What is it that makes a profession a profession and assures its members special status? What do professionals need to be able to claim their turf and establish priority over others who interact wit...

The gold standard: the challenge of evidence-based medicine and standardization in health care

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Acting in An Uncertain World: An Essay on Technical Democracy

Haemophilus influenzae pericarditis and empyema with thyroiditis in an adult. JAMA 1974;230:1426-7. 6 Keifaber RW, Bach RD, McDowell JA. Nonsurgical treatment of Haemophilus influenzae pericarditis in an adult. Am Heart J 1984;108: 168-9. 7 Duke M, Donovan TJ. Haemophilus influenzae pericarditis with cardiac tamponade. Am J Cardiol 1973;31:778-80. 8 Sheikh MU, Lee WR, Koh DS. Serial echographic development of apparent hypertrophic cardiomyopathy with biventricular outflow obstruction: documentation in Haemophilus influenzae pericarditis during hypovolaemia. Am Heart J 1981;102: 1069-71. 9 Buckingham TA, Wilner G, Sugar SJ. Haemophilus influenzae pericarditis in adults. Arch Intern Med 1983;143:1809-10. 10 Baker AS, Eavey RD. Adult supraglottitis. N Engl J Med 1986;314: 1185-6.

https://thorax.bmj.com/content/thoraxjnl/43/7/583.2.full.pdf

Lung Function in Children and Adolescents

Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome

Inflammation plays a critical role in cystic fibrosis (CF) lung pathology and disease progression making it an active area of research and important therapeutic target In this review, we explore the most recent research on the major contributors to the exuberant inflammatory response seen in CF as well as potential therapeutics to combat this response Absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) alters anion transport across CF airway epithelial cells and ultimately results in dehydration of the airway surface liquid The dehydrated airway surface liquid in combination with abnormal mucin secretion contributes to airway obstruction and subsequent infection that may serve as a trigger point for inflammation There is also evidence to suggest that airway inflammation may be excessive and sustained relative to the infectious stimuli Studies have shown dysregulation of both pro-inflammatory mediators such as IL-17 and pro-resolution mediators including metabolites of the eicosanoid pathway Recently, CFTR potentiators and correctors have garnered much attention in the CF community Although these modulators address the underlying defect in CF, their impact on downstream consequences such as inflammation are not known Here, we review pre-clinical and clinical data on the impact of CFTR modulators on inflammation In addition, we examine other cell types including neutrophils, macrophages, and T-lymphocytes that express CFTR and contribute to the CF inflammatory response Finally, we address challenges in developing anti-inflammatory therapies and highlight some of the most promising anti-inflammatory drugs under development for CF

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ppul.24129

Inflammation in cystic fibrosis: An update.

(R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models. The fact that (R)-roscovitine has undergone extensive preclinical safety/pharmacology studies, and phase I and II clinical trials in cancer patients, encourages its repurposing as a CF drug candidate.

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Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis

The French Cystic Fibrosis Registry takes a census of the population of patients and records their annual data transmitted by Cystic Fibrosis Centers (CFCs). Quality of patient data has been a focus in the past years, with the implementation of automated controls before data integration. The objective was to assess, at the 14 CFCs trained in the quality improvement named Hospital Program to Improve Outcomes and Expertise in Cystic Fibrosis (PHARE-M), the quality of the 2012 and 2013 data transmitted to the French Registry with respect to the rules established to obtain forced expiratory volume in 1 second (FEV1%) and anthropometric data. The clinical researcher selected 20 patients at each CFC from age ranges corresponding to different visit frequencies and measurement procedures in order to reach saturation of error causes. The control consisted in comparing source data, pulmonary function tests (PFTs), patient records, and data in the Registry. The audit focused on 242 patients, 2455 consultations and 1855 PFTs. Less than 5% of data concerning weight, height, or FEV1 (L) in the patient records files had discrepancies with source data. Discrepancies on patient height between patient records and PFT files were found in 11% of cases. For one hundred and ten patients (45%), anomalies were found between the patient record and the Registry for the FEV1% and the associated anthropometric measurements mainly related to the interpretation of the selection rule of the venue corresponding to the “best spirometry in the year” and the reference standard used (local standards versus Knudson reference equations). For the 33 children in the age range of 6–17 years old (27% out of 120 children records controlled), the FEV1% value in the Registry presented an average deviation of +4.25% (min. = −9.3%; max. = +16.9%; median = 4%) with the value from the Patient record. This first on-site quality audit of the data transmitted to the Registry pointed out variability in the measurement process at the CFCs. The rule for selecting the data for the Registry was applied differently at some CFCs, and various local References for the FEV1% calculation were used. Avenues for improvement have been identified.

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Lessons from the on-site quality audit of data transmitted to the French cystic fibrosis registry

Resume Comment et jusqu’ou l’experience professionnelle de cliniciens hospitaliers face au diagnostic d’une maladie incurable peut-elle etre transformee par une technologie biomedicale comme le depistage neonatal systematique (DNS) ? Cet article entend, a partir des resultats issus d’un questionnaire diffuse aupres des centres de ressources et de competences de la mucoviscidose et des entretiens menes aupres des equipes soignantes, reveler de nouvelles pratiques professionnelles exigeant transversalite, flexibilite et pluriprofessionnalisation qui se heurtent aux formes rigides et cloisonnees de l’hopital. Cette tension est exacerbee par le fait que les medecins sont amenes a construire la legitimite d’une forme d’experience clinique nouvelle qui les eloigne du soin curatif pour en faire des cogestionnaires de biographie des enfants atteints. Plus encore, bien que le DNS porte en son sein les progres scientifiques et techniques de la medecine et de la biologie, il ouvre le champ des inconnues et concourt a l’emergence de la figure du « bien portant suspect ». Au final, cette forme de professionnalite inedite laisse augurer une reconfiguration de l’experience professionnelle des medecins, de plus en plus affectee par les technologies medicales.

L'expérience professionnelle du médecin hospitalier à l'épreuve du dépistage : le cas de l'annonce du diagnostic de la mucoviscidose

La mucoviscidose occupe, parmi les maladies genetiques rares, une place particuliere par sa relative frequence (1/4600 naissances) et sa complexite : son expression clinique et pronostique est extremement variable et progressive. Il en resulte que le pronostic individuel est difficilement previsible au moment du diagnostic. A ce jour, il n'existe pas de traitement curatif de l'affection, les traitements sont symptomatiques ou preventifs et reposent essentiellement sur la prise en charge respiratoire, digestive et nutritionnelle. Pourtant, depuis 2002, les pouvoirs publics ont mis en place le depistage neonatal systematique de la mucoviscidose (DNSM) en France (Vailly, 2006) afin que chaque enfant, pour lequel le diagnostic est confirme, beneficie d'une prise en charge immediate selon un protocole de soins national. Neanmoins, l'instauration de ce depistage de masse suscite encore de nombreuses controverses, notamment parce qu'il ne repond pas a l'ensemble des criteres homologues par l'Organisation Mondiale de la Sante, ne conduisant pas a un « traitement efficace demontre » de la maladie. Ici se lit un bouleversement consequent dans l'experience professionnelle du medecin dont « l'objectif n'est plus de traiter au sens de guerir mais de gerer la maladie » (Baszanger, 1986, p. 17). Notre propos vise a rendre compte des repercussions engendrees par la mise en place du DNSM par les politiques publiques sur l'experience professionnelle des medecins hospitaliers, et plus precisement d'une communaute specialisee – celle des pediatres en mucoviscidose 1 – en pretant attention aux trois dimensions qui la traversent : la dimension organisationnelle, relationnelle et technique (Dubet, 1994). Autrement dit, quels roles professionnels emergent des lors que ces derniers n'interviennent plus aupres d'individus malades mais sont amenes a faire de la prevention aupres de populations pre-symptomatiques ? Pour y repondre, le processus d'annonce constitue une entree analytique privilegiee en ce qu'il est desormais regule par des recommandations visant une harmonisation des pratiques dans le cadre d'un depistage de masse. Ce processus a cela d'exceptionnel qu'il revient, par un devoilement plus ou moins progressif et plus ou moins long d'une anomalie genetique, a faire entrer un nourrisson asymptomatique dans le statut de malade, a enoncer la maladie a sa famille, quand bien meme le traitement curatif est inexistant. Il met en jeu une pluralite de phases clefs, de structures, de professionnels, de micro-annonces, d'instants critiques, qu'il s'agit d'expliciter pour une vision elargie des bouleversements de l'experience professionnelle des pediatres (Figure 1, p. 17). La mise en place du DNSM agit directement sur la dimension organisationnelle de l'experience professionnelle des pediatres en mucoviscidose. D'abord parce qu'elle a

https://hal.archives-ouvertes.fr/hal-01373375/document

L. Guéganton

Papers

Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis

Lessons from the on-site quality audit of data transmitted to the French cystic fibrosis registry

L'expérience professionnelle du médecin hospitalier à l'épreuve du dépistage : le cas de l'annonce du diagnostic de la mucoviscidose

L’expérience professionnelle du médecin hospitalier à l’épreuve du dépistage :

WS19.4 CF quality improvement program: a pilot phase to experiment the US QIP approach in France