Major Outcomes in Atrial Fibrillation Patients with One Risk Factor: Impact of Time in Therapeutic Range

BACKGROUND: The benefits and harms of oral anticoagulation (OAC) therapy in patients with only one stroke risk factor (i.e. CHA2DS2-VASc= 1 in males, or 2 in females) has been subject of debate. METHODS: We analysed all patients with only one stroke risk factor from the merged datasets of SPORTIF III and V trials. Anticoagulation control was defined according to time in therapeutic range (TTR). RESULTS: Of the original trial cohort, 1,097 patients had only one stroke risk factor. Stroke/systemic thromboembolic event had an incidence of 0.9 per 100 patient-years, with an incidence of 1.6 per 100 patient-years for all-cause death and 2.3%/patient-years for the composite outcome of stroke/systemic thromboembolic event/all-cause death. There were no significant differences in the risk for stroke/systemic thromboembolic event between sexes, nor between the different stroke risk factors amongst these atrial fibrillation patients with only one stroke risk factor. Cox regression analysis in patients treated with warfarin only found TTR to be inversely associated with stroke/systemic thromboembolic event (p=0.034) and all-cause death (p=0.015). Chronic heart failure was significantly associated with the outcome of all-cause death (p=0.0019) and the composite outcome of stroke/systemic thromboembolic event/all-cause death (p=0.021). There was a significant inverse linear association between TTR and the cumulative risk for both stroke/systemic thromboembolic event and all-cause death (both p<0.001). CONCLUSIONS: In atrial fibrillation patients with only one additional stroke risk factor (i.e. CHA2DS2-VASc= 1 in males or 2 in females), rates of major adverse events (stroke/systemic thromboembolic event, mortality) were high, despite anticoagulation. TTR in warfarin-treated patients was inversely associated with the occurrence of both stroke/systemic thromboembolic event and all-cause death

Atrial fibrillation as a clinical model of multimorbidity: current evidence, experimental data and a proposal for management

La Fibrillazione Atrial (FA) rappresenta una delle più diffuse aritmie cardiache nella popolazione generale. Nel corso degli ultimi anni, è emerso in maniera sempre più rilevante come i pazienti con FA siano ad elevato rischio di eventi cardiovascolari e morte, oltre che di eventi tromboembolici. Il rischio di morte e morte cardiovascolare è associato indipendentemente con diverse comorbidità sia cardiovascolari che non. Il concetto di multimorbidità è diventato di grande attualità nella valutazione clinica, soprattutto dei pazienti anziani. Attraverso l'analisi di cinque differenti corti di pazienti con FA (retrospettivo, RCT, European-wide, pazienti anziani ospedalizzati) si è potuto mettere in evidenza come esista uno stretto rapporto tra FA e multimorbidità e come nei pazienti con FA la multimorbidità sia in grado di influenza la gestione, l'andamento clinico e soprattutto il rischio di eventi clinici maggiori. L'uso di strategie integrate che contemplino la valutazione della multimorbidità da parte di medici, come l'internista, capaci di gestire accuratamente la multimorbidità, sono raccomandate al fine di ottenere una significativa riduzione del rischio di eventi clinici

The Variance Profile

The variance profile is defined as the power mean of the spectral density function of a stationary stochastic process. It is a continuous and non-decreasing function of the power parameter, p, which returns the minimum of the spectrum (p → −∞), the interpolation error variance (harmonic mean, p = −1), the prediction error variance (geometric mean, p = 0), the unconditional variance (arithmetic mean, p = 1) and the maximum of the spectrum (p → ∞). The variance profile provides a useful characterisation of a stochastic processes; we focus in particular on the class of fractionally integrated processes. Moreover, it enables a direct and immediate derivation of the Szego-Kolmogorov formula and the interpolation error variance formula. The paper proposes a non-parametric estimator of the variance profile based on the power mean of the smoothed sample spectrum, and proves its consistency and its asymptotic normality. From the empirical standpoint, we propose and illustrate the use of the variance profile for estimating the long memory parameter in climatological and financial time series and for assessing structural change.Predictability; Interpolation; Non-parametric spectral estimation; Long memory.

Chronic kidney disease, time in therapeutic range and adverse clinical outcomes in anticoagulated patients with non-valvular atrial fibrillation: observations from the SPORTIF trials

Background: Chronic kidney disease (CKD) is highly prevalent in atrial fibrillation (AF) patients and associated with an increased risk of adverse outcomes. Our objectives were to study clinical features associated with CKD in AF patients and the impact of CKD on anticoagulation control, as reflected by time in therapeutic range (TTR). We also determined the impact of CKD and TTR in predicting adverse outcomes. Methods and Results: We analysed pooled datasets from SPORTIF III and V trials, including 3646 patients assigned to warfarin with data on renal function. CKD (creatinine clearance . 70%, whilst diabetes mellitus, aspirin use and CKD were inversely associated with TTR. >. 70%. On Cox regression analysis, CKD was an independent predictor for stroke (p = 0.006) and death (p . 70% was independently associated with a lower risk of stroke (p = 0.024), death (p = 0.001) and major bleeding (p = 0.001). Conclusions: CKD is highly prevalent amongst AF patients and a risk factor for stroke and death. Adjusting for CKD, good quality anticoagulation control (TTR. >. 70%) was an independent predictor for lower risks of stroke, death and major bleeding

Risultati clinico-strumentali del trattamento dell'artrosi trapezio-metacarpale mediante artroplastica di interposizone

Introduzione: La rizoartrosi (artrosi trapezio-metacarpale) rappresenta il 10% delle localizzazioni artrosiche di tutto il corpo. L’ artroplastica di interposizione secondo Robinson prevede l’esecuzione di trapeziectomia ed innesto tendineo con emi Abduttore Lungo del Pollice (APL) inserito nel gap creato dalla trapeziectomia. Lo scopo dello studio è quello di valutare i risultati clinici e strumentali dell’artroplastica di interposizione ad un follow-up di medio-lungo termine valutando mediante studio RMN l’evoluzione del innesto, ed una sua eventuale associazione con gli risultati clinici. Materiali e Metodi: Da Luglio 2006 a Maggio 2012, sono stati trattati chirurgicamente 75 pazienti affetti da rizoartrosi.64 pazienti rientravano nei criteri di inclusione dello studio. La valutazione clinica è stata effettuata mediante Grind test, Kapandji test, DASH score, VAS score, valutazione della ROM in abduzione radiale, e soddisfazione soggettiva del paziente. L’esame strumentale è stato effettuato mediante RX in antero-posteriore e laterale, sono state inoltre analizzate sequenze T1-, T2-, STIR-, Spin Echo e Gradient Echo-MRI alla RMN. Risultati: 44 pazienti (68.75%) sono risultati pienamente soddisfatti, 16 pazienti (25%) hanno riportato grande beneficio e hanno ripreso tutte le attività quotidiane con limitazione minima. Solo 4 pazienti (6.25%) non sono stati soddisfatti dell’intervento. La distanza scafo-metacarpale (SMD) valutata radiograficamente nel 1 mese post operatorio ha mostrato un valore medio di 6.6±1.7SD mm. All’ultimo follow-up il valore medio (SMD) è risultato essere di 4.3±1.2SD mm, con una migrazione prossimale media di 2.3±0.9SD mm. La valutazione con RMN ha mostrato nel 100% dei pazienti la presenza di tessuto fibroso residuo nello spazio tra la base del primo metacarpo e lo scafoide. Nel 37.5% dei pazienti è stata osservata la presenza di edema osseo subcondrale. Il 50% dei pazienti mostravano sinovite reattiva alla RMN. Discussione/Conclusioni: L’artroplastica di interposizione è un trattamento sicuro e validato per il trattamento dei pazienti affetti da rizoartrosi di stadio III-IV secondo Eaton-Littler che garantisce buoni risultati clinici ed il ritorno alle normali attività di vita quotidiana. La quantità di tessuto fibroso residuo interposto dopo la trapeziectomia sembra essere correlate a migliori risultati clinico / radiografici e maggiore soddisfazione da parte dei pazienti

Use of NOACs in the Perioperative Management of Patients with Atrial Fibrillation::To Stop, Bridge or Continue?

Over the last decade, the availability of non-vitamin K antago- nist oral anticoagulants (NOACs) has significantly changed the daily clinical practice in managing thromboembolic risk in patients with atrial fibrillation (AF).1 Guidelines for AF man- agement have established that NOACs are the preferred treat- ment for the majority of AF patients;2 however, recent data from ‘real-life’ registries clearly show that a significant pro- portion of patients are still treated with vitamin K antago- nists.3–8 Nevertheless, the role of NOACs still seems to be debated in some specific circumstances, such as their role in the peri-operative management of patients with AF, in relation to interruption or continuation of anticoagulation

Association Between Peripheral Artery Disease and Incident Risk of Atrial Fibrillation: Strong Evidence Coming From Population-Based Cohort Studies

Peripheral artery disease (PAD) is largely prevalent and evident among the general population. 1 PAD recognizes multiple risk factors, and it is associated with an increased risk of morbidity and mortality. 1 Similarly, atrial fibrillation (AF) is the most prevalent and incident arrhythmia, associated with an increased risk for stroke and major cardiovascular outcomes. 2 In recent years, accumulating evidence suggests that a strong relationship exists between PAD and AF. 3 Both the conditions share similar major risk factors and common epidemiologic characteristics. Also, it is largely known that the concomitant presence of these conditions significantly increases the risk of major adverse events.(3

Transformations and Seasonal Adjustment: Analytic Solutions and Case Studies

We address the problem of seasonal adjustment of a nonlinear transformation of the original time series, such as the Box-Cox transformation of a time series measured on a ratio scale, or the Aranda-Ordaz transformation of proportions, which aims at enforcing two essential features: additivity and orthogonality of the components. The posterior mean and variance of the seasonally adjusted series admit an analytic finite representation only for particular values of the transformation parameter, e.g. for a fractional Box-Cox transformation parameter. Even if available, the analytical derivation can be tedious and difficult. As an alternative we propose to compute the two conditional moments of the seasonally adjusted series by means of numerical and Monte Carlo integration. The former is both fast and reliable in univariate applications. The latter uses the algorithm known as the simulation smoother and it is most useful in multivariate applications. We present several case studies dealing with robust seasonal adjustment under the square root and the fourth root transformation, the seasonal adjustment of the ratio of two series, and the adjustment of time series of proportions. Our overall conclusion is that robust seasonal adjustment under transformations can be carried out routinely and that the possibility of transforming the scale ought to be considered as a further option for improving the quality of seasonal adjustment

Use of idarucizumab in reversing dabigatran anticoagulant effect: a critical appraisal

Use of non-vitamin K antagonist oral anticoagulants is spreading in the real world. Despite that, a strong need for antidotes/reversal agents is still reported by several physicians. Idarucizumab is a humanized monoclonal antibody fragment that binds specifically to dabigatran. Idarucizumab was approved in 2015 by the US Food and Drugs Administration and European Medicines Agency for reversal of anticoagulation activity in dabigatrantreated patients. This review briefly summarizes the experimental evidence about effectiveness and safety of idarucizumab. Furthermore, we review the current recommendations and experts' point of view about the use of antidotes/reversal agents in patients reporting a major bleeding event