Niveau de préparation des diplômés à une carrière en médecine interne générale avant et après la reconnaissance de la surspécialité : objectifs atteints et besoins évolutifs dans le programme d’études

Background: A survey of General Internal Medicine (GIM) graduates published in 2006 revealed large training gaps that informed the development of the first national GIM objectives of training in 2010. The first recognized GIM certification examination was written by candidates in 2014. The landscape is again changing with the introduction in 2019 of competency-by-design (CBD) to GIM training. This study aims to examine pre-existing and emerging training gaps with standardization of GIM curricula and identify new training needs to inform CBD curricula.  Methods: GIM graduates from all 16 Canadian programs from 2014 -2019 were emailed a survey modeled after the original study published in 2006. Graduates were asked about their preparedness and importance ratings for various elements of practice. Results: Many of the previously identified gaps (difference between importance and preparedness ratings) have been resolved in specific clinical areas (obstetrical and perioperative medicine) and skills (exercise stress testing) although some still require ongoing work in areas such as substance use disorders. Importantly, gaps still exist in preparedness for some intrinsic roles (e.g. managerial skills). Conclusions:  The development of a national GIM curriculum has helped close some educational gaps but some still exist. Our study provides data needed to meet the evolving needs of our graduates.Contexte : Une enquête auprès des diplômés en médecine interne générale (MIG), publiée en 2006, a révélé d’importantes lacunes dans leur formation, menant à l’élaboration des premiers objectifs nationaux de formation en MIG en 2010. Le premier examen de certification en MIG a été organisé en 2014. Le paysage est à nouveau en train de changer avec l’introduction en 2019 de la compétence par conception (CPC) dans la formation en MIG. Cette étude vise à examiner les lacunes de formation préexistantes et émergentes avec la normalisation de la formation en MIG et à identifier les nouveaux besoins de formation pour éclairer la définition des programmes de formation selon l’approche fondée sur les compétences.  Méthodes : Les diplômés des 16 programmes canadiens en MIG entre 2014 et 2019 ont reçu par courriel un sondage inspiré de l’étude originelle publiée en 2006. Les diplômés ont été interrogés sur leur état de préparation et sur l’importance qu’ils accordaient à divers éléments de la pratique. Résultats : Un grand nombre des lacunes décelées précédemment (différence entre les cotes d’importance et de préparation) ont été comblées dans des domaines cliniques spécifiques (médecine obstétrique et périopératoire) et par rapport à des compétences spécifiques (tests de stress à l’effort); dans certains domaines, comme les troubles liés à l’utilisation de substances psychoactives, les efforts doivent être poursuivis. Il est important de noter que des lacunes subsistent dans la préparation à certains rôles intrinsèques (par exemple, les compétences de gestionnaire). Conclusion : L’élaboration d’un programme national de formation en MIG a permis de combler certaines lacunes en matière de formation, mais des carences subsistent. Notre étude fournit les données nécessaires pour répondre aux besoins évolutifs de nos diplômés

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination

Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αβ elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αβ elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism

Diagnosis of Barrett’s esophagus and Esophageal Varices using a Magnetically Assisted Capsule Endoscopy system

Background and AimsMagnetically assisted capsule endoscopy (MACE) potentially offers a comfortable, patient friendly, and community-based alternative to gastroscopy (EGD). This pilot study aims to explore whether this approach can be used to accurately diagnose Barrett’s esophagus and esophageal varices.MethodsThe MiroCam Navi capsule system was used to examine the upper GI tract in patients due to undergo a clinically indicated EGD. A total of 50 participants were enrolled, of which 34 had known pathology, 17 Barrett’s esophagus (BE), 17 esophageal varices (EV), with 16 controls. Patients underwent the MACE procedure, with the operator blinded to the indication and any previous endoscopic diagnoses. The subsequent EGD was performed by an endoscopist blinded to the MACE findings. Diagnostic yield, comfort and patient preference between the 2 modalities were compared.ResultsParticipants had a mean age of 61 years old, a M:F ratio of 2.1:1, a mean body mass index (BMI) of 29.5, with an average chest measurement of 105.3 cm. Forty-seven patients undertook both procedures; 3 patients were unable to swallow the capsule. With the use of the magnet, it was possible to hold the capsule within the esophagus for a mean duration of 190 seconds and up to a maximum of 634 seconds. A correct real-time MACE diagnosis was made in 11 of 15 patients with EV (sensitivity 73.3% [95% CI, 44.9% - 92.2%] and specificity 100% [95% CI, 89.1% - 100%]) and 15 of 16 patients with BE (sensitivity 93.8% [95% CI, 69.8% - 99.8%] and a specificity of 100% [95% CI, 88.8% - 100%]). MACE was considered more comfortable than conventional endoscopy (p [less than] 0.0001) with a mean score of 9.2 with MACE compared with 6.7 with EGD, when assessed on a 10-point scale. No MACE or EGD -elated adverse events occurred.ConclusionThis pilot study demonstrates that MACE is both safe and well tolerated by patients. Accuracy for the diagnosis of BE was high and may therefore have a role in screening for this condition

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

A comparative analysis of graduate preparedness for a career in General Internal Medicine before and after national subspecialty recognition to inform curricular changes: Have we met the mark?

Background: A survey of General Internal Medicine (GIM) graduates published in 2006 revealed large training gaps that informed the development of the first national GIM objectives of training in 2010. The first recognized GIM certification examination was written by candidates in 2014. The landscape is again changing with the introduction in 2019 of competency-by-design (CBD) to GIM training. This study aims to examine pre-existing and emerging training gaps with standardization of GIM curricula and identify new training needs to inform CBD curricula.Methods: GIM graduates from all 16 Canadian programs from 2014 -2019 were emailed a survey modeled after the original study published in 2006. Graduates were asked about their preparedness and importance ratings for various elements of practice.Results: Many of the previously identified gaps (difference between importance and preparedness ratings) have been resolved in specific clinical areas (obstetrical and perioperative medicine) and skills (exercise stress testing) although some still require ongoing work in areas such as substance use disorders. Importantly, gaps still exist in preparedness for some intrinsic roles (e.g. managerial skills).Conclusions: The development of a national GIM curriculum has helped close some educational gaps but some still exist. Our study provides data needed to meet the evolving needs of our graduates.Contexte : Une enquête auprès des diplômés en médecine interne générale (MIG), publiée en 2006, a révélé d’importantes lacunes dans leur formation, menant à l’élaboration des premiers objectifs nationaux de formation en MIG en 2010. Le premier examen de certification en MIG a été organisé en 2014. La formation est à nouveau en train de changer avec l’introduction en 2019 de la compétence par conception (CPC) dans la formation en MIG. Cette étude vise à examiner les lacunes de formation préexistantes et émergentes avec la normalisation de la formation en MIG et à identifier les nouveaux besoins de formation pour éclairer la définition des programmes de formation selon l’approche fondée sur les compétences.Méthodes : Les diplômés des 16 programmes canadiens en MIG entre 2014 et 2019 ont reçu par courriel un sondage inspiré de l’étude originelle publiée en 2006. Les diplômés ont été interrogés sur leur état de préparation et sur l’importance qu’ils accordaient à divers éléments de la pratique.Résultats : Un grand nombre des lacunes décelées précédemment (différence entre les cotes d’importance et de préparation) ont été comblées dans des domaines cliniques spécifiques (médecine obstétrique et périopératoire) et par rapport à des compétences spécifiques (tests de stress à l’effort); dans certains domaines, comme les troubles liés à l’utilisation de substances psychoactives, les efforts doivent être poursuivis. Il est important de noter que des lacunes subsistent dans la préparation à certains rôles intrinsèques (par exemple, les compétences de gestionnaire).Conclusion : L’élaboration d’un programme national de formation en MIG a permis de combler certaines lacunes en matière de formation, mais des carences subsistent. Notre étude fournit les données nécessaires pour répondre aux besoins évolutifs de nos diplômés

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination

Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αβ elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αβ elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism