ABSTRACT
CONTEXT: Objective Structured Clinical Examinations (OSCEs) are an increasingly popular evaluation modality for medical students. While the face-to-face interaction allows for more in-depth assessment, it may cause standardization problems. Methods to quantify, limit or adjust for examiner effects are needed. METHODS: Data originated from 3 OSCEs undergone by 900-student classes of 5th- and 6th-year medical students at Université Paris Cité in the 2022-2023 academic year. Sessions had five stations each, and one of the three sessions was scored by consensus by two raters (rather than one). We report OSCEs' longitudinal consistency for one of the classes and staff-related and student variability by session. We also propose a statistical method to adjust for inter-rater variability by deriving a statistical random student effect that accounts for staff-related and station random effects. RESULTS: From the four sessions, a total of 16,910 station scores were collected from 2615 student sessions, with two of the sessions undergone by the same students, and 36, 36, 35 and 20 distinct staff teams in each station for each session. Scores had staff-related heterogeneity (p<10-15), with staff-level standard errors approximately doubled compared to chance. With mixed models, staff-related heterogeneity explained respectively 11.4%, 11.6%, and 4.7% of station score variance (95% confidence intervals, 9.5-13.8, 9.7-14.1, and 3.9-5.8, respectively) with 1, 1 and 2 raters, suggesting a moderating effect of consensus grading. Student random effects explained a small proportion of variance, respectively 8.8%, 11.3%, and 9.6% (8.0-9.7, 10.3-12.4, and 8.7-10.5), and this low amount of signal resulted in student rankings being no more consistent over time with this metric, rather than with average scores (p=0.45). CONCLUSION: Staff variability impacts OSCE scores as much as student variability, and the former can be reduced with dual assessment or adjusted for with mixed models. Both are small compared to unmeasured sources of variability, making them difficult to capture consistently.
Subject(s)
Clinical Competence , Educational Measurement , Observer Variation , Students, Medical , Humans , Educational Measurement/methods , Educational Measurement/standards , Clinical Competence/standards , Education, Medical, Undergraduate/standards , Paris , Reproducibility of ResultsABSTRACT
BACKGROUND: Von Hippel-Lindau disease (VHL) is a rare autosomal dominant hereditary cancer-predisposition syndrome caused by germline pathogenic variants (PV) in VHL gene. It is associated with a high penetrance of benign and malignant vascular tumors in multiples organs, including pancreatic neuroendocrine tumors (PanNETs), whose long-term natural history is ill-known. METHODS: Patients with both documented germline PV in VHL gene and PanNETs included in the French PREDIR database between 1995 and 2022 were included. Primary endpoint was the proportion of patients with PanNET-related metastases and secondary endpoint was overall survival (OS). Genotype/phenotype correlations were studied. RESULTS: We included 121 patients with 259 PanNETs. Median age at diagnosis was 38 years. Median follow-up was 89.5 months. PanNET surgical resection was performed in 51 patients. Overall, 29 patients (24%) had metastases (5 synchronous, 10 metachronous), with a higher risk in case of larger PanNET size (p=0.0089; best threshold 28 mm) and grade 2 PanNET (p=0.048), and a pejorative prognostic impact (p=0.043). Patients with PV in VHL exon 1 had larger PanNETs (p=0.018), more often metastatic disease (48% vs 11.5%; p < 0.001) and a trend toward shorter OS (p=0.16). CONCLUSION: The risk of metastases associated to VHL-related PanNETs remains low (24%) but increases with tumor size >28 mm, higher grade and in case of PV located VHL exon 1. These data might help improving the management of these patients, who should be referred to an expert center.
ABSTRACT
De novo germline pathogenic variants (gPV) of the BReast CAncer 1 (BRCA1) gene are very rare. Only a few have been described up to date, usually in patients with a history of ovarian or breast cancer. Here, we report the first case of an incidental de novo BRCA1 germline pathogenic variant which was identified within the framework of the Plan France Médecine Génomique (PFMG) 2025 French national tumor sequencing program. The proband was a 29-year-old man diagnosed with metastatic osteosarcoma. Tumor whole exome sequencing identified a BRCA1 c.3756_3759del p.(Ser1253Argfs*10) pathogenic variant without loss-of-heterozygosity. A low genomic instability score and the absence of single base substitution signatures of homologous recombination deficiency suggested that the BRCA1 variant was not driver in the osteosarcoma tumorigenesis. Germline whole genome sequencing asserted the germline nature of this variant, with a 36% allele frequency, suggesting a mosaicism caused by a post-zygotic mutational event. The proband's family (parents and siblings) were not carriers of this variant confirming the de novo occurrence. Tumor sequencing programs like the French PFMG 2025 have been implemented worldwide and may help identify new gPV, including de novo variants.
ABSTRACT
We report a large series of 40 patients presenting EPAS1-mutated paraganglioma (PGL) in whom we investigated a cause underlying chronic hypoxia. Four patients suffered from hypoxaemic heart disease. In patients with available haemoglobin electrophoresis results, 59% presented with a haemoglobin disorder, including six with sickle cell disease, five with sickle cell trait and two with heterozygous haemoglobin C disease. Histological and transcriptomic characterization of EPAS1 tumours revealed increased angiogenesis and high similarities with pseudohypoxic PGLs caused by VHL gene mutations. Sickle haemoglobinopathy carriers could thus be at increased risk for developing EPAS1-PGLs, which should be taken into account in their management and surveillance.