Eficacia y posible posicionamiento del tezepelumab para tratar el asma grave

Phenotype; Thymic stromal lymphopoietin; Uncontrolled asthmaFenotip; Limfopoetina estromal tímica; Asma no controladaFenotipo; Linfopoyetina estromal tímica; Asma no controladaThe excellent results for monoclonal antibodies in the treatment of severe uncontrolled asthma (SUCA) represent a milestone in current treatment of asthmatic disorders. Remaining, however, are several subsidiary areas for improvement in which new biologics are expected to make a decisive contribution. These biologics include tezepelumab, a monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP). TSLP is an epithelial-release cytokine (alarmin) that plays a key role in initiating both the innate (group 2 innate lymphoid cell (ILC) pathway) and the acquired (T helper 2 (Th2) pathway) immune responses by activating the type 2 (T2) asthma inflammatory pathway through both. It is also thought that it may additionally intervene in the neutrophilic non-T2 inflammatory pathway (via interaction with ILC3 and interleukin-17). Six clinical trials that included 2187 patients with uncontrolled asthma, with 2 or more exacerbations in the previous year, on medium/high-dose inhaled corticosteroids and at least 1 other controller, have demonstrated – irrespective of T2 endotype (and possibly also non-T2 endotype) – the efficacy and safety of tezepelumab, as it significantly reduces exacerbations (61.7%–66%) and bronchial hyperresponsiveness, and improves lung function, disease control, and quality of life. Tezepelumab could be indicated for the treatment of patients with, independently of the T2 phenotype (eosinophilic and non-eosinophilic), and may even be the only biologic available for treatment of non-T2 SUCA.Los excelentes resultados de los anticuerpos monoclonales en el tratamiento del asma grave no controlada (AGNC) constituyen un hito en el tratamiento actual de los trastornos asmáticos. Sin embargo, aún quedan varios aspectos complementarios susceptibles de mejorar para los que se esperan contribuciones decisivas de los nuevos biofármacos, entre los cuales se encuentra el tezepelumab, un anticuerpo monoclonal que bloquea la linfopoyetina estromal tímica (TSLP). La TSLP es una citocina de liberación epitelial (alarmina) que desempeña una función clave en el inicio de las respuestas inmunitarias tanto innata (vía de las células linfocíticas innatas [ILC] del grupo 2) como adaptativa (vía de los linfocitos T cooperadores 2 [Th2]), activando la vía inflamatoria del asma del tipo 2 (T2) mediante ambas. También se cree que puede intervenir en la vía inflamatoria neutrofílica con T2 baja (mediante la interacción con los ILC3 y la interleucina 17). En seis ensayos clínicos que incluyeron a 2.187 pacientes con asma no controlada, dos o más exacerbaciones en el año anterior, a tratamiento con corticosteroides inhalados en dosis medias o altas y con un mínimo de un tratamiento preventivo adicional, se ha demostrado la eficacia y seguridad del tezepelumab sin importar el endotipo T2 (y posiblemente tampoco el endotipo no T2), ya que reduce significativamente las exacerbaciones (61,7-66%) y la hiperreactividad bronquial y mejora la función pulmonar, el control de la enfermedad y la calidad de vida. El tezepelumab puede estar indicado para tratar a pacientes con asma grave, independientemente del fenotipo T2 (eosinofílico y no eosinofílico), y tal vez sea incluso el único biofármaco existente para el tratamiento del AGNC no T2.This article was funded by the Barcelona Respiratory Network (BRN) who did not participate in the articles selected or writing of the manuscript

In Vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular Optical Coherence Tomography in Pulmonary Arterial Hypertension : A New Prognostic Marker of Adverse Clinical Follow-Up

The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT (area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm 2, % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (<22%). Events occurred in 6 (1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Efectividad y eficiencia de una consulta monográfica hospitalaria para pacientes con EPOC e insuficiencia respiratoria

Objetivo: Puesto que no existe un modelo asistencial claro para la atención a los pacientes con enfermedad pulmonar obstructiva crónica e insuficiencia respiratoria crónica, se ha evaluado la efectividad y eficiencia de una consulta externa hospitalaria monográfica controlada por el Servicio de Neumología. Pacientes y métodos: Se ha realizado un estudio prospectivo de un año de seguimiento con control histórico. La población estaba constituida por 124 pacientes (105 varones; edad media ± desviación estándar de 69 ± 7 años; capacidad vital forzada: 64,6 ± 16,1%; volumen espiratorio forzado en el primer segundo: 35,6 ± 12,8%; presión arterial de oxígeno: 56,6 ± 8,3 mmHg; presión arterial de anhídrido carbónico: 49,8 ± 6,7 mmHg). En cada visita trimestral se practicaron una espirometría forzada y una gasometría arterial, y al inicio y al final del estudio se pasó un cuestionario de calidad de vida (Chronic Respiratory Disease Questionnaire, elaborado por Guyatt). Se estudiaron las siguientes variables: espirometría forzada, gasometría arterial, calidad de vida, número de ingresos en urgencias y planta, duración media de la hospitalización, ahorro de días de hospitalización, coste medio de las visitas en urgencia, coste medio de las hospitalizaciones para el Servei Català de la Salut (SCS) y el hospital, coste medio total por paciente para el SCS y el hospital, y coste agregado para el SCS y el hospital. Los resultados se compararon con los datos de los pacientes registrados en la Corporació Parc Taulí durante el año previo. Resultados: Se observó una mejoría estadísticamente significativa de la capacidad vital forzada y presión arterial de oxígeno (56,6 ± 8,2 frente a 59,1 ± 8,9 mmHg); el volumen espiratorio forzado en el primer segundo mejoró (875 ± 282 frente a 912 ± 321 ml), pero sin significación (p = 0,17), así como un descenso significativo de la presión arterial de anhídrido carbónico, número de ingresos en planta (1,16 ± 1,15 frente a 0,67 ± 1,17) y urgencias (2,06 ± 1,9 frente a 1,5 ± 2,1), duración media de la hospitalización (14,2 ± 19 frente a 8,1 ± 16 días) y días total de hospitalización (se ahorraron 756 días de hospitalización), coste medio de visitas en urgencias y hospitalización para el hospital (2.246 ± 3.007 frente a 1.297 ± 2.639 ¿) y el SCS, y costes agregados tanto para el hospital (­40.011 frente a ­-6.048 ¿) como para el SCS (238.513 frente a 152.312 ¿). El índice de calidad de vida mejoró, pero no significativamente. Conclusiones: El cambio de la atención sanitaria de estos pacientes ha generado una mejoría asistencial (efectividad) reduciendo notablemente los costes económicos (eficiencia) tanto para el financiador (SCS) como para el proveedor de servicios sanitarios (hospital), sin que se hayan observado cambios en la calidad de vida de los pacientes

Medición transcutánea de la presión parcial de anhídrido carbónico y de la saturación de oxígeno: validación del monitor SenTec

Técnicas y procedimientos. Volumen 42, Número 05, Mayo 2006 Texto completo Anterior | Siguiente Descargar PDF Buscar en medline artículos de: Ch Domingo E Canturri A Marín Buscar: Búsqueda avanzada Medición transcutánea de la presión parcial de anhídrido carbónico y de la saturación de oxígeno: validación del monitor SenTec Ch Domingoa, E Canturria, M Lujána, A Morenoa, H Espuelasa y A Marína. aServei de Pneumologia. Corporació Sanitària Parc Taulí. Sabadell. Barcelona. España. (Arch Bronconeumol 2006; 42: 246 - 251) Objetivo: Validar un monitor que mide la saturación de oxígeno y la presión parcial de anhídrido carbónico por vía transcutánea (SpO2 y PtcCO2). Pacientes y métodos: Se ha realizado un estudio observacional en el que se incluyó a 140 pacientes de raza caucásica, no fumadores y sin ictericia. Se les realizó: espirometría forzada, medición de la SpO2 y PtcCO2 mediante el monitor SenTec y gasometría arterial (lectura en 2 gasómetros) durante la fase de estabilización del monitor. En la evaluación estadística se compararon los valores de las 2 mediciones de gasometría arterial mediante media de diferencias para la presión arterial de anhídrido carbónico (PaCO2) y la saturación de oxígeno (SaO2). Se calculó la media aritmética entre las 2 gasometrías, además del coeficiente de correlación de Pearson (r) y el coeficiente de correlación intraclase (CCI) entre SaO2 y SpO2 y PaCO2 y PtcCO2 como medida de concordancia. Se aplicó el análisis de Bland y Altman para el estudio de la dispersión de datos. Resultados: Se rechazó a 10 pacientes debido a un error sistemático por problemas del gas calibrador. El tiempo medio (± desviación estándar) de estabilización del monitor antes de lectura fue de 13,9 ± 2,4 min. El volumen espiratorio forzado en el primer segundo fue superior al 80% en 40 pacientes; se situó entre el 60 y el 79% en 23; entre el 40 y el 59% en 30, y fue menor del 40% en 37. La media de diferencias entre las gasometrías arteriales fue: para la PaCO2, 0,28 ± 1,0 mmHg; para la SaO2, ­0,06 ± 0,86%, y para la presión arterial de oxígeno, ­-0,9 ± 2,7 mmHg. En cuanto a la correlación y concordancia, los resultados fueron los siguientes: para la SaO2 y SpO2, r = 0,74 y CCI = 0,73; para la PaCO2 y PtcCO2, r = 0,92 y CCI = 0,92. El análisis por subgrupos no mostró diferencias destacables. El análisis de Bland y Altman no demostró dispersión significativa de datos. Se observó que el monitor SenTec infravaloró los valores de SaO2 alrededor del 1% y sobrevaloró los de PaCO2 en 1 mmHg. Conclusiones: El tiempo de estabilización aconsejable del monitor SenTec antes de realizar una lectura es de 20 min. Las sobrevaloraciones e infravaloraciones del monitor carecen de traducción clínica. Por último, los valores obtenidos de SpO2 y PtcCO2 del monitor validado son fiables

Prueba de la diferencia de potencial nasal para el diagnóstico de la fibrosis quística

En la gran mayoría de los pacientes con fibrosis quística (FQ), el diagnóstico se sospecha por unos síntomas clínicos típicos y debe confirmarse mediante la determinación en sudor de una concentración de cloro elevada en 2 días separados o mediante la identificación de 2 mutaciones en un estudio genético. Para evidenciar el anormal comportamiento de la proteína de membrana CFTR (cystic fibrosis transmembrane conductance regulator), encargada del transporte de cloro, se ha ideado la prueba de la diferencia de potencial nasal (DPN), especialmente útil en pacientes con concentraciones de cloro normales y en los que no se identifican las 2 mutaciones del gen de la FQ. Para la realización de la DPN se requieren 2 electrodos conectados a un voltímetro (dispositivo de medida Tholy-Medicap®), uno colocado sobre la mucosa nasal del cornete inferior, y otro en el tejido celular subcutáneo del antebrazo. Un valor inferior a -­40 mV se considera patológico. Los valores obtenidos en sujetos sanos no sobrepasan nunca este valor. Se precisan 2 determinaciones anormales de DPN registradas en 2 días separados para aceptar la disfunción de la CFTR. Pueden observarse falsos negativos cuando la integridad del epitelio está alterada. En la FQ, tras la aplicación de amilorida la diferencia de potencial se reduce de modo más llamativo que en sanos, y la aplicación de isoproterenol o fenoterol después de amilorida no provoca respuesta debido al defecto genético que impide la activación de los canales de cloro