Trajectoires de soins chez les patients souffrants d’une maladie pulmonaire obstructive chronique

Pour les patients souffrants d’une maladie pulmonaire obstructive chronique (MPOC), il existe de nombreuses façons de cheminer dans le système de santé québécois. Toutefois, ces trajectoires de soins (TS) ne sont pas bien décrites dans la littérature et leur impact sur la mortalité demeure inconnu. Les objectifs du projet sont d’identifier et de caractériser les TS des patients MPOC, puis d’en évaluer l’association avec la mortalité. Pour ce faire, nous avons créé une cohorte rétrospective de 3352 Québécois, atteints d’une MPOC, ayant répondu à l’Enquête sur la santé des collectivités canadiennes (ESCC) entre 2007 et 2013. Trois banques de données administratives du Québec (RAMQ, MED-ÉCHO et RED/D) ont été jumelées aux données de l’ESCC pour mesurer les TS sur 2 ans, et ce, à l’aide de l’analyse de séquences. Les caractéristiques des patients ont été comparées entre les TS grâce au test du khi-2 et au V-test. Nous avons réalisé des modèles de Cox, bruts et ajustés pour les facteurs confondants, dans le but d’évaluer l’association entre les TS et la mortalité sur un maximum de 5 ans. Suite à l’analyse de séquences, 6 TS ont été identifiées : 1) faible utilisation des services de santé: toutes causes (44,7%); 2) utilisation moyenne des services de santé: toutes causes (27,7%); 3) grande utilisation des services de santé surtout chez l’omnipraticien: causes respiratoires (4,4%); 4) grande utilisation des services de santé surtout chez l’omnipraticien: autres causes que respiratoires (6,5%); 5) grande utilisation des services de santé surtout chez le spécialiste: autres causes que respiratoires (6,3%); 6) grande utilisation des services de santé surtout en soins aigus: toutes causes (10,4%). Les caractéristiques qui ont permis de distinguer l’appartenance des patients à une TS sont l’âge, le statut tabagique et matrimonial, le niveau d’éducation, l’indice de comorbidité et la santé perçue. Les patients des TS 2, 4 et 6 étaient significativement plus à risque de décès que les patients de la TS 1. Ainsi, une meilleure compréhension des TS et de leur association avec la mortalité pourrait aider les décideurs et les cliniciens à mieux identifier les patients à risque et allouer judicieusement les services et les ressources afin d’optimiser la gestion de la MPOC.Patients with chronic obstructive pulmonary disease (COPD) navigate in the healthcare system in different ways. However, those trajectories of care (ToCs) are not well described and their impact on mortality is unknown. Therefore, our research project’s objectives were to identify and characterize the ToCs of COPD patients and to evaluate the association between those ToCs and mortality. To do so, we conducted a retrospective cohort study with 3352 COPD patients living in Quebec, who answered the Canadian Community Health Survey between 2007 and 2013. Three Quebec health administrative databases (RAMQ, MED-ÉCHO and RED/D) were linked to the survey data to measure ToCs over a 2-year period, using sequence analysis. Patients’ characteristics were compared between ToCs with chi-square and V tests. At last, we evaluated the association between ToCs and death over a maximum of 5 years, using Cox models adjusted for potential confounders. Following sequence analysis, 6 ToCs were identified: 1) low use of healthcare services: all causes (44.7%); 2) medium use of healthcare services: all causes (27.7%); 3) high use of healthcare services mainly with general practitioners (GPs): respiratory causes (4.4%); 4) high use of healthcare services mainly with GPs: other causes than respiratory (6.5%); 5) high use of healthcare services mainly with specialists: other causes than respiratory (6.3%) and 6) high use of healthcare services mainly in acute care: all causes (10.4%). Patients’ characteristics that best-described the trajectories’ membership were age, smoking status, marital status, level of education, comorbidity index and, patients’ perceived health. Patients belonging to trajectories 2, 4 and 6 were significantly more at risk of death than patients belonging to the first trajectory. Thus, a better understanding of the ToCs in Quebec and their association with mortality could help policymakers and clinicians for the allocation of care and health resources, thereby promoting least fatal ToCs

The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells

Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express the lectin langerin and that reside in their immature state in epidermis. Paradoxically, in mice permitting diphtheria toxin (DT)–mediated ablation of LCs, epidermal LCs reappeared with kinetics that lagged behind that of their putative progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed that a major fraction of the langerin+, skin-derived DCs found in LNs originates from a developmental pathway that is independent from that of epidermal LCs. This pathway, the existence of which was unexpected, originates in the dermis and gives rise to langerin+ dermal DCs (DDCs) that should not be confused with epidermal LCs en route to LNs. It explains that after DT treatment, some langerin+, skin-derived DCs reappear in LNs long before LC-derived DCs. Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin+ DDCs were found to coexist in wild-type mice. Moreover, DT-mediated ablation of epidermal LCs opened otherwise filled niches and permitted repopulation of adult noninflammatory epidermis with BM-derived LCs. Our results stress that the langerin+ DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models

Competition from emerging countries, international relocation and their impacts on employment

International relocation has become a topical issue in recent months, in France as elsewhere in Europe. This working paper is a set of four articles. Guillaume Daudin and Sandrine Levasseur provide an assessment of the impact of international relocation on French employment. Georges Pujals deals with offshore outsourcing in the financial sector from a European perspective. Catherine Mathieu and Henri Sterdyniak focus on policy measures taken or to be taken in face of job losses in the French economy. Jean-Luc Gaffard and Michel Quéré show that free competition alone is not optimal for European economies and that a combination of structural and growth oriented macroeconomic policies is needed

GENETICS OF PARASITIC INFECTIONS

ABSTRACT: Parasites cause much suffering mainly in countries of the southern hemisphere. Hundreds of millions of individuals are infected by schistosomes, leishmanias, plasmodiums, trypanosomes, and various other parasites, and severe clinical disease occurs in a sizable fraction of the infected population causing death and severe sequelae. The outcome, asymptomatic, subclinical or clinical disease, of an infection depends mostly on the parasite and on its host. Several groups analyzing the genetics of human susceptibility to parasites have began to identify the critical steps of the pathogenic mechanisms in a few parasitic infections such as malaria and schistosomiasis. The present article, which is not meant to be an exhaustive review of the field, illustrates the progresses made in this field from pioneer studies in animals to works in endemic populations using modern strategies of human genetics. A variety of parasites cause chronic infections that last for long periods of time in their human host without much clinical symptoms; in some subjects, however, parasites cause severe disease. These pathological disorders may become apparent after 10 to 20 years of infection as in subjects infected by Schistosoma mansoni or by Trypanosoma cruzi, or within a few weeks of infection in patients affected by Leishmania donovani or by Plasmodium falciparum. Various studies have attempted to identify the factors that cause disease to develop in only a fraction of the population exposed to parasites. Much attention has been given to the environment because parasite transmission depends markedly on environmental factors including vector density, vector distribution, and parasite virulence. Parasites, because they have a large genome, have developed very sophisticated mechanisms, like antigenic variation, to escape immune destruction. The plasticity of the parasite genome is so large that it is tempting to link the different clinical and subclinical forms caused by the infection to the existence of clones of different virulence/pathogenicity in the parasite population. This view is unlikely to apply to parasites such as Schistosoma mansoni that, in a given endemic area, express homogenous antigenic and pathogenic properties; it might apply, however, to infections by protozoan parasites such as plasmodium or leishmanias that are highly polymorph and multiply rapidly within their human hosts allowing for emerging variants. The importance of host genetics in disease development has been difficult to assess because of the multiplicity of the environmental factors, including parasite heterogeneity, that may determine disease. The role of genetics was first addressed in experimental models in which environmental variables can be controlled and measured. Animal studies allowed the discovery of the most interesting NRAMP1 gene, which likely plays an important role in innate immunity against intracellular pathogens. Studies on human genetics and susceptibility to parasitic infections began with observations of the high prevalence of mutated alleles of the ␤ globin gene in areas of malaria high endemicity, leading to the hypothesis that these alleles were protective against severe malaria. This observation was then further supported by the results of case control studies. Comparable strategies were used to demonstrate that certain HLA 1 haplotypes The present article will summarize the observations made in schistosome, leishmania and plasmodium infections. All three parasites are a major threat for human health in the southern hemisphere Genetics of Leishmania Infections in Experimental Models The first evidence for an important role of genetic factors in the control of infections was reported in experimental models. Studies of animals have the advantage over human studies to allow for the control of environmental factors and of the parasite (heterogeneity, size of the inoculum, etc.). In addition, genetic analysis is easier than in humans since animals can be bred. As discussed in another chapte

Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops

Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3×108 cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer’s patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer’s patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac-derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80(hi)CD11b(lo) primitive macrophages and Ly6C(hi)CD11b(hi) fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF-deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life

Emploi des seniors : les leçons des pays de réussite

Du fait du vieillissement de la population, l’emploi des seniors devient un enjeu primordial de la politique du travail dans les pays européens. Retarder l’âge de fin d’activité permettrait d’augmenter le niveau de production et d’équilibrer les systèmes de retraite sans réduire le niveau des retraites. Encore faut-il que les seniors soient effectivement employés. Les réformes en cours des systèmes de retraite font courir le risque qu’une partie importante des travailleurs seniors ne trouvent pas d’emploi et soient contraints de partir à la retraite avec un faible niveau de pension. Aussi, l’article étudie-t-il la stratégie suivie par les pays qui ont réussi à maintenir un taux d’emploi des seniors élevé (Suède, Danemark, Royaume-Uni) ou qui ont connu des relèvements importants de ce taux durant ces dernières années (Finlande, Pays-Bas). Ceux-ci sont généralement des pays proches du plein emploi, même si les facteurs de plein emploi diffèrent : temps partiel, stratégie macroéconomique qui allie recherche de la compétitivité et politique expansionniste, libéralisation du marché du travail ou gestion par les partenaires sociaux, développement d’emplois sociaux. Ils ont bénéficié d’institutions favorables (faiblesse des hausses de salaire à l’ancienneté, meilleures conditions de travail). La stratégie libérale diminue les retraites, ce qui incite les seniors à travailler, quitte à accepter des salaires plus bas, ce qui est permis par la flexibilité du marché du travail. La stratégie des pays nordiques, le vieillissement actif, organise une mobilisation sociale afin d’augmenter les emplois disponibles pour les seniors et d’inciter ceux-ci à prolonger leurs carrières : amélioration des conditions de travail, formation permanente, refonte des carrières, lutte contre les discriminations liées à l’âge, campagne de sensibilisation, accords au niveau des branches et des entreprises. La France n’a guère cette tradition d’accord entre État et partenaires sociaux. Or un compromis social fructueux est un préalable nécessaire. Il devrait comporter une différentiation des conditions de départ à la retraite selon les professions et des garanties sur l’évolution du taux de remplacement.Older workers’ employment rates are high in three EU countries (Sweden, Denmark, UK) and have risen substantially in Finland and the Netherlands in recent years. These five countries are also close to full employment, even if the factors behind their employment performance differ. Labour market institutions are a factor (moderate wage increases for older workers, better working conditions). In countries with a liberal strategy, early-retirement schemes have been abolished; older workers are requested to work and accept lower wages, which is allowed by labour market flexibility. In Nordic countries, the active ageing strategy relies on a social mobilisation to increase jobs available for older workers and to give them incentives to work longer. The article concludes that France should consider the experience from Nordic countries to set up a fruitful social compromise