Prevalence, characteristics, and impact of adverse events in 34 Madrid hospitals. The ESHMAD study

Introduction: Adverse Events (AE) are one of the main problems in healthcare. Therefore, many policies have been developed worldwide to mitigate their im pact. The Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD) measures the results of them in the region. Methods: Cross-sectional study, conducted in May 2019, in hospitalised patients in 34 public hospitals using the Harvard Medical Practice Study methodology. A logistic regression model was carried out to study the association of the variables with the presence of AE, calibrated and adjusted by patient. Results: A total of 9975 patients were included, estimating a prevalence of AE of 11.9%. A higher risk of AE was observed in patients with surgical procedures (OR[CI95%]: 2.15[1.79 to 2.57], vs. absence), in Intensive Care Units (OR[CI95%]: 1.60[1.17 to 2.17], vs. Medical) and in hospitals of medium complexity (OR[CI95%]: 1.45[1.12 to 1.87], vs. low complexity). A 62.6% of AE increased the length of the stay or it was the cause of admission, and 46.9% of AE were considered prevent able. In 11.5% of patients with AE, they had contributed to their death. Conclusions: The prevalence of AE remains similar to the previously estimated one in studies developed with the same methodology. AE keep leading to longer hospital stays, contributing to patient's death, showing that it is necessary to put focus on patient safety again. A detailed analysis of these events has enabled the detection of specific areas for improvement according to the type of care, centre and patient

Experimental infection of Eurasian wild boar with Mycobacterium avium subsp. avium

The Eurasian wild boar (Sus scrofa) is increasingly relevant as a host for several pathogenic mycobacteria. We aimed to characterize the first experimental Mycobacterium avium subsp. avium (MAA) infection in wild boar in order to describe the lesions and the immune response as compared to uninfected controls. Twelve 1-4-month-old wild boar piglets were housed in class III bio-containment facilities. Four concentrations of MAA suspension were used: 10, 102 and 104 mycobacteria (2 animals each, oropharyngeal route) and 2.5×106 mycobacteria (2 animals each by the oropharyngeal and nasal routes). No clinical signs were observed and pathology evidenced a low pathogenicity of this MAA strain for this particular host. Bacteriological and pathological evidence of successful infection after experimental inoculation was found for the group challenged with 2.5×106 mycobacteria. These four wild boar showed a positive IFN-γ response to the avian PPD and the real-time RT-PCR data revealed that three genes, complement component C3, IFN-γ and RANTES, were significantly down regulated in infected animals. These results were similar to those found in naturally and experimentally M. bovis-infected wild boar and may constitute biomarkers of mycobacterial infection in this species.The study was funded by INIA-MICINN research grant FAU2006-00017 and Plan NacionalAGL2008-03875. Studies on TB at IREC are also supported by Grupo Santander—Fundación Marcelino Botin.Peer Reviewe

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

Assessment of an oral Mycobacterium bovis BCG vaccine and an inactivated M. bovis preparation for wild boar in terms of adverse reactions, vaccine strain survival, and uptake by nontarget species

Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment.This is a contribution to Plan Nacional I+D+i AGL2011-30041 from the Ministerio de Economía y Competitividad (MINECO), Spain, and FEDER and to EU FP7 grant WildTBvac. B.B.-B. and I.D.-D. were supported by MINECO grants BES-2009-017401 and BES-2012-052490, respectively. J.A.B. was supported by MICINN grant FPU12/00980.Peer Reviewe

A Spanish-language patient safety questionnaire to measure medical and nursing students' attitudes and knowledge

Objective. To design and validate a questionnaire for assessing attitudes and knowledge about patient safety using a sample of medical and nursing students undergoing clinical training in Spain and four countries in Latin America. Methods. In this cross-sectional study, a literature review was carried out and total of 786 medical and nursing students were surveyed at eight universities from five countries (Chile, Colombia, El Salvador, Guatemala, and Spain) to develop and refine a Spanish-language questionnaire on knowledge and attitudes about patient safety. The scope of the questionnaire was based on five dimensions (factors) presented in studies related to patient safety culture found in PubMed and Scopus. Based on the five factors, 25 reactive items were developed. Composite reliability indexes and Cronbach''s alpha statistics were estimated for each factor, and confirmatory factor analysis was conducted to assess validity. After a pilot test, the questionnaire was refined using confirmatory models, maximum-likelihood estimation, and the variance-covariance matrix (as input). Multiple linear regression models were used to confirm external validity, considering variables related to patient safety culture as dependent variables and the five factors as independent variables. Results. The final instrument was a structured five-point Likert self-administered survey (the "Latino Student Patient Safety Questionnaire") consisting of 21 items grouped into five factors. Compound reliability indexes (Cronbach''s alpha statistic) calculated for the five factors were about 0.7 or higher. The results of the multiple linear regression analyses indicated good model fit (goodness-of-fit index: 0.9). Item-total correlations were higher than 0.3 in all cases. The convergent-discriminant validity was adequate. Conclusions. The questionnaire designed and validated in this study assesses nursing and medical students'' attitudes and knowledge about patient safety. This instrument could be used to indirectly evaluate whether or not students in health disciplines are acquiring and thus likely to put into practice the professional skills currently considered most appropriate for patient safety

Phenolic compounds reduce the fat content in caenorhabditis elegans by affecting lipogenesis, lipolysis, and different stress responses

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPRER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

Ewing sarcoma is characterized by chromosomal translocations fusing the EWS gene with various members of the ETS family of transcription factors, most commonly FLI1. EWS-FLI1 is an aberrant transcription factor driving Ewing sarcoma tumorigenesis by either transcriptionally inducing or repressing specific target genes. Herein, we showed that Sprouty 1 (SPRY1), which is a physiological negative feedback inhibitor downstream of fibroblast growth factor (FGF) receptors (FGFRs) and other RAS-activating receptors, is an EWS-FLI1 repressed gene. EWS-FLI1 knockdown specifically increased the expression of SPRY1, while other Sprouty family members remained unaffected. Analysis of SPRY1 expression in a panel of Ewing sarcoma cells showed that SPRY1 was not expressed in Ewing sarcoma cell lines, suggesting that it could act as a tumor suppressor gene in these cells. In agreement, induction of SPRY1 in three different Ewing sarcoma cell lines functionally impaired proliferation, clonogenic growth and migration. In addition, SPRY1 expression inhibited extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling induced by serum and basic FGF (bFGF). Moreover, treatment of Ewing sarcoma cells with the potent FGFR inhibitor PD-173074 reduced bFGF-induced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. Taken together, our data indicate that EWS-FLI1-mediated repression of SPRY1 leads to unrestrained bFGF-induced cell proliferation, suggesting that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease.FC-A, LG-G, JCL, AS, PG-M, SEL-P, SM and JA are supported by Asociación Pablo Ugarte and Miguelañez SA, ASION-La Hucha de Tomás, Fundación La Sonrisa de Alex and Instituto de Salud Carlos III (PI12/00816 and Spanish Cancer Network RTICC RD12/0036/0027). TGPG is supported by a grant from ‘Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München (WiFoMed)’, the Daimler and Benz Foundation in cooperation with the Reinhard Frank Foundation, by LMU Munich’s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the ‘Mehr LEBEN für krebskranke Kinder—Bettina-Bräu-Stiftung’, the Walter Schulz Foundation, the Fritz Thyssen Foundation (FTH-40.15.0.030MN) and by the German Cancer Aid (DKH-111886 and DKH-70112257). The ‘Genetics and Biology of Cancers’ team (TGPG, DS and OD) is supported by grants from the Ligue Nationale Contre Le Cancer (Equipe labellisée). This work was also supported by the European PROVABES, ASSET and EEC FP7 grants. We also thank the following associations for their invaluable support: the Société Française des Cancers de l’Enfant, Courir pour Mathieu, Dans les pas du Géant, Olivier Chape, Les Bagouzamanon, Enfants et Santé and les Amis de Claire. We thank Dr S Navarro (University of Valencia, Valencia, Spain) and Dr TJ Triche (Children’s Hospital Los Angeles, Los Angeles, USA) for providing us with Ewing sarcoma cell lines A4573 and TTC-466, respectively.S

A Spanish-language patient safety questionnaire to measure medical and nursing students' attitudes and knowledge.

[EN] OBJECTIVE: To design and validate a questionnaire for assessing attitudes and knowledge about patient safety using a sample of medical and nursing students undergoing clinical training in Spain and four countries in Latin America. METHODS: In this cross-sectional study, a literature review was carried out and total of 786 medical and nursing students were surveyed at eight universities from five countries (Chile, Colombia, El Salvador, Guatemala, and Spain) to develop and refine a Spanish-language questionnaire on knowledge and attitudes about patient safety. The scope of the questionnaire was based on five dimensions (factors) presented in studies related to patient safety culture found in PubMed and Scopus. Based on the five factors, 25 reactive items were developed. Composite reliability indexes and Cronbach's alpha statistics were estimated for each factor, and confirmatory factor analysis was conducted to assess validity. After a pilot test, the questionnaire was refined using confirmatory models, maximum-likelihood estimation, and the variance-covariance matrix (as input). Multiple linear regression models were used to confirm external validity, considering variables related to patient safety culture as dependent variables and the five factors as independent variables. RESULTS: The final instrument was a structured five-point Likert self-administered survey (the "Latino Student Patient Safety Questionnaire") consisting of 21 items grouped into five factors. Compound reliability indexes (Cronbach's alpha statistic) calculated for the five factors were about 0.7 or higher. The results of the multiple linear regression analyses indicated good model fit (goodness-of-fit index: 0.9). Item-total correlations were higher than 0.3 in all cases. The convergent-discriminant validity was adequate. CONCLUSIONS: The questionnaire designed and validated in this study assesses nursing and medical students' attitudes and knowledge about patient safety. This instrument could be used to indirectly evaluate whether or not students in health disciplines are acquiring and thus likely to put into practice the professional skills currently considered most appropriate for patient safety

Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.This research was supported by Plan Nacional I+D+I AGL2011-30041 from Ministerio de Economía y Competitividad (MINECO), Spain and FEDER. This is also a contribution to EU FP7 grant WildTBvac and the EU FP7 ANTIGONE project number 278976. R.C. Galindo was funded by MEC, Spain. B. Beltrán-Beck was supported by MINECO grant BES-2009-017401.Peer Reviewe