Antiviral treatment for SARS-CoV-2 infection in the current situation: a position paper of the Spanish Society of Emergency Medicine (SEMES). / Posicionamiento de la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) ante el tratamiento antiviral frente al SARS-CoV-2 en la situación epidemiológica actual.

SUMMARY: COVID-19 continues to pose a significant threat: mortality stands at nearly twice that of influenza, and the incidence rate is growing as the population's vaccination rate decreases, particularly in Spain and other areas of Europe. Given this situation, it is vitally important know whether medical protocols are consistent and appropriately implemented by health care staff in the interest of preventing possible inefficiency or inequity. Physicians from hospital emergency departments met to study their hospitals' usual clinical practices for managing SARS-CoV-2 infection and to determine their expert opinions on the use of antiviral agents. The participating physicians then reached consensus on evidencebased recommendations for strategies that would optimize emergency treatment.

RESUMEN: Actualmente, la COVID-19 sigue representando una amenaza significativa, con una mortalidad cercana al doble de la ocasionada por la gripe y con una incidencia variable debido a una disminución en la tasa de vacunación de la población, especialmente en el contexto europeo y español. Ante este panorama, es de vital importancia comprobar que los protocolos médicos están consolidados y son debidamente implementados por los profesionales sanitarios, con la finalidad de evitar posibles ineficiencias o inequidades. A través de reuniones con profesionales de urgencias se han observado las prácticas clínicas habituales en los servicios de urgencias hospitalarios para pacientes con infección por SARS-CoV-2, con la finalidad de comprender la perspectiva de estos profesionales acerca del uso de antivirales y, tras un consenso de expertos basados en la evidencia actual, se han generado estas de recomendaciones para poder enfocar estrategias que optimicen el tratamiento de los pacientes en estos servicios.

Effect of early initiation of noninvasive ventilation in patients transported by emergency medical service for acute heart failure.

BACKGROUND: While the indication for noninvasive ventilation (NIV) in severely hypoxemic patients with acute heart failure (AHF) is often indicated and may improve clinical course, the benefit of early initiation before patient arrival to the emergency department (ED) remains unknown. OBJECTIVE: This study aimed to assess the impact of early initiation of NIV during emergency medical service (EMS) transportation on outcomes in patients with AHF. DESIGN: A secondary retrospective analysis of the EAHFE (Epidemiology of AHF in EDs) registry. SETTING: Fifty-three Spanish EDs. PARTICIPANTS: Patients with AHF transported by EMS physician-staffed ambulances who were treated with NIV at any time during of their emergency care were included and categorized into two groups based on the place of NIV initiation: prehospital (EMS group) or ED (ED group). OUTCOME MEASURES: Primary outcome was the composite of in-hospital mortality and 30-day postdischarge death, readmission to hospital or return visit to the ED due to AHF. Secondary outcomes included 30-day all-cause mortality after the index event (ED admission) and the different component of the composite primary endpoint considered individually. Multivariate logistic regressions were employed for analysis. RESULTS: Out of 2406 patients transported by EMS, 487 received NIV (EMS group: 31%; EMS group: 69%). Mean age was 79 years, 48% were women. The EMS group, characterized by younger age, more coronary artery disease, and less atrial fibrillation, received more prehospital treatments. The adjusted odds ratio (aOR) for composite endpoint was 0.66 (95% CI: 0.42-1.05). The aOR for secondary endpoints were 0.74 (95% CI: 0.38-1.45) for in-hospital mortality, 0.74 (95% CI: 0.40-1.37) for 30-day mortality, 0.70 (95% CI: 0.41-1.21) for 30-day postdischarge ED reconsultation, 0.80 (95% CI: 0.44-1.44) for 30-day postdischarge rehospitalization, and 0.72 (95% CI: 0.25-2.04) for 30-day postdischarge death. CONCLUSION: In this ancillary analysis, prehospital initiation of NIV in patients with AHF was not associated with a significant reduction in short-term outcomes. The large confidence intervals, however, may preclude significant conclusion, and all point estimates consistently pointed toward a potential benefit from early NIV initiation.

Use of digoxin in the emergency department to treat patients with acute heart failure and its impact on short-term outcomes. / Uso de digoxina endovenosa en urgencias para tratar pacientes con insuficiencia cardiaca aguda y su impacto en la evolución a corto plazo.

OBJECTIVES: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. MATERIAL AND METHODS: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. RESULTS: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. CONCLUSION: Digoxin continues to be used in one out of ten ED patients who are not already on long-term treatment with the drug. Digoxin use is associated with cardiac decompensation triggered by atrial fibrillation with rapid ventricular response, younger age, women, and patients with better initial NYHA function status but possibly more severe decompensation. Digoxin use leads to a longer ED stay but is safe, as it is not associated with need for admission, prolonged hospitalization, or short-term mortality.

OBJETIVO: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. METODO: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. RESULTADOS: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. CONCLUSIONES: La digoxina continúa utilizándose en uno de cada 10 pacientes con ICA atendidos en urgencias que no utilizaban este fármaco de manera habitual. Su uso se relaciona con un paciente cuya ICA ha sido descompensada por una FA con respuesta ventricular rápida, más joven y más frecuentemente mujer, en mejor clase funcional de la NYHA basal y con una descompensación posiblemente más grave. El uso de digoxina conlleva una estancia en urgencias más prolongada, pero su uso es seguro, pues no se asocia a la necesidad de ingreso, hospitalización prolongada o mortalidad a corto plazo.

Medical training programs: comparisons between family and community medicine, internal medicine, intensive care medicine, anesthesiology and critical care, and emergency medicine. / Análisis comparativo de los Programas de Formación Sanitaria Especializada de Medicina Familiar y Comunitaria, Medicina Interna, Medicina Intensiva, Anestesiología y Reanimación y Medicina de Urgencias y Emergencias.

OBJECTIVES: To analyze whether current medical residency training programs in Spain foster the acquisition of knowledge and skills that enable specialists to provide emergency and urgent medical care. MATERIAL AND METHODS: We studied documents related to the content of residency programs for the following 4 specialties in effect in June 2021: internal medicine, intensive care medicine, anesthesiology and critical care, and family and community medicine. Program descriptions were obtained from the website of the Spanish Ministry of Health and the professional associations for each specialty. The associations' unofficial drafts and proposed updates were also studied. For emergency and urgent medicine, we studied drafts and updates of proposals presented to the Ministry of Health by the Spanish Society of Emergency Medicine (SEMES) in 2010 and an updated version presented in 2021. The proposals were drafted by the SEMES committee to promote specialization in emergency medicine. RESULTS: Existing residency programs treat the management of urgent events from diverse points of view related to hospital settings (internal medicine focusing on admitted patients, anesthesiology on patients in perioperative settings, and intensive care on those in their specialized units) or to primary care centers (family medicine), where they are an extension of routine care. The residents' rotations in emergency medicine vary. In anesthesiology, intensive care medicine, and family medicine, training occurs while residents are on call - in the first year for trainees in anesthesiology and intensive care medicine but throughout the 4-year residency (with time decreasing each year) for trainees in family medicine. Internal medicine offers an initial 3-month rotation in emergency medicine in the early phase and then assigns on-call shifts, without specifying a number. The proposed program submitted by SEMES includes wide-ranging contact with emergencies in various hospital settings (observation ward, trauma care, and pediatric care). Training in out-of-hospital emergencies and emergency and urgent care resource coordination centers are also included. CONCLUSION: Currently available residency training in Spain does not provide appropriate preparation for practicing emergency medicine. Emergency medicine has its own body of theory and settings for practice that differ from those of other specialties. Therefore, at present there is a training gap in Spain that should be filled by creating a specialization in emergency medicine.

OBJETIVO: Analizar si con las especialidades actuales se adquieren los conocimientos y habilidades necesarios para desempeñar las funciones propias de la Medicina de Urgencias y Emergencias (MUE). METODO: Mediante análisis de contenido documental, se comparan los programas formativos de Medicina Interna (MI), Medicina Intensiva (MIV), Anestesiología y Reanimación (AyR) y Medicina Familiar y Comunitaria (MFyC) vigentes a fecha de junio de 2021, accesibles tanto en el portal web de Ministerio de Sanidad (MS), como a través de las sociedades científicas de las especialidades, incluidos los borradores no oficiales y propuestas de actualización de los programas y del programa de formación elaborado por la Comisión Promotora de la Especialidad de MUE, presentado por SEMES (Sociedad Española de Medicina de Urgencias y Emergencias) al MS en 2010 y actualizado en 2021. RESULTADOS: Los programas formativos de las especialidades existentes en la actualidad contemplan el manejo de las enfermedades urgentes de forma heterogénea en sus distintas áreas asistenciales (MI en las áreas de hospitalización, AyR en el perioperatorio y MIV en unidades de críticos) o como extensión de la actividad asistencial en el centro de salud (MFyC). Los periodos formativos en el área de la MUE son variables y se realizan en el caso de AyR, MIV y MFyC en un formato exclusivo de guardias (AyR y MIV únicamente durante el primer año y MFyC a lo largo de los 4 años de residencia, con porcentaje decreciente conforme avanza el tiempo de formación), y en el de MI a través de un rotatorio inicial de 3 meses durante su primera etapa formativa, y el resto del tiempo a través de guardias, sin especificar su número. La propuesta del programa de formación en MUE detalla un contacto amplio y específico tanto en los SUH, incluyendo todas sus áreas asistenciales propias (observación, urgencias traumatológicas y pediátricas) como en los dispositivos de emergencias extrahospitalarias y centros coordinadores de urgencias y emergencias. CONCLUSIONES: No es posible la adecuada preparación para desarrollar la MUE con la oferta formativa actual. La MUE presenta un cuerpo doctrinal y ámbito de actuación propios que son diferentes de los de otras especialidades. Esto provoca que en España exista un vacío formativo que se solventaría mediante la creación de una especialidad primaria en MUE.

Safety of perioperative hyperthermic intraperitoneal chemotherapy with gemcitabine in patients with resected pancreatic adenocarcinoma: a pilot study of the clinical trial EudraCT 2016-004298-41.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine, after cytoreductive surgery, may reduce the tumor progression of pancreatic cancer through the reduction of the neoplastic volume and the subpopulation of residual pancreatic cancer stem cells, improving the survival of patients with pancreatic cancer and decreasing the recurrence of the disease. METHODS: A pilot study is performed with the first ten patients in the experimental group. A randomized study (phase II-III clinical trial) that requires a population of 42 patients, with 21 patients in each group. All patients have a diagnosis of ductal adenocarcinoma of the pancreas, which will be surgically resected with curative intention. (I) Group I: after an R0 resection, patients receive individualized adjuvant treatments. (II) Group II: after an R0 resection, HIPEC is performed with gemcitabine (120 mg/m2 for 30 min), and they also receive individualized adjuvant treatments. To analyze the safety of the procedure, the main variables measured were as follows: grades of complications by means of the Clavien-Dindo system: pancreas surgery complications (e.g., pancreatic fistula, perioperative hemorrhage, delayed gastric emptying, biliary fistula), operative mortality, and laboratory parameters to control system functions. Values were measured three times: preoperatively, twenty-four hours after surgery, and on the 7th postoperative day. RESULTS: From 2018 to 2019, 31 patients were recruited for our clinical trial. Fifteen patients were excluded because of intraoperative unresectability or a different intraoperative histologic diagnosis. Ten patients were included in the experimental group (resection plus HIPEC gemcitabine). The mean age was 65±7 years, and six patients were female (60%). We confirmed the histologic diagnosis of ductal pancreatic adenocarcinoma in all patients prior to HIPEC. Total pancreatectomy was performed in five patients. The surgical median time was 360 min, and the hospital stay was 11 days. Four patients showed complications classified as Clavien-Dindo type II and one showing type I. Six patients were classified as having stage III tumors. To date, no hospital mortality, locoregional recurrence, or differences between the two groups in terms of perioperative complications, biochemical and gasometric values, or Clavien-Dindo complication grades were observed. CONCLUSIONS: Our clinical pilot study demonstrated a similar perioperative outcome that allows the trial until main objectives are achieved.

A Spanish Intentional Mass-Casualty Incidents Medical Response Model: Delphi Consensus.

The increase in global violence in recent years has changed the paradigm of emergency health care, requiring early medical response to victims in hostile settings where the usual work cannot be done safely. In Spain, this specific role is provided by the Tactical Environment Medical Support Teams (in Spanish, EMAETs). The Victoria I Consensus document defines and recognizes this role, whose main lines of work are the emergency medical response to the tactical team and to the victims in areas under indirect threat, provided that the tactical operators can guarantee their safety. To reinforce the suitability of this approach, we submitted the possible outcomes of this response model to a panel of national experts to assess this proposal in the different areas of Spain. The chosen research design is a conventional Delphi method, based on the content of the Victoria I Consensus response model. The panel of 52 expert reviewers from 11 different regions were surveyed anonymously; a high degree of accord was recognized when the congruence of the responses exceeded 75%. Consensus agreement was reached in all sections of the survey after two iterations. Specific contributions and recommendations were made to achieve unanimous consensus despite the population and resource differences in the country. Our results suggest that the EMAET approach is useful in areas with short response times. However, in more sparsely populated areas, this may not be feasible, and a more pragmatic response model may be suitable.

Analysis of clinical characteristics and outcomes in patients with COVID-19 based on a series of 1000 patients treated in Spanish emergency departments. / Evaluación de las características clínicas y evolución de pacientes con COVID-19 a partir de una serie de 1000 pacientes atendidos en servicios de urgencias españoles.

OBJECTIVES: To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) treated in hospital emergency departments (EDs) in Spain, and to assess associations between characteristics and outcomes. MATERIAL AND METHODS: Prospective, multicenter, nested-cohort study. Sixty-one EDs included a random sample of all patients diagnosed with COVID-19 between March 1 and April 30, 2020. Demographic and baseline health information, including concomitant conditions; clinical characteristics related to the ED visit and complementary test results; and treatments were recorded throughout the episode in the ED. We calculated crude and adjusted odds ratios for risk of in-hospital death and a composite outcome consisting of the following events: intensive care unit admission, orotracheal intubation or mechanical ventilation, or in-hospital death. The logistic regression models were constructed with 3 groups of independent variables: the demographic and baseline health characteristics, clinical characteristics and complementary test results related to the ED episode, and treatments. RESULTS: The mean (SD) age of patients was 62 (18) years. Most had high- or low-grade fever, dry cough, dyspnea, and diarrhea. The most common concomitant conditions were cardiovascular diseases, followed by respiratory diseases and cancer. Baseline patient characteristics that showed a direct and independent association with worse outcome (death and the composite outcome) were age and obesity. Clinical variables directly associated with worse outcomes were impaired consciousness and pulmonary crackles; headache was inversely associated with worse outcomes. Complementary test findings that were directly associated with outcomes were bilateral lung infiltrates, lymphopenia, a high platelet count, a D-dimer concentration over 500 mg/dL, and a lactate-dehydrogenase concentration over 250 IU/L in blood. CONCLUSION: This profile of the clinical characteristics and comorbidity of patients with COVID-19 treated in EDs helps us predict outcomes and identify cases at risk of exacerbation. The information can facilitate preventive measures and improve outcomes.

OBJETIVO: Describir las características clínicas de los pacientes con COVID-19 atendidos en los servicios de urgencias hospitalarios (SUH) españoles y evaluar su asociación con los resultados de su evolución. METODO: Estudio multicéntrico, anidado en una cohorte prospectiva. Participaron 61 SUH que incluyeron pacientes seleccionados aleatoriamente de todos los diagnosticados de COVID-19 entre el 1 de marzo y el 30 de abril de 2020. Se recogieron características basales, clínicas, de exploraciones complementarias y terapéuticas del episodio en los SUH. Se calcularon las odds ratio (OR) asociadas a la mortalidad intrahospitalaria y al evento combinado formado por el ingreso en unidad de cuidados intensivos (UCI), la intubación orotraqueal o ventilación mecánica invasiva (IOT/ VMI), crudas y ajustadas con modelos de regresión logística para tres grupos de variables independientes: basales, clínicas y de exploraciones complementarias. RESULTADOS: La edad media fue de 62 años (DE 18). La mayoría manifestaron fiebre, tos seca, disnea, febrícula y diarrea. Las comorbilidades más frecuentes fueron las enfermedades cardiovasculares, seguidas de las respiratorias y el cáncer. Las variables basales que se asociaron independientemente y de forma directa a peores resultados evolutivos (tanto a mortalidad como a evento combinado) fueron edad y obesidad; las variables clínicas fueron disminución de consciencia y crepitantes a la auscultación pulmonar, y de forma inversa cefalea; y las variables de resultados de exploraciones complementarias fueron infiltrados pulmonares bilaterales y cardiomegalia radiológicos, y linfopenia, hiperplaquetosis, dímero-D > 500 mg/dL y lactato-deshidrogenasa > 250 UI/L en la analítica. CONCLUSIONES: Conocer las características clínicas y la comorbilidad de los pacientes con COVID-19 atendidos en urgencias permite identificar precozmente a la población más susceptible de empeorar, para prever y mejorar los resultados.

New approach to indole alkaloids based on the intramolecular Pauson-Khand reaction.

The synthesis of indoles bearing alkenyl and alkynyl moieties in different positions of the nucleus is described. These compounds are used as substrates for the intermolecular Pauson-Khand reaction leading to tetracyclic cyclopentenones with formation of additional five- to seven-membered rings. Products are related to alkaloids such as mitosenes, clausines, ergotamines, or apogeissochizines.

The Pauson-Khand reaction, a powerful synthetic tool for the synthesis of complex molecules.

There are still some synthetic chemists who hesitate to use metal-mediated or -catalysed reactions. The Pauson-Khand reaction (PKR) is a powerful transformation that has now been sufficiently well developed to be routinely considered when planning a synthesis, especially of polycyclic complex molecules. This tutorial review aims to encourage the use of this process explaining the best ways of performing a PKR both in the stoichiometric and the catalytic version, showing the scope of the process and its limitations. Additionally, asymmetry can be introduced in the reaction using several strategies, which will be discussed. The most recent examples of the synthetic applications of the PKR in natural product synthesis will give the reader an idea of the great usefulness of this reaction.