Evaluation of integrated care services in Catalonia: population-based and service-based real-life deployment protocols

Background: Comprehensive assessment of integrated care deployment constitutes a major challenge to ensure quality, sustainability and transferability of both healthcare policies and services in the transition toward a coordinated service delivery scenario. To this end, the manuscript articulates four different protocols aiming at assessing large-scale implementation of integrated care, which are being developed within the umbrella of the regional project Nextcare (2016–2019), undertaken to foster innovation in technologically-supported services for chronic multimorbid patients in Catalonia (ES) (7.5 M inhabitants). Whereas one of the assessment protocols is designed to evaluate population-based deployment of care coordination at regional level during the period 2011–2017, the other three are service-based protocols addressing: i) Home hospitalization; ii) Prehabilitation for major surgery; and, iii) Community-based interventions for frail elderly chronic patients. All three services have demonstrated efficacy and potential for health value generation. They reflect different implementation maturity levels. While full coverage of the entire urban health district of Barcelona-Esquerra (520 k inhabitants) is the main aim of home hospitalization, demonstration of sustainability at Hospital Clinic of Barcelona constitutes the core goal of the prehabilitation service. Likewise, full coverage of integrated care services addressed to frail chronic patients is aimed at the city of Badalona (216 k inhabitants). Methods: The population-based analysis, as well as the three service-based protocols, follow observational and experimental study designs using a non-randomized intervention group (integrated care) compared with a control group (usual care) with a propensity score matching method. Evaluation of cost-effectiveness of the interventions using a Quadruple aim approach is a central outcome in all protocols. Moreover, multi-criteria decision analysis is explored as an innovative method for health delivery assessment. The following additional dimensions will also be addressed: i) Determinants of sustainability and scalability of the services; ii) Assessment of the technological support; iii) Enhanced health risk assessment; and, iv) Factors modulating service transferability. Discussion: The current study offers a unique opportunity to undertake a comprehensive assessment of integrated care fostering deployment of services at regional level. The study outcomes will contribute refining service workflows, improving health risk assessment and generating recommendations for service selection.publishedVersio

Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model

Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH

Effectiveness of PRECEDE model for health education on changes and level of control of HbA1c, blood pressure, lipids, and body mass index in patients with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Individual health education is considered to be essential in the overall care of patients with type 2 diabetes (DM2), although there is some uncertainty regarding its metabolic control benefits. There have been very few randomized studies on the effects of individual education on normal care in DM2 patients with a control group, and none of these have assessed the long-term results. Therefore, this study aims to use this design to assess the effectiveness of the PRECEDE (Predisposing, Reinforcing, Enabling, Causes in Educational Diagnosis, and Evaluation) education model in the metabolic control and the reduction of cardiovascular risk factors, in patients with type 2 diabetes.</p> <p>Methods</p> <p>An open community effectiveness study was carried out in 8 urban community health centers in the North-East Madrid Urban Area (Spain). Six hundred patients with DM2 were randomized in two groups: PRECEDE or conventional model for health promotion education. The main outcome measures were glycated hemoglobin A1c, body mass index (BMI), blood pressure, lipids and control criteria during the 2-year follow-up period.</p> <p>Results</p> <p>Glycated hemoglobin A1c and systolic blood pressure (SBP) levels decreased significantly in the PRECEDE group (multivariate analysis of covariance, with baseline glycated hemoglobin A1c, SBP, and variables showing statistically significant differences between groups at baseline visits). The decrease levels in diastolic blood pressure (DBP), triglycerides and LDL cholesterol were nonsignificant. PRECEDE increased compliance in all control criteria, except for LDL cholesterol. BMI did not change during the study in either of the two models analyzed.</p> <p>Conclusions</p> <p>PRECEDE health education model is a useful method in the overall treatment in patients with type 2 diabetes, which contributes to decrease glycated hemoglobin A1c and SBP levels and increase the compliance in all the control criteria, except for LDL cholesterol.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01316367">NCT01316367</a></p

Inferring the Regulatory Network of the miRNA-mediated Response to Biotic and Abiotic Stress in Melon

[EN] Background: MiRNAs have emerged as key regulators of stress response in plants, suggesting their potential as candidates for knock-in/out to improve stress tolerance in agricultural crops. Although diverse assays have been performed, systematic and detailed studies of miRNA expression and function during exposure to multiple environments in crops are limited. Results: Here, we present such pioneering analysis in melon plants in response to seven biotic and abiotic stress conditions. Deep-sequencing and computational approaches have identified twenty-four known miRNAs whose expression was significantly altered under at least one stress condition, observing that down-regulation was preponderant. Additionally, miRNA function was characterized by high scale degradome assays and quantitative RNA measurements over the intended target mRNAs, providing mechanistic insight. Clustering analysis provided evidence that eight miRNAs showed a broad response range under the stress conditions analyzed, whereas another eight miRNAs displayed a narrow response range. Transcription factors were predominantly targeted by stressresponsive miRNAs in melon. Furthermore, our results show that the miRNAs that are down-regulated upon stress predominantly have as targets genes that are known to participate in the stress response by the plant, whereas the miRNAs that are up-regulated control genes linked to development. Conclusion: Altogether, this high-resolution analysis of miRNA-target interactions, combining experimental and computational work, Illustrates the close interplay between miRNAs and the response to diverse environmental conditions, in melon.The authors thank Dr. A. Monforte for providing melon seeds and Dra. B. Pico (Cucurbits Group - COMAV) for providing melon seeds and Monosporascus isolate respectively. This work was supported by grants AGL2016-79825-R, BIO2014-61826-EXP (GG), and BFU2015-66894-P (GR) from the Spanish Ministry of Economy and Competitiveness (co-supported by FEDER). The funders had no role in the experiment design, data analysis, decision to publish, or preparation of the manuscript.Sanz-Carbonell, A.; Marques Romero, MC.; Bustamante-González, AJ.; Fares Riaño, MA.; Rodrigo Tarrega, G.; Gomez, GG. (2019). Inferring the Regulatory Network of the miRNA-mediated Response to Biotic and Abiotic Stress in Melon. BMC Plant Biology. 1-17. https://doi.org/10.1186/s12870-019-1679-0S117Zhang B. MicroRNAs: a new target for improving plant tolerance to abiotic stress. J Exp Bot. 2015;66:1749–61.Zhu JK. Abiotic stress signaling and responses in plants. Cell. 2016;167:313–24.Bielach A, Hrtyan M, Tognetti VB. Plants under stress: involvement of auxin and Cytokinin. Int J Mol Sci. 2017;4(18):7.Zarattini M, Forlani G. 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Validation of diabetes mellitus and hypertension diagnosis in computerized medical records in primary health care

<p>Abstract</p> <p>Background</p> <p>Computerized Clinical Records, which are incorporated in primary health care practice, have great potential for research. In order to use this information, data quality and reliability must be assessed to prevent compromising the validity of the results.</p> <p>The aim of this study is to validate the diagnosis of hypertension and diabetes mellitus in the computerized clinical records of primary health care, taking the diagnosis criteria established in the most prominently used clinical guidelines as the gold standard against which what measure the sensitivity, specificity, and determine the predictive values.</p> <p>The gold standard for diabetes mellitus was the diagnostic criteria established in 2003 American Diabetes Association Consensus Statement for diabetic subjects. The gold standard for hypertension was the diagnostic criteria established in the Joint National Committee published in 2003.</p> <p>Methods</p> <p>A cross-sectional multicentre validation study of diabetes mellitus and hypertension diagnoses in computerized clinical records of primary health care was carried out. Diagnostic criteria from the most prominently clinical practice guidelines were considered for standard reference.</p> <p>Sensitivity, specificity, positive and negative predictive values, and global agreement (with kappa index), were calculated. Results were shown overall and stratified by sex and age groups.</p> <p>Results</p> <p>The agreement for diabetes mellitus with the reference standard as determined by the guideline was almost perfect (κ = 0.990), with a sensitivity of 99.53%, a specificity of 99.49%, a positive predictive value of 91.23% and a negative predictive value of 99.98%.</p> <p>Hypertension diagnosis showed substantial agreement with the reference standard as determined by the guideline (κ = 0.778), the sensitivity was 85.22%, the specificity 96.95%, the positive predictive value 85.24%, and the negative predictive value was 96.95%. Sensitivity results were worse in patients who also had diabetes and in those aged 70 years or over.</p> <p>Conclusions</p> <p>Our results substantiate the validity of using diagnoses of diabetes and hypertension found within the computerized clinical records for epidemiologic studies.</p

AMI radio continuum observations of young stellar objects with known outflows

We present 16 GHz (1.9 cm) deep radio continuum observations made with the Arcminute Microkelvin Imager (AMI) of a sample of low-mass young stars driving jets. We combine these new data with archival information from an extensive literature search to examine spectral energy distributions (SEDs) for each source and calculate both the radio and sub-mm spectral indices in two different scenarios: (1) fixing the dust temperature (Td) according to evolutionary class; and (2) allowing Td to vary. We use the results of this analysis to place constraints on the physical mechanisms responsible for the radio emission. From AMI data alone, as well as from model fitting to the full SED in both scenarios, we find that 80 per cent of the objects in this sample have spectral indices consistent with freefree emission. We find an average spectral index in both Td scenarios, consistent with freefree emission. We examine correlations of the radio luminosity with bolometric luminosity, envelope mass and outflow force, and find that these data are consistent with the strong correlation with envelope mass seen in lower luminosity samples. We examine the errors associated with determining the radio luminosity and find that the dominant source of error is the uncertainty on the opacity index, beta. We examine the SEDs for variability in these young objects, and find evidence for possible radio flare events in the histories of L1551 IRS 5 and Serpens SMM 1

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Evaluation of integrated care services in Catalonia: Population-based and service-based real-life deployment protocols

Background: Comprehensive assessment of integrated care deployment constitutes a major challenge to ensure quality, sustainability and transferability of both healthcare policies and services in the transition toward a coordinated service delivery scenario. To this end, the manuscript articulates four different protocols aiming at assessing large-scale implementation of integrated care, which are being developed within the umbrella of the regional project Nextcare (2016-2019), undertaken to foster innovation in technologically-supported services for chronic multimorbid patients in Catalonia (ES) (7.5 M inhabitants). Whereas one of the assessment protocols is designed to evaluate population-based deployment of care coordination at regional level during the period 2011-2017, the other three are service-based protocols addressing: i) Home hospitalization; ii) Prehabilitation for major surgery; and, iii) Community-based interventions for frail elderly chronic patients. All three services have demonstrated efficacy and potential for health value generation. They reflect different implementation maturity levels. While full coverage of the entire urban health district of Barcelona-Esquerra (52

A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by Prunus necrotic ringspot virus and Peach latent mosaic viroid

[EN] Background: Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Results: Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Conclusions: Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in infected peach fruits. These field studies can help to fully understand plant-pathogen interactions and to develop appropriate crop protection strategies.We thank Drs M.A. Perez-Amador y J. Gadea for helping in the result analysis. This work was supported by grant BIO2011-25018 from the Spanish granting agency Direccion General de Investigacion Cientifica for the transcriptomic analyses and from the grant 2009CL0020 from the bilateral project INIA-Chile/CSIC-Spain for the phytosanitary evaluation. MC Herranz was the recipient of a contract from the Juan de la Cierva program of the Ministerio de Educacion y Ciencia of Spain.Herranz Gordo, MDC.; Niehl, A.; Rosales, M.; Fiore, N.; Zamorano, A.; Granell Richart, A.; Pallás Benet, V. (2013). 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