Rare diseases social epidemiology: analysis of inequalities.

Rare disease patients experience particular obstacles in accessing high quality healthcare. These obstacles include but are not limited to: (i) lack of scientific knowledge of their disease, (ii) lack of access to correct diagnosis, (iii) delays in diagnosis, (iv) lack of appropriate multidisciplinary healthcare, (v) lack of quality information and support at the time of diagnosis, (vi) undue social consequences, (vii) inequities and difficulties in access to treatment, rehabilitation and care, (viii) dissatisfaction with and loss of confidence in medical and social services, (ix) denied treatment by health professionals and (x) lack of availability of orphan drugs. Three surveys and their subsequent analysis, conducted by the European Organisation for Rare Diseases (EURORDIS), a non-governmental patient driven alliance of European patient organisations, demonstrate several of these obstacles by describing the experience of rare disease patients across 18 rare diseases and over 24 European countries as well as highlighting inequalities that exist between them.

[Involvement of researchers with patient associations: what is the role of their opinions, their clinical activity and their nature?]. / Engagement des chercheurs auprès des associations - Quel rôle jouent leurs opinions, leur activité clinique et leur genre ?

Although the involvement of patient associations in biomedical research is well known, conversely, researchers' views and perceptions of these associations have remained unknown. For this reason, Inserm's Patients' Association Liaison Group (GRAM) launched the CAIRNET survey in 2012, based on questionnaires and interviews conducted with researchers working at Inserm. The variety of their opinions made it possible to distinguish four profiles, the committed, the pragmatic, the reticent and the distant. Thus 41 % of respondents reported ongoing relationships with at least one association, 72 % for the committed and 16 % for the distant. Although these relationships are formed more easily among researchers involved in clinical activity, they also encourage collaborations between clinicians and basic researchers. The apparently lower degree of involvement of female researchers proved to be associated with a lower level of clinical activity, limited permanent recruitment, and a lower hierarchical status.

Role of the quorum-sensing system in experimental pneumonia due to Pseudomonas aeruginosa in rats.

The virulence of Pseudomonas aeruginosa is partly controlled by the las quorum-sensing system. A rat model of acute pneumonia was used to investigate the pathophysiological impact of this system by comparing the virulence of the wild-type virulent laboratory strain PAO1 with that of its lasR-deleted mutant PAOR. In comparison with PAO1, PAOR was avirulent after an instillation of 106 cfu (mortality rates, 72 versus 0%, respectively; p < 0.0001). A ten-fold higher inoculum slightly increased the mortality rate induced by PAOR (25%), which remained lower than that induced by PAO1 (75%, p = 0.0001). In addition, with both inocula lung and bronchoalveolar lavage bacterial counts were significantly lower in rats infected with PAOR than with PAO1 (p

Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system.

Pseudomonas aeruginosa is an important opportunistic pathogen that produces a variety of cell-associated and secreted virulence factors. P. aeruginosa infections are difficult to treat effectively because of the rapid emergence of antibiotic-resistant strains. In this study, we analyzed whether the amoeba Dictyostelium discoideum can be used as a simple model system to analyze the virulence of P. aeruginosa strains. The virulent wild-type strain PAO1 was shown to inhibit growth of D. discoideum. Isogenic mutants deficient in the las quorum-sensing system were almost as inhibitory as the wild type, while rhl quorum-sensing mutants permitted growth of Dictyostelium cells. Therefore, in this model system, factors controlled by the rhl quorum-sensing system were found to play a central role. Among these, rhamnolipids secreted by the wild-type strain PAO1 could induce fast lysis of D. discoideum cells. By using this simple model system, we predicted that certain antibiotic-resistant mutants of P. aeruginosa should show reduced virulence. This result was confirmed in a rat model of acute pneumonia. Thus, D. discoideum could be used as a simple nonmammalian host system to assess pathogenicity of P. aeruginosa.