Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial

AbstractPurposeTo evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS).MethodsIn this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400mg/day) either as add-on to first AED monotherapy, or as later add-on to 1–3 concomitant AEDs after ≥2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24-week Maintenance Phase.Results456 patients received ≥1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved ≥50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1±16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment-emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks’ treatment, respectively. 178/353 (50.4%) patients achieved ≥50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8±14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%).ConclusionsLacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Multiple invasions, Wolbachia and human‑aided transport drive the genetic variability of Aedes albopictus in the Iberian Peninsula

Este artículo contiene 15 páginas, 7 figuras, 1 tabla.The Asian tiger mosquito, Aedes albopictus, is one of the most invasive species in the world. Native to the tropical forests of Southeast Asia, over the past 30 years it has rapidly spread throughout tropical and temperate regions of the world. Its dramatic expansion has resulted in public health concerns as a consequence of its vector competence for at least 16 viruses. Previous studies showed that Ae. albopictus spread has been facilitated by human-mediated transportation, but much remains unknown about how this has affected its genetic attributes. Here we examined the factors that contributed to shaping the current genetic constitution of Ae. albopictus in the Iberian Peninsula, where the species was first found in 2004, by combining population genetics and Bayesian modelling. We found that both mitochondrial and nuclear DNA markers showed a lack of genetic structure and the presence of worldwide dominant haplotypes, suggesting regular introductions from abroad. Mitochondrial DNA showed little genetic diversity compared to nuclear DNA, likely explained by infection with maternally transmitted bacteria of the genus Wolbachia. Multilevel models revealed that greater mosquito fluxes (estimated from commuting patterns and tiger mosquito population distribution) and spatial proximity between sampling sites were associated with lower nuclear genetic distance, suggesting that rapid short- and medium-distance dispersal is facilitated by humans through vehicular traffic. This study highlights the significant role of human transportation in shaping the genetic attributes of Ae. albopictus and promoting regional gene flow, and underscores the need for a territorially integrated surveillance across scales of this disease-carrying mosquito.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness (MINECO, Plan Estatal I+D+I CGL2013-43139-R), “la Caixa” Foundation (ID 100010434) under agreement HR18-00336, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 853271).Peer reviewe

Programa de vigilància de les infeccions relacionades amb l’atenció sanitària de Catalunya (VINCat): manual VINCat

Atenció sanitària; Infeccions; Enquesta; MetodologiaAtención sanitaria; Infecciones; Encuesta; MetodologíaHealth care; Infections; Poll; MethodologyEl VINCat és un programa del Servei Català de la Salut que estableix un sistema de vigilància unificat de les infeccions relacionat amb l’atenció sanitària (IRAS) als centres de salut de Catalunya. La seva missió és contribuir a reduir les taxes d’aquestes infeccions mitjançant la vigilància epidemiològica activa i continuada. El programa es fonamenta en la tasca que porten a terme els professionals dels equips multidisciplinaris de control d’infecció dels centres de salut catalan

Programa de vigilància de les infeccions relacionades amb l’atenció sanitària de Catalunya (VINCat): manual VINCat

Atenció sanitària; Infeccions; Enquesta; MetodologiaAtención sanitaria; Infecciones; Encuesta; MetodologíaHealth care; Infections; Poll; MethodologyEl compliment d’aquest objectiu es fa mitjançant una enquesta puntual de prevalença. L’objectiu del protocol de prevalença de les infeccions relacionades amb l'atenció sanitària (IRAS) és que aquest es pugui implementar a tots els centres, sense necessitat d’afegir-hi recursos especials. La Comissió d’Infeccions de cada centre ha de designar el personal encarregat de l’estudi i ha de treballar amb l’ajuda del personal de medicina i d’infermeria assistencial responsable del malalt, i amb la col·laboració de serveis centrals com el de microbiologia. És important que els professionals que recullen les dades tinguin experiència en vigilància de les IRAS i coneguin les definicions i la metodologia de treball. Recomanem que hi hagi un coordinador que assumeixi les tasques d’informació, formació i validació de les dades, que ha de ser un membre del Grup de Control de la Infecció

Informe VINCat

Infeccions nosocomials; Hospitals; Vigilància epidemiològicaInfecciones nosocomiales; Hospitales; Vigilancia epidemiológicaNosocomial infections; Hospitals; Epidemiological surveillanceVINCat és un programa del Servei Català de la Salut que estableix un sistema de vigilància unificat de les infeccions nosocomials als hospitals de Catalunya. La seva missió és contribuir a reduir les taxes d’aquestes infeccions mitjançant la vigilància epidemiològica activa i continuada. El programa es fonamenta en la tasca que porten a terme els professionals dels equips multidisciplinaris de control d’infecció dels hospitals catalans.VINCat is a program of the Catalan Health Service that establishes a unified surveillance system for nosocomial infections in hospitals in Catalonia. Its mission is to help reduce the rates of these infections through active and ongoing epidemiological surveillance. The program is based on the work carried out by the multidisciplinary teams of infection control of Catalan hospitals.VINCat es un programa del Servicio Catalán de la Salud que establece un sistema de vigilancia unificado de las infecciones nosocomiales en los hospitales de Cataluña. Su misión es contribuir a reducir las tasas de estas infecciones mediante la vigilancia epidemiológica activa y continuada. El programa se fundamenta en la tarea que llevan a cabo los profesionales de los equipos multidisciplinares de control de infección de los hospitales catalanes

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Desenvolupament de sistema SAR per a plataformes UAV de tipus multicopter

SAR system development for UAV multicopter platformsThis thesis describes the optimization of a synthetic aperture radar (SAR) at X-band and its integration into an unmanned aerial vehicle (UAV) of type octocopter. For such optimization the SAR system functionality was extended from singlepol to fulpol and it has been optimized at hardware level in order to improve its quality against noise figure. After its integration into the octocopter platform, its features has been used in order to be able to make preprogrammed routes and to perform fully autonomous apertures. Motion compensation techniques have been studied also for processing higher quality images by the analysis of inertial data from the platform and the phase story of points of the image during the aperture. The UAV model used it’s the Spreading Wings S1000 made by the manufacturer Dji and the SAR system it’s the ARBRES-X developed by the UPC.Esta tesis describe la optimización de un radar de apertura sintética (SAR) en banda X y su integración en un vehículo aéreo no tripulado (UAV) de tipo octocóptero. Para dicha optimización se ha extendido su funcionalidad de singlepol a fulpol y se ha optimizado a nivel de hardware para mejorar su calidad a nivel de ruido. Tras su integración en la plataforma octocóptero se han aprovechado sus funcionalidades para que pueda realizar vuelos prepogramados y realizar aperturas de manera completamente autónoma. También se han estudiado técnicas de compensación de movimiento para poder procesar imágenes de mayor calidad mediante el análisis de datos inerciales de la plataforma y la historia de fase de puntos de la imagen durante la apertura. El modelo de UAV utilizado es el Spreading Wings S1000 del fabricante Dji, y el sistema SAR es el ARBRES-X desarrollado por la UPC.Aquesta tesi descriu l'optimització d'un radar d'obertura sintètica (SAR) en banda X i la seva integració en un vehicle aeri no tripulat (UAV) de tipus octocópter. Per a aquesta optimització s'ha estès la seva funcionalitat de singlepol a fulpol i s'ha optimitzat a nivell de hardware per millorar la seva qualitat a nivell de soroll. Després de la seva integració a la plataforma octocópter s'han aprofitat les seves funcionalitats perquè pugui realitzar vols prepogramats i realitzar obertures de manera completament autònoma. També s'han estudiat tècniques de compensació de moviment per poder processar imatges de major qualitat mitjançant l'anàlisi de dades inercials de la plataforma i la història de fase de punts de la imatge durant l’apertura. El model de UAV utilitzat és el Spreading Wings S1000 del fabricant DJI, i el sistema SAR és el ARBRES-X desenvolupat per la UPC