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For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or dasatinib. To date, very few studies have evaluated the genetic predisposition associated with CVE development on TKI treatment. In this retrospective study of 102 CML patients, 26 CVEs were reported during an average follow-up of over 10 years. Next-generation sequencing identified pathogenic/likely pathogenic mutations in genes associated with myeloid malignancies in 24.5% of the diagnostic samples analyzed. Patients with a recorded CVE had more myeloid mutations (0.48 vs. 0.14, p = 0.019) and were older (65.1 vs. 55.7 years, p = 0.016). Age ≥ 60 years and receiving a 2G-TKI in first-line were CVE risk factors. The presence of a pathogenic somatic myeloid mutation was an independent risk factor for CVE on any TKI (HR 2.79, p = 0.01), and significantly shortened the CV event-free survival of patients who received first-line imatinib (by 70 months, p = 0.011). Indeed, 62% of patients on imatinib with mutations had a CVE vs. the 19% on imatinib with a mutation and no CVE. In conclusion, myeloid mutations detectable at diagnosis increase CVE risk, particularly for patients on imatinib, and might be considered for first-line TKI choice.

The “epithelial barrier hypothesis” states that a barrier dysfunction can result in allergy development due to tolerance breakdown. This barrier alteration may come from the direct contact of epithelial and immune cells with the allergens, and indirectly, through deleterious effects caused by environmental changes triggered by industrialization, pollution, and changes in the lifestyle. Apart from their protective role, epithelial cells can respond to external factors secreting IL-25 IL-33, and TSLP, provoking the activation of ILC2 cells and a Th2-biased response. Several environmental agents that influence epithelial barrier function, such as allergenic proteases, food additives or certain xenobiotics are reviewed in this paper. In addition, dietary factors that influence the allergenic response in a positive or negative way will be also described here. Finally, we discuss how the gut microbiota, its composition, and microbe-derived metabolites, such as short-chain fatty acids, alter not only the gut but also the integrity of distant epithelial barriers, focusing this review on the gut-lung axis.

Cancer preventive services (gynaecological cancer screening, colon cancer screening) and cardiometabolic screening are recommended by guidelines to individuals. People with diabetes were less likely to receive them than those without diabetes in some studies. To analyse differences in the coverage of preventive services in people with diabetes compared to non-diabetic individuals and in people with diabetes according to sex and household income. We analysed data collected from the European Health Interview Survey 2013–2015, including individuals aged 40–74 (n = 179,318), 15,172 with diabetes from 29 countries. The income of a household (HHI) was described in quintiles. The relationship between the coverage of preventive services (cardiometabolic, vaccination, cancer screening) and sociodemographic characteristics was analysed with multiple logistic regression. Women comprised 53.8% of the total and 40% were 60–74 years. People with diabetes compared to those without diabetes had higher reported coverage of cardiometabolic screening (98.4% vs. 90.0% in cholesterol measurement; 97.0% vs. 93.6% in blood pressure measurement), colorectal cancer screening (27.1% vs. 24.6%) but lower coverage of gynaecological cancer screening (mammography: 29.2% vs. 33.5%, pap smear test: 28.3% vs. 37.9%). Among diabetic patients, women were less likely to receive cholesterol screening (OR = 0.81; 95% CI: 0.72–0.91) and colon cancer screening (OR = 0.79; 95% CI: 0.73–0.86) compared to men. Being affluent was positively associated with receiving cardiometabolic screening and mammography in diabetic patients. People with diabetes reported higher coverage of preventive services except gynaecological cancer screening. Disparities were found in diabetes among women and less affluent individuals.

Background SARS-CoV-2 infection may produce symptoms for longer than 4 weeks (long COVID). Its duration, causes and consequences are still not well known. The objective of this study is to estimate the prevalence of long COVID, its signs and symptoms and the use of resources in adult patients in Primary Care (PC). Methods Observational, descriptive, retrospective case series study performed in PC. Patients older than 18 years who had a positive polymerase chain reaction test for SARS-CoV-2 from February 29th until April 15th, 2020 were included. Variables related to clinical symptoms and use of resources were registered from 4 weeks after the confirmed COVID-19 case notification, up to 39 weeks. Results Mean age of the 267 patients analyzed was 57 years old (16.0 SD) and 55.8% were women. In the acute phase, 61.8% of the patients required hospitalization and 43.8% suffered bilateral pneumonia. Long COVID prevalence found was 45.7% (CI 95% 39.6–51.9), and 53.3% of them had symptoms longer than 12 weeks. Most common symptoms were dyspnea (45.1%, CI 95% 36.1–54.3), asthenia (42.6%, CI 95% 33.7–51.9), cough (24.6%, CI 95% 17.2–33.2), and neuropsychiatric disorders (18%, CI 95% 11.7–26). 98.4% of long COVID patients required contact with PC during follow-up, with an average of 6.7 (5.0 SD) contacts. At least 45.1% had a lab test, 34.4% a chest x-ray and 41.8% required work leave. Factors associated with a higher number of contacts with PC included developing ARDS (IRR 1.7, CI 95% 1.2–2.2), long COVID (IRR 2.9, CI 95% 2.5–3.4), requiring a work leave (IRR 2.4, CI 95% 2.1–2.9), and the need of hospitalization (IRR 1.5, CI 95% 1.2–1.9). Conclusion Almost half of the patients of this study developed long COVID, similar to preceding works. Most frequent persistent symptoms were dyspnea, asthenia, and cough. Use of resources such as lab tests, chest x-rays, work leaves, PC appointments and hospital referrals, was two to six times greater among long COVID patients, in contrast with those who did not develop long COVID. Requiring hospitalization and having a severe disease at onset was associated to a higher number of PC contacts.

Background To estimate the prevalence of symptoms and signs related to a COVID-19 case series confirmed by polymerase chain reaction (PCR) for SARS-CoV-2. Risk factors and the associated use of health services will also be analysed. Methods Observational, descriptive, retrospective case series study. The study was performed at two Primary Care Health Centres located in Madrid, Spain. The subjects studied were all PCR SARS-CoV-2 confirmed cases older than 18 years, diagnosed from the beginning of the community transmission (March 13) until April 15, 2020. We collected sociodemographic, clinical, health service utilization and clinical course variables during the following months. All data was gathered by their own attending physician, and electronic medical records were reviewed individually. Statistical analysis: A descriptive analysis was carried out and a Poisson regression model was adjusted to study associated factors to Health Services use. Results Out of the 499 patients studied from two health centres, 55.1% were women and mean age was 58.2 (17.3). 25.1% were healthcare professionals. The most frequent symptoms recorded related to COVID-19 were cough (77.9%; CI 95% 46.5–93.4), fever (77.7%; CI95% 46.5–93.4) and dyspnoea (54.1%, CI95% 46.6–61.4). 60.7% were admitted to hospital. 64.5% first established contact with their primary care provider before going to the hospital, with a mean number of 11.4 Healthcare Providers Encounters with primary care during all the follow-up period. The number of visit-encounters with primary care was associated with being male [IRR 1.072 (1.013, 1.134)], disease severity {from mild respiratory infection [IRR 1.404 (1.095, 1.801)], up to bilateral pneumonia [IRR 1.852 (1.437,2.386)]}, and the need of a work leave [IRR 1.326 (1.244, 1.413]. Conclusion Symptoms and risk factors in our case series are similar to those in other studies. There was a high number of patients with atypical unilateral or bilateral pneumonia. Care for COVID has required a high use of healthcare resources such as clinical encounters and work leaves.

Clinical trials have demonstrated that some patients with chronic myeloid leukemia (CML) treated for several years with tyrosine kinase inhibitors (TKIs) who have maintained a molecular response can successfully discontinue treatment without relapsing. Treatment free remission (TFR) can be reached by approximately 50% of patients who discontinue. Despite having similar levels of deep molecular response and an identical duration of treatment, the factors that influence the successful discontinuation of CML patients remain to be determined. In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR. We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.

Background: Clinical practice guidelines (CPGs) have great teaching potential for health professionals in training, although their use is limited. The objective of this study was to evaluate the effectiveness and adherence to e-EDUCAGUIA teaching strategy using educational game with simulated clinical scenarios to implement a CPG on antimicrobial therapy compared to the usual dissemination strategies in improving the knowledge and skills of family medicine residents.Methods: This was a multicentre cluster-randomized clinical trial in 7 teaching units in Madrid (Spain). Intervention: educational games based on CPG recommendations, compared with the passive dissemination of the guideline. Main outcome variable: knowledge and skills questionnaire scores one month after the intervention. The difference in mean scores between the intervention and control groups at one month was determined, along with the 95% CI using generalized linear models.Results: A total of 202 residents participated (104 in the intervention group and 98 in the control group). One hundred residents performed the post-test at one month (45 in the intervention group vs. 55 in the control group). The differences favoured the intervention group in terms of both the final scores at month (11.4, 95% CI 6.9–15.9) and the change from baseline scores (11.9, 95% CI 5.9–17.9), with estimated effect sizes of 0.88 for the between-groups difference and 0.75 for the change in baseline difference. For each additional hour of training in evidence-based medicine there was a an increase of 0.28 points (95 % CI 0.15–0.42). Conclusions: The e-EDUCAGUIA strategy improves the knowledge and skills of medicine residents for clinical decision-making during short-term antimicrobial therapy. Adherence to educational games in the absence of specific incentives is moderate.Trial registration: ClinicalTrials.gov Identifier: NCT02210442. Registered 6 August 2014, https://www.clinicaltrials.gov/ct2/show/NCT02210442

Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.

Purpose of Review Clinical factors alone do not enable us to differentiate which patients will maintain treatment-free remission (TFR) from those who are likely to relapse. Thus, patient-specific factors must also play a role. This review will update the reader on the most recent studies presenting biological factors that can help predict tyrosine kinase inhibitor (TKI) discontinuation success. Recent Findings Cellular and molecular factors with a suggested role in TFR include immune factors and leukemic stem cell (LSC) persistence; the BCR::ABL1 transcript type, halving time, and BCR::ABL1 DNA and RNA positivity; as well as other molecular factors such as somatic mutations, RNA expression, and telomere length. Summary Our review presents several biomarkers with predictive value for TFR but also highlights areas of unmet need. Future discontinuation guidelines will likely include biological factors for the personalization of TFR prediction. However, it will be important that such advances do not prevent more patients from making a TKI discontinuation attempt.

The COVID-19 pandemic and the associated public health emergency have affected patients and health services in non-COVID-19 pathologies. Several studies have shown its dissociation from health services, with a decrease in emergency department visits, in hospital admissions for non-COVID-19 pathologies, as well as in the reported weekly incidence of acute illnesses and new diagnoses in primary care. In parallel, the pandemic has had direct and indirect effects on people with chronic diseases; the difficulties in accessing health services, the interruption of care, the saturation of the system itself and its reorientation towards non-face-to-face formats has reduced the capacity to prevent or control chronic diseases. All this has also had an impact on the different areas of people's lives, creating new social and economic difficulties, or aggravating those that existed before the pandemic. All these circumstances have changed with each epidemic wave. We present a review of the most relevant studies that have been analyzing this problem and incorporate as a case study the results of a retrospective observational study carried out in Primary Care in the Madrid Health Service, which provides health coverage to a population of more than 6 million people, and whose objective was to analyze the loss of new diagnoses in the most prevalent pathologies such as common mental health problems, cardiovascular and cerebrovascular diseases, type 2 diabetes, chronic obstructive pulmonary disease, and breast and colon tumors, in the first and second waves. Annual incidence rates with their confidence interval were calculated for each pathology and the monthly frequency of new codes recorded between 1/01/2020 and 12/31/2020 was compared with the monthly mean of observed counts for the same months between 2016 and 2019. The annual incidence rate for all processes studied decreased in 2020 except for anxiety disorders. Regarding the recovery of lost diagnoses, heart failure is the only diagnosis showing an above-average recovery after the first wave. To return to pre-pandemic levels of diagnosis and follow-up of non-COVID-19 pathology, the healthcare system must reorganize and contemplate specific actions for the groups at highest risk.

Background Several studies have shown a correlation between an altered metabolome and respiratory allergies. The epithelial barrier hypothesis proposes that an epithelial barrier dysfunction can result in allergic diseases development. Der p 1 allergen from house dust mite is a renowned epithelial barrier disruptor and allergy initiator due to its cysteine‐protease activity. Here, we compared the metabolic profile of the bronchial epithelium exposed or not to Der p 1 during barrier establishment to understand its active role in allergy development. Methods Calu‐3 cells were cultivated in air‐liquid interface cultures and exposed to either Der p 1 or Ole e 1 allergens during barrier establishment. The comparative metabolomics analysis of apical and basolateral media were performed using liquid chromatography and capillary electrophoresis both coupled to mass spectrometry. Results We showed that epithelial barrier disruption by Der p 1 was associated with a specific metabolic profile, which was highly dependent on the state of the epithelium at the time of contact. Moreover, an apical‐basolateral distribution of the metabolites was also observed, indicating a compartmentalization of the response with differential metabolic patterns. A number of metabolites were changed by Der p 1, mainly related to amino acids metabolism, such as L‐arginine, L‐kynurenine and L‐methionine. Conclusion This work is the first report on the metabolic response in human bronchial epithelial cells associated with cysteine‐protease Der p 1 activity, which could contribute to allergy development. Moreover, it supports a reformulated epithelial barrier hypothesis that might help to explain allergies and their increasing prevalence.

Resumen: Objetivo: Estudiar si en pacientes mayores de 65 años con tratamientos antihipertensivos e hipolipemiantes los cambios de fármacos bioequivalentes con diferente apariencia se asocian a un aumento de errores de uso y pérdida de adherencia al tratamiento. Diseño: Estudio observacional, longitudinal, prospectivo, de cohorte de 1 año de seguimiento entre el 1 de enero de 2013 y el 31 de diciembre de 2014. Emplazamiento: Centros de Salud de la Comunidad de Madrid. Participantes: Pacientes ≥ 65 años con diagnóstico de HTA (CIAP K86) y/o dislipidemia (CIAP T93) en tratamiento con enalapril y/o amlodipino y/o simvastatina. Mediciones principales: Se recogieron mediante entrevista en consulta variables sociodemográficas (edad, sexo, nivel de estudios), clínicas, adherencia (test de Morisky-Green y recuento directo), errores de medicación (número y tipo), cambios de fármacos y número, parámetros bioquímicos (colesterol total, colesterol HDL, colesterol LDL, triglicéridos) y variable combinada (error y/o adherencia). Se realizaron 5 visitas: una basal y 4 trimestrales. Resultados: Se incluyeron 274 pacientes, edad media 72 (6,6) años, 47,8% mujeres. Presentaron algún cambio de medicamento 134 pacientes (48,9%), con una mediana de cambios de 3 (RIQ 1-5) y máximo de 11. El riesgo de presentar algún error o disminuir la adherencia estaba aumentado en expuestos a cambios en todas las visitas con RR 1,14 (1,16-1,69) al año de seguimiento. El error más frecuente fue la pérdida de dosis. Por cada cambio la probabilidad de un evento combinado aumenta en un 41%. Conclusiones: Los cambios realizados entre fármacos bioequivalentes con diferente apariencia podrían aumentar el número de errores de medicación y disminuir la adherencia. Habría que realizar más estudios para valorar en qué medida afecta al control de la enfermedad.No se contempla el apartado intervención por tratarse de un estudio observacional. Abstract: Objective: To study whether the changes in bioequivalent drugs with different appearances are associated with an increase in lack of adherence and medication use errors, in patients > 65 years old treated with antihypertensive and lipid-lowering medications. Design: Observational longitudinal prospective cohort study with a one-year follow-up period between 1 January 2013 and 31 December 2014. Location: Primary Healthcare Centres in the Community of Madrid. Participants: Patients ≥ 65 years-old with a diagnosis of hypertension and/or dyslipidaemia receiving treatment with Enalapril and/or Amlodipine and/or Simvastatin. Main measurements: Variables collected during a Primary Care consultation by means of a personal interview were: sociodemographic (age, gender, level of education), clinical variables, adherence (Morisky-Green test and direct counting), medication errors (number and type), medication changes and number, analytical (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) and combined variable (error and/or adherence). There were 1 baseline and 4 quarterly visits. Results: The study included 274 patients with a mean age 72 (6.6) years, of whom 47.8% were female. Some medication changes were observed in 134 patients (48.9%), with a median of 3 (IQR 1-5) and a maximum of 11 changes. The risk of presenting with a medication use error or decreased adherence was increased in patients exposed to changes in all visits with RR 1.14 (1.16-1.69) at one year of follow-up. The most frequent error was the loss of dose. For each change in medication, the probability of a combined event increases by 41%. Conclusions: The changes made in bioequivalent drugs with different appearance could increase the number of medication use errors and decrease the adherence. More studies should be carried out to assess how much this affects the control of the disease.The intervention section is not considered because it is an observational study. Palabras clave: Isoapariencia, Medicamentos genéricos, Hipertensión, Dislipidemia, Cumplimiento, Adherencia, Error medicación, Keywords: Medication appearance, Generic drugs, Hypertension, Dyslipidaemia, Compliance, Adherence, Medication error

Resumen: Objetivo: El objetivo es estimar la prevalencia de consumos de riesgo de drogas y patrones de consumo en atención primaria. Diseño: Estudio multicéntrico descriptivo transversal. Emplazamiento: Cinco centros de salud del área Sur de Madrid. Participantes: Población consultante en atención primaria entre 16-100 años. Mediciones: Se utilizó el test ASSIST validado al castellano de la Organización Mundial de la Salud para el cribado de consumo de drogas. Se calculó la puntuación total para cada droga. Resultados: Se realizaron un total de 441 cribados. La edad media fue de 51,3 años y un 56,1% presentó algún consumo de riesgo moderado o grave para alguna de las 9 sustancias cribadas. Las drogas con cribado de riesgo más consumidas fueron el tabaco (41,7%), el alcohol (15,4%), los sedantes o los hipnóticos (13,7%) y el cannabis (5,7%), encontrándose algunas diferencias: los hombres consumían más alcohol y cannabis; las mujeres tenían mayor consumo de sedantes/hipnóticos que los hombres. Se observó policonsumo en un 16% de los sujetos. Conclusiones: Existen riesgos derivados del consumo tabaco, alcohol, sedantes y cannabis en atención primaria. Existe una mayor prevalencia de sedantes e hipnóticos. Abstract: Objective: The aim of this study is to estimate risky-drug use patterns of consumption of primary care patients. Design: Multicentric descriptive cross-sectional study. Setting: five primary health care centers of the South of Madrid. Participants: all patients between 16-100 year-old consulting with their family physician. Measurements: Spanish-validated World Health Organization ASSIST test was use to screen risky drug use in primary care. Total points scored at the test were obtained. Results: A sum of 441 screening test were collected. Mean age was 51,3 years and 51.6% of patients presented a moderate-severe risky drug use out of the nine drugs tested. The more frequent drug use screened were tobacco (41.7%) followed by alcohol (15.4%), hypnotics (13.7%) and cannabis (5.7%). Differences were found between genders in the patterns: men had higher risky drug uses compared to women regarding alcohol and cannabis. Women had higher sedatives/hypnotics consumption prevalence. A 16% of patients presented with polyconsumption drug use patterns. Conclusions: There is risk derived from drug misuse in primary care for tobacco, alcohol, hypnotics and cannabis as detected by the ASSIST test. There is a higher rate of hypnotics than expected. Palabras clave: Cribado, Trastornos relacionados con sustancias, Atención Primaria, Alcohol, smoking and substances involvement screening test, Keywords: Screening, Substances-Related disorders, Primary Care, Alcohol, smoking and substances involvement screening test

Resumen: Objetivo: Describir el estado de salud autopercibida (SAP) en la población de entre 65 y 74 años de España y Portugal y analizar los factores asociados a buena salud medidos en la Encuesta Europea de Salud (European Health Interview Survey [EHIS]) de 2014. Diseño: Análisis retrospectivo de datos secundarios provenientes de la EHIS de 2014. Ámbito: Comunitario. Participantes: Se analizaron todos los individuos entre 65 y 74 años de España y Portugal encuestados con datos disponibles. Mediciones principales: Se recogió la SAP en cinco niveles (de muy buena a muy mala) con escala Likert, variables sociodemográficas, clínicas, enfermedades crónicas, estilos de vida y utilización de recursos sanitarios. Se realizó un análisis multivariante mediante un modelo de regresión logística (muy buena/buena SAP vs resto) para estudiar el efecto del país ajustado por los diferentes factores sociodemográficos, clínicos y/o de estilos de vida usando estimadores robustos. Resultados: Se estudió un total de 5.977 sujetos, de los cuales el 42,6% eran hombres y el 57,5% mujeres. La buena SAP varió entre países (52,9% España vs. 19% Portugal; p

Background: Current epidemiological situation has prompted the consideration of multimorbility (MM) as a prevalent condition, influenced by age, educational level and social support, related to unfavorable social and health determinants. Primary Care (PC) has a key role in its approach but further training of professionals in MM is required. The evidence on the effectiveness of training interventions in MM is still limited. Knowing the experiences, opinions and training needs of professionals is essential to enhance training interventions. Objectives: Identify perceived training needs by PC health professionals (doctors and nurses) in MM and polypharmacy. Methods: Design: Cross-sectional study based on an online survey (anonymous-ad hoc questionnaire). Participants and recruitment: 384 doctors and nurses working in healthcare centers and out-of-hospital emergencies of the Spanish National Health System. Non-probabilistic convenience sampling via email addressed to Health Institutions, and social networks. Data: Demographic characteristics and professional profile data (close-ended and multiple-choice questions) will be collected. Open-ended questions will be used to identify training needs, difficulties and resources about MM; required skills to care patients with MM will be assessed using a 4-item ordinal scale. Analysis: Coding of data prior to analysis. Descriptive statistical analysis, participation and completion rates of the questionnaire and estimation of absolute and relative frequencies and 95% confidence intervals in close-ended questions. Content analysis with inductive methodology in open-ended questions. Ethics: Ethical approval, Online informed consent. Conclusions: The identification of training needs of health professionals who care for patients with MM will be necessary data for developing highly effective training activities.

To estimate the prevalence of symptoms and signs related to a COVID-19 case series confirmed by polymerase chain reaction (PCR) for SARS-CoV-2. Risk factors and the associated use of health services will also be analysed.Observational, descriptive, retrospective case series study. The study was performed at two Primary Care Health Centres located in Madrid, Spain. The subjects studied were all PCR SARS-CoV-2 confirmed cases older than 18 years, diagnosed from the beginning of the community transmission (March 13) until April 15, 2020. We collected sociodemographic, clinical, health service utilization and clinical course variables during the following months. All data was gathered by their own attending physician, and electronic medical records were reviewed individually.A descriptive analysis was carried out and a Poisson regression model was adjusted to study associated factors to Health Services use.Out of the 499 patients studied from two health centres, 55.1% were women and mean age was 58.2 (17.3). 25.1% were healthcare professionals. The most frequent symptoms recorded related to COVID-19 were cough (77.9%; CI 95% 46.5-93.4), fever (77.7%; CI95% 46.5-93.4) and dyspnoea (54.1%, CI95% 46.6-61.4). 60.7% were admitted to hospital. 64.5% first established contact with their primary care provider before going to the hospital, with a mean number of 11.4 Healthcare Providers Encounters with primary care during all the follow-up period. The number of visit-encounters with primary care was associated with being male [IRR 1.072 (1.013, 1.134)], disease severity {from mild respiratory infection [IRR 1.404 (1.095, 1.801)], up to bilateral pneumonia [IRR 1.852 (1.437,2.386)]}, and the need of a work leave [IRR 1.326 (1.244, 1.413].Symptoms and risk factors in our case series are similar to those in other studies. There was a high number of patients with atypical unilateral or bilateral pneumonia. Care for COVID has required a high use of healthcare resources such as clinical encounters and work leaves.

Resumen: Objetivo: Analizar el papel de las unidades docentes (UD) de atención familiar y comunitaria como agentes facilitadores de la implementación de guías de práctica clínica (GPC) y los factores asociados a un mayor esfuerzo en esta tarea. Material y métodos: Diseño: estudio descriptivo transversal con enfoque analítico. Participantes: UD en España (n = 94). Mediciones principales: Variables recogidas mediante encuesta autocumplimentada en 5 dominios: características de las UD, actividad formativa dirigida a la práctica clínica basada en pruebas, importancia atribuida a esta actividad, responsabilidad sobre implementación de GPC y percepción sobre barreras y facilitadores para su uso. Análisis descriptivo y multivariante siendo la variable dependiente el esfuerzo percibido de las UD para implementar GPC. Resultados: Respondieron 45 UD (47,9%). El 42,2% (IC 95%: 27,8-56,6) de sus responsables ha dirigido proyectos de investigación y el 31,1% (IC 95%:17,6- 44,6) ha participado en elaborar GPC. Organizaban una media de 51 horas (DE 47,2) de formación en práctica clínica basada en pruebas. El 97,7% (IC 95%:93,3-100) consideraba fundamental que los residentes conozcan y apliquen GPC y el 93,3% (IC 95%: 86,0-100) consideran los tutores responsables de implementarlas. Se relacionaron con un mayor esfuerzo de las UD la participación del responsable en GPC (coef.: 0,58; IC 95%: 0,00-1,16), la importancia dada a que los residentes las conozcan (coef.: 0,89; IC 95%: 0,24-1,54) y que estas parezcan aplicables (coef.: 0,35; IC 95%: –0,01-0,70). Conclusiones: Las UD reconocen la importancia de las GPC y consideran a los tutores responsables de su implementación. El esfuerzo de las UD para implementar GPC se relacionó con la experiencia previa de los responsables, la percepción de aplicabilidad y de necesidad de los residentes. Abstract: Objective: To analyze the role of Family and Community Care Trainig Units as facilitators of the implementation of Clinical Practice Guidelines (CPG) and the factors associated with a greater effort in this task. Material and methods: Design: Cross-sectional descriptive study with analytical approach. Participants: Training Units in Spain (N = 94). Main measurements: Variables were collected through a self-completed survey into five domains: characteristics of Training Units, training activity directed at evidence-based clinical practice (EBPP), importance attributed to this activity, responsibility for EBPP implementation, perception of barriers and facilitators to its use. Descriptive and multivariate analysis with the dependent variable being the perceived effort of the training unit to implement CPG. Results: 45 Training Units responded (47.9%). 42.2%(CI 95%: 27.8-56.6) of their coordinators have directed research projects and 31.1% (CI 95%:17.6-44.6) have participated in elaborating CPG. They organized an average of 51 hours (SD 47.2) of training in PCBP. 97.7% (CI95%:93.3-100) considered it fundamental that the residents ow and apply PCBP and 93.3% (CI95%:86.0-100) considered that tutors are responsible for the implementation. The participation of the coordinator in CPG (coef: 0.58; IC 95%: 0.00-1.16), awareness of how important is that residents know about CPG (coef: 0.89; IC 95%: 0.24-1.54) and that CPG appear to be widely applicable. applicable (coef: 0.35; IC 95%: -0.01-0.70) were related to a greater effort by the training units. Conclusions: The training units recognize the importance of CPGs and consider that tutors are responsible for their implementation. Training Units effort to implement CPG was related to unit coordinators previous experience, the perception of applicability and residents needs.

Background Caregivers of patients with chronic conditions or disability experience fatigue, burden and poor health-related quality of life. There is evidence of the effectiveness of support interventions for decreasing this impact. However, little is known about the benefits of home-based nursing intervention in primary health care. Objectives To evaluate the effectiveness of a home-based, nurse-led-intervention (CuidaCare) on the quality of life of caregivers of individuals with disabilities or chronic conditions living in the community, measured at 12-month follow-up. Methods A pragmatic, two-arm, cluster-randomized controlled trial with a 1-year follow-up period was performed between June 2013 and December 2015. Consecutive caregivers aged 65 years or older, all of whom assumed the primary responsibility of caring for people with disabling conditions for at least 6 months a year, were recruited from 22 primary health care centers. Subsequently, 11 centers were randomly assigned to usual care group, and 11 were assigned to the intervention group. The caregivers in the intervention group received the usual care and additional support (cognitive restructuring, health education and emotional support). The primary outcome was quality of life, assessed with the EQ-5D instrument (visual analog scale and utility index score); the secondary outcome variables were perception of burden, anxiety, and depression. Data were collected at baseline, at the end of the intervention, and at the 6- and 12-month follow-up visits. We analyzed the primary outcome as intention-to-treat, and missing data were added using the conditional mean single imputation method. Results A total of 224 caregivers were included in the study (102 in the intervention group and 122 in the usual care group). Generalized Estimating Equation models showed that the CuidaCare intervention was associated with a 5.46 point (95% CI: 2.57; 8.35) change in the quality of life, as measured with the visual analog scale adjusted for the rest of the variables at 12 months. It also produced an increase of 0.04 point (95% CI: 0.01; 0.07) in the utilities. No statistically significant differences were found between the two groups at 12 months with respect to the secondary outcomes. Conclusions The findings suggest that incorporating a home-based, nurse-led-intervention for caregivers into primary care can improve the health-related quality of life of caregivers of patients with chronic or disabling conditions.

Objetivo Describir el estado de salud autopercibida (SAP) en la población de entre 65 y 74 años de España y Portugal y analizar los factores asociados a buena salud medidos en la Encuesta Europea de Salud (European Health Interview Survey [EHIS]) de 2014. Diseño Análisis retrospectivo de datos secundarios provenientes de la EHIS de 2014. Ámbito Comunitario. Participantes Se analizaron todos los individuos entre 65 y 74 años de España y Portugal encuestados con datos disponibles. Mediciones principales Se recogió la SAP en cinco niveles (de muy buena a muy mala) con escala Likert, variables sociodemográficas, clínicas, enfermedades crónicas, estilos de vida y utilización de recursos sanitarios. Se realizó un análisis multivariante mediante un modelo de regresión logística (muy buena/buena SAP vs resto) para estudiar el efecto del país ajustado por los diferentes factores sociodemográficos, clínicos y/o de estilos de vida usando estimadores robustos. Resultados Se estudió un total de 5.977 sujetos, de los cuales el 42,6% eran hombres y el 57,5% mujeres. La buena SAP varió entre países (52,9% España vs. 19% Portugal; p

Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specific-immunotherapy. In this work, we achieved the development of a protein chimera able to promote specific cell death on effector cells involved in the allergic reaction. Der p 1 allergen was chosen as cell-targeting domain and the powerful ribotoxin α-sarcin as the toxic moiety. The resultant construction, named proDerp1αS, was produced and purified from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were effectively conserved in proDerp1αS. Immunotoxin impact was assayed by using effector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1αS, was exclusively observed on Der p 1 sera sensitized-humRBL-2H3 cells, but not when treated with non-allergic sera. Most notably, equivalent IgE-binding and degranulation were observed with both proDerp1αS construct and native Der p 1 when using purified basophils from sensitized patients. However, proDerp1αS did not cause any cytotoxic effect on these cells, apparently due to its lack of internalization after their surface IgE-binding, showing the complex in vivo panorama governing allergic reactions. In conclusion, herein we present proDerp1αS as a proof of concept for a potential and alternative new designs of therapeutic tools for allergies. Development of new, and more specific, second-generation of immunotoxins following proDerp1αS, is further discussed.

BackgroundThe steady rise in multimorbidity entails serious consequences for our populations, challenges healthcare systems, and calls for specific clinical approaches of proven effectiveness. The MULTIPAP Study comprises three sequential projects (MULTIPAP and MULTIPAP Plus RCTs, and the MULTIPAP Cohort). Results of MULTIPAP RCT are presented.AimTo evaluate the effectiveness of a complex, patient-centred intervention in young-old patients with multimorbidity and polypharmacy.MethodPragmatic cluster-randomised clinical trial in a primary healthcare setting. GPs were randomly allocated to either conventional care or the MULTIPAP intervention based on the Ariadne Principles with two components: GPs e-training (that is, eMULTIPAP addresses specific, key concepts on multimorbidity, polypharmacy and shared decision-making) and GP–patient-centred interview. Young-old patients aged 65–74 years with multimorbidity and polypharmacy were included. Main outcome: difference in the Medication Appropriateness Index (MAI) after 6-month follow-up between groups. Secondary outcomes: MAI, quality of life, patient perception, health services use, treatment adherence and cost-effectiveness after 12-month follow-up.Results117 GPs from 38 Spanish primary health care recruited 593 patients randomly assigned to the intervention/control groups. Difference in MAI scores between groups in the intention-to-treat analysis after 6 months’ follow-up: −2.42 (−4.27 to −0.59), P = 0.009 (adjusted difference in mean MAI score −1.81(−3.35 to −0.27), P = 0.021). Secondary outcomes: not significant, including quality of life (adjusted difference in mean EQ-5D-5L (VAS) 2.94 (−1.39 to 7.28), P = 0.183, EQ-5D-5L (index) −0.006(−0.034 to 0.022), P = 0.689).ConclusionThe intervention significantly improved medication appropriateness. The observed quality of life improvement was not significant. GPs e-training in multimorbidity has shown to be feasible and well accepted by the professionals. Future studies may test whether this format facilitates implementation.

The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in DNMT3A, TET2, and ASXL1 (DTA genes) was positively associated with age for the whole cohort (p = 0.025, OR: 1.047, 95% CI: 1.006&ndash, 1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients (p = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of &ge, 1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, p = 0.0024). Specifically, mutations in TET2 were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95% CI: 1.15&ndash, 11.83, p = 0.031). Our results suggest that pathogenic DTA mutations, and particularly TET2 mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of TET2 and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort.

Resumen: Objetivo: El objetivo de esta revisión es actualizar el estado del arte de las diferentes formas de sobreutilización, sobrediagnóstico y sobretratamiento dentro de la salud mental. Método: Se realizó una revisión narrativa utilizando las fuentes de datos de Medline hasta 2018 y se seleccionaron estudios en humanos donde el sobrediagnóstico era objeto de tratamiento en el desarrollo del artículo porque se centrase en su discusión o se abordase como tema principal, no aquellos en los que se mencionase de forma somera. Resultados: Se obtuvieron más de 200 referencias relacionadas con sobrediagnóstico y sobretratamiento en Salud Mental, de las cuales 40 fueron revisiones narrativas. Las principales se relacionaron con el estudio de criterios diagnósticos más que con la estimación de la sobreutilización médica en Salud Mental. Trastornos de ansiedad y depresión, trastorno bipolar y trastorno por déficit de atención e hiperactividad agrupan el mayor número de referencias en este ámbito. Conclusiones: La variedad en la terminología y la dificultad de la objetivación en Salud Mental hacen de este campo un nicho para el sobrediagnóstico. Palabras clave: Sobrediagnóstico, Sobretratamiento, Sobreutilización de servicios sanitarios, Tráfico de enfermedades

Annexins are a multigene family of proteins involved in aggregation and fusion processes of biological membranes. One of its best-known members is annexin A2 (or p36), capable of binding to acidic phospholipids in a calcium-dependent manner, as occurs with other members of the same family. In its heterotetrameric form, especially with protein S100A10 (p11), annexin A2 has been involved as a determinant factor in innumerable biological processes like tumor development or anticoagulation. However, the subcellular coexistence of different pools of the protein, in which the monomeric form of annexin A2 is growing in functional relevance, is to date poorly described. In this work we present an exhaustive structural and functional characterization of monomeric human annexin A2 by using different recombinant mutants. The important role of the amphipathic N-terminal α-helix in membrane binding and aggregation has been analyzed. We have also studied the potential implication of lateral "antiparallel" protein dimers in membrane aggregation. In contrast to what was previously suggested, formation of these dimers negatively regulate aggregation. We have also confirmed the essential role of three lysine residues located in the convex surface of the molecule in calcium-free and calcium-dependent membrane binding and aggregation. Finally, we propose models for annexin A2-mediated vesicle aggregation mechanisms.

Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease.

Objetivo Analizar el papel de las unidades docentes (UD) de atención familiar y comunitaria como agentes facilitadores de la implementación de guías de práctica clínica (GPC) y los factores asociados a un mayor esfuerzo en esta tarea. Material y métodos Diseño: estudio descriptivo transversal con enfoque analítico. Participantes UD en España (n = 94). Mediciones principales Variables recogidas mediante encuesta autocumplimentada en 5 dominios: características de las UD, actividad formativa dirigida a la práctica clínica basada en pruebas, importancia atribuida a esta actividad, responsabilidad sobre implementación de GPC y percepción sobre barreras y facilitadores para su uso. Análisis descriptivo y multivariante siendo la variable dependiente el esfuerzo percibido de las UD para implementar GPC. Resultados Respondieron 45 UD (47,9%). El 42,2% (IC 95%: 27,8-56,6) de sus responsables ha dirigido proyectos de investigación y el 31,1% (IC 95%:17,6- 44,6) ha participado en elaborar GPC. Organizaban una media de 51 horas (DE 47,2) de formación en práctica clínica basada en pruebas. El 97,7% (IC 95%:93,3-100) consideraba fundamental que los residentes conozcan y apliquen GPC y el 93,3% (IC 95%: 86,0-100) consideran los tutores responsables de implementarlas. Se relacionaron con un mayor esfuerzo de las UD la participación del responsable en GPC (coef.: 0,58; IC 95%: 0,00-1,16), la importancia dada a que los residentes las conozcan (coef.: 0,89; IC 95%: 0,24-1,54) y que estas parezcan aplicables (coef.: 0,35; IC 95%: –0,01-0,70). Conclusiones Las UD reconocen la importancia de las GPC y consideran a los tutores responsables de su implementación. El esfuerzo de las UD para implementar GPC se relacionó con la experiencia previa de los responsables, la percepción de aplicabilidad y de necesidad de los residentes.

Background: Several studies on the epidemiology of autoimmune diseases performed within the past several decades revealed a prevalence of Sjogren Syndrome (SS) between 0.3% and 4.83% (1). More recent studies revealed a lower prevalence between 31/100,000 to 49/100,000 (2 3). The exact prevalence of SS is unknown due to the heterogeneity of the populations and geographic areas studied, the utilization of different diagnostic tests or the lack of a unique classification criteria for the disease. Also, the disease may have an insidious onset and a variable course with a broad spectrum of clinical manifestations, so the diagnosis may be delayed or SS patients may be missed and misclassified as other rheumatic disease. Besides, SS can occur alone (primary SS) or in association with other specific systemic autoimmune rheumatic diseases (secondary SS). Objectives: The aim of our study was to determine the prevalence of SS in the Community of Madrid (CM) and to describe the sociodemographic and clinical characteristics of these patients. Methods: Population-based cross-sectional study in the CM, Spain. The information source for SS cases was the Registry of rare diseases in the CM (SIERMA). A descriptive analysis of the main sociodemographic and clinical characteristics of SS cases was performed. Prevalence per 10,000 inhabitants in people with 18 years of age and over, stratified by sex and their 95% confidence intervals (CI) were calculated for 2015. The denominator was the people registered at the Population Register in the middle of the period (July 2015). Results: There were 4,778 cases of SS in SIERMA and 389 (8,1%) of them were already dead. 4434 (92.8%) were women. The median age was 64,7 years (15,4), and the maximum age was 103 years. The disease was most frequent in the sixth decade with 1079 cases (22,6%), in the seventh decade with 1120 cases (23,4%) and in the eighth decade with 935 cases (19,6). 3116 cases (65.2%) were classified as primary SS (pSS) and 1662 (34.8%) as secondary SS (sSS). Among the sSS the main rheumatological conditions associated were rheumatoid arthritis (58%), lupus (24,5%), systemic Sclerosis (10,5%); mixed connective tissue (4%), inflammatory muscle disease (2%) and vasculitis (1%). The prevalence of SS in adults (≥ 18 years of age) was 8.4/10,000 with a 95% CI: 8.2 – 8.7 (14.9% in women and 0,8% in men). The prevalence of pSS was 5.5/10,000 (CI 5,3 – 5,7) and for sSS was 2.8/10,000 (95%CI: 2.7-3). Conclusion: SS mainly affects females during the sixth, seventh and eight decades of life, and shows a female:male ratio of 9:1. Two out of three cases of SS identified were classified as pSS. The main rheumatological conditions associated were rheumatoid arthritis and lupus. The estimated prevalence of SS in the Community of Madrid population is lower than the observed in previous studies whereas the prevalence of pSS is similar than the observed in current studies. References: [1] Toms M, Logar D, Grmek M, Perkovic T, Kveder T. Prevalence of Sjogren’s syndrome in Slovenia. Rheumatology. 1999;38:164–70. [2] Sardu C, Cocco E, Mereu A, Massa R, Cuccu A, Marrosu MG, et al. Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity. Ashour HM, editor. PLoS One [Internet]. 2012 Mar 2;7(3):e32487. Available from: http://dx.plos.org/10.1371/journal.pone.0032487 [3] Prevalencia de las enfermedades raras: Datos bibliograficos », Informes Periodicos de Orphanet, Serie Enfermedades Raras, Enero 2019, Numero 1 : Listado por orden alfabetico de enfermedades o grupo de enfermedades http://www.orpha.net/orphacom/cahiers/docs/ES/Prevalencia_de_las_enfermedades_raras_por_orden_alfabetico.pdf Disclosure of Interests: None declared

Aeroallergens are airborne substances-mainly proteins-capable of triggering Th2-immune responses in respiratory allergies. They enter into the body through the upper airways, reaching the mucosa afterward. Mucosae lining at the luminal side consists of an epithelial barrier completely covered by mucus and pulmonary surfactant. Both pulmonary surfactant and plasma membrane of the epithelial cells represent two physiological phospholipid-based barriers where allergens first impact before triggering their biological effects. The interaction of allergens with lipids at relevant physiological surfaces could promote structural changes on the molecule, resulting on a potential modification of its allergenic properties. In this work, we have first described the surface and phospholipid interaction capabilities of the clinically relevant aeroallergen Ole e 1, the main allergen of olive tree pollen. By using epifluorescence microscopy of Langmuir transferred films, we observed that lipid-packed ordered domains may function as a preferential location for allergen to accumulate at the air-liquid interface, an effect that is abolished in the presence of cholestenone. The possible implications of phospholipid-interfacial effects in the modification of allergen structural and functional properties will be discussed.

Multimorbidity (MM) is a widespread problem and it poses unsolved issues like the healthcare professionals' training. A training curriculum has been proposed, but it has not been sufficiently explored in a clinical context. The eMULTIPAP course is part of the MULTIPAP complex intervention, applied through a pragmatic controlled, cluster randomized clinical trial to general practitioners (GP) and his/her patients with MM with 12 months follow-up. The eMULTIPAP course is based on problem-based learning, constructivism and Ariadne principles. It has been assessed according to the Kirkpatrick model and has shown knowledge improvement and high applicability of learning with more motivation to consider MM in the clinical practice. It has also improved the Medication Appropriateness Index at 6-months and at 12- months. We conclude that the eMULTIPAP course generates significant changes in GP's learning, enhancing clinical practice in multimorbidity scenarios.

Ole e 7 allergen from Olea europaea pollen possesses a major clinical relevance because it produces severe symptoms, such as anaphylaxis, in allergic patients exposed to high olive pollen counts. Ole e 7 is a non-specific lipid transfer protein (nsLTP) characterized by the presence of a tunnel-like hydrophobic cavity, which may be suitable for hosting and, thus, transporting lipids -as it has been described for other nsLTPs-. The identification of the primary amino acid sequence of Ole e 7, and its production as a recombinant allergen, allowed characterizing its lipid-binding properties and its effect at air-liquid interfaces. Fluorescence and interferometry experiments were performed using different phospholipid molecular species and free fatty acids to analyse the lipid-binding ability and specificity of the allergen. Molecular modelling of the allergen was used to determine the potential regions involved in lipid interaction. Changes in Ole e 7 structure after lipid interaction were analysed by circular dichroism. Changes in the IgE binding upon ligand interaction were determined by ELISA. Wilhelmy balance measurements and fluorescence surfactant adsorption tests were performed to analyse the surface activity of the allergen. Using these different approaches, we have demonstrated the ability of Ole e 7 to interact and bind to a wide range of lipids, especially negatively charged phospholipids and oleic acid. We have also identified the protein structural regions and the residues potentially involved in that interaction, suggesting how lipid-protein interactions could define the behaviour of the allergen once inhaled at the airways. This work was supported by SAF2014-53209-R and SAF2017-86483-R grants from the Ministerio de Economía y Competitividadto R.B. and M.V., and to M.V., respectively, RTI2018-094564-B-I00 from the Spanish Ministry of Science and Universities andP2018/NMT4389 from the Regional Government of Madrid to J.P-G. and A.C., and RIRAAF Network RD12/0013/0015 grant and ARADyAL Network RD16/0006 grant from the Instituto de Salud Carlos III (ISCIII) co-founded by Fondo Europeo de Desarrollo Regional -FEDER-for the Thematic Networks and Co-operative Research Centres.A.J. and C.M. acknowledge PI-01119-2016 from the Consejería de Salud (Junta de Andalucía) and the Alergosur Foundation. JC.L-R., P.SS-A. and C.G-M. are recipients of a FPU fellowship from the Ministerio de Educación, Cultura y Deporte. We also gratefully acknowledge the financial support from theAES-ISCIII for the PI17CIII/00045 grant to R.B. We also thank the excellent technical support of Sara Abián. Sí

Resumen Objetivo El objetivo de esta revisión es actualizar el estado del arte de las diferentes formas de sobreutilización, sobrediagnóstico y sobretratamiento dentro de la salud mental. Método Se realizó una revisión narrativa utilizando las fuentes de datos de Medline hasta 2018 y se seleccionaron estudios en humanos donde el sobrediagnóstico era objeto de tratamiento en el desarrollo del artículo porque se centrase en su discusión o se abordase como tema principal, no aquellos en los que se mencionase de forma somera. Resultados Se obtuvieron más de 200 referencias relacionadas con sobrediagnóstico y sobretratamiento en Salud Mental, de las cuales 40 fueron revisiones narrativas. Las principales se relacionaron con el estudio de criterios diagnósticos más que con la estimación de la sobreutilización médica en Salud Mental. Trastornos de ansiedad y depresión, trastorno bipolar y trastorno por déficit de atención e hiperactividad agrupan el mayor número de referencias en este ámbito. Conclusiones La variedad en la terminología y la dificultad de la objetivación en Salud Mental hacen de este campo un nicho para el sobrediagnóstico.

ResumenObjetivoEstimar la proporción de resultados positivos en el cribado del trastorno bipolar (TB) entre los pacientes de atención primaria que consultan por problemas de naturaleza psicológica, y analizar sus características.DiseñoEstudio descriptivo transversal multicéntrico.EmplazamientoDiecinueve consultas de atención primaria en diferentes comunidades autónomas.PacientesLa muestra estuvo formada por 360 pacientes consecutivos de atención primaria con edades entre 18 y 70años visitados por síntomas psicológicos.MedicionesEl cribado para TB se realizó mediante el Mood Disorders Questionnaire. Se obtuvieron datos sobre calidad de vida (EuroQol-5D), impacto funcional (Sheehan Disability Inventory) y, mediante revisión de historias clínicas, datos sobre comorbilidad psiquiátrica y consumo de psicofármacos.ResultadosSe obtuvo una proporción de cribados positivos del 11,9% (IC95%: 8,8-15,7%). Solo en 2 de estos pacientes estaba registrado el diagnóstico de TB, y aunque más de la mitad recibían tratamiento con antidepresivos, solo 2 recibían tratamiento con estabilizadores del estado de ánimo. El cribado positivo se asocia a peor calidad de vida, a disfunción laboral, social y familiar, y a mayor estrés percibido.ConclusionesEl cribado del TB en pacientes de atención primaria con otros problemas psicológicos da lugar a una notable proporción de resultados positivos, lo que indica que puede haber una prevalencia relevante de pacientes con TB, la mayor parte de ellos no diagnosticados y no tratados adecuadamente. Es necesario profundizar en la investigación para determinar el eventual papel que puede o debe asumir la atención primaria en la detección, el diagnóstico o el manejo de este trastorno.AbstractObjectiveTo estimate the proportion of positive results in the screening of bipolar disorder (BD) among primary care patients presenting with psychological symptoms, and to analyze their characteristics.DesignMulticenter cross-sectional study.SettingsNineteen Primary Care clinics in different Spanish regions.PatientsA total of 360 consecutive primary care patients aged 18 to 70, presenting with psychological symptoms.MeasurementsScreening for BP was performed by means of the Mood Disorders Questionnaire. Data on quality of life (EuroQol-5D) and functional impairment (Sheehan Disability Inventory) were obtained. Data on psychiatric comorbidity and data on the use of psychotropic medication were acquired by review of medical records.ResultsOf the patients screened, 11.9% were positive (95%CI: 8.8%-15.7%). Only two patients had a diagnosis of BP in their clinical records and, although more than half received treatment with antidepressants, only two received treatment with mood stabilizers. Positive screening is associated with work, social and family dysfunction, greater perceived stress and poor quality of life.ConclusionsBD screening in primary care patients with psychological problems leads to a striking proportion of positive results, indicating that there may be a significant prevalence of BP patients, most of them undiagnosed and untreated. Further research is needed to determine the role that Primary Care can or should assume in the screening, diagnosis and management of this disorder.

La multimorbilidad, definida como la presencia de dos o más enfermedades crónicas en un mismo individuo, conlleva consecuencias negativas para la persona e importantes retos para los sistemas sanitarios. En atención primaria, donde recae esencialmente la atención de este grupo de pacientes, la consulta es más compleja que la de un paciente con una única enfermedad debido, entre otros, al hecho de tener que manejar mayor cantidad de información clínica, disponer de poca evidencia científica para abordar la multimorbilidad, y tener que coordinar la labor de múltiples profesionales para garantizar la continuidad asistencial. Además, para poder implementar correctamente los planes de tratamiento en estos pacientes es necesario un proceso de toma de decisiones compartida médico-paciente. Entre las distintas herramientas disponibles para apoyar dicho proceso, recientemente se ha desarrollado una dirigida específicamente a pacientes con multimorbilidad en atención primaria y que se describe en el presente artículo: los principios Ariadne. Multimorbidity, defined as the coexistence of two or more chronic conditions in one same individual, has negative consequences for people suffering from it and it poses a real challenge for health systems. In primary care, where most of these patients are attended, the clinical management of multimorbidity can be a complex task due, among others, to the high volume of clinical information that needs to be handled, the scarce scientific evidence available to approach multimorbidity, and the need for coordination among multiple health providers to guarantee continuity of care. Moreover, the adequate implementation of the care plan in these patients requires a process of shared decision making between patient and physician. One of the available tools to support this process, which is specifically directed to patients with multimorbidity in primary care, is described in the present article: the Ariadne principles.

Environmental proteases have been widely associated to the pathogenesis of allergic disorders. Der p 1, a cysteine-protease from house dust mite (HDM) Dermatophagoides pteronyssinus, constitutes one of the most clinically relevant indoor aeroallergens worldwide. Der p 1 protease activity depends on the redox status of its catalytic cysteine residue, which has to be in the reduced state to be active. So far, it is unknown whether Der p 1-protease activity could be regulated by host redox microenvironment once it reaches the lung epithelial lining fluid in addition to endogenous mite components. In this sense, Glutathione-S-transferase pi (GSTpi), an enzyme traditionally linked to phase II detoxification, is highly expressed in human lung epithelial cells, which represent the first line of defence against aeroallergens. Moreover, GSTpi is a generalist catalyst of protein S-glutathionylation reactions, and some polymorphic variants of this enzyme has been associated to the development of allergic asthma. Here, we showed that human GSTpi increased the cysteine-protease activity of Der p 1, while GSTmu (the isoenzyme produced by the mite) did not alter it. GSTpi induces the reduction of Cys residues in Der p 1, probably by rearranging its disulphide bridges. Furthermore, GSTpi was detected in the apical medium collected from human bronchial epithelial cell cultures, and more interesting, it increased cysteine-protease activity of Der p 1. Our findings support the role of human GSTpi from airways in modulating of Der p 1 cysteine-protease activity, which may have important clinical implications for immune response to this aeroallergen in genetically susceptible individuals. Keywords: House dust mite, Cysteine-protease, Der p 1, GSTpi, GSTmu, Allergen

Fungi establish a complex network of biological interactions with other organisms in nature. In many cases, these involve the production of toxins for survival or colonization purposes. Among these toxins, ribotoxins stand out as promising candidates for their use in biotechnological applications. They constitute a group of highly specific extracellular ribonucleases that target a universally conserved sequence of RNA in the ribosome, the sarcin-ricin loop. The detailed molecular study of this family of toxic proteins over the past decades has highlighted their potential in applied research. Remarkable examples would be the recent studies in the field of cancer research with promising results involving ribotoxin-based immunotoxins. On the other hand, some ribotoxin-producer fungi have already been studied in the control of insect pests. The recent role of ribotoxins as insecticides could allow their employment in formulas and even as baculovirus-based biopesticides. Moreover, considering the important role of their target in the ribosome, they can be used as tools to study how ribosome biogenesis is regulated and, eventually, may contribute to a better understanding of some ribosomopathies.

Objetivo: Evaluar la temporalidad y el perfil psicosocial de las conductas suicidas atendidas en el Hospital Universitario Central de Asturias (HUCA). Diseño: Estudio prospectivo. Pacientes: Fueron estudiados 1.633 sujetos que acudieron al Servicio de Urgencias por presentar conducta suicida durante el trienio 2003-2005. Resultados: Los sujetos que han realizado algún tipo de conducta suicida, se caracterizan por pertenecer al grupo de edad comprendido entre los 30 y 39 años, mujer, soltera, que convive con familia propia, con estudios primarios, inactiva económica y laboralmente, y de nacionalidad española. En relación al patrón de temporalidad, las tentativas de suicidio se caracterizan por ser llevadas a cabo durante las horas de la tarde, en días de semana, y durante los meses estivales. Objetive: To evaluate the temporality and the psicosocial profile of some suicidal behaviours that were taken care of in the Asturias Central University Hospital (HUCA). Design: Prospective study. Patients: 1633 subjects, who were assisted in the Emergency Unit due to a suicide attempt, were studied in 2003-2005. Results: The subjects who have had some kind of suicidal behaviour are usually 30-39 years old, female, single, living with their family, with primary education, unemployed, and of Spanish nationality. In regard to the temporality pattern, suicide attempts are commited in the evening, during weekdays, and in summer time. O objetivo é avaliar a temporalidade e o perfil psico-social das condutas suicidas atendidas no Hospital Universitário Central de Astúrias (HUCA). O estudo tem um desenho prospectivo. Os sujeitos do estudo foram 1633 pacientes, que recorreram ao Serviço de Urgências por apresentar conduta suicida, durante o triênio de 2003 a 2005. Os resultados mostraram que os sujeitos que desenvolveram conduta desse tipo, têm como perfil o fato de pertencerem ao grupo etário compreendido entre 30 e 39 anos; mulher, solteira, que convive com família própria, com estudos primários, inativa do ponto de vista econômica e trabalhista, e de nacionalidade espanhola. Em relação ao padrão de temporalidade, as tentativas de suicídio caracterizam-se por serem concretizadas durante o período vespertino, em dias de semana, e durante os meses de verão.

Brief Counseling Intervention (BCI) and Medical advice (MA) are psychotherapeutic approaches used for the treatment of binge drinkers in Primary Care. Although binge drinking is a common pattern of alcohol misuse in Europe and in the US, no studies have evaluated those subjects who do not respond to Brief Counseling Interventions or Medical Advice.To determine the clinical and demographic characteristics of binge drinkers in whom BCI or MA are not effective in reducing harmful alcohol use.This is a secondary analysis of data from a randomized alcohol brief intervention trial with a 12-month follow-up period. A total of 674 subjects (89%) participated right through to the end of the study. The primary outcome measure was change in harmful alcohol use from baseline to 12 months.The strongest baseline predictors of harmful alcohol use during follow-up were educational status, young adults, and high number of cigarettes smoked, present family history of alcoholism, treatment condition and number of drinks per episode of binge drinking.Binge drinkers are a heterogeneous group that responds to brief intervention or MA but in a subgroup of them these interventions fail to prevent harmful alcohol use. Other interventions should be implemented for these subjects.La Intervención Breve (IB) y el Consejo Médico simple (CM) son intervenciones psicoterapéuticas usadas para el tratamiento del consumo de alcohol por atracones en Atención Primaria. A pesar de la frecuencia de este patrón de abuso en Europa y en los Estados Unidos, ningún estudio ha evaluado las características de los sujetos que no responden a esas dos técnicas. Objetivo. Determinar las características demográficas y clínicas de los bebedores por atracones en los que la IB y el CM no son efectivos para la reducción del consumo perjudicial de alcohol. Métodos. Se trata de un análisis secundario de los datos obtenidos en un ensayo aleatorizado de intervención breve en alcohol con un período de seguimiento de 12 meses. Un total de 674 sujetos (89%) participaron durante todo el estudio hasta el final. La variable principal fue el cambio en el uso perjudicial de alcohol tras 12 meses de seguimiento. Resultados. Para ambos grupos de tratamiento las variables que predecían la continuidad en el consumo perjudicial tras el seguimiento eran: bajo nivel educativo, ser jóvenes, el número de cigarrillos fumados, la historia familiar de alcoholismo y la gravedad del consumo de alcohol basalmente. Conclusiones. Las características clínicas y sociodemográficas de los sujetos con un patrón de consumo de alcohol por atracones atendidos en Atención primaria influyen en el pronóstico de las Intervenciones breves y del Consejo Médico.