Obstructive sleep apnoea: Improving healthcare services by combining process modelling and population analysis.

CONTEXT: Disease management broke through in the early 1990s to counterbalance hyper-specialization with a more comprehensive approach. Its role became immediately relevant in chronic conditions and, consequently, in Obstructive Sleep Apnoea (OSA). This is a common chronic condition for which is important to organise services at the local level, taking into account organisational factors and the characteristics of the assisted population. OBJECTIVES: The aim of this work is to propose and apply, coherently with a disease management approach, a combination of healthcare process modelling and population analysis as a way to identify critical issues and explore shared solutions. METHODS: A multidisciplinary working group was created with scholars who are skilled in process analysis, statistics and medicine. Through semi-structured interviews and on-site meetings, healthcare processes were represented with a standard graphical language: Unified Modeling Language™. Population analysis was based on statistical analysis performed on a 5-year retrospective cohort assisted by a Community Pulmonary Service. RESULTS: A shared graphic presentation of the current healthcare process and the results of the statistical analyses constituted the knowledge base to identify critical issues and recommend corresponding solutions, which include: a) refine the local patient database with additional details on comorbidities and risk factors; b) support a greater involvement of "gate-keepers" in the screening phase; c) provide practical tools for the definition of strategies to increment the adherence to therapy; d) include recommendations for physical exercise and interdisciplinary cooperation; and e) define process indicators for measuring the quality of the screening and therapeutic phases. CONCLUSION: The concomitant analyses of formalised processes and critical risk factors represent a useful approach for systematically identifying areas of improvement in healthcare processes and allow us to discuss solutions. Moreover, the specific adoption of UML® for graphical modelling and representation of patient care processes allows us to formalise them by adopting a standard language that can be taken as the basis for implementing web services to support the execution of the modelled processes.

Identification of commensal bacterial strains that modulate Yersinia enterocolitica and dextran sodium sulfate-induced inflammatory responses: implications for the development of probiotics.

An increasing body of evidence suggests that probiotic bacteria are effective in the treatment of enteric infections, although the molecular basis of this activity remains elusive. To identify putative probiotics, we tested commensal bacteria in terms of their toxicity, invasiveness, inhibition of Yersinia-induced inflammation in vitro and in vivo, and modulation of dextran sodium sulfate (DSS)-induced colitis in mice. The commensal bacteria Escherichia coli, Bifidobacterium adolescentis, Bacteroides vulgatus, Bacteroides distasonis, and Streptococcus salivarius were screened for adhesion to, invasion of, and toxicity for host epithelial cells (EC), and the strains were tested for their ability to inhibit Y. enterocolitica-induced NF-kappaB activation. Additionally, B. adolescentis was administered to mice orally infected with Y. enterocolitica and to mice with mucosae impaired by DSS treatment. None of the commensal bacteria tested was toxic for or invaded the EC. B. adolescentis, B. distasonis, B. vulgatus, and S. salivarius inhibited the Y. enterocolitica-induced NF-kappaB activation and interleukin-8 production in EC. In line with these findings, B. adolescentis-fed mice had significantly lower results for mean pathogen burden in the visceral organs, intestinal tumor necrosis factor alpha mRNA expression, and loss of body weight upon oral infection with Y. enterocolitica. In addition, the administration of B. adolescentis decelerated inflammation upon DSS treatment in mice. We suggest that our approach might help to identify new probiotics to be used for the treatment of inflammatory and infectious gastrointestinal disorders.

Lactobacillus fermentum attenuates the proinflammatory effect of Yersinia enterocolitica on human epithelial cells.

BACKGROUND: Lactobacilli represent a major component of the human microbiota. In this study we investigated whether and how Lactobacillus fermentum inhibits the proinflammatory responses of human epithelial cells on Yersinia enterocolitica infection. METHODS: Human epithelial cells were exposed to Y. enterocolitica pYV(-) or L. fermentum or to both strains, combinations of heat-killed L. fermentum or supernatant of L. fermentum cultures and Y. enterocolitica. The modulation of Y. enterocolitica induced IL-8 levels in the culture supernatants was determined and activation of Rac, p38, and NF-kappaB was investigated. RESULTS: Exposure of human epithelial cells to L. fermentum does not induce NF-kappaB activation and subsequent IL-8 secretion in HeLa cells, whereas Y. enterocolitica induces NF-kappaB activation and high levels of IL-8. Viable L. fermentum, supernatant of L. fermentum cultures, but not heat-killed L. fermentum, inhibited IL-8 secretion of HeLa cells triggered by Y. enterocolitica. Lactobacillus fermentum-exposed HeLa cells showed decreased Rac, p38, and NF-kappaB activation after Y. enterocolitica infection. Treatment of L. fermentum supernatants with phospholipase C abolished the inhibitory effect, indicating that a secreted phospholipid mediates the antiinflammatory properties of L. fermentum. Adhesion to or invasion of Y. enterocolitica into epithelial cells was not altered by coincubation with L. fermentum. CONCLUSION: Our results lead to the conclusion that L. fermentum inhibits the Y. enterocolitica-induced IL-8 production by a possibly secreted phospholipid of <10 kDa molecular weight. These data suggest that L. fermentum may have probiotic properties modulating intestinal inflammatory responses and might offer new therapeutic strategies in the treatment of intestinal inflammatory diseases.