Testing for Vitamin D in High-Risk COPD in Outpatient Clinics in Spain: A Cross-Sectional Analysis of the VITADEPOC Study.

Background: Vitamin D deficiency has been associated with an accelerated deterioration in lung function and increased exacerbations in chronic obstructive pulmonary disease (COPD). 25(OH) vitamin D levels have been indicated as a potentially useful marker for adverse results related to COPD. Methods: VITADEPOC is a cross-sectional clinical study recruiting consecutive patients with high-risk COPD. The objective of our study was to investigate vitamin D determination frequency in patients with high-risk COPD in clinical practice at outpatient clinics in Spain and to describe the factors associated with vitamin D testing. We also aimed to determine the frequency of vitamin D deficiency in these patients. Results: Only 51 (44%) patients underwent vitamin D determination and 33 (28.4%) had received vitamin D supplements in clinical practice. The patients who underwent testing for vitamin D in clinical practice were more often women (58.8% vs. 26.2%, p < 0.001) with comorbidities such as osteoporosis (19.6% vs. 6.2%, p < 0.001) or chronic renal failure (7.8% vs. 0%, p < 0.001) and with exacerbator phenotype (55% vs. 32.3%, p = 0.015). A total of 63 (54.3%) patients had serum vitamin D levels <20 ng/mL at the inclusion visit. Of these, 29 (46%) had serum vitamin D levels <12 ng/mL (severe deficiency). Having a history of inhaled corticosteroids (OR 3.210, p < 0.016), being treated with a cycle of systemic corticosteroids (OR 2.149, p < 0.002), and having a lower physical activity level (OR 3.840, p < 0.004) showed a statistically significant positive association with vitamin D deficiency. Conclusion: The testing of vitamin D levels in patients with high-risk COPD treated at outpatient respiratory clinics in Spain is infrequent. However, when tested, a severe deficiency is detected in one in four patients. Efforts to optimize case detection in COPD are needed.

Accelerated immunosenescence, oxidation and inflammation lead to a higher biological age in COPD patients.

Chronic obstructive pulmonary disease (COPD) is characterised by inflammatory and oxidative alterations in the lung and extrapulmonary compartments, through involvement of the immune system. Several leukocyte functions are health markers and good predictors of longevity, and high pro-inflammatory and oxidative states are related to more aged profiles. Here, we aimed to investigate the aging rate in terms of immunosenescence in COPD men with respect to healthy age-matched controls. Several neutrophil (adherence, chemotaxis, phagocytosis, superoxide anion stimulated production) and lymphocyte (adherence, chemotaxis, lymphoproliferation, natural killer activity) functions, cytokine concentrations released in response to lipopolysaccharide (tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, IL-10) and redox parameters (intracellular glutathione content, basal superoxide anion level) were assessed in circulating leukocytes of men with moderate and severe stages of COPD, and compared to healthy age-matched volunteers. The biological age or aging rate in each participant was determined using the values of leukocyte functions. The results indicated impairment of immune functions in COPD patients, both in innate and adaptive immunity, and higher pro-inflammatory and oxidative states in peripheral leukocytes than controls. In general, these changes were more remarkable at the severe stage of airway obstruction. Importantly, COPD patients were found to be aging at a faster rate than age-matched healthy counterparts.

Noninvasive electrical stimulation of oropharyngeal muscles in obstructive sleep apnea.

Introduction: Continuous positive airway pressure (CPAP) therapy remains the standard treatment for obstructive sleep apnea. However, its proven effect is useless if the patient does not tolerate the treatment. The electrical stimulation approach has been investigated for several decades now and it seems that the implantable devices for invasive electrical stimulation of hypoglossal nerve are viewed as effective with some of them already approved for human use.Areas covered: in this review, we intent to summarize the existing records of noninvasive stimulation in sleep apnea to make the scientific community aware of the details before deciding on its future. We believe that this is a battle still to fight and more could be done bearing in mind the safety of this method.Expertopinion: noninvasive electrical stimulation has been left behind based on few, small and inconsistent studies using different stimulation parameters. These studies are difficult to compare and to draw conclusions.Electrical stimulation is a field for research in the treatment of obstructive sleep apnea, with many aspects still to be discovered, and which may become a therapeutic alternative to the use of CPAP in certain patients.

Assessing the Usefulness of the Prevexair Smartphone Application in the Follow-Up High-Risk Patients with COPD.

INTRODUCTION: This manuscript analyzes the exacerbations recorded by the Prevexair application through the daily analysis of symptoms in high-risk patients with COPD and explores its usefulness in assessing clinical stability with respect to that reported in visits. PATIENTS AND METHODS: This study is a multi-centre cohort of COPD patients with the exacerbator phenotype who were monitored over 6 months. The Prevexair application was installed on the patients' smartphones. Patients used the app to record symptom changes, use of medication and use of healthcare resources. It is not established a recommended action plan when worsening of symptoms. At their clinical visit during the follow-up period, patients were asked about exacerbations suffered during these 6 months of monitoring. The investigators who conducted the visit were blinded about the Prevexair app records. RESULTS: The patients experienced a total of 185 exacerbations according to daily records in the app whereas only 64 exacerbations were recalled during medical visits. Perception became more accurate for severe exacerbations (kappa 0.6577), although we found no factors that predicted poor recall. The proportion of 72.5% patients were classified as unstable if the exacerbations captured by Prevexair were used to define stability, versus 47.8% if the exacerbations recall in visit was used. Two-thirds of the exacerbations recorded in the Prevexair application were not reported to doctors during their clinical visits. Almost half were treated with oral corticosteroids and/or antibiotics and more than one-quarter of the exacerbations treated did not seek medical attention. CONCLUSION: The findings of this cohort study confirm that patients do not always remember the exacerbations suffered during their medical visit. The prevexair application is useful in monitoring COPD patients at high risk, in order to a better assessment of exacerbations of COPD during medical visits. Further research must be carried out to evaluate this strategy in clinical practice.

La figura docente del profesor contratado doctor vinculado: situación actual en España y la experiencia de Andalucía / The figure of the tenure-eligible lecturer: current situation Spain and experience in Andalusia

En este documento se refieren las bases legales nacionales y, más en concreto, las autonómicas andaluzas que dan respaldo a la figura del profesor contratado doctor vinculado y a la posibilidad de convocar las plazas correspondientes en las facultades de medicina de las universidades públicas españolas. Se exponen, asimismo, las características asistenciales y académicas que deben darse para llevar a cabo la convocatoria pública de dichas plazas. Se resume, a continuación, cuál es la situación actual existente en relación con dicha figura del profesorado en las facultades de medicina españolas. Se analizan también las ventajas y las posibles limitaciones que actualmente se derivan de contar con profesores contratados doctores vinculados y ello tanto para los médicos especialistas eventualmente interesados en optar a una de estas plazas como para el centro sanitario y la facultad de medicina correspondientes. Finalmente, se reseña la posible utilidad del documento elaborado por la Conferencia Nacional de Decanos de Facultades de Medicina de España (CNDFME) en la Asamblea General que se celebró en la Facultad de Medicina de Oviedo del 17 al 19 de mayo del 2018 y actualizado en marzo de 2020

A discussion is presented on the national legal foundations, and more specifically, those of Andalusia, that support the figure of the tenure-eligible lecturer and the possibility of filling the corresponding positions in the faculties of medicine in Spanish public universities are discussed. The clinical and academic characteristics that they must have in order to fill those public positions are also presented. The current situation as regards such a figure as a lecturer in Spanish faculties of medicine is then summarised. An analysis is made of the advantages and the possible limitations arising from having a tenure-eligible lecturer, and how this affects both the medical specialists possibly interested in opting for one of these positions, as well as for the corresponding health centres and faculties of medicine. Finally, mention is made of the possible use of the document prepared by the National Conference of Medical Faculty Deans (CNDFME) in the General Assembly held in the Oviedo Faculty of Medicine from 17 to 19 May 2018, and updated in March 2020

Efficacy of rituximab in slowing down progression of rheumatoid arthritis-related interstitial lung disease: data from the NEREA Registry.

OBJECTIVES: To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS: A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS: A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION: RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified.

El hospital universitario: criterios para su acreditación / The university hospital: Criteria for its accreditation

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La enseñanza de la práctica clínica en la Facultad de Medicina de la Universidad Complutense de Madrid / Teaching of clinical practice in the Faculty of Medicine of the Complutense University of Madrid

Se describe la metodología de instrucción y evaluación en práctica clínica y el grado de implicación del profesorado en esta tarea en la Unidad Docente del Hospital 12 de Octubre (Facultad de Medicina, Universidad Complutense de Madrid). A pesar de algunas disfunciones curriculares, nuestros estudiantes alcanzan un buen nivel de competencia clínica al final del grado. Algunos profesores tienen un conocimiento limitado de los roles docentes que pueden asumir, por lo que deberían recibir formación específica. Idealmente, la enseñanza clínica ha de implicar a todos los profesionales que cuidan del paciente en el contexto extra- e intrahospitalario

We describe the methodology for instruction and assessment of clinical practice and analyze the profile and teaching roles of faculty at the Teaching Unit of the Hospital 12 de Octubre (Faculty of Medicine, Complutense University of Madrid). Despite some structural limitations in curriculum development our students reach a good final level of clinical competence. The need for trainers to understand the different roles they can assume, improving faculty development and involving all the professionals taking care of the patient in the teaching process are emphasized

Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion.

BACKGROUND: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. METHODS: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. RESULTS: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 Kaplan-Meier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. CONCLUSIONS: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion.

Health literacy and health outcomes in chronic obstructive pulmonary disease.

BACKGROUND: There is little information worldwide about the impact of health literacy (HL) on clinical outcomes of COPD. Our aim was to quantify inadequate HL in Spain, as measured by the Short Assessment of Health Literacy for Spanish Adults questionnaire, and to examine the associations between HL and both COPD outcomes and health status. METHODS: 296 COPD patients of 68(SD = 9) years and a FEV1%predicted of 53%(SD = 18%) were enrolled and followed-up for one year. 59% showed "inadequate" HL. RESULTS: Individuals with inadequate HL were older (70[SD = 9] vs 65[SD = 8] years; p < 0.001) and had less knowledge of their disease, as measured by the low HL-COPD questionnaire, (6.9[SD = 2.3] vs 7.5[SD = 1.9]; p < 0.001). While their lung function was no different, they reported significant differences in mMRC (1.6[SD = 1] vs 1.4[SD = 1]; p < 0.001), CAT (19.2[SD = 8.1] vs 18.3[SD = 7.5]; p = 0.049), and EQ-5 (3.1[SD = 2.2] vs 2.3[SD = 1.9]; p < 0.00). Those with inadequate HL had also higher risk of having ≥2 comorbidities (OR = 1.87; 95%CI = 1.14-3.08), need of assistance (OR = 2.5; 95%CI = 1.5-4.2), anxiety/depression (OR = 1.9; 95%CI = 1.2-3.0), admissions or visits to the emergency department (OR = 1.70; 95%CI = 1.1-2.7), and all-cause deaths in the following year (3.8% (SE = 1.1%) vs 0%; p = 0.051). CONCLUSIONS: Inadequate HL is prevalent among COPD patients and it is related to health status and relevant clinical outcomes of the disease. HL needs to be considered when planning the care for COPD patients.

Conocimientos de la población general sobre la enfermedad pulmonar obstructiva crónica y sus determinantes: situación actual y cambios recientes / The General Public’s Knowledge of Chronic Obstructive Pulmonary Disease and Its Determinants: Current Situation and Recent Changes

Antecedentes: El objetivo de este estudio fue determinar el nivel de conocimiento actual sobre la enfermedad pulmonar obstructiva crónica (EPOC) y sus determinantes en la población general de España, y compararlo con una encuesta similar realizada en 2002. Métodos: En septiembre de 2011 se realizó un estudio epidemiológico observacional transversal, mediante entrevista telefónica, con una muestra representativa de entre 40 y 80 años de edad en las 17 comunidades autónomas. Resultados: Se obtuvo un total de 6.528 respuestas (porcentaje de respuesta del 13,1%), con el 53% de mujeres y una edad media de 59,8 años. Respecto al tabaco, el 19,4% eran fumadores actuales, mientras que el 27,9% referían ser exfumadores. Solo el 17,0% refería espontáneamente que conocía el término EPOC. La Comunidad Valenciana era la que tenía un mayor grado de desconocimiento de la EPOC (91%), mientras que Aragón era la que lo tenía menor (73,7%). Pese a todo, la EPOC está considerada una enfermedad grave, solo por debajo de la angina de pecho. Comparando estos resultados con la encuesta anterior de 2002, se aprecian mejoras significativas respecto al conocimiento de la EPOC (8,6 vs. 17,0%), con una marcada variabilidad según la comunidad autónoma (p<0,05). Actualmente tan solo el 4,7% de la población española conoce que existe la Estrategia Nacional de EPOC, aunque el 86,0% tiene una opinión favorable/muy favorable sobre la nueva Ley antitabaco. Conclusión: El desconocimiento sobre la EPOC y sus determinantes en la población general se mantiene elevado respecto a 2002, por lo que son necesarias más y mejores intervenciones divulgativas y de concienciación(AU)

Background: The objective of this study was to determine the level of knowledge about chronic obstructive pulmonary disease (COPD) and its determinants in the general population of Spain, and to compare it with a similar survey conducted in 2002. Methods: We conducted a cross-sectional, observational, epidemiological study in September 2011 by means of a telephone interview with a representative sample of individuals aged 40-80 years living in all 17 regions of Spain. Results: A total of 6,528 responses were obtained (response rate of 13.1%), 53% of respondents were females with a mean age of 59.8 years. Regarding tobacco use, 19.4% were current smokers while 27.9% reported being former smokers. Only 17.0% spontaneously recognized the term «COPD». Valencia was the region with the highest degree of ignorance regarding COPD (91%), while Aragon had the lowest (73.7%). Nevertheless, COPD is considered a severe disease, following angina pectoris in severity. Upon comparing these results with the previous survey from 2002, we observed significant improvements in the knowledge and understanding of COPD (8.6% vs. 17.0%), with a marked variability between the regions (P<.05). Currently, only 4.7% of the Spanish population knows that there is a National Strategy for COPD, although 86.0% have a favorable or very favorable opinion about the new Anti-tobacco Law. Conclusion: The lack of knowledge about COPD and its determinants in the general population remains high compared to 2002; thus, more and better educational and awareness programs are necessary(AU)

Monitoring breathing rate at home allows early identification of COPD exacerbations.

BACKGROUND: Respiratory frequency increases during exacerbations of COPD (ECOPD). We hypothesized that this increase can be detected at home before ECOPD hospitalization. METHODS: To test this hypothesis, respiratory frequency was monitored at home daily for 3 months in 89 patients with COPD (FEV1, 42.3% ± 14.0%; reference) who were receiving domiciliary oxygen therapy (9.6 ± 4.0 h/d). RESULTS: During follow-up, 30 patients (33.7%) required hospitalization because of ECOPD. In 21 of them (70%), mean respiratory frequency increased (vs baseline) during the 5 days that preceded it (from 15.2 ± 4.3/min to 19.1 ± 5.9/min, P < .05). This was not the case in patients without ECOPD (16.1 ± 4.8/min vs 15.9 ± 4.9/min). Receiver operating characteristic analysis showed that 24 h before hospitalization, a mean increase of 4.4/min (30% from baseline) provided the best combination of sensitivity (66%) and specificity (93%) (area under the curve [AUC] = 0.79, P < .05). Two days before hospitalization, a mean increase of 2.3/min (15% change from baseline) was associated with a sensitivity of 72% and a specificity of 77% (AUC = 0.76, P < .05). CONCLUSIONS: Respiratory frequency can be monitored daily at home in patients with COPD receiving domiciliary oxygen therapy. In these patients, breathing rate increases significantly days before they require hospitalization because of ECOPD. This may offer a window of opportunity for early intervention.

The general public's knowledge of chronic obstructive pulmonary disease and its determinants: current situation and recent changes.

BACKGROUND: The objective of this study was to determine the level of knowledge about chronic obstructive pulmonary disease (COPD) and its determinants in the general population of Spain, and to compare it with a similar survey conducted in 2002. METHODS: We conducted a cross-sectional, observational, epidemiological study in September 2011 by means of a telephone interview with a representative sample of individuals aged 40-80 years living in all 17 regions of Spain. RESULTS: A total of 6,528 responses were obtained (response rate of 13.1%), 53% of respondents were females with a mean age of 59.8 years. Regarding tobacco use, 19.4% were current smokers while 27.9% reported being former smokers. Only 17.0% spontaneously recognized the term «COPD¼. Valencia was the region with the highest degree of ignorance regarding COPD (91%), while Aragon had the lowest (73.7%). Nevertheless, COPD is considered a severe disease, following angina pectoris in severity. Upon comparing these results with the previous survey from 2002, we observed significant improvements in the knowledge and understanding of COPD (8.6% vs. 17.0%), with a marked variability between the regions (P<.05). Currently, only 4.7% of the Spanish population knows that there is a National Strategy for COPD, although 86.0% have a favorable or very favorable opinion about the new Anti-tobacco Law. CONCLUSION: The lack of knowledge about COPD and its determinants in the general population remains high compared to 2002; thus, more and better educational and awareness programs are necessary.

Neutral sphingomyelinase, NADPH oxidase and reactive oxygen species. Role in acute hypoxic pulmonary vasoconstriction.

The molecular mechanisms underlying hypoxic pulmonary vasoconstriction (HPV) are not yet properly understood. Mitochondrial electron transport chain (ETC) and NADPH oxidase have been proposed as possible oxygen sensors, with derived reactive oxygen species (ROS) playing key roles in coupling the sensor(s) to the contractile machinery. We have recently reported that activation of neutral sphingomyelinase (nSMase) and protein kinase C ζ (PKCζ) participate in the signalling cascade of HPV. Herein, we studied the significance of nSMase in controlling ROS production rate in rat pulmonary artery (PA) smooth muscle cells and thereby HPV in rat PA. ROS production (analyzed by dichlorofluorescein and dihydroethidium fluorescence) was increased by hypoxia in endothelium-denuded PA segments and their inhibition prevented hypoxia-induced voltage-gated potassium channel (K(V) ) inhibition and pulmonary vasoconstriction. Consistently, H(2) O(2) , or its analogue t-BHP, decreased K(V) currents and induced a contractile response, mimicking the effects of hypoxia. Inhibitors of mitochondrial ETC (rotenone) and NADPH oxidase (apocynin) prevented hypoxia-induced ROS production, K(V) channel inhibition and vasoconstriction. Hypoxia induced p47(phox) phosphorylation and its interaction with caveolin-1. Inhibition of nSMase (GW4869) or PKCζ prevented p47(phox) phosphorylation and ROS production. The increase in ceramide induced by hypoxia (analyzed by immunocytochemistry) was inhibited by rotenone. Exogenous ceramide increased ROS production in a PKCζ sensitive manner. We propose an integrated signalling pathway for HPV which includes nSMase-PKCζ-NADPH oxidase as a necessary step required for ROS production and vasoconstriction.

Tutores de residentes de neumología en España: resultados de las reuniones formativas anuales / No disponible

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