Pediatric Autoimmune or Primary Sclerosing Cholangitis: Metronidazole Effectiveness on Biochemical Data, Bile Acid Profile, and Gut Microbiota: A Pilot Study

Objectives: Autoimmune hepatitis and primary sclerosing cholangitis (PSC) can both be present, resulting in autoimmune sclerosing cholangitis (ASC). PSC physiopathology could be based on the cross-talk between gut microbiota and bile acids (BAs); antibiotics are an innovative therapy. This pilot study assesses metronidazole (MTZ)'s effectiveness in ASC or PSC patients according to the stage of the disease, and its effects on biochemical parameters, BA profiles, and gut microbiota. Methods: ASC or PSC patients from Cliniques universitaires Saint-Luc's pediatric hepato-gastroenterology division were enrolled retrospectively and prospectively; both datasets were merged. MTZ was administered over at least 14 days on top of standard treatment (ursodeoxycholic acid, azathioprine, and steroids). Fecal and blood samples were collected before (T0) and at MTZ day 14 (T14). Sustained biochemical remission was defined by the reduction of transaminases (AST and ALT), gamma-glutamyl transferase (GGT), and CRP until 12 months post-MTZ. Results: A total of 18 patients (mean age, 13.2 ± 4.5 years) were enrolled (13 ASC and 5 PSC), and divided in remission or relapse patients. CRP, AST, ALT, and GGT levels decreased post-MTZ in both groups (excepting GGT in relapse patients), with decreases between T0 and T14 being significant for AST and ALT. Relapse patients were older (P = 0.0351) and in late-disease stage, with mainly large-duct PSC (P = 0.0466). In remission patients, the mean plasma relative abundance of hydrophilic BA increased by +6.3% (P = 0.0391) after MTZ. Neither at baseline nor T14, there were significant differences in gut microbiota recorded. Conclusion: These data are likely indicative of long-term benefits following MTZ therapy at early-stage ASC or PSC, with increased hydrophilic BA abundance. Multicenter prospective studies are needed. Keywords: autoimmune sclerosing cholangitis; bile acid profile; gut microbiota dysbiosis; metronidazole; overlap syndrome; primary sclerosing cholangitis

Eco-Phoques : Bases scientifiques pour une meilleure connaissance des phoques et de leurs interactions avec les activités humaines en Manche Nord-Est: Rapport final pour la région Hauts-de-France et l’AFB.

Two seal species are found year-round in the Région Hauts-de-France (North of France): the harbour seal (Phoca vitulina), observed for decades in the area and still increasing, and the grey seal (Halicheorus grypus), more recently settled, which numbers have increased exponentially this last decade. While harbour seals are observed at all seasons and seem to be very faithful to their haulout sites, grey seals, mostly adult males, are mainly abundant in the area seasonally (during summer). More harbour seals are also counted on their haulout sites during summer, but this is most likely only due to their spending more time ashore during the breeding and moulting seasons. The maximum number of seals simultaneously censused on the haulout sites from baie de Somme to Dunkerque was 709 harbour seals in July 2017, and 402 grey seals in July 2016. These maxima increased these last years, even if in some haulout areas the yearly maximum counts remain stable since 2015. Telemetry tracking showed that harbour seals from the baie de Somme make very coastal movements, and forage mostly in front of (or close vicinity, a few kilometres away from) the baie de Somme. They can travel over a few tens or a hundred of kilometres, sometimes moving from one colony to another, as also shown by photo-identification matching between the baie d’Authie and baie de Canche. However, telemetry showed that grey seals move at a much larger scale, travelling over tens and hundreds of kilometres, foraging in the middle of the English Channel, in baie de Somme or along the coasts of Hauts-de-France, sometimes further in the North Sea where they return for breeding. Photo-identification also highlighted individual movements between baie de Somme, baie d’Authie and phare de Walde. This technique showed that seals from both species were faithful to their haulout sites. This site fidelity was higher in harbour seals, but a significant proportion of grey seals also came back from one year to the next. The haulout site at phare de Walde seems to be a step-over area for grey seals (from the Southern North Sea), with more photoidentified individuals observed only once. The seals’ diet, estimated from faeces sampled in baie de Somme (and also Walde for grey seals) consisted of 86% [95% confidence interval: 68-100%, in biomass] of flat fish and 14% [5-25%] of round fish for harbour seals, and of 61% [38-87%] of flat fish, 29% [13-54%] of round fish and 10% [1-23%] of cephalopods for grey seals. In both seal species, flat fish species were mainly plaice, flounder or different sole species, and the main round fish species in grey seals was herring. Additional diet analysis from stomach samples of stranded seals suggested that cephalopods may be underestimated in the grey seal diet especially. Trophic overlap between both seal species was high, but a higher inter-individual variability was observed in grey seals, considered as individual specialists, than in harbour seals, rather considered as specialized at the colony level. The analysis of ecological tracers (carbon and nitrogen stable isotopes) showed that results of seal diet obtained exclusively in baie de Somme cannot always be generalized to the whole region, and that the trophic niche of harbour seals was included in that of grey seals. All these results (on diet and tracers) suggest interactions between both species, and potentially competition, that could evolve in the future if grey seal numbers continue to grow. From 2015 to 2017, total prey consumption by seals from baie de Somme and baie d’Authie increased from 592 [490-701] to 750 [632-878] tons per year for harbour seals and from 422 [369-476] to 750 [675-827] tons per year for grey seals. Seasonal variations in total consumption were limited for harbour seals, but larger for grey seals, mostly abundant in the area during summer. During this summer season, their prey consumption most likely exceeds that of harbour seals. Both seal species are strongly interacting with each other, but less so with fishery activities, except for trammelers for which the fishing effort strongly overlaps with harbour seal foraging areas (overlap 18 times higher between trammelers and harbour seals than between all fishing gear and harbour seals). Sport and tourism activities also cause interactions with seals, that are either seen as positive (e.g. seals attract tourism, contribute to the regional identity…) or negative (risks of disturbance of the seals). Users along the coast are conscious of these interactions, and it seems necessary to maintain the existing monitoring in order to better evaluate those interactions, in a context of increasing seal populations

Career intentions of medical students in the UK: a national, cross-sectional study (AIMS study)

Objective To determine current UK medical students’ career intentions after graduation and on completing the Foundation Programme (FP), and to ascertain the motivations behind these intentions.Design Cross-sectional, mixed-methods survey of UK medical students, using a non-random sampling method.Setting All 44 UK medical schools recognised by the General Medical Council.Participants All UK medical students were eligible to participate. The study sample consisted of 10 486 participants, approximately 25.50% of the medical student population.Outcome measures Career intentions of medical students postgraduation and post-FP, motivations behind these career intentions, characterising the medical student population and correlating demographic factors and propensity to leave the National Health Service (NHS).Results The majority of participating students (8806/10 486, 83.98%) planned to complete both years of the FP after graduation, with under half of these students (4294/8806, 48.76%) intending to pursue specialty training thereafter. A subanalysis of career intentions after the FP by year of study revealed a significant decrease in students’ intentions to enter specialty training as they advanced through medical school. Approximately a third of surveyed students (3392/10 486, 32.35%) intended to emigrate to practise medicine, with 42.57% (n=1444) of those students not planning to return. In total, 2.89% of students intended to leave medicine altogether (n=303). Remuneration, work-life balance and working conditions were identified as important factors in decision-making regarding emigration and leaving the profession. Subgroup analyses based on gender, type of schooling, fee type and educational background were performed. Only 17.26% of surveyed students were satisfied or very satisfied with the overall prospect of working in the NHS.Conclusions The Ascertaining the career Intentions of UK Medical Students study highlights UK students’ views and career intentions, revealing a concerning proportion of those surveyed considering alternative careers or emigration. Addressing factors such as remuneration, work-life balance and working conditions may increase retention of doctors and improve workforce planning efforts

The role of medical schools in UK students’ career intentions: findings from the AIMS study

Abstract Objectives To investigate differences in students’ career intentions between UK medical schools. Design Cross-sectional, mixed-methods online survey. Setting The primary study included all 44 UK medical schools, with this analysis comprising 42 medical schools. Participants Ten thousand four hundred eighty-six UK medical students. Main outcome measures Career intentions of medical students, focusing on differences between medical schools. Secondary outcomes included variation in medical students’ satisfaction with a prospective career in the NHS, by medical school. Results 2.89% of students intended to leave medicine altogether, with Cambridge Medical School having the highest proportion of such respondents. 32.35% of respondents planned to emigrate for practice, with Ulster medical students being the most likely. Of those intending to emigrate, the University of Central Lancashire saw the highest proportion stating no intentions to return. Cardiff Medical School had the greatest percentage of students intending to assume non-training clinical posts after completing FY2. 35.23% of participating medical students intended to leave the NHS within 2 years of graduating, with Brighton and Sussex holding the highest proportion of these respondents. Only 17.26% were satisfied with the prospect of working in the NHS, with considerable variation nationally; Barts and the London medical students had the highest rates of dissatisfaction. Conclusions This study reveals variability in students’ career sentiment across UK medical schools, emphasising the need for attention to factors influencing these trends. A concerning proportion of students intend to exit the NHS within 2 years of graduating, with substantial variation between institutions. Students’ intentions may be shaped by various factors, including curriculum focus and recruitment practices. It is imperative to re-evaluate these aspects within medical schools, whilst considering the wider national context, to improve student perceptions towards an NHS career. Future research should target underlying causes for these disparities to facilitate improvements to career satisfaction and retention. </jats:sec