Assessing the Pilot Implementation of the Integrated Multimorbidity Care Model in Five European Settings: Results from the Joint Action CHRODIS-PLUS.

Multimorbidity, the coexistence of several chronic conditions in a patient, represents a great challenge for healthcare systems and society. The Integrated Multimorbidity Care Model (IMCM) was recently designed within the Joint Action on chronic diseases and promoting healthy ageing across the life cycle (CHRODIS) to ensure the continuity of care for patients with multimorbidity. The IMCM was implemented in five European pilot sites in Spain, Italy, and Lithuania, within the Joint Action CHRODIS-PLUS. The effect of these pilot interventions was assessed pre- and post-implementation by 17 healthcare managers, using the Assessment of Chronic Illness Care (ACIC) measure, and by 226 patients with the Patient Assessment of Care for Chronic Conditions (PACIC+) survey. The ACIC total score significantly increased (5.23 to 6.71, p = 0.022) after the intervention, with differences across sites. A significant increase in the PACIC+ summary score was found ranging from 3.25 at baseline to 4.03 after the intervention (p < 0.001), and 58% of the sample perceived an improvement in care. Higher PACIC+ scores after the intervention were associated to lower baseline values in the respective PACIC+ dimension and to greater changes in ACIC Part 1 (delivery system organization). The IMCM implementation can help improve the quality of care for patients with multimorbidity.

Microbiological quality of saffron from the main producer countries.

A microbiological study of saffron spice was undertaken in the context of a European research project (Methodologies for Implementing International Standards for Saffron Purity and Quality, the acronym for which is SAFFIC), analyzing 79 samples obtained from the main producer countries, namely Greece, Iran, Italy, Morocco, and Spain. Current microbiological quality criteria are the same as for other spices, but saffron is added in minute quantities during the cooking process, so the health risk associated with microbial contamination might be lower. We did not detect Salmonella either by culture or by PCR methods in any sample, and Escherichia coli was only found in five samples. Enterobacteriaceae were frequently found (70.9% of the samples), but most of them belonged to species of probable environmental origin. Aerobic sporulated bacteria were also common, but only three samples contained Bacillus cereus at low levels (<200 CFU g(-1)). Clostridium perfringens counts were also very low, with only one sample reaching >100 CFU g(-1), an acceptable value. Overall, microbial contamination in saffron was markedly lower than it was in other spices.

A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS.

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings.

Dissecting the transcriptional activation function of the cell wall integrity MAP kinase.

The cell wall integrity signalling MAP kinase of Saccharomyces cerevisiae, Slt2p/Mpk1p, is activated in response to cell wall stress. Slt2 and its mammalian orthologue ERK5 are unusual among MAP kinases, in that they possess the ability to activate transcription of a GAL1-lacZ reporter when fused to the DNA-binding domain of the Gal4 transcription factor. In this study, we demonstrate that transcriptional activation of a Gal4-Slt2p fusion is responsive to cell wall stress and requires phosphorylation of Slt2p. We identify two neighbouring but separable transcription activation domains within the C-terminal half of Slt2p. Additionally, we present data suggesting that intramolecular interactions controlled by phosphorylation of Slt2p regulate the function of these domains, which are masked by the N-terminal catalytic domain under inactive conditions. Finally, we demonstrate that Slt2p self-associates, probably through a glutamine-rich region within the C-terminal half of the protein.

Reciprocal regulation between Slt2 MAPK and isoforms of Msg5 dual-specificity protein phosphatase modulates the yeast cell integrity pathway.

Dual-specificity protein phosphatases (DSPs) are involved in the negative regulation of mitogen-activated protein kinases (MAPKs) by dephosphorylating both threonine- and tyrosine-conserved residues located at the activation loop. Here we show that Msg5 DSP activity is essential for maintaining a low level of signaling through the cell integrity pathway in Saccharomyces cerevisiae. Consistent with a role of this phosphatase on cell wall physiology, cells lacking Msg5 displayed an increased sensitivity to the cell wall-interfering compound Congo Red. We have observed that the N-terminal non-catalytic region of this phosphatase was responsible for binding to the kinase domain of Slt2, the MAPK that operates in this pathway. In vivo and in vitro experiments revealed that both proteins act on each other. Msg5 bound and dephosphorylated activated Slt2. Reciprocally, Slt2 phosphorylated Msg5 as a consequence of the activation of the cell integrity pathway. In addition, alternative use of translation initiation sites at MSG5 resulted in two protein forms that are functional on Slt2 and became equally phosphorylated following activation of this MAPK. Under activating conditions, a decrease in the affinity between Msg5 and Slt2 was observed, leading us to suggest that the mechanism by which Slt2 controls the action of Msg5 was via the modulation of protein-protein interactions. Our results indicate the existence of posttranscriptional mechanisms of regulation of DSPs in yeast and provide new insights into the negative control of the cell integrity pathway.