Cost-effectiveness analysis of using innovative therapies for the management of moderate-to-severe ulcerative colitis in Spain

Background: To evaluate the cost-effectiveness of tofacitinib in comparison to vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC) after failure or intolerance to conventional therapy (bio-naive) or first-line biologic treatment (bio-experienced), from the Spanish National Health System (NHS) perspective. Methods: A lifetime Markov model with eight-week cycles was developed including five health states: remission, response, active UC, remission after surgery, and death. Response and remission probabilities (for induction and maintenance periods) were obtained from a multinomial network meta-analysis. Drug acquisition – biosimilar prices included – (ex-factory price with mandatory deductions), adminis- tration, surgery, patient management, and adverse event management costs (€, year 2019) were considered. A 3% discount rate (cost/outcomes) was applied. Probabilistic and deterministic sensitivity analyses (PSA) were conducted. Results: Tofacitinib was dominant versus vedolizumab (both in bio-naive and bio-experienced patients) entailing total cost savings of €23,816 (bio-naïve) and €11,438 (bio-experienced). Differences in quality- adjusted life-year (QALY) were smaller than 0.1 for both populations. PSA results showed that tofacitinib has a high probability of being cost-effective (bio-naïve: 82.5%; bio-experienced: 90.6%) versus vedolizumab. Conclusions: From the Spanish NHS perspective, tofacitinib could be a dominant treatment (less costly and more effective) in comparison to vedolizumab, with relevant cost savings and similar QALY gains

Nuevos análisis traceológicos, arqueométricos y petrológicos de material metálico y lítico recuperado en un lugar sagrado de la Cultura de las Motillas: Castillejo del Bonete (Terrinches, Ciudad Real)

Castillejo del Bonete es fue un lugar sagrado utilizado durante el III y II milenios cal BC al sur de La Mancha. Se usó como monumento de culto y funerario; dispone de corredores y construcciones orientados a los solsticios. Los resultados de su estudio han sido publicados en revistas científicas nacionales e internacionales. El trabajo aquí presentado aporta los recientes resultados del estudio analítico de diferentes clases de materiales arqueológicos selectos depositados en este lugar: estelas funerarias, cuentas, útiles metálicos y líticos. En cuanto a la piedra tallada, se han llevado a cabo análisis de uso en diferentes piezas. Respecto a la piedra pulida, se ha desarrollado un análisis con microscopio electrónico de barrido de una cuenta de caolinita roja, así como análisis traceológicos de brazales de arquero. Análisis paleontológicos y petrológicos se han realizado sobre una estela funeraria encontrada en el interior de la cueva mortuoria. Esta serie de analíticas realizadas sobre materiales selectos se añade a las hasta ahora existentes, ya publicadas. En el estado actual de conocimientos es posible afirmar que la cultura material enterrada en Castillejo del Bonete en su mayor parte no difiere de la utilizada durante la vida cotidiana, pero fue amortizada para ser puesta al servicio de un ritual que giró en torno a los ancestros y un culto solar. Esa tradición prolongó durante las Edades del Cobre y el Bronce, siendo un reflejo de los inicios de la jerarquización social y de la monumentalización del territorio al sur de la Meseta

Cerro Ortega (Villanueva de la Fuente, Ciudad Real): un abrigo sepulcral con inhumación multiple durante la transición neolítico-calcolítico al sur de la meseta

Este trabajo supone una actualización de la documentación disponible sobre la necrópolis del Cerro Ortega, que incluye nuevas dataciones absolutas y su contexto cultural. Se aportan datos y materiales inéditos sobre algunos sitios arqueológicos fundamentales para comprender los procesos de cambio cultural entre los IV y III milenios cal BC en el interior peninsular: Cerro Ortega (Villanueva de la Fuente), Villamayor de Calatrava, Vega de los Morales (Aldea del Rey), Cueva Maturras (Argamasilla de Alba) y La Jalbegada (San Lorenzo de Calatrava), entre otros. La presentación de pulseras de piedra, ídolos, adornos personales de concha, hueso, pizarra, clinocloro, clinoferrosilita y calcita, así como la orientación a eventos astronómicos de un refugio sepulcral, proporciona información sobre los aspectos simbólicos de las primeras comunidades productoras de La Mancha. El estudio permite avanzar en el conocimiento de las bases neolíticas que permitieron formar el substrato calcolítico de la Cultura de las Motillas

Prospective Study of BK Virus Infection in Patients with Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) have an immune-deficient baseline status further modulated by immunosuppressive therapy that may promote the reactivation of latent viruses such as BK virus (BKV). The aim of this prospective study was to determine the prevalence of BKV infection in IBD patients and its potential relationship with the immunosuppressive treatment. Paired urine and plasma samples from 53 consecutive patients with IBD and 53 controls were analyzed. BKV detection was performed by conventional PCR and positive samples were further quantified by real-time PCR. No viremia was detected. BKV viruria was significantly more common in IBD patients than among the controls (54.7% versus 11.3%; P<0.0001). The only risk factor for BKV viruria in IBD was age (47.2±16.3 versus 37.8±15.2; P=0.036), and there was a trend towards higher rate of viruria in outpatients (61.5% versus 38.5%; P=0.096) and in those not receiving ciprofloxacin (59.5% versus 40.5%; P=0.17). A clear impact of the immunosuppressive regimen on BKV infection could not be demonstrated

Cerro Ortega (Villanueva de la Fuente, Ciudad Real-Spain): a sepulcral shelter with multiple inhumation during the Neolithic-Chalcolithic transition in the South of the Iberian Plateau

Este trabajo supone una actualización de la documentación disponible sobre la necrópolis del Cerro Ortega, que incluye nuevas dataciones absolutas y su contexto cultural. Se aportan datos y materiales inéditos sobre algunos sitios arqueológicos fundamentales para comprender los procesos de cambio cultural entre los IV y III milenios cal BC en el interior peninsular: Cerro Ortega, Villamayor de Calatrava, Vega de los Morales (Aldea del Rey), Cueva Maturras (Argamasilla de Alba) y La Jalbegada, entre otros. La presentación de pulseras de piedra, ídolos, adornos personales de concha, hueso, pizarra, clinocloro, clinoferrosilita y calcita, así como la orientación a eventos astronómicos de un refugio sepulcral, proporciona información sobre los aspectos simbólicos de las primeras comunidades productoras de La Mancha. El estudio permite avanzar en el conocimiento de las bases neolíticas que permitieron formar el substrato calcolítico de la Cultura de las Motillas.This work is an update of the available documentation on the Cerro Ortega necropolis, which includes new absolute dates and its cultural context. Unpublished data and materials are provided on some fundamental archaeological sites to understand the processes of cultural change between the IV and III millennia cal BC in the interior of Iberia: Cerro Ortega, Villamayor de Calatrava, Vega de los Morales (Aldea del Rey), Cueva Maturras (Argamasilla de Alba) and La Jalbegada, among others. The presentation of stone bracelets, idols, personal adornments of shell, bone, slate, clinochlore, clinoferrosilite and calcite, as well as the orientation to astronomical events of a sepulchral shelter, provides information about the symbolic aspects of the first producing communities of La Mancha. The study allows us to observe the Neolithic bases that allowed to form the Chalcolithic substratum of the Culture of the Motillas.Depto. de Prehistoria, Historia Antigua y ArqueologíaFac. de Geografía e HistoriaTRUEMinisterio de Ciencia e Innovación (MICINN)pu

Additional file 2 of Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial

Additional file 2. AEMPS Approval Document Spanish

Additional file 1 of Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial

Additional file 1. Ethics Committees Approval Document

Additional file 3 of Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial

Additional file 3. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective