Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project) / Síntomas y complicaciones gastrointestinales en pacientes hospitalizados por COVID-19, estudio internacional, multicéntrico, de cohorte, prospectivo (proyecto TIVURON)

Background: Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19. Methods: This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant. Results: Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464–0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328–0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms. Conclusion: GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.

Antecedentes: Estudios retrospectivos evidencian que la enfermedad por coronavirus (COVID-19) conlleva síntomas y complicaciones gastrointestinales (GI). Nuestro objetivo fue evaluar prospectivamente las manifestaciones GI de pacientes hospitalizados por COVID-19. Métodos: Estudio internacional, multicéntrico, de cohorte, prospectivo, que seleccionó a pacientes con COVID-19 en 31 centros de España, México, Chile y Polonia, entre mayo-septiembre de 2020. Los pacientes fueron seguidos hasta 15 días tras el alta y completaron cuestionarios que evaluaban los síntomas y complicaciones GI. Se realizó un análisis descriptivo, bivariante y multivariante de los resultados. Se consideró significativa p<0,05. Resultados: Se incluyeron 829 pacientes; 129 (15,6%) presentaron COVID-19 grave, 113 (13,7%) requirieron ingreso en UCI y 43 (5,2%) fallecieron. Al ingreso, los síntomas GI más prevalentes fueron anorexia (n=413; 49,8%), diarrea (n=327; 39,4%), náuseas/vómitos (n=227; 27,4%) y dolor abdominal (n=172; 20,7%), que resultaron de intensidad leve/moderada y se resolvieron durante el seguimiento. Un tercio de los pacientes presentaron daño hepático. La COVID-19 no grave se asoció con la presencia de ≥2 síntomas GI al ingreso (OR 0,679; IC 95%: 0,464-0,995; p=0,046) y/o diarrea durante la hospitalización (OR 0,531; IC 95%: 0,328-0,860; p=0,009). El análisis multivariante reveló que los peores resultados hospitalarios no se asociaron de forma independiente con el daño hepático o los síntomas GI. Conclusión: Los síntomas GI fueron más frecuentes de lo que se había documentado, resultaron leves, se resolvieron rápidamente y no se asociaron de forma independiente con COVID-19 grave. El daño hepático fue una complicación frecuente en los pacientes hospitalizados que no se asoció de forma independiente con COVID-19 grave.(AU)

Evaluating the efficacy of Quantum Molecular Resonance (QMR) electrotherapy in mixed-type dry eye patients / Evaluación de la eficacia de la electroterapia de resonancia molecular cuántica (QMR) en pacientes con ojo seco de tipo mixto

Purpose: To evaluate the efficacy and safety of the low-power, high-frequency electrical current treatment administered by the Rexon-Eye device, in a cohort of patients affected by mixed-type dry eye disease (DED) of medium to severe level. Patients and methods: In this prospective, non-randomized, interventional clinical study, eighteen mixed type DED patients were treated. Treatment was a specific type of electrotherapy, Quantum Molecular Resonance (QMR®), administered by means of the Rexon-Eye® device (Resono Ophthalmic, Sandrigo, Italy) with a protocol of one 20-min session per week, for 4 weeks. Patients were examined at baseline and one month after the last treatment, utilizing the Ocular Surface Disease Index (OSDI) questionnaire and clinical signs: non-invasive tear break-up time (NIBUT), Oxford staining, meibum quality, meibography, meibomian gland expressibility, tear meniscus height (TMH), Schirmer's test, ocular inflammation expressed by MMP-9 concentration. Results: Subjective benefit in OSDI was reported (p = 0.013). Improvement was also observed in NIBUT (p < 0.001), Oxford staining (p = 0.002), expressible meibomian glands number (p = 0.001) and meibum quality (p < 0.001). A remarkable benefit was present in inflammation, as evidenced by the reduction of MMP-9 (p = 0.003). Changes, although not statistically significant, were also present in TMH (p = 0.076) and Schirmer's test (p = 0.675), whereas no change was observed in meibography score. No adverse event was reported. Conclusion: In this mixed-type DED patients’ cohort, Rexon-Eye proved to be effective and safe in improving subjective and objective ocular parameters, as well as capable to normalize inflammatory markers.(AU)

Adhesión real al dimetilfumarato en pacientes con esclerosis múltiple remitente-recurrente / Actual adherence to dimethyl fumarate in patients with relapsing-remitting multiple sclerosis

Introducción: La esclerosis múltiple es una enfermedad neurológica crónica con numerosos tratamientos modificadores de la enfermedad disponibles, incluido el dimetilfumarato (DMF), una terapia de primera línea para la esclerosis múltiple remitente-recurrente. Aunque las tasas de discontinuación del DMF suelen ser bajas en los ensayos clínicos, la falta de adhesión al tratamiento se asocia con peores resultados clínicos. Evaluar la adhesión en el mundo real y los factores predictivos es fundamental para mejorar los resultados clínicos de los pacientes. Este estudio evaluó la adhesión al DMF durante 24 meses en una cohorte de pacientes tratados en un centro portugués. Pacientes y métodos: Estudio prospectivo no intervencionista, de un solo centro, con un seguimiento de 24 meses. El estudio incluyó a pacientes adultos con esclerosis múltiple remitente-recurrente tratados con DMF en la práctica clínica habitual. Se calculó la adhesión al DMF y se consideró que los pacientes eran adherentes si el valor estaba por encima del 80%. Se compararon variables clínicas y sociodemográficas entre grupos. Resultados: De los 80 pacientes incluidos, el 74% eran mujeres, con una edad media de 39 años y una edad media en el momento del diagnóstico de 32 años. Veintiséis pacientes no habían recibido tratamiento previo. La adhesión varió entre el 93, el 82 y el 87,5% a los 6, 12 y 24 meses, respectivamente. No se encontraron diferencias entre los pacientes que no habían recibido tratamiento previo y los que sí lo habían recibido. Conclusión: Este análisis en el mundo real mostró una adhesión significativa al tratamiento con DMF durante dos años por parte de los pacientes portugueses. No obstante, estos resultados deben interpretarse considerando los cambios sustanciales en las consultas externas y las diversas restricciones periódicas debidas a la pandemia de COVID-19, que afectaron en gran medida al seguimiento de los pacientes y a la recopilación de datos.(AU)

Introduction: Multiple sclerosis is a chronic neurological disease with numerous disease-modifying treatments available, including dimethyl fumarate (DMF), a first-line therapy for relapsing-remitting multiple sclerosis. Although rates of discontinuation of DMF are generally low in clinical trials, non-adherence to treatment is associated with poorer clinical outcomes. Assessing real-world adherence and predictive factors is critical to be able to improve clinical outcomes for patients. This study evaluated adherence to DMF over 24 months in a cohort of patients treated in a Portuguese healthcare centre. Patients and methods: A prospective, non-interventional, single-centre study with 24 months’ follow-up was conducted. The study included adult patients with relapsing-remitting multiple sclerosis treated with DMF in routine clinical practice. Adherence to DMF was calculated and patients were considered to have adhered if the value was above 80%. Clinical and socio-demographic variables were compared between groups. Results: Of the 80 patients included, 74% were women, with a mean age of 39 years and a mean age of 32 years at diagnosis. Twenty-six patients had not received any previous treatment. Adherence varied between 93, 82 and 87.5% at 6, 12 and 24 months, respectively. No differences were found between patients who had not received any prior treatment and those who had been treated. Conclusion: This real-world analysis showed significant adherence to DMF treatment by Portuguese patients over a period of two years. However, these results must be interpreted in the light of the substantial changes in outpatient consultations and the various periodic restrictions due to the COVID-19 pandemic, which had an important effect on patient follow-up and data collection.(AU)

Identificación de pacientes hospitalizados con riesgo nutricional al ingreso valorado con la Nutritional Risk Screening / Identification of hospitalized patients with nutritional risk at admission assessed with the Nutrition Risk Screening

Objetivo: Determinar la prevalencia de riesgo nutricional en el ingreso hospitalario de pacientes adultos y analizar su asociación con factores sociodemográficos y clínicos de los pacientes. Método: Estudio transversal, analítico y prospectivo realizado a pacientes del Hospital de la Santa Creu i Sant Pau de Barcelona entre noviembre y diciembre de 2018, durante las primeras 48 h de ingreso hospitalario. Para detectar la desnutrición se utilizó la Nutritional Risk Screening (NRS-2002). Se recogieron datos sociodemográficos (edad, sexo), clínicos (diagnóstico de ingreso, unidad y comorbilidades) y antropométricos (peso, talla e IMC). La asociación entre la NRS y los factores de estudio se estimó mediante un modelo de regresión logística. Resultado: Se incluyeron 285 pacientes con una edad media de 69,6 años (DS 15), de los cuales, 56,5% (161) tenían ≥ 70 años. La prevalencia de riesgo de desnutrición en el ingreso hospitalario era de 35,1% (IC 95%: 29,8-41,1%), siendo 15,9 veces mayor en pacientes con una estancia previa en cuidados intensivos (OR 15,90; 1,82-139,11: p 0,012); 10,35 veces mayor en pacientes neumonía severa (OR 10,35; 2,48-41,91: p 0,004) y 5,6 veces mayor en pacientes con AVC (OR 5,63; 1,71-18,53: p 0,004). Conclusiones: La prevalencia de riesgo nutricional al ingreso era elevada y factores como la neumonía severa, el AVC y los ingresos previos en UCI se asociaron a mayor riesgo de desnutrición. Sin embargo, los hallazgos de este estudio deben interpretarse con cautela debido a las limitaciones de los criterios de gravedad de la Nutritional Risk Screening y a las características de la población estudiada.(AU)

Objective: To determine the prevalence of nutritional risk in the hospital admission of adult patients and to analyze its association with sociodemographic and clinical factors of the patients. Method: Cross-sectional, analytical and prospective study carried out on patients at the Hospital de la Santa Creu i Sant Pau in Barcelona between November and December 2018, during the first 48 hours of hospital admission. The Nutritional Risk Screening (NRS-2002) was used to detect malnutrition. Sociodemographic (age, sex), clinical (admission diagnosis, unit and comorbidities) and anthropometric (weight, height and BMI) data were collected. The association between the NRS and the study factors was estimated using a logistic regression model. Result: 285 patients with a mean age of 69.6 years (SD 15) were included, of which 56.5% (161) were ≥ 70 years. The prevalence of risk of malnutrition on hospital admission was 35.1% (95% CI: 29.8%-41.1%), being 15.9 times higher in patients with a previous stay in intensive care (OR 15 .90, 1.82-139.11: p 0.012); 10.35 times higher in patients with severe pneumonia (OR 10.35; 2.48-41.91: p 0.004) and 5.6 times higher in patients with stroke (OR 5.63; 1.71-18.53: p 0.004). Conclusions: The prevalence of nutritional risk at admission was high and factors such as severe pneumonia, stroke and previous ICU admissions were associated with a higher risk of malnutrition. However, the findings of this study should be interpreted with caution due to the limitations of the severity criteria of the Nutrition Risk Screening.(AU)

Implementación del uso del SPECT portátil para valoración de márgenes quirúrgicos en cáncer de mama con indicación de ROLL. Primeros resultados / Implementation of the use of SPECT-portable for evaluation of surgical margins in breast cancer with indication of ROLL: First results

Objetivo principal: comparar la efectividad para la comprobación de márgenes quirúrgicos entre SPECT portátil y la mamografía de la pieza (RxM). Objetivo secundario: estandarizar un protocolo preintraquirúrgico mediante SPECT portátil y evaluar el tiempo requerido en el uso de esta técnica. Material y métodos Estudio longitudinal prospectivo con 36 pacientes (39 lesiones) diagnosticadas de cáncer de mama con criterios para realización SNOLL/ROLL. Se realiza en estudio prequirúrgico de la lesión tumoral, tras la administración ecoguiada de [99mTc]Tc-nanocoloides de albúmina/[99mTc]Tc-macroagregados de albúmina, en la lesión tumoral. Mediante SPECT portátil se obtienen imágenes híbridas (óptico + SPECT) e imágenes de navegación en 3D con sonda gamma. En quirófano se obtienen 4-5 imágenes con SPECT portátil, I) sobre piel para localización tumoral II) tras exposición de lecho para guía de resección, III) del lecho tras exéresis, IV y V) a la pieza quirúrgica. Se decide ampliación o no de márgenes considerando tres criterios: a) actividad residual (cps) en bordes de resección del lecho; b) análisis visual de la captación en la pieza; c) una distancia mínima de 10mm de los bordes de la pieza hasta el centro de mayor captación, más el radio de la lesión. En este estudio se valora la concordancia de: la medición de la profundidad entre ecografía y SPECT portátil en el estudio prequirúrgico; los márgenes quirúrgicos entre SPECT portátil vs. RxM, teniendo de técnica de referencia anatomía patológica (AP); del tiempo quirúrgico empleado con SPECT portátil (AU)

Objectives Main objective: To compare the effectiveness for checking surgical margins between SPECT-portable and mammography of the piece (RxM). Secondary objective: To standardize a pre-operative protocol using SPECT-portable and to evaluate the time required in the use of this technique. Material and method Prospective longitudinal study with 36 patients (39 lesions) diagnosed with breast cancer (CM) with criteria for SNOLL/ROLL. A pre-surgical study of the tumor lesion was performed, after the eco-guided administration of 99mTc-nanocolloids of albumin/99mTc-macroaggregates of albumin, in the tumor lesion. Hybrid images (optical+SPECT) and 3D navigation images with gamma probe are obtained using freehandSPECT. In the operating room, 4–5 images are obtained with freehandSPECT, (I) on skin for tumor location, (II) after exposure of surgical bed for resection guide, (III) of the surgical bed after exeresis, (IV and V) the anterior–posterior and lateral surface of the surgical specimen. The three criteria to decide to extend the margins are: (a) residual activity (cps) at the edges of the surgical bed resection; (b) visual analysis of the uptake in the specimen; (c) a minimum distance of 10mm from the edges of the specimen to the center of greatest uptake, plus the radius of the lesion. We study the concordance of: the depth measurement between ultrasound and freehandSPECT; the surgical margins between freehandSPECT vs. mammography of the specimen (RxM), considering anatomical pathology (AP) as the gold standard technique as reference; surgical time used with freehandSPECT and RxM. Results Intraoperative localization was performed in all cases. False negative (FN: no detection margin affected) with freehandSPECT: 9 margins; with RxM: 8 (AU)

Proceso de atención prehospitalaria y resultados hospitalarios del código ictus: estudio comparativo entre unidades de soporte vital básico y avanzado / Prehospital care process and hospital outcomes in stroke-code cases: comparison of basic and advance life support ambulance attendance

Objetivos: Comparar el proceso asistencial prehospitalario y los resultados hospitalarios de los pacientes categorizados como Código Ictus (CI) en función del tipo de ambulancia que realiza la primera valoración, y analizar los factores asociados con un buen resultado funcional y la mortalidad a los 3 meses. Método: Estudio observacional de cohortes prospectivo multicéntrico. Incluyó todos los CI atendidos por un sistema de emergencias prehospitalario desde enero del 2016 a abril del 2022. Se recogieron variables prehospitalarias y hospitalarias. La variable de clasificación fue el tipo de ambulancia que asiste el CI: unidad de soporte vital básico (USVB) o avanzado (USVA). Las variables de resultado principal fueron la mortalidad y el estado funcional de los ictus isquémicos sometidos a tratamiento de reperfusión a los 90 días del episodio. Resultados: Se incluyeron 22.968 pacientes, de los cuales 12.467 (54,3%) presentaron un ictus isquémico con un buen estado funcional previo. El 93,1% fueron asistidos por USVB y se solicitó una USVA en el 1,6% de los casos. A pesar de presentar diferencias en el perfil clínico del paciente atendido y en los tiempos del proceso CI prehospitalario, el tipo de unidad no mostró una asociación independiente con la mortalidad (OR ajustada 1,1; IC 95%: 0,77-1,59) ni con el estado funcional a los 3 meses (OR ajustada 1,05; IC 95%: 0,72-1,47). Conclusiones: El porcentaje de complicaciones de los pacientes con CI atendidos por USVB es bajo. El tipo de unidad que asistió al paciente inicialmente no se asoció ni con el resultado funcional ni con la mortalidad a los 3 meses. (AU)

Objectives: To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional outcome at 3 months. Methods: Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode. Results: Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio [aOR], 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47). Conclusions: The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study. (AU)

Rendimiento de tres escalas de fragilidad para predecir resultados adversos a 30 días en los pacientes mayores dados de alta en los servicios de urgencias / Performance of 3 frailty scales for predicting adverse outcomes at 30 days in older patients discharged from emergency departments

Objetivo: Comparar la capacidad de tres escalas de fragilidad, Clinical Frailty Scale (CFS), Functional Index eMergency (FIM) e Identification Senior at Risk (ISAR), para predecir resultados adversos (RA) a 30 días en los pacientes mayores dados de alta desde el servicio de urgencias hospitalario (SUH). Método: Análisis secundario del registro FRAIL-Madrid que incluyó pacientes $ 75 años dados de alta de 10 SUH de Madrid durante un periodo de 3 meses entre 2018 y 2019. Se definió fragilidad como CFS $ 4, FIM $ 2 e ISAR $ 3. Las variables de resultado fueron revisita en urgencias, hospitalización, deterioro funcional, muerte y la variable compuesta por algún RA de los anteriores en los 30 días posteriores al alta del SUH. Resultados: Se incluyeron 619 pacientes, la edad media fue de 84 años (DE 7), 59,1% eran mujeres. Hubo 339 pacientes (54,8%) identificados como frágiles en el SUH según CFS $ 4, 386 (62,4%) según FIM $ 2 y 301 (48,6%) según ISAR $ 3. Hubo 226 pacientes (36,5%) que presentaron algún RA a los 30 días tras el alta (21,5% revisita, 12,6% hospitalización, 18,4% deterioro funcional y 3,6% muerte). El área bajo la curva (ABC) de la escala CFS fue de 0,66 (0,62-0,70; p = 0,022), de FIM 0,67 (0,62-0,71; p = 0,021) y de ISAR 0,64 (0,60-0,69; p = 0,023). La presencia de fragilidad fue un factor independiente de presentar algún RA a los 30 días tras el alta (CFS $ 4 ORa 3,18 [IC 95% 2,02-5,01, p < 0,001], FIM $ 2 ORa 3,49 [IC 95% 2,15-5,66, p < 0,001] e ISAR $ 3 ORa 2,46 [IC 95% 1,60-3,79, p < 0,001]). Conclusiones: Las tres escalas estudiadas –CFS, FIM, ISAR– son útiles y tienen una capacidad similar para identificar al paciente mayor frágil dado de alta del SUH con alto riesgo de presentar RA (muerte, deterioro funcional, hospitalización o revisita al SUH) a los 30 días. (AU)

Objective: To compare the ability of 3 frailty scales (the Clinical Frailty Scale [CFS], the Functional Index – eMergency [FIM], and the Identification of Seniors at Risk [ISAR] scale) to predict adverse outcomes at 30 days in older patients discharged from hospital emergency departments (EDs). Methods: Secondary analysis of data from the FRAIL-Madrid registry of patients aged 75 years or older who were discharged from Madrid EDs over a period of 3 months in 2018 and 2019. Frailty was defined by a CFS score over 4, a FIM score over 2, or an ISAR score over 3. The outcome variables were revisits to an ED, hospitalization, functionaldecline, death, and a composite variable of finding any of the previously named variables within 30 days of discharge. Results: A total of 619 patients were studied. The mean (SD) age was 84 (7) years, and 59.1% were women. The CFS identified as frail a total of 339 patients (54.8%), the FIM 386 (62.4%), and the ISAR 301 (48.6%). An adverse outcome occurred within 30 days in 226 patients (36.5%): 21.5% revisited, 12.6% were hospitalized, 18.4% experienced functional decline, and 3.6% died. The areas under the receiver operating characteristic curves were as follows: CFS, 0.66 (95% CI, 0.62-0.70; P = .022); FIM, 0.67 (95% CI, 0.62-0.71; P = .021), and ISAR, 0.64 (95% CI, 0.60-0.69; P = .023). Adjusted odds ratios (aOR) showed that frailty was an independent risk factor for presenting anyof the named adverse outcomes: aOR for CFS >4, 3.18 (95% CI, 2.02-5.01), P < .001; aOR for FIM > 2, 3.49 (95% CI, 2.15-5.66), P < .001; and aOR for ISAR >3, 2.46 (95% CI, 1.60-3.79), P < .001. Conclusions: All 3 scales studied — the CFS, the FIM and the ISAR — are useful for identifying frail older patients at high risk of developing an adverse outcome (death, functional decline, hospitalization, or revisiting the ED) within 30 days after discharge. (AU)

Monocyte distribution width (MDW) as an infection indicator in severe patients attending in the Emergency Department: a pilot study / Ancho de distribución de los monocitos como indicador de infección en pacientes graves atendidos en Urgencias: estudio piloto

Background. The aim of the present study was to evaluate the diagnostic performance of monocyte distribution width (MDW) as a biomarker for sepsis diagnosis in severe patients attended in the Emergency Department for different conditions and not only infections. Methods. We performed an observational study in a consecutive prospective cohort including severe patients attending the Emergency Department with different conditions. MDW and other biomarkers were determined from samples obtained during the first care of patients. The diagnostic performance of the different biomarkers was determined based on the final diagnosis at patient discharge. Results: One hundred two patients, with a mean age of 76.7 (SD 16.5) years were included, 53 being (51.9%) male. Among the patients included, 65 (63.7%) had an infectious disease while the remaining had other different conditions. A MDW cut-off of 20.115 provided the best accuracy to identify infected patients, with a sensitivity of 89.2 (95% CI 79.4-94.7), a specificity of 89.2 (95% CI 75.3-95.7), a positive predictive value of 93.5 (95% CI 84.6-97.5), a negative predictive value of 82.5% (95% CI 68.0-91.3), a positive likelihood ratio of 8.25 (3.26-20.91), and a negative likelihood ratio of 0.12 (0.06-0.24). The area under the receiver operating characteristic curve for infection according to MDW was 0.943 (95% CI 0.897-0.989; p<0.001). Conclusions: A MDW > 20.115 may be associated with infection and could help to distinguish between infected and non-infected patients in severe patients. These results must be confirmed in new studies due to the limited patient sample included. (AU)

Introducción: El objetivo del presente estudio fue evaluar el desempeño diagnóstico del ancho de distribución de monocitos (MDW) como biomarcador para el diagnóstico desepsis entre pacientes graves atendidos en el servicio de urgencias por diferentes afecciones y no solo por infecciones. Métodos: Realizamos un estudio observacional en una cohorte prospectiva consecutiva que incluyó pacientes graves desde el punto de vista clínico que acudían a urgencias con diferentes patologías. El MDW y otros biomarcadores se determinaron a partir de muestras obtenidas durante la primera atención de los pacientes. Se estudio la precisión de los diferentes biomarcadores para apoyar el diagnósticode infección, basándonos en el diagnóstico final al alta del paciente. Resultados: Se incluyeron 102 pacientes, con una edad media de 76,7 (DE 16,5) años, siendo 53 (51,9%) del sexo masculino. Entre los pacientes incluidos, 65 (63,7%) pacientes tenían una enfermedad infecciosa y el resto otras condiciones diferentes. Un punto de corte MDW de 20,115proporcionó la mejor precisión para identificar pacientes infectados, con un sensibilidad de 89,2 (IC 95 % 79,4-94,7), una especificidad de 89,2 (IC 95 % 75,3-95,7), un valor predictivo positivo de 93,5 (IC 95 % 84,6-97,5), un valor predictivo negativo de 82,5% (IC 95% 68,0-91,3), un coeficiente de probabilidad positivo de 8,25 (3,26-20,91), y uncoeficiente de probabilidad negativo de 0,12 (0,06-0,24). El área bajo la curva característica operativa del receptor para la infección del MDW fue de 0,943 (IC del 95 %: 0,897-0,989; p<0,001). Conclusiones: Un MDW > 20.115 se asocia a padecer una enfermedad infecciosa en un paciente grave y podría ayudar a distinguir entre pacientes infectados y no infectados. Estos resultados deben ser confirmados en nuevos estudios debido a la muestra limitada de pacientes incluidos. (AU)

Calidad de la voz cantada en sopranos. Influencia del texto y el acompañamiento musical en el canto de ópera / quality of the singing voice in sopranos. Influence of the text and the musical accompaniment in the opera singing

Introducción y objetivos La voz cantada en canto de ópera utiliza diferentes mecanismos técnicos con finalidad artística. Queremos determinar si la calidad del sonido cantado se ve afectada por un trabajo consciente sobre el acompañamiento musical y el texto. Analizamos la señal acústica y la percepción subjetiva. La altura de tono estudiada en voz de soprano es el La4 (880Hz) sobre la vocal /a/. Hemos elegido un tono y una vocal que pueden generarse mediante diferentes estrategias en cuanto a los ajustes fonorresonanciales. Materiales y métodosHemos realizado un estudio prospectivo con 20 sopranos, libres de enfermedad, que han cantado una frase del aria «Deh, vieni non tardar» y otra del aria «Dove sono i bei momento». de la ópera Le nozze di Figaro, compuesta por W.A. Mozart. En primer lugar, se grabó cada frase cantada de modo espontáneo y una segunda vez, tras un trabajo propuesto sobre el contenido del texto y aspectos musicales del acompañamiento como son: ritmo, armonía, textura y dirección de la frase. Las participantes prolongaron la emisión del La4 algo más de 3s manteniendo el contexto de la frase. La señal acústica ha sido analizada mediante el programa PRAAT y se ha utilizado un cuestionario de la escala visual analógica (EVA) para recoger las percepciones subjetivas Resultados La media de edad fue de 36±11 años (rango entre 20 y 58), la media de años cantando fue de 17±12 años (rango entre 3 y 35). No se han encontrado diferencias estadísticamente significativas, aunque sí se aprecia una mejoría de la EVA en la segunda frase tras la intervención. Conclusiones Los parámetros de análisis acústico son estables y la EVA tiende a mejorar cuando se realiza un trabajo de toma de conciencia del texto y el acompañamiento instrumental. (AU)

Introduction and objectives Opera singing voice uses different technical tools for artistic purposes. We want to define if the quality of the sung sound is affected by an aware work on the musical accompaniment and the text. We analyze the acoustic signal and the subjective perception. The pitch studied in the soprano voice is A4 (880Hz) with the vowel /a/. We have chosen a tone and a vowel that can be generated by different strategies in terms of phonoresonance adjustments. Materials and methods We have carried out a prospective study with 20 sopranos, without voice pathology, who have sung a phrase from the aria Deh, vieni non tarda and another from the aria Dove sono i bei momenti from the opera Le nozze di Figaro, by W.A. Mozart. First, each phrase sung spontaneously was recorded and then a second time, after a proposed work on the content of the text and musical aspects of the accompaniment such as: rhythm, harmony, texture and direction of the phrase. The participants prolonged the emission of the A4 for more than three seconds, maintaining the context of the sentence. The acoustic signal has been analyzed using the PRAAT program and a VAS (Visual Analogue Scale) questionnaire has been used to collect subjective perceptions. Results The mean age was 36±11 years (range between 20 and 58) and the mean number of years singing was 17±12 years (range between 3 and 35). No statistically significant differences were found, although an improvement in the VAS was seen in the second sentence after the intervention. Conclusions The acoustic analysis parameters are stable, and the VAS tends to improve when an awareness of the text and the instrumental accompaniment is carried out. (AU)

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis.

BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative. AIM: To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication. METHODS: We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I2 statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. RESULTS: The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The overall risk of bias was low to moderate in all but a single report, with an average critical appraisal score across all studies of 79.02%. A total of 2936 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I 2 = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study. CONCLUSION: Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.

Association between human papillomavirus infection or immunization and risk for rheumatoid arthritis.

Background: Human papillomavirus (HPV) is a virus primarily transmitted through sexual contact. Little is known about the association between HPV infection or immunization and the risk for rheumatoid arthritis (RA). The purpose of this study was to evaluate whether HPV infection or immunization is related to the risk for RA in adults. Methods: Data were obtained from the 2007-2016 National Health and Nutrition Examination Survey (NHANES). We developed three independent multivariate logistic regression models to evaluate the association between HPV infection or immunization and the risk for RA in adults. Results: Finally, we analyzed 15,677 and 8,944 subjects, respectively. In all models, HPV infection was positively associated with an increased prevalence of RA in adults aged 18-59 years, with the highest value of the odds ratio (OR) in model 2 (after weighting: OR 1.095, 95% CI 1.092, 1.097), whereas HPV immunization significantly reduced the prevalence of RA in adults aged 18-59 years, with the lowest OR in model C (after weighting: OR 0.477, 95% CI 0.472, 0.481). These associations persisted after correction for confounders such as age, sex, race, education level, marital status, smoking, diabetes, hypertension, hyperlipidemia, and BMI. Conclusion: In summary, our study suggests that HPV infection is positively associated with the prevalence of RA in adults, and HPV immunization can reduce the prevalence of RA in adults. However, our findings need more powerful to prove these associations through rigorously designed prospective studies.

[Risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery].

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.

Longitudinal mortality of preserved ratio impaired spirometry in a middle-aged Asian cohort.

BACKGROUND: Although preserved ratio impaired spirometry (PRISm) has been determined to have poor prognosis, it is a heterogeneous state, and studies regarding its prognosis in Asians are limited. This study investigated the long-term all-cause and cardiovascular mortality of patients with PRISm compared with those of patients with chronic obstructive pulmonary disease (COPD) and normal individuals in the Korean middle-aged general population. METHODS: Participants were recruited between 2001 and 2002 from a community-based prospective cohort in South Korea. Mortality data were collected over a 16.5-year mean follow-up period. The all-cause and cardiovascular mortality risks of PRISm were compared between patients with COPD and healthy controls. RESULTS: The PRISm group had a mean age of 53.4 years and mean body mass index of 24.9 kg/m2; furthermore, 55.2% of the PRISm patients had never smoked, and the prevalence of comorbidities was not higher than that in the other groups. Compared with normal individuals, PRISm patients did not show increased all-cause mortality, whereas COPD patients showed increased all-cause mortality (PRISm: adjusted hazard ratio [aHR], 1.19; 95% confidence interval [CI], 0.85-1.65; COPD: aHR, 1.34, 95% CI, 1.07-1.69). Furthermore, the PRISm patients did not show increased cardiovascular mortality compared with normal individuals (PRISm: aHR, 1.65; 95% CI, 0.92-2.95; COPD: aHR, 1.83; 95% CI, 1.09-3.07). CONCLUSION: In our population-based cohort, all-cause and cardiovascular mortality risk did not increase in individuals with PRISm compared with normal individuals. Further studies are needed to distinguish a lower-risk subgroup of PRISm with certain characteristics, such as middle-aged, light-smoking Asians without additional cardiovascular risk.

Impact of (long) COVID on athletes' performance: a prospective study in elite football players.

OBJECTIVES: To investigate possible persistent performance deficits after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in elite athletes. METHODS: A prospective cohort study in three Belgian professional male football teams was performed during the 2020 - 2021 season. Participants were submitted to strength, jump, and sprint tests and an aerobic performance test (the Yo-Yo Intermittent Recovery test (YYIR)). These tests were repeated at fixed time intervals throughout the season. Assessment of SARS-CoV-2 infection was performed by a polymerase chain reaction (PCR) test before each official game. RESULTS: Of the 84 included participants, 22 were infected with SARS-CoV-2 during follow-up. At the first testing after infection (52.0 ± 11.2 days after positive PCR testing) significantly higher percentages of maximal heart rate (%HRmax) were seen - within the isolated group of infected players- during (p = .006) and after the YYIR (2 min after, p = .013), compared to pre-infection data. This increase in %HRmax was resolved at the second YYIR testing after infection (127.6 ± 33.1 days after positive PCR testing). Additionally, when comparing the first test after infection in formerly infected to non-infected athletes, significantly higher %HRmax were found during (p < .001) and after the YYIR test (p < .001),No significant deficits were found for the jump, muscular strength or sprint tests.Aerobic performance seems compromised even weeks after infection. Simultaneously, anaerobic performance seemed to be spared. Because of the potential detrimental effects on the immune system, caution might be advised with high-intensity exposure until aerobic performance is restored.KEY MESSAGESElite football players' aerobic performance seems to be affected for weeks after they return to sports after a SARS-CoV-2 infection.Similarly, anaerobic performance tests showed no discernible changes between both before and after SARS-CoV-2 infections.Regular YYIR testing is recommended to monitor aerobic performance after SARS-CoV-2 infection.

Clinical decision support systems to improve drug prescription and therapy optimisation in clinical practice: a scoping review.

OBJECTIVE: Clinical decision support systems (CDSSs) can reduce medical errors increasing drug prescription appropriateness. Deepening knowledge of existing CDSSs could increase their use by healthcare professionals in different settings (ie, hospitals, pharmacies, health research centres) of clinical practice. This review aims to identify the characteristics common to effective studies conducted with CDSSs. MATERIALS AND METHODS: The article sources were Scopus, PubMed, Ovid MEDLINE and Web of Science, queried between January 2017 and January 2022. Inclusion criteria were prospective and retrospective studies that reported original research on CDSSs for clinical practice support; studies should describe a measurable comparison of the intervention or observation conducted with and without the CDSS; article language Italian or English. Reviews and studies with CDSSs used exclusively by patients were excluded. A Microsoft Excel spreadsheet was prepared to extract and summarise data from the included articles. RESULTS: The search resulted in the identification of 2424 articles. After title and abstract screening, 136 studies remained, 42 of which were included for final evaluation. Most of the studies included rule-based CDSSs that are integrated into existing databases with the main purpose of managing disease-related problems. The majority of the selected studies (25 studies; 59.5%) were successful in supporting clinical practice, with most being pre-post intervention studies and involving the presence of a pharmacist. DISCUSSION AND CONCLUSION: A number of characteristics have been identified that may help the design of studies feasible to demonstrate the effectiveness of CDSSs. Further studies are needed to encourage CDSS use.

Fertility and contraceptive dynamics amidst COVID-19: who is at greatest risk for unintended pregnancy among a cohort of adolescents and young adults in Nairobi, Kenya?

OBJECTIVES: Among youth in Nairobi, we (1) characterised fertility and contraceptive use dynamics by gender; (2) estimated pregnancy prevalence over the pandemic; and (3) assessed factors associated with unintended pandemic pregnancy for young women. DESIGN: Longitudinal analyses use cohort data collected at three timepoints prior to and during the COVID-19 pandemic: June to August 2019 (pre-pandemic), August to October 2020 (12-month follow-up) and April to May 2021 (18-month follow-up). SETTING: Nairobi, Kenya. PARTICIPANTS: At initial cohort recruitment, eligible youth were aged 15-24 years, unmarried and residing in Nairobi for at least 1 year. Within-timepoint analyses were restricted to participants with survey data per round; trend and prospective analyses were restricted to those with complete data at all three timepoints (n=586 young men, n=589 young women). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes comprised fertility and contraceptive use for both genders, and pregnancy for young women. Unintended pandemic pregnancy (assessed at 18-month follow-up) was defined as a current or past 6-month pregnancy with intent to delay pregnancy for more than 1 year at 2020 survey. RESULTS: While fertility intentions remained stable, contraceptive dynamics varied by gender-young men both adopted and discontinued coital-dependent methods, whereas young women adopted coital-dependent or short-acting methods at 12-month follow-up (2020). Current pregnancy was highest at 2020 (4.8%), and approximately 2% at 2019 and 2021. Unintended pandemic pregnancy prevalence was 6.1%, with increased odds for young women recently married (adjusted OR (aOR)=3.79; 95% confidence interval (CI) 1.83-7.86); recent contraceptive use was protective against unintended pandemic pregnancy (aOR=0.23; 95% CI 0.11-0.47). CONCLUSIONS: Current pregnancy in Nairobi was highest at the height of the COVID-19 pandemic (2020), and subsided to pre-pandemic levels by 2021 data collection; however, requires further monitoring. New marriages posed considerable risk for unintended pandemic pregnancy. Contraceptive use remains a crucial preventive strategy to averting unintended pregnancy, particularly for married young women.

Validation of a rapid SARS-CoV-2 antibody test in general practice.

OBJECTIVES: To validate a rapid serological test (RST) for SARS-CoV-2 antibodies used in seroprevalence studies in healthcare providers, including primary healthcare providers (PHCPs) in Belgium. DESIGN: A phase III validation study of the RST (OrientGene) within a prospective cohort study. SETTING: Primary care in Belgium. PARTICIPANTS: Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages patients were eligible in the seroprevalence study. For the validation study, all participants who tested positive (376) on the RST at the first testing timepoint (T1) and a random sample of those who tested negative (790) and unclear (24) were included. INTERVENTION: At T2, 4 weeks later, PHCPs performed the RST with fingerprick blood (index test) immediately after providing a serum sample to be analysed for the presence of SARS-CoV-2 immunoglobulin G antibodies using a two-out-of-three assay (reference test). PRIMARY AND SECONDARY OUTCOME MEASURES: The RST accuracy was estimated using inverse probability weighting to correct for missing reference test data, and considering unclear RST results as negative for the sensitivity and positive for the specificity. Using these conservative estimates, the true seroprevalence was estimated both for T2 and RST-based prevalence values found in a cohort study with PHCPs in Belgium. RESULTS: 1073 paired tests (403 positive on the reference test) were included. A sensitivity of 73% (a specificity of 92%) was found considering unclear RST results as negative (positive). For an RST-based prevalence at T1 (13.9), T2 (24.9) and T7 (70.21), the true prevalence was estimated to be 9.1%, 25.9% and 95.7%, respectively. CONCLUSION: The RST sensitivity (73%) and specificity (92%) make an RST-based seroprevalence below (above) 23% overestimate (underestimate) the true seroprevalence. TRIAL REGISTRATION NUMBER: NCT04779424.

Faecal microbiota transplantation to prevent complications after allogeneic stem cell transplantation for haematological malignancies: a study protocol for a randomised controlled phase-II trial (the FMT-allo study).

INTRODUCTION: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to graft-versus-host disease (GvHD) and infectious complications. Alterations of the intestinal microbiota plays a major role in the development of allo-HSCT complications. The gut microbiota could be restored by faecal microbiota transplantation (FMT). However, there are no published randomised studies assessing the efficacy of FMT for GvHD prophylaxis. METHODS AND ANALYSIS: This prospective, open-label, multi-centre, parallel-group, randomised phase-II clinical trial has been designed to assess the effect of FMT on toxicity in patients treated with myeloablative allo-HSCT for haematological malignancy. Based on Fleming's single-stage sample size estimation procedure, the design plans to include 60 male and female patients aged 18 or over per arm, to be randomly assigned to two groups, one with and one without (control group) FMT. The primary endpoint is GvHD-free relapse-free survival rate at 1 year after allo-HSCT. Secondary endpoints are outcome measures of the impact of FMT on allo-HSCT-related morbidity and mortality (overall survival and progression-free survival at 1 and 2 years, haematological parameters, infectious complications, tolerance and safety of FMT). The primary endpoint will be evaluated according to assumptions of the single-stage Fleming design, compared between groups by a log-rank test and further investigated in a multivariate marginal structural Cox model taking into account centre effect. The proportional-hazard hypothesis will be verified using Schoenfeld's test and by plotting residuals. ETHICS AND DISSEMINATION: The local institutional review board (CPP Sud-Est II, France) issued approval on 27 January 2021. The French national authorities issued approval on 15 April 2021. The outcome of the study will be disseminated via peer-reviewed publications and at congresses. TRIAL REGISTRATION NUMBER: NCT04935684.

COVID-19 vaccine effectiveness among healthcare workers: a hospital-based cohort study.

OBJECTIVES: Healthcare workers (HCWs) were the first to be prioritised for COVID-19 vaccination. This study aims to estimate the COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 symptomatic infection among HCWs in Portuguese hospitals. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We analysed data from HCWs (all professional categories) from three central hospitals: one in the Lisbon and Tagus Valley region and two in the central region of mainland Portugal, between December 2020 and March 2022. VE against symptomatic SARS-CoV-2 infection was estimated as one minus the confounder adjusted HRs by Cox models considering age group, sex, self-reported chronic disease and occupational exposure to patients diagnosed with COVID-19 as adjustment variables. RESULTS: During the 15 months of follow-up, the 3034 HCWs contributed a total of 3054 person-years at risk, and 581 SARS-CoV-2 events occurred. Most participants were already vaccinated with a booster dose (n=2653, 87%), some are vaccinated with only the primary scheme (n=369, 12.6%) and a few remained unvaccinated (n=12, 0.4%) at the end of the study period. VE against symptomatic infection was 63.6% (95% CI 22.6% to 82.9%) for HCWs vaccinated with two doses and 55.9% (95% CI -1.3% to 80.8%) for HCWs vaccinated with one booster dose. Point estimate VE was higher for individuals with two doses taken between 14 days and 98 days (VE=71.9%; 95% CI 32.3% to 88.3%). CONCLUSION: This cohort study found a high COVID-19 VE against symptomatic SARS-CoV-2 infection in Portuguese HCWs after vaccination with one booster dose, even after Omicron variant occurrence. The small sample size, the high vaccine coverage, the very low number of unvaccinated individuals and the few events observed during the study period contributed to the low precision of the estimates.

Effects of qCON and qNOX-guided general anaesthesia management on patient opioid use and prognosis: a study protocol.

INTRODUCTION: The adverse effects of general anaesthetic drugs (especially opioids) cannot be ignored. However, current nociceptive-monitoring techniques still lack consistency in guiding the use of opioids. This trial will study the demand for opioid use and patient prognosis in qCON and qNOX-guided general anaesthesia management. METHODS AND ANALYSIS: This prospective, randomised, controlled trial will randomly recruit 124 patients undergoing general anaesthesia for non-cardiac surgery in equal numbers to either the qCON or BIS group. The qCON group will adjust intraoperative propofol and remifentanil dosage according to qCON and qNOX values, while the BIS group will adjust according to BIS values and haemodynamic fluctuations. The differences between the two groups will be observed in remifentanil dosing and prognosis. The primary outcome will be intraoperative remifentanil use. Secondary outcomes will include propofol consumption; the predictive ability of BIS, qCON and qNOX on conscious responses, noxious stimulus and body movements; and changes in cognitive function at 90 days postoperatively. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Ethics Committee of the Tianjin Medical University General Hospital (IRB2022-YX-075-01). Participants gave informed consent to participate in the study before taking part. The study results will be published in peer-reviewed journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059877.