72 research outputs found

    Non Abelian TQFT and scattering of self dual field configuration

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    A non-abelian topological quantum field theory describing the scattering of self-dual field configurations over topologically non-trivial Riemann surfaces, arising from the reduction of 4-dim self-dual Yang-Mills fields, is introduced. It is shown that the phase space of the theory can be exactly quantized in terms of the space of holomorphic structures over stable vector bundles of degree zero over Riemann surfaces. The Dirac monopoles are particular static solutions of the field equations. Its relation to topological gravity is discussed.Comment: 13 pages, Late

    OP0291 TOFACITINIB FOR THE TREATMENT OF POLYARTICULAR COURSE JUVENILE IDIOPATHIC ARTHRITIS: RESULTS OF A PHASE 3, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED WITHDRAWAL STUDY

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    Background:Tofacitinib is an oral JAK inhibitor that is being investigated for JIA.Objectives:To assess tofacitinib efficacy and safety in JIA patients (pts).Methods:This was a Phase 3, randomised, double-blind (DB), placebo (PBO)-controlled withdrawal study in pts aged 2−<18 years with polyarticular course JIA (pcJIA), PsA or ERA (NCT02592434). In the 18-week open-label Part 1, pts received weight-based tofacitinib doses (5 mg BID or lower). Pts with ≥JIA ACR30 response at Week (W)18 were randomised 1:1 in the DB Part 2 (W18−44) to continue tofacitinib or switch to PBO. Primary endpoint: disease flare rate by W44. Key secondary endpoints: JIA ACR50/30/70 response rates; change from Part 2 baseline (Δ) in CHAQ-DI at W44. Other efficacy endpoints: time to disease flare in Part 2; JADAS27-CRP in Parts 1 and 2. PsA/ERA pts were excluded from these efficacy analyses. Safety was evaluated in all pts up to W44.Results:225 enrolled pts with pcJIA (n=184), PsA (n=20) or ERA (n=21) received tofacitinib in Part 1. At W18, 173/225 (76.9%) pts entered Part 2 (pcJIA n=142, PsA n=15, ERA n=16). In pcJIA pts, disease flare rate in Part 2 was significantly lower with tofacitinib vs PBO by W44 (p=0.0031; Fig 1a). JIA ACR50/30/70 response rates (Fig 1b) and ΔCHAQ-DI (Fig 1c) at W44, and time to disease flare in Part 2 (Fig 2a), were improved with tofacitinib vs PBO. Tofacitinib reduced JADAS27-CRP in Part 1; this effect was sustained in Part 2 (Fig 2b). Overall, safety was similar with tofacitinib or PBO (Table): 77.3% and 74.1% had adverse events (AEs); 1.1% and 2.4% had serious AEs. In Part 1, 2 pts had herpes zoster (non-serious) and 3 pts had serious infections (SIs). In Part 2, SIs occurred in 1 tofacitinib pt and 1 PBO pt. No pts died.Conclusion:In pcJIA pts, tofacitinib vs PBO resulted in significantly fewer disease flares, and improved time to flare, disease activity and physical functioning. Tofacitinib safety was consistent with that in RA pts.Table.Safety in all ptsPart 1Part 2TofacitinibaN=225TofacitinibaN=88PBO N=85Pts with events, n (%)AEs153 (68.0)68 (77.3)63 (74.1)SAEs7 (3.1)1 (1.1)2 (2.4)Permanent discontinuations due to AEs26 (11.6)16 (18.2)29 (34.1)AEs of special interest Death000 Gastrointestinal perforationb000 Hepatic eventb3 (1.3)00 Herpes zoster (non-serious and serious)2 (0.9)c00 Interstitial lung diseaseb000 Major adverse cardiovascular eventsb000 Malignancy (including non-melanoma skin cancer)b000 Macrophage activation syndromeb000 Opportunistic infectionb000 SI3 (1.3)1 (1.1)d1 (1.2) Thrombotic event (deep vein thrombosis, pulmonary embolismbor arterial thromboembolism)000 Tuberculosisb000a5 mg BID or equivalent weight-based lower dose in pts <40 kgbAdjudicated eventscBoth non-seriousdOne SAE of pilonidal cyst repair was coded to surgical procedures instead of infections, and was inadvertently not identified as an SI. Following adjudication, the SAE did not meet opportunistic infection criteria; it is also included in the table as an SIAE, adverse event; BID, twice daily; PBO, placebo; pts, patients; SAE, serious AE; SI, serious infectionAcknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Olga Synoverska Speakers bureau: Sanofi, Tracy Ting: None declared, Carlos Abud-Mendoza Speakers bureau: Eli Lilly, Pfizer Inc, Alberto Spindler Speakers bureau: Eli Lilly, Yulia Vyzhga Grant/research support from: Pfizer Inc, Katherine Marzan Grant/research support from: Novartis, Vladimir Keltsev: None declared, Irit Tirosh: None declared, Lisa Imundo: None declared, Rita Jerath: None declared, Daniel Kingsbury: None declared, Betül Sözeri: None declared, Sheetal Vora: None declared, Sampath Prahalad Grant/research support from: Novartis, Elena Zholobova Grant/research support from: Novartis and Pfizer Inc, Speakers bureau: AbbVie, Novartis, Pfizer Inc and Roche, Yonatan Butbul Aviel: None declared, Vyacheslav Chasnyk: None declared, Melissa Lerman Grant/research support from: Amgen, Kabita Nanda Grant/research support from: Abbott, AbbVie, Amgen and Roche, Heinrike Schmeling Grant/research support from: Janssen, Pfizer Inc, Roche and USB Bioscience, Heather Tory: None declared, Yosef Uziel Speakers bureau: Pfizer Inc, Diego O Viola Grant/research support from: Bristol-Myers Squibb, GSK, Janssen and Pfizer Inc, Speakers bureau: AbbVie and Bristol-Myers Squibb, Holly Posner Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Keith Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ann Wouters Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cheng Chang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Richard Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Irina Lazariciu Consultant of: Pfizer Inc, Employee of: IQVIA, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ricardo Suehiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alberto Martini Consultant of: AbbVie, Eli Lily, EMD Serono, Janssen, Novartis, Pfizer, UCB, Daniel J Lovell Consultant of: Abbott (consulting and PI), AbbVie (PI), Amgen (consultant and DSMC Chairperson), AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (PI), Celgene, Forest Research (DSMB Chairman), GlaxoSmithKline, Hoffman-La Roche, Janssen (co-PI), Novartis (consultant and PI), Pfizer (consultant and PI), Roche (PI), Takeda, UBC (consultant and PI), Wyeth, Employee of: Cincinnati Children's Hospital Medical Center, Speakers bureau: Wyeth, Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novarti

    The "Statinth" wonder of the world: a panacea for all illnesses or a bubble about to burst

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    After the introduction of statins in the market as effective lipid lowering agents, they were shown to have effects other than lipid lowering. These actions were collectively referred to as 'pleiotropic actions of statins.' Pleiotropism of statins formed the basis for evaluating statins for several indications other than lipid lowering. Evidence both in favour and against is available for several of these indications. The current review attempts to critically summarise the available data for each of these indications

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Evaluación del estado nutricio en una población mexicana de pacientes adultos con artritis reumatoide Assessment of nutritional status in a Mexican population of adult patients with rheumatoid arthritis

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    Antecedentes: La artritis reumatoide (AR) representa un estado inflamatorio crónico que se acompaña de potenciales complicaciones a nivel multiorgánico. Se ha descrito una alta prevalencia de alteraciones nutricias en pacientes con AR, las cuales en conjunto, pueden repercutir negativamente en el curso y pronóstico de la enfermedad ya sea a través de un incremento en la incidencia de morbilidades cardiovasculares o bien imponiendo limitaciones funcionales adicionales a las ya existentes por la enfermedad de base.Propósito: Evaluar nutricionalmente en términos de composición corporal y patrón de ingesta dietaria a una población mexicana con diagnóstico de AR.Material y métodos: Se evaluaron 100 pacientes ambulatorios con el diagnóstico de AR que acuden al servicio de consulta externa de un centro regional de reumatología en San Luís Potosí México. Se determinaron las variables antropométricas, composición corporal por análisis de bioimpedancia eléctrica (BIA) y patrones dietarios.Resultados: Se incluyeron un total de 87 (87%) mujeres y 13 (13%) varones. La edad media fue de 47,6 &plusmn; 13,3 años, con una evolución promedio de la enfermedad de 10,18 &plusmn; 9,02 años. 79% de los pacientes se encontraban en clase funcional II y 21% en clase funcional III. El índice de masa corporal promedio fue de 26,8 &plusmn; 4,4 kg/m2 , 65% de los pacientes presentaron índices de masa corporal (IMC) en rango de sobrepeso u obesidad y solo el 2% en rango de desnutrición. 48% de la muestra presentó depleción de masa magra y 94% presentaron incremento en el porcentaje de grasa corporal estimados por BIA y antropometría. 34 pacientes (34%) presentaron circunferencia abdominal por arriba de los puntos de corte para el diagnóstico de síndrome metabólico. En cuanto a las características cualitativas de la dieta el 90% de la muestra consumía una dieta inadecuada, con una ingesta calórica diaria promedio de 26.49 &plusmn; 8.24 kcal. por día; la ingesta de proteínas fue óptima en la totalidad de la población. Conclusión: Existe una elevada prevalencia de alteraciones nutricias en la población mexicana con AR, los hallazgos mas frecuentes en este estudio fueron disminución en masa magra, incremento en reserva grasa, ingesta calórica disminuida y dietas cualitativamente inadecuadas. Se requieren estrategias de intervención para el abordaje y tratamiento nutricional de pacientes con AR como medidas potenciales que modifiquen el curso y pronóstico de la enfermedad.Background: Rheumatoid arthritis (RA) represents a life-long chronic inflammatory process frequently associated to potential multiorganic complications. Cardiovascular diseases and nutritional alterations are increased in AR populations and represent potential factors that alter negatively the disease course and prognosis. Purpose: To evaluate nutritional status from a Mexican AR population, including body composition, anthropometrics and dietary patterns. Material and methods: There were included 100 RA outpatients from a regional rheumatic centre located in San Luis Potosi México. Nutritional assessment included anthropometric evaluation, bioelectrical impedance analysis (BIA) and dietary patterns evaluation. Results: 100 RA out-patients were included. Mean age was 47.6 &plusmn; 13.3 years, with a mean disease course of 10.18 &plusmn; 9.02. 79% of patients were in RA functional class II and 21% in class III. Average body mass index 26.8 &plusmn; 4.4 kg/m2 According to body mass index categories, 65% patients were within the range of overweight and obesity and 2% of patients were undernourished. Mean waist circumference 86.7 &plusmn; 11.1 cm, 34% of patients showed waist circumference values over the limits established for the definition of metabolic syndrome. Lean body mass was diminished in 48% patients. Body fat mass estimated by anthropometry and BIA was increased in 94 patients (94%). Dietary parameters: Mean energy intake was 26.4 &plusmn; 8.2 kcal/kg. There was qualitative nutritional inadequacy in 90 patients (90%). Protein intake was optimal in all the patients. Conclusion: Nutritional alterations are highly prevalent in Mexican RA population; our study showed freefat mass depletion, low caloric intake, dietary inadequate parameters and fat mass increments as the more prevalent findings. Nutritional assessment and nutritional strategies are recommended as potential measures to improve RA clinical course and prognosis
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