EPA-based assessment: Clinical teachers’ challenges when transitioning to a prospective entrustment-supervision scale

Background: This study explores the challenges clinical teachers face when first using a prospective entrustment-supervision (ES) scale in a curriculum based on Entrustable Professional Activities (EPAs). A prospective ES scale has the purpose to estimate at which level of supervision a student will be ready to perform an activity in subsequent encounters. Methods: We studied the transition to prospective assessment of medical students in clerkships via semi-structured interviews with twelve purposefully sampled clinical teachers, shortly after the introduction of a new undergraduate EPA-based curriculum and EPA-based assessment employing a prospective ES scale. Results: While some clinical teachers showed a correct interpretation, rating strategies also appeared to be affected by the target supervision level for completion of the clerkship. Instructions to estimate readiness for a supervision level in the future were not always understood. Further, teachers' interpretation of the scale anchors relied heavily on the phrasing. Discussion: Prospective assessment asks clinical teachers to make an extra inference step in their judgement process from reporting observed performance to estimating future level of supervision. This requires a change in mindset when coming from a retrospective, performance-oriented assessment method, i.e., reporting what was observed. Our findings suggest optimizing the ES-scale wordings and improving faculty development

De novo variants in ATXN7L3 lead to developmental delay, hypotonia and distinctive facial features

Deubiquitination is critical for the proper functioning of numerous biological pathways such as DNA repair, cell cycle progression, transcription, signal transduction, and autophagy. Accordingly, pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51). Through exome sequencing and GeneMatching, we identified nine individuals with heterozygous variants in ATXN7L3. The core phenotype included global motor and language developmental delay, hypotonia, and distinctive facial characteristics including hypertelorism, epicanthal folds, blepharoptosis, a small nose and mouth, and low-set posteriorly rotated ears. In order to assess pathogenicity, we investigated the effects of a recurrent nonsense variant [c.340C>T; p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired, as indicated by an increase in histone H2Bub1 levels. This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality. In conclusion, we present clinical information and biochemical characterization supporting ATXN7L3 variants in the pathogenesis of a rare syndromic ND

The impact of unsolicited findings in clinical exome sequencing, a qualitative interview study

Unsolicited findings (UFs) in clinical exome sequencing are variants that are unrelated to the initial clinical question the DNA test was performed for, but that may nonetheless be of medical relevance to patients and/or their families. There is limited knowledge about the impact of UFs on patients' lives. In order to characterise patient perceptions of the impact of an UF, we conducted 20 semi-structured face-to-face interviews with patients and/or their relatives to whom an UF predisposing to oncological disease (n = 10) or predisposing to a cardiac condition (n = 10) had been disclosed. We have identified a psychological, physical and financial aspect of the perceived impact of UF disclosure in exome sequencing. Actionability, understanding, patients' pre-test health and social context were influencing factors, according to our participants. Although most expressed considerable psychological impact initially, all but one participant would choose to undergo genetic testing again, knowing what they know now. These novel findings provide insight in patients' perspectives on the impact of UF disclosure. Our study highlights the value of incorporating patients' perceptions in UF disclosure policy

EPA-based assessment: Clinical teachers’ challenges when transitioning to a prospective entrustment-supervision scale

Background: This study explores the challenges clinical teachers face when first using a prospective entrustment-supervision (ES) scale in a curriculum based on Entrustable Professional Activities (EPAs). A prospective ES scale has the purpose to estimate at which level of supervision a student will be ready to perform an activity in subsequent encounters. Methods: We studied the transition to prospective assessment of medical students in clerkships via semi-structured interviews with twelve purposefully sampled clinical teachers, shortly after the introduction of a new undergraduate EPA-based curriculum and EPA-based assessment employing a prospective ES scale. Results: While some clinical teachers showed a correct interpretation, rating strategies also appeared to be affected by the target supervision level for completion of the clerkship. Instructions to estimate readiness for a supervision level in the future were not always understood. Further, teachers' interpretation of the scale anchors relied heavily on the phrasing. Discussion: Prospective assessment asks clinical teachers to make an extra inference step in their judgement process from reporting observed performance to estimating future level of supervision. This requires a change in mindset when coming from a retrospective, performance-oriented assessment method, i.e., reporting what was observed. Our findings suggest optimizing the ES-scale wordings and improving faculty development

EPA-based assessment: Clinical teachers’ challenges when transitioning to a prospective entrustment-supervision scale

Background: This study explores the challenges clinical teachers face when first using a prospective entrustment-supervision (ES) scale in a curriculum based on Entrustable Professional Activities (EPAs). A prospective ES scale has the purpose to estimate at which level of supervision a student will be ready to perform an activity in subsequent encounters. Methods: We studied the transition to prospective assessment of medical students in clerkships via semi-structured interviews with twelve purposefully sampled clinical teachers, shortly after the introduction of a new undergraduate EPA-based curriculum and EPA-based assessment employing a prospective ES scale. Results: While some clinical teachers showed a correct interpretation, rating strategies also appeared to be affected by the target supervision level for completion of the clerkship. Instructions to estimate readiness for a supervision level in the future were not always understood. Further, teachers' interpretation of the scale anchors relied heavily on the phrasing. Discussion: Prospective assessment asks clinical teachers to make an extra inference step in their judgement process from reporting observed performance to estimating future level of supervision. This requires a change in mindset when coming from a retrospective, performance-oriented assessment method, i.e., reporting what was observed. Our findings suggest optimizing the ES-scale wordings and improving faculty development

De novo variants in ATXN7L3 lead to developmental delay, hypotonia and distinctive facial features: ATXN7L3 variants in developmental delay

International audienceAbstract Deubiquitination is critical for the proper functioning of numerous biological pathways such as DNA repair, cell cycle progression, transcription, signal transduction, and autophagy. Accordingly, pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51). Through exome sequencing and GeneMatching, we identified nine individuals with heterozygous variants in ATXN7L3. The core phenotype included global motor and language developmental delay, hypotonia, and distinctive facial characteristics including hypertelorism, epicanthal folds, blepharoptosis, a small nose and mouth, and low-set posteriorly rotated ears. In order to assess pathogenicity, we investigated the effects of a recurrent nonsense variant [c.340C>T; p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired, as indicated by an increase in histone H2Bub1 levels. This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality. In conclusion, we present clinical information and biochemical characterization supporting ATXN7L3 variants in the pathogenesis of a rare syndromic ND