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    Cost reduction project in a Swiss University Hospital : methods and results of a bottom-up intervention

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    Question under study: High costs, high visibility facilities, such as university hospitals, are prime targets for efforts to control increasing health care costs. Our public university hospital had to reduce its costs by 11 %, and used a participative method to identify possible savings. The methods and results after the 3 years of implementation are critically appraised. Methods: With the methodological help of French consultants, the hospital was divided into 160 analysis units grouped into 6 sectors. Each analysis unit had to describe its tasks and missions, for which a cost was computed. They then had to propose savings up to 22% of the total cost of the unit and evaluate their feasibility and acceptability. The proposals selected by a steering committee had to be implemented within 3 years. Results: Despite important resistances, savings amounting to 11% of the total hospital cost were identified. The 3 years of implementation allowed reaching 78.6% of the total savings target, as some savings proposals had to be delayed or abandoned in order to respect the social contract agreed upon at the beginning of the project. Conclusions : The participative approach was successful in reaching the economic target. However, the necessity of achieving immediate savings for political reasons prevented developing a common philosophy based on the quality of care, which could have led to the adhesion of all employees to the project. Setting a pure economic target might end up destroying the philosophy of a participative project and result in more frustration and grief than success. Contexte: Les structures de soins Ă  coĂ»t Ă©levĂ© et haute visibilitĂ©, comme les hĂŽpitaux universitaires, constituent des cibles de choix dans les efforts de maĂźtrise des coĂ»ts. Le Centre hospitalier universitaire vaudois (CHUV) a dĂ» rĂ©duire ses coĂ»ts de 11%, et utilisĂ© une mĂ©thode participative pour identifier les Ă©conomies potentielles. La mĂ©thode et ses rĂ©sultats aprĂšs 3 ans sont prĂ©sentĂ©s et discutĂ©s. MĂ©thode: Avec le soutien mĂ©thodologique de consultants français, l'hĂŽpital a Ă©tĂ© divisĂ© en 160 unitĂ©s d'analyse groupĂ©es en 6 secteurs. Chaque unitĂ© a dĂ» dĂ©crire ses tĂąches et ses missions, pour lesquelles un coĂ»t a Ă©tĂ© calculĂ©. Elles ont ensuite dĂ» proposer des Ă©conomies allant jusqu'Ă  22% du coĂ»t total de l'unitĂ©, et estimer leur faisabilitĂ© et acceptabilitĂ©. Les propositions retenues par un comitĂ© de pilotage devaient ĂȘtre mises en oeuvre dans les trois annĂ©es suivantes. RĂ©sultats: En dĂ©pit d'importantes rĂ©sistances, des Ă©conomies se montant Ă  11% des coĂ»ts totaux de l'hĂŽpital ont Ă©tĂ© identifiĂ©es. Les 3 ans de mise en oeuvre ont permis d'atteindre 78,6% des Ă©conomies escomptĂ©es. Plusieurs propositions ont dĂ» ĂȘtre diffĂ©rĂ©es ou abandonnĂ©es, afin de prĂ©server les conditions sociales fixĂ©es au dĂ©but du projet. Conclusion: Une approche participative a permis d'atteindre la cible d'Ă©conomies. Toutefois la nĂ©cessitĂ© de rĂ©aliser des Ă©conomies immĂ©diates pour des raisons politiques a empĂȘchĂ© l'Ă©mergence d'une philosophie commune fondĂ©e sur la qualitĂ© des soins, qui aurait permis l'adhĂ©sion de tous les employĂ©s du projet. Fixer des objectifs Ă©conomiques purs peut compromettre un projet participatif, et engendrer davantage de frustration et de rancoeur que de succĂšs. [Auteurs]]]> Hospital Costs ; Hospitals, University ; Cost Control ; Cost Savings eng oai:serval.unil.ch:BIB_FF72071F4B1B 2022-05-07T01:30:55Z openaire documents <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_FF72071F4B1B Genetic and phenotypic attributes of splenic marginal zone lymphoma. info:doi:10.1182/blood.2021012386 info:eu-repo/semantics/altIdentifier/doi/10.1182/blood.2021012386 info:eu-repo/semantics/altIdentifier/pmid/34653238 Bonfiglio, F. Bruscaggin, A. Guidetti, F. Terzi di Bergamo, L. Faderl, M. Spina, V. Condoluci, A. Bonomini, L. Forestieri, G. Koch, R. Piffaretti, D. Pini, K. Pirosa, M.C. Cittone, M.G. Arribas, A. Lucioni, M. Ghilardi, G. Wu, W. Arcaini, L. Baptista, M.J. Bastidas, G. Bea, S. Boldorini, R. Broccoli, A. Buehler, M.M. Canzonieri, V. Cascione, L. Ceriani, L. Cogliatti, S. Corradini, P. Derenzini, E. Devizzi, L. Dietrich, S. Elia, A.R. Facchetti, F. Gaidano, G. Garcia, J.F. Gerber, B. Ghia, P. Gomes da Silva, M. Gritti, G. Guidetti, A. Hitz, F. Inghirami, G. Ladetto, M. Lopez-Guillermo, A. Lucchini, E. Maiorana, A. Marasca, R. Matutes, E. Meignin, V. Merli, M. Moccia, A. Mollejo, M. Montalban, C. Novak, U. Oscier, D.G. Passamonti, F. Piazza, F. Pizzolitto, S. Rambaldi, A. Sabattini, E. Salles, G. Santambrogio, E. ScarfĂČ, L. Stathis, A. StĂŒssi, G. Geyer, J.T. Tapia, G. Tarella, C. Thieblemont, C. Tousseyn, T. Tucci, A. Vanini, G. Visco, C. Vitolo, U. Walewska, R. Zaja, F. Zenz, T. Zinzani, P.L. Khiabanian, H. Calcinotto, A. Bertoni, F. Bhagat, G. Campo, E. De Leval, L. Dirnhofer, S. Pileri, S.A. Piris, M.A. Traverse-Glehen, A. Tzankov, A. Paulli, M. Ponzoni, M. Mazzucchelli, L. Cavalli, F. Zucca, E. Rossi, D. info:eu-repo/semantics/article article 2022-02-03 Blood, vol. 139, no. 5, pp. 732-747 info:eu-repo/semantics/altIdentifier/eissn/1528-0020 urn:issn:0006-4971 <![CDATA[Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-ÎșB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments

    Metabolomic evaluation of PGPR defence priming in wheat (Triticum aestivum L.) cultivars infected with Puccinia striiformis f. sp. tritici (stripe rust)

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    Plant-microbe interactions are a phenomenal display of symbiotic/parasitic relationships between living organisms. Plant growth-promoting rhizobacteria (PGPR) are some of the most widely investigated plant-beneficial microbes due to their capabilities in stimulating plant growth and development and conferring protection to plants against biotic and abiotic stresses. As such, PGPR-mediated plant priming/induced systemic resistance (ISR) has become a hot topic among researchers, particularly with prospects of applications in sustainable agriculture. The current study applies untargeted ultra-high performance liquid chromatography-high-definition mass spectrometry (UHPLC-HDMS) to investigate PGPR-based metabolic reconfigurations in the metabolome of primed wheat plants against Puccinia striiformis f. sp. tricti (Pst). A seed bio-priming approach was adopted, where seeds were coated with two PGPR strains namely Bacillus subtilis and Paenibacillus alvei (T22) and grown under controlled conditions in a glasshouse. The plants were infected with Pst one-week post-germination, followed by weekly harvesting of leaf material. Subsequent metabolite extraction was carried out for analysis on a UHPLC-HDMS system for data acquisition. The data was chemometrically processed to reveal the underlying trends and data structures as well as potential signatory biomarkers for priming against Pst. Results showed notable metabolic reprogramming in primary and secondary metabolism, where the amino acid and organic acid content of primed-control, primed-challenged and non-primed-challenged plants were differentially reprogrammed. Similar trends were observed from the secondary metabolism, in which primed plants (particularly primed-challenged) showed an up-regulation of phenolic compounds (flavonoids, hydroxycinnamic acids-HCAs- and HCA amides) compared to the non-primed plants. The metabolomics-based semi-quantitative and qualitative assessment of the plant metabolomes revealed a time-dependent metabolic reprogramming in primed-challenged and primed-unchallenged plants, indicating the metabolic adaptations of the plants to stripe rust infection over time

    Bayesian networks for disease diagnosis: What are they, who has used them and how?

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    A Bayesian network (BN) is a probabilistic graph based on Bayes' theorem, used to show dependencies or cause-and-effect relationships between variables. They are widely applied in diagnostic processes since they allow the incorporation of medical knowledge to the model while expressing uncertainty in terms of probability. This systematic review presents the state of the art in the applications of BNs in medicine in general and in the diagnosis and prognosis of diseases in particular. Indexed articles from the last 40 years were included. The studies generally used the typical measures of diagnostic and prognostic accuracy: sensitivity, specificity, accuracy, precision, and the area under the ROC curve. Overall, we found that disease diagnosis and prognosis based on BNs can be successfully used to model complex medical problems that require reasoning under conditions of uncertainty.Comment: 22 pages, 5 figures, 1 table, Student PhD first pape

    Impact of polyester and cotton microfibers on growth and sublethal biomarkers in juvenile mussels

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    Anthropogenic microfibres are a prevalent, persistent and globally distributed form of marine debris. Evidence of microfibre ingestion has been demonstrated in a range of organisms, including Mytilus spp. (mussels), but the extent of any impacts on these organisms are poorly understood. This study investigates, for the first time, the effect of exposing juvenile mussels to polyester and cotton microfibres at environmentally relevant concentrations (both current and predicted future scenarios) over a chronic timescale (94 days). Sublethal biomarkers included growth rate, respiration rate and clearance rate. Mussels were exposed to polyester (median length 149 ”m) and cotton (median length 132 ”m) microfibres in three treatments: polyester (~ 8 fibres L−1), polyester (~ 80 fibres L−1) and cotton (~ 80 fibres L−1). Mussels exposed to 80 polyester or cotton microfibres L−1 exhibited a decrease in growth rate of 35.6% (polyester) and 18.7% (cotton), with mussels exposed to ~ 80 polyester microfibres L−1 having a significantly lower growth rate than the control population (P < 0.05). This study demonstrates that polyester microfibres have the potential to adversely impact upon mussel growth rates in realistic future scenarios, which may have compounding effects throughout the marine ecosystem and implications for commercial viability

    Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats

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    Fetal undernutrition predisposes to hypertension development. Since nitric oxide (NO) is a key factor in blood pressure control, we aimed to investigate the role of NO alterations in hypertension induced by fetal undernutrition in rats. Male and female offspring from dams exposed to undernutrition during the second half of gestation (MUN) were studied at 21 days (normotensive) and 6 months of age (hypertension developed only in males). In aorta, we analyzed total and phosphorylated endothelial NO synthase (eNOS, p-eNOS), 3-nitrotyrosine (3-NT), and Nrf2 (Western blot). In plasma we assessed l-arginine, asymmetric and symmetric dimethylarginine (ADMA, SDMA; LC–MS/MS), nitrates (NOx, Griess reaction), carbonyl groups, and lipid peroxidation (spectrophotometry). In iliac arteries, we studied superoxide anion production (DHE staining, confocal microscopy) and vasodilatation to acetylcholine (isometric tension). Twenty-one-day-old MUN offspring did not show alterations in vascular e-NOS or 3NT expression, plasma l-Arg/ADMA ratio, or NOx. Compared to control group, 6-month-old MUN rats showed increased aortic expression of p-eNOS/eNOS and 3-NT, being Nrf2 expression lower, elevated plasma l-arginine/ADMA, NOx and carbonyl levels, increased iliac artery DHE staining and reduced acetylcholine-mediated relaxations. These alterations in MUN rats were sex-dependent, affecting males. However, females showed some signs of endothelial dysfunction. We conclude that increased NO production in the context of a pro-oxidative environment, leads to vascular nitrosative damage and dysfunction, which can participate in hypertension development in MUN males. Females show a better adaptation, but signs of endothelial dysfunction, which can explain hypertension in ageingOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Natur

    Mushroom ÎČ-glucan and polyphenol formulations as natural immunity boosters and balancers: nature of the application

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    Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet. These valuable organisms are more than food, they fi t in perfectly as a novel market group known as nutra-mycoceuticals. Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry. Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients. This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers, ÎČ-glucans. The literature data on their bioavailability, metabolic transformations, preclinical and human clinical research, and safety are discussed. Immunomodulatory mechanisms of polyphenol ingredients are also considered. These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity. Finally, we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity

    Intrathecal versus peripheral inflammatory protein profile in MS patients at diagnosis: a comprehensive investigation on serum and CSF

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    Intrathecal inflammation plays a key role in the pathogenesis of multiple sclerosis (MS). To better elucidate its relationship with peripheral inflammation, we investigated the correlation between cerebrospinal fluid (CSF) and serum levels of 61 inflammatory proteins. Paired CSF and serum samples were collected from 143 treatment-naĂŻve MS patients at diagnosis. A customized panel of 61 inflammatory molecules was analyzed by a multiplex immunoassay. Correlations between serum and CSF expression levels for each molecule were performed by Spearman's method. The expression of sixteen CSF proteins correlated with their serum expression (p-value &lt; 0.001): only five molecules (CXCL9, sTNFR2, IFNα2, Pentraxin-3, and TSLP) showed a Rho value &gt;0.40, suggesting moderate CSF/serum correlation. No correlation between inflammatory serum patterns and Qalb was observed. Correlation analysis of serum expression levels of these sixteen proteins with clinical and MRI parameters pinpointed a subset of five molecules (CXCL9, sTNFR2, IFNα2, IFNÎČ, and TSLP) negatively correlating with spinal cord lesion volume. However, following FDR correction, only the correlation of CXCL9 remained significant. Our data support the hypothesis that the intrathecal inflammation in MS only partially associates with the peripheral one, except for the expression of some immunomodulators that might have a key role in the initial MS immune response

    Type 2 Diabetes Mellitus and its comorbidity, Alzheimer’s disease: Identifying critical microRNA using machine learning

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    MicroRNAs (miRNAs) are critical regulators of gene expression in healthy and diseased states, and numerous studies have established their tremendous potential as a tool for improving the diagnosis of Type 2 Diabetes Mellitus (T2D) and its comorbidities. In this regard, we computationally identify novel top-ranked hub miRNAs that might be involved in T2D. We accomplish this via two strategies: 1) by ranking miRNAs based on the number of T2D differentially expressed genes (DEGs) they target, and 2) using only the common DEGs between T2D and its comorbidity, Alzheimer’s disease (AD) to predict and rank miRNA. Then classifier models are built using the DEGs targeted by each miRNA as features. Here, we show the T2D DEGs targeted by hsa-mir-1-3p, hsa-mir-16-5p, hsa-mir-124-3p, hsa-mir-34a-5p, hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-129-2-3p, and hsa-mir-146a-5p are capable of distinguishing T2D samples from the controls, which serves as a measure of confidence in the miRNAs’ potential role in T2D progression. Moreover, for the second strategy, we show other critical miRNAs can be made apparent through the disease’s comorbidities, and in this case, overall, the hsa-mir-103a-3p models work well for all the datasets, especially in T2D, while the hsa-mir-124-3p models achieved the best scores for the AD datasets. To the best of our knowledge, this is the first study that used predicted miRNAs to determine the features that can separate the diseased samples (T2D or AD) from the normal ones, instead of using conventional non-biology-based feature selection methods

    Pathogenesis and treatment of chronic rhinosinusitis from the perspective of sinonasal epithelial dysfunction

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    BackgroundChronic rhinosinusitis (CRS) is a clinical syndrome primarily characterized by long-term mucosal inflammation of the nasal cavity and sinuses. The pathogenesis of CRS is still unclear due to its high heterogeneity. A number of studies have recently focused on the sinonasal epithelium. Thus, there has been a quantum leap in awareness of the role of the sinonasal epithelium, which is now understood as an active functional organ rather than simply an inert mechanical barrier. Undoubtedly, epithelial dysfunction plays a vital role in the onset and development of CRS.ObjectiveIn this article, we discuss the potential contribution of sinonasal epithelium dysfunction to CRS pathogenesis and explore a few current and developing therapeutic options targeting the sinonasal epithelium.ResultsImpaired mucociliary clearance (MCC) and an abnormal sinonasal epithelial barrier are usually considered to be the main causative factors in CRS. Epithelial-derived bioactive substances, such as cytokines, exosomes, and complements, play a vital role in the regulation of innate and adaptive immunity and contribute to the pathophysiological alterations of CRS. The phenomena of epithelial–mesenchymal transition (EMT), mucosal remodeling, and autophagy observed in CRS offer some novel insights into the pathogenesis of this disease. In addition, existing treatment options targeting disorder of sinonasal epithelium can help to relieve the main symptoms associated with CRS to some extent.ConclusionThe presence of a normal epithelium is fundamental for maintaining homeostasis in the nasal and paranasal sinuses. Here, we describe various aspects of the sinonasal epithelium and highlight the contributions of epithelial dysfunction to CRS pathogenesis. Our review provides sound evidence of the need for in-depth study of the pathophysiological alterations of this disease and for the development of novel epithelium-targeting alternative treatments