologic malignancies. Primary drug‐related toxicities included Grade 1/2 nausea, diarrhea, dyspepsia, and vomiting. Grade 3 toxicities included fatigue, diarrhea, and pain (one of each). Another severe adverse event involved soft tissue necrosis. The overall response rate in evaluable subjects was 33% in treatment‐naïve patients and 28% in patients with recurrent/refractory disease, which did not meet the predefined Bayesian criteria for efficacy.ConclusionAfuresertib has clinical activity in some patients with newly diagnosed and advanced LCH.

Purpose To develop and determine the reliability of a novel measurement instrument assessing the quality of residents’ discharge summaries. Method In 2014, the authors created a discharge summary evaluation instrument based on consensus recommendations from national regulatory bodies and input from primary care providers at their institution. After a brief pilot, they used the instrument to evaluate discharge summaries written by first-year internal medicine residents (n = 24) at a single U.S. teaching hospital during the 2013–2014 academic year. They conducted a generalizability study to determine the reliability of the instrument and a series of decision studies to determine the number of discharge summaries and raters needed to achieve a reliable evaluation score. Results The generalizability study demonstrated that 37% of the variance reflected residents’ ability to generate an adequate discharge summary (true score variance). The decision studies estimated that the mean score from six discharge summary reviews completed by a unique rater for each review would yield a reliability coefficient of 0.75. Because of high interrater reliability, multiple raters per discharge summary would not significantly enhance the reliability of the mean rating. Conclusions This evaluation instrument reliably measured residents’ performance writing discharge summaries. A single rating of six discharge summaries can achieve a reliable mean evaluation score. Using this instrument is feasible even for programs with a limited number of inpatient encounters and a small pool of faculty preceptors.