35 research outputs found
A tRNA-mimic Strategy to Explore the Role of G34 of tRNAGly in Translation and Codon Frameshifting
Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry
Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01â1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23â3.99] compared to eGFR â„90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF
Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry
Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The âAtrial fibrillation Better Careâ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58â0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52â0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58â0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56â0.98) and composite outcome (aHR: 0.76, 95%CI 0.60â0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients
Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry
Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes
Reality beckons: metamodernist depthiness beyond panfictionality
It is often argued that postmodernism has been succeeded by a new dominant cultural logic. We conceive of this new logic as metamodernism. Whilst some twenty-first century texts still engage with and utilise postmodernist practices, they put these practices to new use. In this article, we investigate the metamodern usage of the typically postmodernist devices of metatextuality and ontological slippage in two genres: autofiction and true crime documentary. Specifically, we analyse Ruth Ozekiâs A Tale for the Time Being and the Netflix mini-series The Keepers, demonstrating that forms of fictionalisation, metafictionality and ontological blurring between fiction and reality have been repurposed. We argue that, rather than expand the scope of fiction, overriding reality, the metamodernist repurposing of postmodernist textual strategies generates a kind of âreality-effectâ
A tRNA-mimic Strategy to Explore the Role of G34 of tRNAGly in Translation and Codon Frameshifting
International audienc
Prise en charge de la toxoplasmose oculaire en France : rĂ©sultats dâune Ă©tude Delphi modifiĂ©e
International audienceOBJECTIVE: To evaluate diagnostic and therapeutic practices and then establish a consensus on the management of ocular toxoplasmosis in France through a Delphi study. MATERIALS AND METHODS: Twenty-three French experts in ocular toxoplasmosis were invited to respond to a modified Delphi study conducted online, in the form of two questionnaires, in an attempt to establish a consensus on the diagnosis and management of this pathology. The threshold for identical responses to reach consensus was set at 70 %. RESULTS: The responses of 19 experts out of the 23 selected were obtained on the first questionnaire and 16 experts on the second. The main elements agreed upon by the experts were to treat patients with a decrease in visual acuity or an infectious focus within the posterior pole, to treat peripheral lesions only in the presence of significant inflammation, the prescription of first-line treatment with pyrimethamine-azithromycin, the use of corticosteroid therapy after a period of 24 to 48hours, the prophylaxis of frequent recurrences (more than 2 episodes per year) with trimethoprim-sulfamethoxazole as well as the implementation of prophylactic treatment of recurrences in immunocompromised patients. On the other hand, no consensus emerged with regard to the examinations to be carried out for the etiological diagnosis (anterior chamber paracentesis, fluorescein angiography, serology, etc.), second-line treatment (in the case of failure of first-line treatment), or treatment of peripheral foci. CONCLUSION: This study lays the foundations for possible randomized scientific studies to be conducted to clarify the management of ocular toxoplasmosis, on the one hand to confirm consensual clinical practices and on the other hand to guide practices for which no formal consensus has been demonstrated.RĂ©sumĂ©ObjectifĂvaluer les pratiques diagnostiques et thĂ©rapeutiques puis Ă©tablir un consensus sur la prise en charge de la toxoplasmose oculaire en France grĂące Ă une Ă©tude Delphi.MĂ©thodesVingt-trois experts français de la toxoplasmose oculaire ont Ă©tĂ© invitĂ©s Ă rĂ©pondre Ă une Ă©tude Delphi modifiĂ©e menĂ©e en ligne, sous forme de deux questionnaires, afin de tenter dâĂ©tablir un consensus sur le diagnostic et la prise en charge de cette pathologie. Le seuil de rĂ©ponses identiques pour aboutir Ă un consensus a Ă©tĂ© fixĂ© Ă 70 %.RĂ©sultatsLes rĂ©ponses de 19 experts sur les 23 sĂ©lectionnĂ©s ont Ă©tĂ© obtenues au premier questionnaire et de 16 experts au second. Les principaux Ă©lĂ©ments qui font consensus auprĂšs des experts sont de traiter les patients avec une baisse dâacuitĂ© visuelle ou un foyer infectieux au pĂŽle postĂ©rieur, lâinstauration dâun traitement face Ă un foyer pĂ©riphĂ©rique seulement en cas dâinflammation importante, la prescription dâun traitement de premiĂšre intention par lâassociation pyrimĂ©thamineâazithromycine, lâutilisation dâun traitement par corticostĂ©roĂŻdes aprĂšs un dĂ©lai de 24 Ă 48 h, la prophylaxie des rĂ©cidives frĂ©quentes (plus de 2 Ă©pisodes par an) par trimĂ©thoprime-sulfamĂ©thoxazole ainsi que la mise en place dâun traitement prophylactique des rĂ©cidives chez les patients immunodĂ©primĂ©s. En revanche, aucun consensus ne se dĂ©gage pour les examens Ă rĂ©aliser pour le diagnostic Ă©tiologique (ponction de chambre antĂ©rieure, angiographie Ă la fluorescĂ©ine, sĂ©rologieâŠ), pour les traitements de seconde intention (en cas dâĂ©chec du traitement de premiĂšre ligne) ni pour le traitement des foyers pĂ©riphĂ©riques.ConclusionLa prĂ©sente Ă©tude pose les bases dâĂ©ventuelles Ă©tudes scientifiques randomisĂ©es Ă mener afin de clarifier les prises en charge la toxoplasmose oculaire, dâune part pour confirmer les habitudes cliniques qui font consensus, dâautre part pour guider les pratiques pour lesquelles aucun consensus formel nâest mis en Ă©vidence
Adverse Drug Reaction Reporting Using a Mobile Device Application by Persons with Multiple Sclerosis: A Cluster Randomized Controlled Trial
International audienceIntroduction: Patient reporting adds value to pharmacovigilance. Encouraging it to be done through a mobile device application (App) is a method that should be evaluated.Objective: This study aimed to determine whether the use of an App, compared to traditional use through e-mail, telephone, or the national website, increased suspected adverse drug reaction (ADR) reporting by persons with multiple sclerosis receiving a first-line disease-modifying drug.Methods: An open multi-centric, cluster-randomized controlled trial was conducted (VigipSEP study). Clusters were centers allocated (1:1) to the use of the My eReport FranceÂź App (experimental arm), and traditional reporting (control arm). Persons with multiple sclerosis initiating or switching to a first-line disease-modifying drug between April 2017 and April 2019 were included. The primary outcome was the mean number of ADR reports per patient for the center-level analysis, and the number of ADR reports per patient for the individual-level analysis using the hierarchical Poisson regression model.Results: Twenty-four centers (12 per arm: six public neurologists from the multiple sclerosis academic expert centers, three public neurologists from general hospitals, and three private practice neurologists) were randomized, including 159 patients. The mean number of ADR reports per patient was significantly higher in centers that used the App: 0.47 vs 0.03 in control centers (p = 0.002). At an individual-level analysis, the experimental arm was significantly associated with a relative risk of ADR reports at 18.6 (95% confidence interval 4.1-84.2; p < 0.001), compared to the control arm, adjusted for sex and type of disease-modifying drug.Conclusions: The use of a mobile App increased the ADR reporting by persons with multiple sclerosis receiving a first-line disease-modifying drug. CLINICALTRIALS