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PublicationA multi-criteria decision analysis on the value of nintedanib for interstitial lung diseases.(2022-08-01) Zozaya, Néboa; Arrizubieta Basterrechea, Maria Iciar; Bollo, Elena; Castellví, Iván; Espín, Jaime; Ortego, Norberto; Poveda-Andrés, José Luis; Rodríguez Portal, José Antonio; Rivero, Agustín; Marcos-Rodríguez, José Antonio; Verde, LuisOur aim was to assess the value of nintedanib for non-idiopathic progressive fibrosing interstitial lung disease (non-IPF PF-ILD) and systemic sclerosis-associated ILD (SSc-ILD) in the Spanish context, using a multi-criteria decision analysis (MCDA). Following an adaptation of the Evidence and Value: Impact on DEcision Making (EVIDEM) MCDA methodology, the estimated value of nintedanib was obtained by means of an additive linear model that combined individual weights (100-points distribution) of criteria with the individual scoring of nintedanib in each criterion for every indication, assigned by a multidisciplinary committee of twelve clinicians, patients, pharmacists, and decision-makers. To assess the reproducibility, an alternative weighting method was applied, as well as a re-test of weights and scores at a different moment of time. The experts committee recognized nintedanib as an intervention with a positive value contribution in comparison to placebo for the treatment of non-IPF PF-ILD (0.50 ± 0.16, on a scale from -1 to 1) and SSc-ILD (0.40 ± 0.12), diseases which were considered as very severe and with high unmet needs. The drug was perceived as a treatment that provides an added therapeutic benefit for patients (0.06-0.07), given its proven clinical efficacy (0.05-0.06), slight improvements in patient-reported outcomes (0.01-0.02), and similar safety profile than placebo (-0.04-0.00), which will likely be positioned as a recommended therapy in the next clinical practice guidelines updates. Under this increasingly used methodology, nintedanib has shown to provide a positive value estimate for non-IPF PF-ILD and SSc-ILD when compared to placebo in Spain. PublicationFeasibility study to characterize price and reimbursement decision-making criteria for the inclusion of new drugs in the Spanish National Health System: the cefiderocol example.(2022-05-20) Calleja, Miguel Ángel; Badia, XavierThe reimbursement of medicines by the Spanish National Health System (NHS) is based on a set of criteria included in the Royal Legislative Decree 1/2015 (RDL 1/2015). The Interministerial Committee on Pricing of Medicines and Healthcare Products (CIPM) is responsible for the final price and reimbursement (P&R) decision, including on its resolutions the criteria listed in the law by which the reimbursement of a drug is approved or denied. Nevertheless, the information behind its reasoning is not provided. The present study aims to characterize the P&R criteria of the RDL 1/2015 through criteria definitions from other countries to improve the P&R evaluation in Spain. A multidisciplinary experts panel with relevant experience in drug evaluation and decision making at national, regional, and local level in Spain was selected for this study. A literature review to characterize the criteria listed in the RDL 1/2015 was performed based on the most relevant and recognized Health Technology Assessment (HTA) agencies in Europe, UK, and Canada. Eventually, a feasibility study was performed to evaluate the novel drug cefiderocol using the characterized criteria, including a reflective discussion of the results. Consensus was reached among the multidisciplinary experts on the characterization of the criteria set by the law. The feasibility of their application to a new drug was exploratory, notwithstanding it showed the potential to improve the transparency as well as to offer a more structured rationale for the CIPM to evaluate the inclusion of new drugs in the Spanish NHS. PublicationPredictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.(2022-08-31) Staessen, Jan A; Wendt, Ralph; Yu, Yu-Ling; Kalbitz, Sven; Thijs, Lutgarde; Siwy, Justyna; Raad, Julia; Metzger, Jochen; Neuhaus, Barbara; Papkalla, Armin; von der Leyen, Heiko; Mebazaa, Alexandre; Dudoignon, Emmanuel; Spasovski, Goce; Milenkova, Mimoza; Canevska-Taneska, Aleksandra; Salgueira Lazo, Mercedes; Psichogiou, Mina; Rajzer, Marek W; Fuławka, Łukasz; Dzitkowska-Zabielska, Magdalena; Weiss, Guenter; Feldt, Torsten; Stegemann, Miriam; Normark, Johan; Zoufaly, Alexander; Schmiedel, Stefan; Seilmaier, Michael; Rumpf, Benedikt; Banasik, Mirosław; Krajewska, Magdalena; Catanese, Lorenzo; Rupprecht, Harald D; Czerwieńska, Beata; Peters, Björn; Nilsson, Åsa; Rothfuss, Katja; Lübbert, Christoph; Mischak, Harald; Beige, Joachim; CRIT-CoV-U investigatorsThe SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. German Federal Ministry of Health. PublicationDiagnosis, prognosis, and treatment of brief psychotic episodes: a review and research agenda.(2021-11-29) Fusar-Poli, Paolo; Salazar de Pablo, Gonzalo; Rajkumar, Ravi Philip; López-Díaz, Álvaro; Malhotra, Savita; Heckers, Stephan; Lawrie, Stephen M; Pillmann, FrankBrief psychotic episodes represent an intriguing paradox in clinical psychiatry because they elude the standard knowledge that applies to the persisting psychotic disorders such as schizophrenia. This Review describes key diagnostic considerations such as conceptual foundations, current psychiatric classification versus research-based operationalisations, epidemiology, and sociocultural variations; prognostic aspects including the risk of psychosis recurrence, types of psychotic recurrences, other clinical outcomes, prognostic factors; and therapeutic issues such as treatment guidelines and unmet need of care. The advances and challenges associated with the scientific evidence are used to set a research agenda in this area. We conclude that brief psychotic episodes can be reconceptualised within a clinical staging model to promote innovative translational research and improve our understanding and treatment of psychotic disorders. PublicationThe Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries.(2022) Global Retinoblastoma Study GroupRetinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0-36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8-100·0) for children from high-income countries, 91·2% (89·5-93·0) for children from upper-middle-income countries, 80·3% (78·3-82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76-50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44-18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23-1·56). For children aged 3-7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Queen Elizabeth Diamond Jubilee Trust. PublicationThe Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre, retrospective, MRI-neuropathology diagnostic accuracy study.(2022) Charidimou, Andreas; Boulouis, Gregoire; Frosch, Matthew P; Baron, Jean-Claude; Pasi, Marco; Albucher, Jean Francois; Banerjee, Gargi; Barbato, Carmen; Bonneville, Fabrice; Brandner, Sebastian; Calviere, Lionel; Caparros, François; Casolla, Barbara; Cordonnier, Charlotte; Delisle, Marie-Bernadette; Deramecourt, Vincent; Dichgans, Martin; Gokcal, Elif; Herms, Jochen; Hernandez-Guillamon, Mar; Jäger, Hans Rolf; Jaunmuktane, Zane; Linn, Jennifer; Martinez-Ramirez, Sergi; Martínez-Sáez, Elena; Mawrin, Christian; Montaner, Joan; Moulin, Solene; Olivot, Jean-Marc; Piazza, Fabrizio; Puy, Laurent; Raposo, Nicolas; Rodrigues, Mark A; Roeber, Sigrun; Romero, Jose Rafael; Samarasekera, Neshika; Schneider, Julie A; Schreiber, Stefanie; Schreiber, Frank; Schwall, Corentin; Smith, Colin; Szalardy, Levente; Varlet, Pascale; Viguier, Alain; Wardlaw, Joanna M; Warren, Andrew; Wollenweber, Frank A; Zedde, Marialuisa; van Buchem, Mark A; Gurol, M Edip; Viswanathan, Anand; Al-Shahi Salman, Rustam; Smith, Eric E; Werring, David J; Greenberg, Steven MCerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. US National Institutes of Health (R01 AG26484). PublicationResponse-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial.(2021-12-09) Mauz-Körholz, Christine; Landman-Parker, Judith; Balwierz, Walentyna; Ammann, Roland A; Anderson, Richard A; Attarbaschi, Andische; Bartelt, Jörg M; Beishuizen, Auke; Boudjemaa, Sabah; Cepelova, Michaela; Claviez, Alexander; Daw, Stephen; Dieckmann, Karin; Fernández-Teijeiro, Ana; Fosså, Alexander; Gattenlöhner, Stefan; Georgi, Thomas; Hjalgrim, Lisa L; Hraskova, Andrea; Karlén, Jonas; Kluge, Regine; Kurch, Lars; Leblanc, Thiery; Mann, Georg; Montravers, Francoise; Pears, Jean; Pelz, Tanja; Rajić, Vladan; Ramsay, Alan D; Stoevesandt, Dietrich; Uyttebroeck, Anne; Vordermark, Dirk; Körholz, Dieter; Hasenclever, Dirk; Wallace, William HamishChildren and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma achieve an event-free survival at 5 years of about 90% after treatment with vincristine, etoposide, prednisone, and doxorubicin (OEPA) followed by cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) and radiotherapy, but long-term treatment effects affect survival and quality of life. We aimed to investigate whether radiotherapy can be omitted in patients with morphological and metabolic adequate response to OEPA and whether modified consolidation chemotherapy reduces gonadotoxicity. Our study was designed as a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial, and was carried out at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed intermediate-stage (treatment group 2) and advanced-stage (treatment group 3) classical Hodgkin lymphoma who were younger than 18 years and stratified according to risk using Ann Arbor disease stages IIAE, IIB, IIBE, IIIA, IIIAE, IIIB, IIIBE, and all stages IV (A, B, AE, and BE) were included in the study. Patients with early disease (treatment group 1) were excluded from this analysis. All patients were treated with two cycles of OEPA (1·5 mg/m2 vincristine taken intravenously capped at 2 mg, on days 1, 8, and 15; 125 mg/m2 etoposide taken intravenously on days 1-5; 60 mg/m2 prednisone taken orally on days 1-15; and 40 mg/m2 doxorubicin taken intravenously on days 1 and 15). Patients were randomly assigned to two (treatment group 2) or four (treatment group 3) cycles of COPP (500 mg/m2 cyclophosphamide taken intravenously on days 1 and 8; 1·5 mg/m2 vincristine taken intravenously capped at 2 mg, on days 1 and 8; 40 mg/m2 prednisone taken orally on days 1 to 15; and 100 mg/m2 procarbazine taken orally on days 1 to 15) or COPDAC, which was identical to COPP except that 250 mg/m2 dacarbazine administered intravenously on days 1 to 3 replaced procarbazine. The method of randomisation (1:1) was minimisation with stochastic component and was centrally stratified by treatment group, country, trial sites, and sex. The primary endpoint was event-free survival, defined as time from treatment start until the first of the following events: death from any cause, progression or relapse of classical Hodgkin lymphoma, or occurrence of secondary malignancy. The primary objectives were maintaining 90% event-free survival at 5 years in patients with adequate response to OEPA treated without radiotherapy and to exclude a decrease of 8% in event-free survival at 5 years in the embedded COPDAC versus COPP randomisation to show non-inferiority of COPDAC. Efficacy analyses are reported per protocol and safety in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (trial number NCT00433459) and EUDRACT (trial number 2006-000995-33), and is closed to recruitment. Between Jan 31, 2007, and Jan 30, 2013, 2102 patients were recruited. 737 (35%) of the 2102 recruited patients were in treatment group 1 (early-stage disease) and were not included in our analysis. 1365 (65%) of the 2102 patients were in treatment group 2 (intermediate-stage disease; n=455) and treatment group 3 (advanced-stage disease; n=910). Of these 1365, 1287 (94%) patients (435 [34%] of 1287 in treatment group 2 and 852 [66%] of 1287 in treatment group 3) were included in the titration trial per-protocol analysis. 937 (69%) of 1365 patients were randomly assigned to COPP (n=471) or COPDAC (n=466) in the embedded trial. Median follow-up was 66·5 months (IQR 62·7-71·7). Of 1287 patients in the per-protocol group, 514 (40%) had an adequate response to treatment and were not treated with radiotherapy (215 [49%] of 435 in treatment group 2 and 299 [35%] of 852 in treatment group 3). 773 (60%) of 1287 patients with inadequate response were scheduled for radiotherapy (220 [51%] of 435 in the treatment group 2 and 553 [65%] of 852 in treatment group 3. In patients who responded adequately, event-free survival rates at 5 years were 90·1% (95% CI 87·5-92·7). event-free survival rates at 5 years in 892 patients who were randomly assigned to treatment and analysed per protocol were 89·9% (95% CI 87·1-92·8) for COPP (n=444) versus 86·1% (82·9-89·4) for COPDAC (n=448). The COPDAC minus COPP difference in event-free survival at 5 years was -3·7% (-8·0 to 0·6). The most common grade 3-4 adverse events (intention-to-treat population) were decreased haemoglobin (205 [15%] of 1365 patients during OEPA vs 37 [7%] of 528 treated with COPP vs 20 [2%] of 819 treated with COPDAC), decreased white blood cells (815 [60%] vs 231 [44%] vs 84 [10%]), and decreased neutrophils (1160 [85%] vs 223 [42%] vs 174 [21%]). One patient in treatment group 2 died of sepsis after the first cycle of OEPA; no other treatment-related deaths occurred. Our results show that radiotherapy can be omitted in patients who adequately respond to treatment, when consolidated with COPP or COPDAC. COPDAC might be less effective, but is substantially less gonadotoxic than COPP. A high proportion of patients could therefore be spared radiotherapy, eventually reducing the late effects of treatment. With more refined criteria for response assessment, the number of patients who receive radiotherapy will be further decreased. Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder Gießen, Kinderkrebsstiftung Mainz, Tour der Hoffnung, Menschen für Kinder, Programme Hospitalier de Recherche Clinique, and Cancer Research UK. PublicationBehaviour of aerosols and their role in the transmission of SARS-CoV-2; a scoping review.(2021-10-01) Robles-Romero, José Miguel; Conde-Guillén, Gloria; Safont-Montes, Juan Carlos; García-Padilla, Francisca María; Romero-Martín, MacarenaCovid-19 has triggered an unprecedented global health crisis. The highly contagious nature and airborne transmission route of SARS-CoV-2 virus requires extraordinary measures for its containment. It is necessary to know the behaviour of aerosols carrying the virus to avoid this contagion. This paper describes the behaviour of aerosols and their role in the transmission of SARS-CoV-2 according to published models using a scoping review based on the PubMed, Scopus, and WOS databases. From an initial 530 references, 9 papers were selected after applying defined inclusion criteria. The results reinforce the airborne transmission route as a means of contagion of the virus and recommend the use of face masks, extending social distance to more than 2 metres, and natural ventilation of enclosed spaces as preventive measures. These results contribute to a better understanding of SARS-CoV-2 and help design effective strategies to prevent its spread. PublicationAntimalarials exert a cardioprotective effect in lupus patients: Insights from the Spanish Society of Rheumatology Lupus Register (RELESSER) analysis of factors associated with heart failure.(2022-01-02) Rúa-Figueroa, Iñigo; Rúa-Figueroa, David; Pérez-Veiga, Natalia; Anzola, Ana M; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Fernández-Nebro, Antonio; Sangüesa, Clara; Menor-Almagro, Raúl; Tomero, Eva; Del Val, Natividad; Uriarte-Isazelaya, Esther; Blanco, Ricardo; Andreu, José L; Boteanu, Alina; Narváez, Javier; Cobo, Tatiana; Bohórquez, Cristina; Montilla, Carlos; Salas, Esteban; Toyos, Francisco J; Bernal, José A; Salgado, Eva; Freire, Mercedes; Mas, Antonio J; Expósito, Lorena; Hernández-Beriain, José A; Ibarguengoitia, Oihane; Velloso-Feijoo, María L; Lozano-Rivas, Nuria; Bonilla, Gemma; Moreno, Mireia; Jiménez, Inmaculada; Quevedo-Vila, Víctor; Pecondón, Angela; Aurrecoechea, Elena; Valls, Elia; Mouriño, Coral; Vázquez-Rodríguez, Tomás; Pego-Reigosa, José MFactors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect. PublicationArterial embolization for the control of lower gastrointestinal bleeding. Treatment or complication?(2021-11-10) Valdés-Delgado, T; Jiménez-García, V A; Galván-Fernández, M D PublicationAntiplatelet therapy at discharge and long-term prognosis in Takotsubo syndrome: Insights from the Spanish National Registry (RETAKO).(2022-10-11) Pereyra, Eduardo; Fernández-Rodríguez, Diego; González-Sucarrats, Silvia; Almendro-Delia, Manuel; Martín, Agustín; de Miguel, Irene Martin; Andrés, Mireia; Duran-Cambra, Alberto; Sánchez-Grande-Flecha, Alejandro; Worner-Diz, Fernando; Núñez-Gil, Iván J; RETAKO investigatorsEndothelial dysfunction and platelet activation have been highlighted as possible mediators in Takotsubo syndrome (TTS). Nevertheless, to date, evidence on the usefulness of antiplatelet therapy in TTS remains controversial. The aim of our study is to evaluate long-term prognosis in TTS patients treated with antiplatelet therapy (APT) at hospitalization discharge. An ambispective cohort study from the Spanish National Takotsubo Registry database was performed (June 2002 to March 2017). Patients were divided into two groups: those who received APT at hospital discharge (APT cohort) and those who did not (non-APT cohort). Primary endpoint was all-cause death. Secondary endpoints included the composite of recurrence or readmission and a composite of death, recurrence or readmission. From a total of 741 patients, 728 patients were alive at discharge. Follow-up was performed in 544 patients, who were included in the final analysis: 321 patients (59.0%) in the APT cohort and 223 patients (41.0%) in the non-APT cohort. The APT cohort had a better clinical presentation and received more heart failure and acute coronary syndrome-like therapies (angiotensin converting enzyme inhibitors/angiotensin receptor blockers: 75.1% vs. 51.1%; p Patients with TTS receiving APT at discharge presented better prognosis up to two-years of follow-up compared with their counterparts not receiving APT. PublicationVericiguat in heart failure: From scientific evidence to clinical practice.(2022-04-23) González-Juanatey, J R; Anguita-Sánchez, M; Bayes-Genís, A; Comín-Colet, J; García-Quintana, A; Recio-Mayoral, A; Zamorano-Gómez, J L; Cepeda-Rodrigo, J M; Manzano, LDespite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability. Publication[Impact of the COVID-19 pandemic on the training of otorhinolaryngology residents].(2021-10-09) Sánchez-Gómez, Serafín; Maza-Solano, Juan Manuel; López Flórez, Luz; Parente Arias, Pablo; Lobo Duro, David; Palacios-García, José MaríaTraining in surgical specialties has declined during the COVID-19 pandemic. A study was carried out to further analyze the impact of the COVID-19 pandemic on specific aspects of clinical, training, and research activities performed by the otolaryngology residents in Spain. A cross-sectional qualitative study was conducted during the last two weeks of February 2021. The study consisted of an online survey taken by otolaryngology residents who had undertaken one-year continuing training from February 15, 2020, to February 15, 2021, and consisted of 26 questions exploring the impact of the COVID-19 on the health of the ENT residents and training activities. Categorical variables were reported as frequency and percentage. When indicated, Pearsońs Chi-square test (χ2) with Yates's correction and Pearson's correlation coefficient (r) were used. 143 completed surveys were received from 264 residents (54.17%). 36 residents (25.2%) have suffered from the disease due to SARS-CoV-2. Most of them only developed mild symptoms (86.1%), with 3 requiring hospitalization (8.3%). The origin of infection was unknown in all reported cases and the need for confinement was principally due to either attending an asymptomatic patient in 9 cases (6.3%) or to being supposedly in close contact with an asymptomatic person in 22 (15.4%). 60.1% of the residents surveyed reported having lost more than 6 months of their training period, and in 18.8% of cases, it was as high as 10 and 12 months. There has been a reduction of more than 75% of what was planned in surgical training (P The decline in ENT activity and residents having to assist in other COVID-19 units during the most critical moments of the pandemic, has caused the main reduction in their training capacity. Contagion mainly occurred through contact with asymptomatic carriers during patient care and through supposedly close contact with asymptomatic carriers. Virtual activities have been widely accepted, but they have not completely replaced all residents' training needs. Measures should be implemented to recover lost training, especially surgical practical learning in otology and rhinology. PublicationHypochlorous acid as an antiseptic in the care of patients with suspected COVID-19 infection.(2021-11-18) Gessa Sorroche, M; Relimpio López, I; García-Delpech, S; Benítez Del Castillo, J MThe SARS-CoV-2 virus, which causes COVID-19 disease, is transmitted by aerosols or by contact with infected surfaces. The route of entry to the body is through the nasal, oral or conjunctival mucosa. Health workers must use effective protection measures against the entry of the virus into mucous membranes, both physical and antiseptic filters. There is an antiseptic used in Ophthalmology that we believe could have virucidal action against the SARS-CoV-2 virus, formulated based on 0.01% hypochlorous acid. An exhaustive search has been carried out in the databases of Pubmed and Web of Science to identify relevant articles on the virucidal activity of hypochlorous acid in different concentrations until October 4, 2020. There is evidence of the virucidal efficacy of 0.01% hypochlorous acid against SARS-CoV-2. According to the different scientific publications reviewed, hypochlorous acid has virucidal efficacy against different viruses, among them, SARS-CoV-2. The 0.01% hypochlorous acid could act as an effective antiseptic against SARS-CoV-2, exerting a barrier on the mucosa to prevent COVID-19 infection. It can be used on the eyes, nose and mouth. We consider it necessary to assess its use in the protocol for patient health care in ophthalmology consultations, as well as to recommend its use to the general population to reduce viral load and/or prevent transmission of infection. Additional in vivo studies would be required to confirm its antiseptic action. PublicationHeadache: pregnancy and breastfeeding. Recommendations of the Spanish Society of Neurology's Headache Study Group.(2021-09-14) González-García, N; Díaz de Terán, J; López-Veloso, A C; Mas-Sala, N; Mínguez-Olaondo, A; Ruiz-Piñero, M; Gago-Veiga, A B; Santos-Lasaosa, S; Viguera-Romero, J; Pozo-Rosich, PHeadache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding. This guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding. We hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients. PublicationHypercholesterolemia treatment in a patient with family hypercholesterolemia and myopathy due to carnitine palmitoyltransferase II deficiency with PCSK9 inhibitors.(2021-06-07) Luque Linero, P; Castilla-Guerra, L; Rojas Marcos Rodriguez, I; Rico Corral, M A PublicationProprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance.(2020-12-21) Gil-Núñez, A; Masjuan, J; Montaner, J; Castellanos, M; Segura, T; Cardona, P; Tembl, J I; Purroy, F; Arenillas, J; Palacio, EPatients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels PublicationConsensus statement on the use of alemtuzumab in daily clinical practice in Spain.(2020-01-25) Meca-Lallana, J E; Fernández-Prada, M; García Vázquez, E; Moreno Guillén, S; Otero Romero, S; Rus Hidalgo, M; Villar Guimerans, L M; Eichau Madueño, S; Fernández Fernández, Ó; Izquierdo Ayuso, G; Álvarez Cermeño, J C; Arnal García, C; Arroyo González, R; Brieva Ruiz, L; Calles Hernández, C; García Merino, A; González Platas, M; Hernández Pérez, M Á; Moral Torres, E; Olascoaga Urtaza, J; Oliva-Nacarino, P; Oreja-Guevara, C; Ortiz Castillo, R; Oterino, A; Prieto González, J M; Ramió-Torrentá, L; Rodríguez-Antigüedad, A; Saiz, A; Tintoré, M; Montalbán Gairin, XAlemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. PublicationCalcitonin gene-related peptide in migraine: from pathophysiology to treatment.(2019-07-17) Santos-Lasaosa, S; Belvís, R; Cuadrado, M L; Díaz-Insa, S; Gago-Veiga, A; Guerrero-Peral, A L; Huerta, M; Irimia, P; Láinez, J M; Latorre, G; Leira, R; Pascual, J; Porta-Etessam, J; Sánchez Del Río, M; Viguera, J; Pozo-Rosich, PIt has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients. PublicationHeadache: What to ask, how to examine, and which scales to use. Recommendations of the Spanish Society of Neurology's Headache Study Group.(2019-03-28) Gago-Veiga, A B; Camiña Muñiz, J; García-Azorín, D; González-Quintanilla, V; Ordás, C M; Torres-Ferrus, M; Santos-Lasaosa, S; Viguera-Romero, J; Pozo-Rosich, PHeadache is the most common neurological complaint at the different levels of the healthcare system, and clinical history and physical examination are essential in the diagnosis and treatment of these patients. With the objective of unifying the care given to patients with headache, the Spanish Society of Neurology's Headache Study Group (GECSEN) has decided to establish a series of consensus recommendations to improve and guarantee adequate care in primary care, emergency services, and neurology departments. With the aim of creating a practical document, the recommendations follow the dynamics of a medical consultation: clinical history, physical examination, and scales quantifying headache impact and disability. In addition, we provide recommendations for follow-up and managing patients' expectations of the treatment. With this tool, we aim to improve the care given to patients with headache in order to guarantee adequate, homogeneous care across Spain.