Search

Tocilizumab is an interleukin-6 receptor-blocking agent proposed for the treatment of severe COVID-19; however, limited data are available on their efficacy. The aim of this study was to assess the effect of tocilizumab on the outcomes of patients with COVID-19 pneumonia by using propensity-score-matching (PSM) analysis.A retrospective observational analysis of hospitalized COVID-19 adult patients admitted to the Vall d'Hebron Hospital was performed between March and April 2020. We used the logistic regression to analyze the effect of tocilizumab on mortality, as main outcome, and PSM analysis to further validate their effect. Secondary outcomes were length-of-stay (LOS) and intensive-care-unit (ICU) stay. Same outcomes were also assessed for early tocilizumab administration, within 72 h after admission. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables.A total of 544 COVID-19 patients were included, 197 (36.2%) were treated with tocilizumab of whom 147 were treated within the first 72 h after admission; and 347 were included in the control group. After PSM analyses, the results showed no association between tocilizumab use and overall mortality (OR = 1.03, 95%CI: 0.63-1.68). However, shorter ICU-stay in the tocilizumab group was found compared to the control group (Coefficient -4.27 95%CI: -6.63 to -1.92). Similar results were found in the early tocilizumab cohort.The administration of tocilizumab in patients with moderate to severe COVID-19 did not reduce the risk of mortality in our cohort of patients, regardless of the time of administration.El tocilizumab es un agente bloqueador del receptor de la interleucina 6 propuesto para el tratamiento de la COVID-19 grave; sin embargo, se dispone de datos limitados sobre su eficacia. El objetivo de este estudio fue evaluar el efecto de tocilizumab en los resultados de los pacientes con neumonía por COVID-19 mediante un análisis de emparejamiento porSe realizó un análisis observacional retrospectivo de los pacientes adultos con COVID-19 ingresados en el Hospital Vall d’Hebron entre marzo y abril de 2020. Se utilizó la regresión logística para analizar el efecto de tocilizumab en la mortalidad, como resultado principal, y el análisis PSM para validar aún más su efecto. Los resultados secundarios fueron la duración de la estancia y la estancia en la unidad de cuidados intensivos (UCI). También se evaluaron los mismos resultados para la administración temprana de tocilizumab, dentro de las 72 h posteriores al ingreso. Los pacientes se seleccionaron mediante el emparejamiento de su propensión individual a recibir tratamiento con tocilizumab, condicionado a sus variables demográficas y clínicas.Se incluyeron 544 pacientes de COVID-19, 197 (36,2%) fueron tratados con tocilizumab, de los cuales 147 fueron tratados dentro de las primeras 72 h tras el ingreso; y 347 fueron incluidos en el grupo control. Tras los análisis PSM, los resultados no mostraron ninguna asociación entre el uso de tocilizumab y la mortalidad global (OR = 1,03; IC del 95%: 0,63-1,68). Sin embargo, se encontró una menor estancia en la UCI en el grupo de tocilizumab en comparación con el grupo de control (coeficiente −4,27; IC del 95%: −6,63 − −1,92). Se encontraron resultados similares en la cohorte de tocilizumab temprano.La administración de tocilizumab en pacientes con COVID-19 moderada a grave no redujo el riesgo de mortalidad en nuestra cohorte de pacientes, independientemente del momento de la administración.

Primary immunodeficiency diseases (PID), which are comprised of over 400 genetic disorders, occur when a component of the immune system is diminished or dysfunctional. Patients with PID who require immunoglobulin (IG) replacement therapy receive intravenous IG (IVIG) or subcutaneous IG (SCIG), each of which provides equivalent efficacy. We developed a cost-minimization model to evaluate costs of IVIG versus SCIG from the Spanish National Healthcare System perspective. The base case modeled the annual cost per patient of IVIG and SCIG for the mean doses (per current expert clinical practice) over 1 year in terms of direct (drug and administration) and indirect (lost productivity for adults and parents/guardians of pediatric patients) costs. It was assumed that all IVIG infusions were administered in a day hospital, and 95% of SCIG infusions were administered at home. Drug costs were calculated from ex-factory prices obtained from local databases minus the mandatory deduction. Costs were valued on 2018 euros. The annual modeled costs were €4,266 lower for patients with PID who received SCIG (total €14,466) compared with those who received IVIG (total €18,732). The two largest contributors were differences in annual IG costs as a function of dosage (– €1,927) and hospital administration costs (– €2,688). However, SCIG incurred training costs for home administration (€695). Sensitivity analyses for two dose-rounding scenarios were consistent with the base case. Our model suggests that SCIG may be a cost-saving alternative to IVIG for patients with PID in Spain., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was funded by Shire, a Takeda company.

Background Triple antithrombotic therapy (TT) is recommended for patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, there is a lack of comparative data in a real-world clinical setting between non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists (VKA). The aim of this study was to compare the safety and efficacy of TT with NOAC or VKA after PCI in patients with AF at 1-year of follow-up. Materials and Methods This was an observational retrospective study in 2 tertiary care hospitals during 2013-2016. Patients with indication for anticoagulation due to AF from an initial registry of 5,269 patients undergoing PCI were identified. Safety primary endpoint was the occurrence of major bleeding events as defined by Bleeding Academic Consortium (BARC ≥ 3). The primary efficacy endpoint was defined as major adverse cardiovascular events (MACE). Results A total of 187 consecutive patients on TT were identified: 45.4% of were discharged on NOAC and 54.6% on VKA. Patients who received VKA presented more comorbidities and had a higher bleeding risk than those who received NOACs. Major bleeding events occurred in 17 patients (9%), with a higher rate in the VKA group (3.5% vs. 13% confidence interval, 0.19-0.86, P = 0.02). There were no differences in the rates of major adverse cardiovascular events, stroke or net clinical benefit. Conclusions In this real-world study, patients with AF undergoing PCI treated on NOAC-based TT showed lower bleeding rates than those on VKA, with a lower rate of major bleeding events, while efficacy was similar between groups.

Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population. Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality. A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events. If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

Resumen El objetivo de este estudio es describir la relacion entre incidencia lesional (IL) y estado madurativo de jugadores varones de balonmano formativo (BmF) de alto nivel competicional. Se analizan durante 2 temporadas la incidencia de lesion deportiva de forma prospectiva en 133 jugadores, los criterios de maduracion biologica y la carga fisica de exposicion. Se siguieron los criterios para estudios de epidemiologia lesional segun el consenso UEFA. Las variables utilizadas para analizar el estado madurativo son los estadios de Tanner, la pubertad, el pico de velocidad de crecimiento, el volumen testicular y la edad osea. Se registraron 190 lesiones para un total de 34.222 h de exposicion. La IL total media de todas las categorias fue de 5,6 lesiones/1.000 h de exposicion. En competicion, el valor fue de 21,8 lesiones/1.000 h, y en entrenamiento, de 3,1 lesiones/1.000 h. No se encontraron diferencias estadisticamente significativas entre IL, la edad cronologica y los diferentes estados madurativos por ANOVA. El analisis estadistico multivariante registra cierta tendencia entre las asociaciones de IL en competicion para categoria (p = 0,07), y en la IL en entrenamientos para Tanner (p = 0,091) y pubertad (p = 0,021). En conclusion, si bien no se detectaron diferencias significativas en la IL por edades en jugadores de BmF, si se aprecia una tendencia real en determinados estadios madurativos mediante el analisis multivariante. Esto debera tenerse en cuenta para planificacion entrenamientos y estrategias de prevencion de la lesion deportiva en el contexto del BmF.

Resumen Objetivo Evaluar la incidencia y el patron lesional en el balonmano de elite. Metodo Estudio retrospectivo y transversal de 496 jugadores, de 29 equipos (divididos por categorias segun edad y nivel), durante 5 temporadas (2007-2012), de un club del sur de Europa. El equipo medico evaluo las lesiones y el tiempo de exposicion por equipos. Se siguieron los criterios epidemiologicos segun consenso UEFA y codificacion OSICS-10. Resultados Se registraron 557 lesiones con 117.723 h de exposicion totales. La incidencia lesional media de los equipos fue: 4,9 lesiones/1.000 h de exposicion. Para el equipo Senior A (Profesional) fue de 4,3 (DE 1,8); Senior B, 3,4 (DE 1,6); Juvenil, 5,6 (DE 1,4); Cadete A, 5,5 (DE 2,5); Cadete B, 5,7 (DE 3,2), e Infantil, 4,9 (DE 1,9). No hubo diferencias estadisticamente significativas entre ellos, aunque los seniors tuvieron la mayor cantidad de horas de exposicion (p Las localizaciones mas frecuentes fueron tobillo (18,1%), rodilla (15,3%), muslo (12,9%) y region lumbar (10,6%). Las estructuras afectadas con mas frecuencia fueron la lesion ligamentosa (27,3%) y la lesion «muscular por mecanismo indirecto» (20,5%). Esta ultima mas en el Senior A, y la lesion ligamentosa en las categorias inferiores, aunque no se registraron diferencias significativas entre categorias. Conclusion El patron y la incidencia lesional en el balonmano de elite es uniforme entre los equipos de diferentes categorias, con pequenas diferencias que deberan tenerse en cuenta para optimizar los programas de prevencion en cada categoria del balonmano formativo de elite.

Background and Objectives Fibrinogen deficiency is a cause for massive haemorrhage whose management in emergency situations is the subject of debate. Plasma-derived fibrinogen concentrates are indicated for reversing the haemorrhagic diathesis found in congenital and acquired deficiencies. Materials and Methods We report on the results of an observational study that evaluated the effects of fibrinogen concentrates in patients suffering from various forms of acquired severe hypofibrinogenaemia with life-threatening consumptive thrombo-haemorrhagic disorders (surgery, trauma and digestive haemorrhage), or underlying disease states that limit fibrinogen synthesis (hepatic dysfunction, haematological malignancies). Results Sixty-nine patients were identified and included, in whom most of the processes (62%) corresponded to consumptive hypofibrinogenaemia. After a median dose of 4 g, a mean absolute increase of 1·09 g/l in plasma fibrinogen was measured and coagulation parameters were significantly improved (P

Thirteen patients with myasthenia gravis, unresponsive to prednisone and cyclosporin after thymectomy, received KF506 (tacrolimus) for 12 months, at starting doses of 0.1 mg/kg per day b.i.d. and then adjusted to achieve plasma concentrations between 7 and 8 ng/mL. The doses of prednisone were progressively reduced and finally discontinued. Anti-acetylcholine antibodies and myasthenia gravis score for disease severity decreased significantly and muscular strength increased by 37%. All patients achieved pharmacological remission, 11 were asymptomatic and two had minimal weakness of eyelid closure. Tacrolimus was well tolerated and appears a suitable approach after unsuccessful treatment with conventional immunosuppressants in patients with disabling myasthenia.

Background Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. Objective The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS(2) score

Objective The therapeutic benefit of inhaled corticoids in bronchiectasis not due to cystic fibrosis is still not well documented. The aim of the present study was to assess the efficacy and safety of inhaled corticoids in this disease. Setting This study was conducted at a tertiary university hospital in the city of Barcelona, Catalonia, (Spain). Method A prospective, double-blind, parallel, placebo-masked study was conducted. Seventy-seven patients (40 women; mean age: 68 years) were randomly assigned to receive either 400 mcg budesonide twice daily or placebo and were regularly reviewed for six months. Results Differences in forced vital capacity and forced expiratory volume in the first second between the beginning and end of the study were not significantly lower in the budesonide group than in the placebo group, either in absolute values [−17.4 (386.9) versus −21.4 (375.5)] or in percentages [−1.9(9.5) versus −2.8 (11.6)]. Microbiological criteria applied to evaluate changes between the beginning and end of the study showed no worsening in the budesonide group compared with the control group, whereas a non-significant improvement was obtained in 8.1 % of cases in the budesonide group compared to 3 % in the placebo group. Although significance was only achieved for sputum eosinophils (p = 0.021), a consistent tendency towards improvement was also observed in secondary end-points (symptoms, number and duration of exacerbations, quality of life, sputum cytology and interleukin-8) in the budesonide group. Conclusion Although further studies are required, inhaled corticoid treatment may be efficacious and safe in bronchiectasis not due to cystic fibrosis.

BACKGROUND:Non—cystic fibrosis (CF) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to worsening lung function and increased morbidity and mortality.OBJECTIVE:To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity.METHODS:A double-blind, placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles, each for 6 months, with a one-month washout period. The number of exacerbations, number of hospital admissions, number of hospital admission days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity, density of PA in sputum, emergence of bacterial resistance, and emergence of other opportunistic bacteria were recorded.RESULTS:The number of admissions and days of admission (mean ± SD) during the tobramycin period (0.15 ± 0.37 and 2.05 ± 5.03) were lower than those during the placebo period (0.75 ± 1.16 and 12.65 ± 21.8) (p < 0.047). A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle (p = 0.038). No significant differences were observed in the number of exacerbations, antibiotic use, pulmonary function, and quality of life. The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not with detectable ototoxicity or nephrotoxicity.CONCLUSIONS:Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum. Nevertheless, pulmonary function and quality of life are not improved, and the risk of bronchospasm is appreciable.

Objectives Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p