Adherence to inhalers in patients with severe asthma treated with anti-interleukin-5 biologics.

OBJECTIVE: Given poor medication adherence in severe asthma is difficult to  evaluate in daily practice, using at least two methods concurrently is recommended. We aimed to determine the prevalence of nonadherence  to  inhalers using the Test of Adherence to Inhalers questionnaire and the medication possession ratio obtained from the pharmacy refill data in patients with severe asthma treated with anti-interleukin-5 biologics and to evaluate their concordance. METHOD: This was a cross-sectional retrospective observational study of 53  patients with severe asthma recruited from the severe asthma unit of a tertiary  hospital in Madrid from June to December 2020. We registered demographic data, comorbidities and concomitant therapy for  sthma. Nonadherence was defined as pharmacy refill data < 80% and/or Test of Adherence to Inhalers questionnaire results < 50. Concordance was assessed by determining the Cohen's kappa statistic. Results: The median age was 61 years (interquartile range 51.8-67.0), and 33  (61%) were women. According to the pharmacy refill data lack of  adherence to the primary inhaler was 58.5%. However, when using the Test of  Adherence to Inhalers questionnaire, it was 22.6%. Combining both methods,  17% of patients were considered to have nonadherence to inhalers. Likewise,  when identifying nonadherence by either of these methods, it reached a  prevalence of 64.2%. The pharmacy refill data and Test of Adherence to  Inhalers questionnaire agreed in 53.1% and disagreed in 46.9% of patients (k  = 0.137; 95% confidence interval -0.057 to 0.331; p = 0.318). CONCLUSIONS: We observed a higher prevalence of non-adherence to inhalers  in patients with severe asthma treated with anti-interleukin-5 biologics. The  agreement between the Test of Adherence to Inhalers questionnaire and the  pharmacy refill data is lower when evaluating nonadherence in patients with  severe asthma treated with anti-interleukin-5 biologics. The pharmacy refill  data detect a higher proportion of nonadherence compared with the Test of  Adherence to Inhalers questionnaire.

OBJETIVO: Dado que la mala adherencia a la medicación en el asma grave es  difícil de evaluar en la práctica diaria, se recomienda utilizar al menos dos métodos simultáneamente. El objetivo es determinar la prevalencia de la  falta de adherencia a los inhaladores mediante el cuestionario Test de  Adherencia a los Inhaladores y la ratio de posesión de la medicación obtenida a  partir de los datos de dispensación de la farmacia en pacientes con asma  grave tratados con biológicos anti interleucina 5 y evaluar su concordancia.Método: Estudio observacional retrospectivo transversal de 53 pacientes con  asma grave reclutados en la unidad de asma grave de un hospital terciario de  Madrid de junio a diciembre de 2020. Se registraron datos demográficos, comorbilidades y el tratamiento concomitante para el asma. La  falta de adherencia se definió como una ratio de posesión de la medicación <  80% y/o un valor en los resultados del cuestionario Test de Adherencia a los  Inhaladores < 50. La concordancia se evaluó con el coeficiente kappa de  Cohen. RESULTADOS: La mediana de edad fue de 61 años (rango intercuartílico 51,8- 67,0), y 33 (61%) eran mujeres. Según la ratio de posesión de la medicación,  la falta de adherencia al inhalador primario fue del 58,5%. Sin embargo, al  utilizar el cuestionario Test de Adherencia a los Inhaladores, ésta fue del  22,6%. Combinando ambos métodos, se consideró que el 17% de los  pacientes presentaban no adherencia a los inhaladores. Asimismo, al identificar  la no adherencia por cualquiera de estos métodos, se alcanzó una  prevalencia del 64,2%. El cuestionario Test de Adherencia a los Inhaladores y  la ratio de posesión de la medicación coincidieron en el 53,1% y discreparon en  el 46,9% de los pacientes (k = 0,137; intervalo de confianza del 95% ­0,057 a 0,331; p = 0,318). CONCLUSIONES: Se observó una alta prevalencia de no adherencia a los inhaladores en los pacientes con asma grave tratados con biológicos anti interleucina 5. La concordancia entre el cuestionario Test de Adherencia a los Inhaladores y la ratio de posesión de la medicación es menor cuando se  evalúa la no adherencia en pacientes con asma grave tratados con biológicos  anti interleucina 5. La ratio de posesión de la medicación detecta una mayor  proporción de no adherencia en comparación con el cuestionario Test de  Adherencia a los Inhaladores.

Impact of the withdrawal of renin-angiotensin-aldosterone inhibitors on mortality in COVID-19 patients.

Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.

Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.

Adherencia a los inhaladores en pacientes con asmagrave tratados con biológicos anti interleucina 5 / Adherence to inhalers in patients with severe asthma treated with anti-interleukin-5 biologics

Objetivo: Dado que la mala adherencia a la medicación en el asma gravees difícil de evaluar en la práctica diaria, se recomienda utilizar al menos dosmétodos simultáneamente. El objetivo es determinar la prevalencia de la faltade adherencia a los inhaladores mediante el cuestionario Test de Adherenciaa los Inhaladores y la ratio de posesión de la medicación obtenida a partirde los datos de dispensación de la farmacia en pacientes con asma gravetratados con biológicos anti interleucina 5 y evaluar su concordancia.Método: Estudio observacional retrospectivo transversal de 53 pacientescon asma grave reclutados en la unidad de asma grave de un hospital terciario de Madrid de junio a diciembre de 2020. Se registraron datos demográficos, comorbilidades y el tratamiento concomitante para el asma. La faltade adherencia se definió como una ratio de posesión de la medicación< 80% y/o un valor en los resultados del cuestionario Test de Adherencia alos Inhaladores < 50. La concordancia se evaluó con el coeficiente kappade Cohen.Resultados: La mediana de edad fue de 61 años (rango intercuartílico51,8-67,0), y 33 (61%) eran mujeres. Según la ratio de posesión de lamedicación, la falta de adherencia al inhalador primario fue del 58,5%.Sin embargo, al utilizar el cuestionario Test de Adherencia a los Inhaladores, ésta fue del 22,6%. Combinando ambos métodos, se consideróque el 17% de los pacientes presentaban no adherencia a los inhaladores. Asimismo, al identificar la no adherencia por cualquiera de estos métodos, se alcanzó una prevalencia del 64,2%. El cuestionario Test deAdherencia a los Inhaladores y la ratio de posesión de la medicacióncoincidieron en el 53,1% y discreparon en el 46,9% de los pacientes(k = 0,137; intervalo de confianza del 95% –0,057 a 0,331; p = 0,318).Conclusiones: Se observó una alta prevalencia de no adherencia a losinhaladores en los pacientes con asma grave tratados con biológicos antiinterleucina 5. (AU)

Objective: Given poor medication adherence in severe asthma is difficult to evaluate in daily practice, using at least two methods concurrently isrecommended. We aimed to determine the prevalence of nonadherenceto inhalers using the Test of Adherence to Inhalers questionnaire and themedication possession ratio obtained from the pharmacy refill data inpatients with severe asthma treated with anti-interleukin-5 biologics and toevaluate their concordance.Method: This was a cross-sectional retrospective observational study of53 patients with severe asthma recruited from the severe asthma unit of atertiary hospital in Madrid from June to December 2020. We registereddemographic data, comorbidities and concomitant therapy for asthma.Nonadherence was defined as pharmacy refill data < 80% and/or Testof Adherence to Inhalers questionnaire results < 50. Concordance wasassessed by determining the Cohen’s kappa statistic.Results: The median age was 61 years (interquartile range 51.8-67.0),and 33 (61%) were women. According to the pharmacy refill data lackof adherence to the primary inhaler was 58.5%. However, when usingthe Test of Adherence to Inhalers questionnaire, it was 22.6%. Combiningboth methods, 17% of patients were considered to have nonadherenceto inhalers. Likewise, when identifying nonadherence by either of thesemethods, it reached a prevalence of 64.2%. The pharmacy refill data andTest of Adherence to Inhalers questionnaire agreed in 53.1% and disagreed in 46.9% of patients (k = 0.137; 95% confidence interval −0.057to 0.331; p = 0.318). (AU)

Encuesta a profesionales sanitarios y pacientes sobre el papel del farmacéutico en la Unidad de Enfermedades Inflamatorias Inmunomediadas / The role of the pharmacist within an immune-mediated inflammatory disease unit: Results of a survey of healthcare providers and patients

Objetivo: Evaluar el interés y necesidad de que el farmacéutico desarrolle nuevas actividades propuestas, y potenciar o mantener otras que yase realizaban, antes de que la futura Unidad de Enfermedades Inflamatorias Inmunomediadas inicie su actividad en nuestro hospital. Además,priorizar la incorporación de las nuevas actividades en base a los resultados obtenidos.Método: Diseño observacional transversal unicéntrico mediante unaencuesta realizada en enero de 2020 a todos los profesionales sanitarios de los servicios clínicos implicados y a una muestra de pacientes, yestructurada en dos categorías: Acciones orientadas a la atención farmacéutica al paciente y Acciones orientadas a los profesionales de dichaUnidad. Cada ítem se puntuó de 0 a 10, siendo 10 el máximo interés/necesidad. Se aplicó una matriz de priorización para cuantificar y evaluar cada actividad e implantar las nuevas por orden de priorización.Resultados: Se completaron 90 encuestas (30 de pacientes y 60 deprofesionales). Se analizaron las medianas obtenidas de cada una de las20 actividades propuestas, alcanzándose valores entre 8 y 10. Se compararon valores: en el grupo de farmacéuticos versus médicos se obtuvieron más ítems con diferencias estadísticamente significativas que en elgrupo farmacéuticos versus enfermería, o farmacéuticos versus pacientes. (AU)

Objective: To evaluate the importance and need for pharmacists toexpand their role to new activities and to promote and maintain othersthey already carried out prior to the implementation of a new Immunemediated Inflammatory Diseases Unit to be created in our hospital; toprioritize the new activities incorporated based on the results obtained.Method: This was a single center cross-sectional based on a survey administered during January 2020 to all clinical healthcare providers due to bepart of the new unit, as well as to a sample of patients. It was structuredinto two categories: actions related to patients’ pharmaceutical care, andactions related to practitioners of the Immune-mediated Inflammatory Diseases Unit. Each item was assigned a score from 0 to 10, where 10 indicatedmaximum interest or need. A prioritization template was applied to quantifyand evaluate each activity and implement the new ones in order of priority.Results: A total of 90 responses were obtained (30 from patients and60 from healthcare workers). An analysis was performed of the medianscores of each of the 20 activities proposed, which ranged between 8 and10 points. When comparing the scores obtained, it was observed thatmore statistically significant differences were obtained in the pharmacists vsdoctors group than in the pharmacists vs nurses group, or the pharmacistsvs patients one. After prioritization, the first action taken was to implement electronic prescriptions for outpatients with immune-mediated inflammatorydiseases. (AU)

The role of the pharmacist within an immune-mediated inflammatory disease unit: Results of a survey of healthcare providers and patients.

OBJECTIVE: To evaluate the importance and need for pharmacists to expand  their role to new activities and to promote and maintain others they already  carried out prior to the implementation of a new Immunemediated Inflammatory Diseases Unit to be created in our hospital; to prioritize the new activities incorporated based on the results obtained. METHOD: This was a single center cross-sectional based on a survey  administered during January 2020 to all clinical healthcare providers due to be part of the new unit, as well as to a sample of patients. It was structured into two categories: actions related to patients' pharmaceutical  care, and actions related to practitioners of the Immune-mediated  Inflammatory Diseases Unit. Each item was assigned a score from 0 to 10,  where 10 indicated maximum interest or need. A prioritization template was  applied to quantify and evaluate each activity and implement the new ones in  order of priority. RESULTS: A total of 90 responses were obtained (30 from patients and 60 from  healthcare workers). An analysis was performed of the median scores of each  of the 20 activities proposed, which ranged between 8 and 10 points. When  comparing the scores obtained, it was observed that more statistically  significant differences were obtained in the pharmacists vs doctors group than  in the pharmacists vs nurses group, or the pharmacists vs patients one. After  prioritization, the first action taken was to implement electronic prescriptions  for outpatients with immune-mediated inflammatory diseases. CONCLUSIONS: The survey revealed the expectations of healthcare providers and patients regarding the role pharmacists should play in the newly created unit and provided an insight into the most valued activities. This information will be useful in prioritizing the implementation of the new activities to be carried out by the unit.

Objetivo: Evaluar el interés y necesidad de que el farmacéutico desarrolle nuevas actividades propuestas, y potenciar o mantener otras que ya se realizaban, antes de que la futura Unidad de Enfermedades Inflamatorias Inmunomediadas inicie su actividad en nuestro hospital. Además, priorizar la incorporación de las nuevas actividades en base a los  resultados obtenidos.Método: Diseño observacional transversal unicéntrico mediante una encuesta  realizada en enero de 2020 a todos los profesionales sanitarios de los servicios  clínicos implicados y a una muestra de pacientes, y estructurada en dos  categorías: Acciones orientadas a la atención farmacéutica al paciente y  Acciones orientadas a los profesionales de dicha Unidad. Cada ítem se puntuó  de 0 a 10, siendo 10 el máximo interés/necesidad. Se aplicó una matriz de  priorización para cuantificar y evaluar cada actividad e implantar las nuevas  por orden de priorización.Resultados: Se completaron 90 encuestas (30 de pacientes y 60 de profesionales). Se analizaron las medianas obtenidas de cada una de las 20  actividades propuestas, alcanzándose valores entre 8 y 10. Se compararon valores: en el grupo de farmacéuticos versus médicos se  obtuvieron más ítems con diferencias estadísticamente significativas que en el grupo farmacéuticos versus enfermería, o farmacéuticos versus pacientes. Tras la priorización, la primera acción fue implantar la prescripción electrónica en pacientes externos con enfermedades inflamatorias inmunomediadas.Conclusiones: La encuesta ha permitido conocer las expectativas de los  profesionales sanitarios y pacientes sobre la actividad del farmacéutico en  dicha Unidad, cuantificar las actividades más valoradas y priorizar la  implantación de nuevas actividades.

Conservative Treatment for Childhood and Adolescent Obesity: Real World Follow-Up Profiling and Clinical Evolution in 1300 Patients.

Background: Limited therapeutic tools and an overwhelming clinical demand are the major limiting factors in pediatric obesity management. The optimal protocol, environment, body mass index (BMI) change targets and duration of obesity-oriented interventions remain to be elucidated. Aims: We aimed to characterize the singularities of follow-up, anthropometric and metabolic evolution of a large cohort of pediatric patients with obesity in a specialized university hospital outpatient obesity unit. Patients and methods: Follow-up duration (up to seven years), attrition rate and anthropometric and metabolic evolution of 1300 children and adolescents with obesity were studied. An individualized analysis was conducted in patients attaining a high level of weight loss (over 1.5 BMI-SDS (standard deviation score) and/or 10% of initial weight; n = 252; 19.4%) as well as in "metabolically healthy" patients (n = 505; 38.8%). Results: Attrition rate was high during the early stages (11.2% prior to and 32.5% right after their initial metabolic evaluation). Mean follow-up time was 1.59 ± 1.60 years (7% of patients fulfilled 7 years). The highest BMI reduction occurred in the first year (-1.11 ± 0.89 SDS, p < 0.001 in 72.5% of patients). At the end of the follow-up, improvements in glucose and lipid metabolism parameters were observed (both p < 0.05), that were highest in patients with the greatest weight reduction (all p < 0.01), independent of the time spent to achieve weight loss. The pubertal growth spurt negatively correlated with obesity severity (r = -0.38; p < 0.01) but patients attaining adult height exceeded their predicted adult height (n = 308, +1.6 ± 5.4 cm; p < 0.001). "Metabolically healthy" patients, but with insulin resistance, had higher blood pressure, glucose, uric acid and triglyceride levels than those without insulin resistance (all p < 0.05). Preservation of the "metabolically healthy" status was associated with BMI improvement. Conclusions: Behavioral management of children with obesity can be effective and does not impair growth but is highly conditioned by high attrition. The best results regarding BMI reduction and metabolic improvement are achieved in the first year of intervention and can be preserved if follow-up is retained.

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2 ± 15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

ANTECEDENTES: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada. MÉTODOS: Se estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio. RESULTADOS: Se incluyó a 918 pacientes (edad 63,2 ± 15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas). CONCLUSIÓN: La hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos.

Inhaled bronchodilators use and clinical course of adult inpatients with Covid-19 pneumonia in Spain: A retrospective cohort study.

BACKGROUND: In the current coronavirus health crisis, inhaled bronchodilators(IB) have been suggested as a possible treatment for patients hospitalized. Patients with evidence of Covid-19 pneumonia worldwide have been prescribed these medications as part of therapy for the disease, an indication for which this medications could be ineffective taken on account the pathophysiology and mechanisms of disease progression. OBJECTIVE: The main objective was to evaluate whether there is an association between IB use and length of stay. Primary end points were the number of days that a patient stayed in the hospital and death as a final event in a time to event analysis. Pneumonia severity, oxygen requirement, involved drugs, comorbidity, historical or current respiratory diagnoses and other drugs prescribed to treat coronavirus pneumonia were also evaluated. METHODS: A descriptive, observational, cross-sectional study was performed in this tertiary hospital in Madrid (Spain). Data were obtained regarding patients hospitalized with Covid-19, excluding those who were intubated. The primary and secondary outcomes such as duration of hospitalization and death were compared in patients who received IB with those in patients who did not. RESULTS: 327 patients were evaluated, mean age was 64.4 ± 15.8 years. Median length of hospitalization stay was 10 days. Of them 292 (89.3%) overcame the disease, the remaining 35 died. Patients who had received IB did not have less mortality rate (odds ratio 0.839; 95% CI: 0.401 to 1.752) and less hospitalization period when compared with patients who did not received IB (odds ratio 1.280; 95% CI: 0.813 to 2.027). There was no significant association between IB use and recovery or death. Hypertension and diabetes were the most common comorbidities. The prevalence of chronic respiratory disease in our cohort was low (21.1%). Anticholinergics were the IB more frequently prescribed for Covid-19 pneumonia. Better response in patients treated with inhaled corticosteroids was not observed. CONCLUSION: Off-label indication of inhaled-bronchodilators for Covid-19 patients are common in admitted patients. Taken on account our results, the use of IB for coronavirus pneumonia apparently is not associated with a significantly patient's improvement. Our study confirms the hypothesis that inhaled bronchodilators do not improve clinical outcomes or reduce the risk of Covid-19 mortality. This could be due to the fact that the virus mainly affects the lung parenchyma and the pulmonary vasculature and probably not the airway. More researches are necessary in order to fill the gap in evidence for this new indication.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price / Evolución del coste de medicamentos biológicos en pacientes con artritis reumatoide en un hospital terciario. Factores influyentes en dicha evolución

Objective: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. Methods: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. Results: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). Conclusion: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.(AU)

Objetivo: Evaluar la evolución del coste por paciente/año y del coste por paciente/año/medicamento en pacientes en tratamientos con biológicos con artritis reumatoide (AR). Analizar y cuantificar los factores influyentes en dicha evolución tales como la optimización de medicamentos biológicos, el uso de biosimilares y los descuentos oficiales y los obtenidos tras procedimientos negociados. Además, evaluar parámetros clínicos de la actividad propios de la enfermedad en dichos pacientes. Métodos: Estudio retrospectivo, observacional, realizado en un hospital terciario español. Se incluyeron pacientes adultos diagnosticados de AR en tratamiento con biológicos desde 2009 a 2017. Resultados: Se incluyeron 320, 270 y 389 pacientes en 2009, 2013 y 2017, respectivamente. El coste paciente/año disminuyó de 10.798€ en 2009, 7.491€ en 2013 a 7.116€ en 2017. En 2017, debido a la competencia establecida, se alcanzaron descuentos del 14 y del 29,5% en etanercept y su biosimilar; 11,5, 17,8, 17,9 y 17,3% en adalimumab, certolizumab, golimumab y tocilizumab IV, respectivamente, así como un 24,6% y 43,1% en infliximab y su biosimilar. El porcentaje de pacientes optimizados en 2017 alcanzó el 35.2%. El ahorro anual en 2017 fue de 1.288.535€ (830.000€ debido a la optimización de dosis y/o pautas de administración, 249.666€ correspondiente al 7,5% del descuento oficial y 208.868€ tras procedimientos negociados). Conclusión: El coste anual por paciente en AR disminuyó considerablemente debido a diferentes factores, tales como, descuentos en la adquisición de medicamentos debido a descuentos oficiales y procedimientos negociados, junto a la optimización de terapias, siendo este último el factor que más contribuyó en dicho descenso.(AU)

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2±15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19.

AIMS: Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. METHODS AND RESULTS: COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50-66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). CONCLUSION: The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial 'quick' prognostic stratification in COVID-19.

Characterization of NT-proBNP in a large cohort of COVID-19 patients.

AIMS: Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis. METHODS AND RESULTS: Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit). CONCLUSION: NT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.

Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price.

OBJECTIVE: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. METHODS: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. RESULTS: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). CONCLUSION: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.

Off-label use of inhaled bronchodilators in hospitalised patients in Spain: a multicentre observational study.

BACKGROUND: Off-label prescription of inhaled bronchodilators (IB) is frequent, despite the fact that they can be ineffective and increase avoidable healthcare costs. OBJECTIVE: To analyse the frequency of off-label prescription of IB in hospitalised patients. Indications and level of evidence, involved drugs, medical specialties prescribing off-label IB and patients' adherence to IBs were also evaluated. METHOD: A descriptive, observational, cross-sectional study was performed in four tertiary hospitals in Spain. The main outcome measure was the number of patients prescribed off-label IBs. Prescriptions were checked against the European Medicines Agency-approved indications. The level of evidence supporting off-label prescription of IBs (according to MICROMEDEX 2.0) was also analysed. Patients were interviewed to test differences (off-label vs on-label) in adherence and knowledge about their inhaled therapy. RESULTS: 217 patients were prescribed IBs, 92 of whom were givend off-label IBs (54.7% men, mean age 73.9±12.9 years). The most common off-label prescriptions for IBs were: unspecified dyspnoea (not related to COPD or asthma) (27.2%), respiratory infections (23.9%) and heart failure (22.8%). 76.8% of patients did not have evidence supporting them. Beta2-agonist+corticosteroids and anticholinergics were most commonly prescribed off-label. Internal Medicine was the main medical specialty involved. There were no differences between off-label and on-label users in terms of patients' knowledge about treatment and adherence. CONCLUSION: Off-label indications for IBs are common in hospitalised patients and are generally indicated without scientific support. Dyspnoea not related to COPD or asthma, respiratory infections and heart failure were the main off-label indications, most frequently treated with anticholinergics and beta2-agonists+corticosteroids, for which their efficacy and safety has not been proved. Our results show that prescribing needs to be improved to follow the evidence that exists. Moreover, further research focused on off-label indications is needed to clarify whether they are effective, safe and cost-effective.

Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications.

AIMS: Data on the impact of COVID-19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID-19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline-directed medical therapy (GDMT) and worse outcomes during hospitalization. METHODS AND RESULTS: Data for a total of 3080 consecutive patients with confirmed COVID-19 infection and follow-up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N-terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in-hospital mortality. CONCLUSIONS: Patients with COVID-19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID-19 diagnosis. The withdrawal of GDMT was associated with higher mortality.

Bragg Peak Localization with Piezoelectric Sensors for Proton Therapy Treatment.

A full chain simulation of the acoustic hadrontherapy monitoring for brain tumours is presented in this work. For the study, a proton beam of 100 MeV is considered. In the first stage, Geant4 is used to simulate the energy deposition and to study the behaviour of the Bragg peak. The energy deposition in the medium produces local heating that can be considered instantaneous with respect to the hydrodynamic time scale producing a sound pressure wave. The resulting thermoacoustic signal has been subsequently obtained by solving the thermoacoustic equation. The acoustic propagation has been simulated by FEM methods in the brain and the skull, where a set of piezoelectric sensors are placed. Last, the final received signals in the sensors have been processed in order to reconstruct the position of the thermal source and, thus, to determine the feasibility and accuracy of acoustic beam monitoring in hadrontherapy.

Impact on Outcomes across KDIGO-2012 AKI Criteria According to Baseline Renal Function.

Acute kidney injury (AKI) and Chronic Kidney Disease (CKD) are global health problems. The pathophysiology of acute-on-chronic kidney disease (AoCKD) is not well understood. We aimed to study clinical outcomes in patients with previous normal (pure acute kidney injury; P-AKI) or impaired kidney function (AoCKD) across the 2012 Kidney Disease Improving Global Outcomes (KDIGO) AKI classification. We performed a retrospective study of patients with AKI, divided into P-AKI and AoCKD groups, evaluating clinical and epidemiological features, distribution across KDIGO-2012 criteria, in-hospital mortality and need for dialysis. One thousand, two hundred and sixty-nine subjects were included. AoCKD individuals were older and had higher comorbidity. P-AKI individuals fulfilled more often the serum creatinine (SCr) ≥ 3.0× criterion in AKI-Stage3, AoCKD subjects reached SCr ≥ 4.0 mg/dL criterion more frequently. AKI severity was associated with in-hospital mortality independently of baseline renal function. AoCKD subjects presented higher mortality when fulfilling AKI-Stage1 criteria or SCr ≥ 3.0× criterion within AKI-Stage3. The relationship between mortality and associated risk factors, such as the net increase of SCr or AoCKD status, fluctuated depending on AKI stage and stage criteria sub-strata. AoCKD patients that fulfil SCr increment rate criteria may be exposed to more severe insults, possibly explaining the higher mortality. AoCKD may constitute a unique clinical syndrome. Adequate staging criteria may help prompt diagnosis and administration of appropriate therapy.

Acoustic Localization of Bragg Peak Proton Beams for Hadrontherapy Monitoring.

Hadrontherapy makes it possible to deliver high doses of energy to cancerous tumors by using the large energy deposition in the Bragg-peak. However, uncertainties in the patient positioning and/or in the anatomical parameters can cause distortions in the calculation of the dose distribution. In order to maximize the effectiveness of heavy particle treatments, an accurate monitoring system of the deposited dose depending on the energy, beam time, and spot size is necessary. The localized deposition of this energy leads to the generation of a thermoacoustic pulse that can be detected using acoustic technologies. This article presents different experimental and simulation studies of the acoustic localization of thermoacoustic pulses captured with a set of sensors around the sample. In addition, numerical simulations have been done where thermo-acoustic pulses are emitted for the specific case of a proton beam of 100 MeV.

Persistence of biological agents over an eight-year period in rheumatoid arthritis and spondyloarthritis patients / Persistencia de medicamentos biológicos durante ocho años en pacientes con artritis reumatoide y espondiloartritis

Objective: To calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. Method: Retrospective observational study that included patients affected by rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started treatment with biological agents between January 2009 and December 2012 and followed until December 2016. Results: 132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06 months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab, infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second line: tocilizumab was the most persistent drug (median 22.1 months) in rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. Conclusions: Tocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment

Objetivo: Calcular y analizar la persistencia global y por medicamento, en primera y segunda línea de tratamiento, en pacientes con artritis reumatoide, espondiloartritis axial radiográfica y no radiográfica y artritis psoriásica durante un periodo de ocho años. Método: Estudio retrospectivo observacional de persistencia en pacientes que iniciaron su terapia con medicamentos biológicos entre enero de 2009 y diciembre de 2012 en seguimiento hasta diciembre de 2016. Resultados: Se analizaron 132, 87 y 33 pacientes con artritis reumatoide, espondiloartritis y artritis psoriásica, respectivamente. La persistencia mediana global para los biológicos en primera y segunda línea fueron: 30,9 meses y 14 meses, respectivamente, en artritis reumatoide; 63,06 meses y 25,6 meses en espondiloartritis. No se alcanzó la persistencia mediana en los ocho años de seguimiento en artritis psoriásica (> 70 meses) (p = 0,002 para la función de supervivencia entre patologías en primera línea). Persistencia mediana alcanzada en primera línea por medicamento: tocilizumab (58,3 meses), seguido de etanercept (44 meses) en artritis reumatoide (p = 0,79); en espondiloartritis golimumab y etanercept fueron los más persistentes (no alcanzaron la mediana), seguidos de adalimumab (44 meses) e infliximab (50,1 meses). En artritis psoriásica, golimumab seguido de infliximab y etanercept fueron los más persistentes (no alcanzaron la mediana), y adalimumab (59,4 meses). Persistencia mediana alcanzada en segunda línea por medicamento: tocilizumab (22,1 meses) en artritis reumatoide. Golimumab fue el más persistente en espondiloartritis y artritis psoriásica (sin alcanzar la mediana). Conclusiones: Tocilizumab y etanercept fueron los medicamentos más persistentes en artritis reumatoide, y golimumab en espondiloartritis y artritis psoriásica en primera y segunda línea de tratamiento