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Background A public health student service was set up by the French government in 2018 with the aim of increasing awareness of primary health promotion among the 47,000 students of medicine and other health professions. It is an annual program involving community-based actions on nutrition, physical activity, addiction or sexuality. Our objective was to evaluate its implementation at local level and the different experiences of the stakeholders. Methods A quasi-experimental study using process evaluation was performed in a Faculty of Medicine in Paris. Quantitative and qualitative data were collected from medical students who carried out preventive health actions, in the institutions in which the actions took place and from a subsample of beneficiaries. Results One hundred and eight actions were carried out by 341 students in 23 educational or social institutions, mostly high schools ( n  = 12, 52%). Two thirds of the students did not feel sufficiently prepared to deliver preventive health interventions (65.7%, 224/341); however the beneficiaries found that the interventions were good (278/280, 99,2%). Nineteen (83%) of the host institutions agreed to welcome health service students again, of which 9 required some modifications. For students, the reporting of a satisfactory health service experience was associated with the reporting of skills or knowledge acquisition ( p  < 0.01). Delivering actions in high schools and to a medium-sized number of beneficiaries per week was associated with students’ satisfaction. No effect of gender or theme of prevention was observed. For 248/341 (72.7%) students, the public health service program prompts them to address prevention issues in the future. Conclusion The public health service undertaken by medical students through the program is a feasible and acceptable means of delivering preventive actions. Reinforcement of training and closer interaction with the host institutions would improve results.

According to an international survey in 2013/2014, in France, 32% of 15-year-olds consumed soft drinks daily (vs 16% in England and 11% in Canada); 90% reported less than 60 min of moderate to vigorous daily activity (current worldwide recommendation) (vs 86% in England and 78% in Canada); and 19% smoked at least once a week (vs 7% in England and 5% in Canada).2 In light of those numbers, France will probably have a high prevalence of chronic diseases in the next generation of adults. The government decided to relaunch primary prevention to try to fight against preventable morbidity and to reduce the costs it generates in France: €20.4 billion for obesity, €15 billion for excessive alcohol drinking and €26.6 billion for tobacco-related diseases. [...]the health service aims to educate all future health professionals to primary prevention through the construction and development of concrete actions. [...]the health service has the ambition to reduce health geographical and social inequalities, ensuring the territorial distribution of actions. For the first year of implementation, four priority topics were identified: nutrition and cardiovascular risk factors, physical activity, addictions, sexual health and contraceptive methods, as they are major concerns especially in youth for the French public health system.

Continuing medical education is important but time-consuming for general practitioners (GPs). Current learning approaches are limited and lack the ability to engage some practitioners. Serious games are new learning approaches that use video games as engaging teaching material. They have significant advantages in terms of efficiency and dissemination. The aim of this study was to create a serious game and to evaluate it in terms of effectiveness and satisfaction, comparing it with a traditional method of continuing education-article reading. We produced a prototype video game called Hygie on the 5 most common reasons of consultation in general practice using 9 articles from independent evidence-based medicine journals (reviews from Prescrire and Minerva). We created 51 clinical cases. We then conducted a double-blinded randomized trial comparing the learning provided by a week of access to the game versus source articles. Participants were GPs involved as resident supervisors in 14 French university departments of family practice, recruited by email. Primary outcomes were (1) mean final knowledge score completed 3 to 5 weeks after the end of the intervention and (2) mean difference between knowledge pretest (before intervention) and posttest (3 to 5 weeks after intervention) scores, both scaled on 10 points. Secondary outcomes were transfer of knowledge learned to practice, satisfaction, and time spent playing. A total of 269 GPs agreed to participate in the study. Characteristics of participants were similar between learning groups. There was no difference between groups on the mean score of the final knowledge test, with scores of 4.9 (95% CI 4.6-5.2) in the Hygie group and 4.6 (95% CI 4.2-4.9) in the reading group (P=.21). There was a mean difference score between knowledge pre- and posttests, with significantly superior performance for Hygie (mean gain of 1.6 in the Hygie group and 0.9 in the reading group; P=.02), demonstrating a more efficient and persistent learning with Hygie. The rate of participants that reported to have used the knowledge they learned through the teaching material was significantly superior in the Hygie group: 77% (47/61) in the Hygie group and 53% (25/47) in the reading group; odds ratio 2.9, 95% CI 1.2-7.4. Moreover, 87% of the opinions were favorable, indicating that Hygie is of interest for updating medical knowledge. Qualitative data showed that learners enjoyed Hygie especially for its playful, interactive, and stimulating aspects. We conclude that Hygie can diversify the offering for continuing education for GPs in an effective, pleasant, and evidence-based way. ClinicalTrials.gov NCT03486275; https://clinicaltrials.gov/ct2/show/NCT03486275.

Background A public health student service was set up by the French government in 2018 with the aim of increasing awareness of primary health promotion among the 47,000 students of medicine and other health professions. It is an annual program involving community-based actions nutrition, physical activity, addiction or sexuality. Our objective was to evaluate its implementation at local level and the different experiences of the stakeholders. Methods A quasi-experimental study using process evaluation was performed in a Faculty of Medicine in Paris. Quantitative and qualitative data were collected from medical students who carried out preventive health actions, in the institutions in which the actions took place and from a subsample of beneficiaries. Results One hundred and eight actions were carried out by 341 students in 23 educational or social institutions, mostly high schools (n=12, 52%). Two thirds of the students did not feel sufficiently prepared to deliver preventive health interventions (65.7%, 224/341); however the beneficiaries found that the interventions were good (278/280, 99,2%). Nineteen (83%) of the host institutions agreed to welcome health service students again, of which 9 required some modifications. For students, the reporting of a satisfactory health service experience was associated with the reporting of skills or knowledge acquisition (p<0.01). Delivering actions in high schools and to a medium-sized number of beneficiaries per week was associated with students’ satisfaction. No effect of gender or theme of prevention was observed. For 248/341 (72.7%) students, the public health service program prompts them to address prevention issues in the future. Conclusion The public health service undertaken by medical students through the program is a feasible and acceptable means of delivering preventive actions. Reinforcement of training and closer interaction with the host institutions would improve results.

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrPSc). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrPSc seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation.

Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. However, several lines of evidence have raised concerns that further cases of vCJD could emerge as a result of prolonged incubation and/or secondary transmission. Emerging evidence from peripheral tissue distribution studies employing high-sensitivity assays suggests that all forms of human prion disease carry a theoretical risk of iatrogenic transmission. Finally, emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments.Despite the declining incidence of variant Creutzfeldt–Jakob disease, prion diseases remain a threat to public health. In this Review, Suvankar Pal and colleagues provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance is still vital.

Glucocorticoids represent the mainstay of therapy for a broad spectrum of immune-mediated inflammatory diseases. However, the molecular mechanisms underlying their anti-inflammatory mode of action have remained incompletely understood 1 . Here we show that the anti-inflammatory properties of glucocorticoids involve reprogramming of the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and consequent inhibition of the inflammatory response. The glucocorticoid receptor interacts with parts of the pyruvate dehydrogenase complex whereby glucocorticoids provoke an increase in activity and enable an accelerated and paradoxical flux of the tricarboxylic acid (TCA) cycle in otherwise pro-inflammatory macrophages. This glucocorticoid-mediated rewiring of mitochondrial metabolism potentiates TCA-cycle-dependent production of itaconate throughout the inflammatory response, thereby interfering with the production of pro-inflammatory cytokines. By contrast, artificial blocking of the TCA cycle or genetic deficiency in aconitate decarboxylase 1, the rate-limiting enzyme of itaconate synthesis, interferes with the anti-inflammatory effects of glucocorticoids and, accordingly, abrogates their beneficial effects during a diverse range of preclinical models of immune-mediated inflammatory diseases. Our findings provide important insights into the anti-inflammatory properties of glucocorticoids and have substantial implications for the design of new classes of anti-inflammatory drugs. Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.

Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD. We recruited patients older than 18 years old who had a diagnosis of definite or probable sporadic CJD or genetic forms of the disease via Italian reference centres and the French national referral system. Patients were randomly assigned (ratio 1:1) to receive oral doxycycline (100 mg daily) or placebo under double-blind conditions from the day of randomisation to death. Centralised randomisation was done independently of enrolment or evaluation of patients using a minimisation method in Italy and a simple randomisation in France. Participants, caregivers, and clinicians were masked to group assignment. The primary efficacy variable was the survival time from randomisation. Interim analyses were planned to detect a significant effect of treatment as early as possible. This trial is registered with EudraCT, 2006-001858-27 for the Italian study and 2007-005553-34 for the French study. From April 12, 2007, to Aug 19, 2010, in Italy, and from Jan 30, 2009, to Jan 10, 2012, in France, 121 patients with CJD were enrolled in the study, 62 of whom were randomly assigned to the treatment group and 59 to the placebo group. The first interim analysis showed absence of superiority of doxycycline compared with placebo, and the trial was stopped for futility. Efficacy analyses did not show significant differences between patients treated with doxycycline and placebo with regard to survival times (HR 1·1, 95% CI 0·8–1·7, p=0·50). Serious adverse events were judged not to be related to treatment, whereas a relation was deemed probable or possible for five non-serious adverse events that occurred in each treatment group. Doxycycline at a dose of 100 mg per day was well tolerated but did not significantly affect the course of CJD, at variance with the results of previous observational studies. Our experience could be useful in the design of large multinational controlled trials of potential anti-prion molecules in this rare disease. Agenzia Italiana Farmaco, Italian Ministry of Health, AIEnP, and French Ministry of Health.

IntroductionSporadic CJD (sCJD) is universally fatal. While median survival is 5 months, there is consider- able heterogeneity with some surviving weeks while others survive several months or years. We sought to evaluate characteristics influencing disease duration, and the performance of latest diagnostic criteria incorporating cortical ribboning on MRI brain and the RT-QuIC assay.Methods501 autopsy-confirmed cases from surveillance centres in the UK, France, Germany and Italy were stratified into short (<75 days), typical (75-222 days) and long (>222 days) survival groups. We evaluated clinical features, investigation results, and diagnostic criteria classification.ResultsShort survival was associated with male sex (p=0.02) and older age (p=0.004). Prion protein gene codon 129 polymorphism status greatly influenced duration (p=<0.001, with longest survival in methionine- valine heterozygotes). Extrapyramidal features were most frequent in long survivors (p=0.04). EEG and 14-3-3 were most sensitive with short survival (p<0.001), RT-QuIC with typical survival (p=0.03) and MRI sen- sitivity did not vary (p=0.4). Previous diagnostic criteria lacked sensitivity in long survivors (p=0.001) while updated criteria were equivalent between groups (p=0.19): sensitivity for long survivors increased 27.7%.ConclusionsThis study demonstrates important factors influencing survival and associated phenotypes. The latest diagnostic criteria for sCJD have significantly enhanced diagnosis in long survivors.

A total of 10-15% of human transmissible spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP). We examined the phenotype, distribution, and frequency of genetic TSEs (gTSEs) in different countries/geographical regions. We collected standardised data on gTSEs between 1993 and 2002 in the framework of the EUROCJD collaborative surveillance project. Our results show that clinicopathological phenotypes include genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker disease (GSS). Genetic TSE patients with insert mutation in the PRNP represent a separate group. Point and insertional mutations in the PRNP gene varies significantly in frequency between countries. The commonest mutation is E200K. Absence of a positive family history is noted in a significant proportion of cases in all mutation types (12-88%). FFI and GSS patients develop disease earlier than gCJD. Base pair insertions associated with the Creutzfeldt-Jakob disease (CJD) phenotype, GSS, and FFI cases have a longer duration of illness compared to cases with point mutations and gCJD. Cerebrospinal fluid 14-3-3 immunoassay, EEG, and MRI brain scan are useful in the diagnosis of CJD with point mutations, but are less sensitive in the other forms. Given the low prevalence of family history, the term \"gTSE\" is preferable to \"familial TSE\". Application of genetic screening in clinical practice has the advantage of early diagnosis and may lead to the identification of a risk of a TSE.