Atrial fibrillation and treatment changes in cryptogenic stroke patients with an implantable loop recorder for continuous cardiac rhythm monitoring

Introduction: This interim analysis evaluates the risk profile and incidence of atrial fibrillation (AF) in patients who underwent continuous monitoring with an implantable loop recorder (ILR) for cryptogenic (unexplained) stroke or transient ischemic attack (TIA). Methods: The observational INSIGHT XT study prospectively enrolled patients who received an ILR with dedicated diagnostics for atrial fibrillation, irrespective of the clinical indication. Of 1002 patients enrolled in the study between Aug 2008 and Jan 2012, 121 received the ILR to evaluate cryptogenic stroke or TIA. The definition of cryptogenic stroke/TIA was at the investigators' appraisal and no unified approach to patient work-up was required. This analysis includes 74 patients with cryptogenic stroke or TIA for whom at least one follow-up visit was available at the time of interim analysis. Results: The mean age was 63±12 (50% female). Stroke was the index event in 46 of 74 (62%) of patients. 61% had hypertension, 14% diabetes, and none had heart failure. The mean CHADS2 score was 3.0±0.8 and the mean CHA2DS2VASc score 4.0±1.2. Most patients (72%) had no prior symptoms or cardiac rhythm disturbances, whereas 18% had a history of prior palpitations. Sixty-seven patients were taking antiplatelet medication and four were on oral anticoagulation (OAC) at enrollment. During a median follow up of 12 months (IQR 7 to 18) AF was reported in 17 patients (23%) and two patients were started on OAC and 10 patients were converted from antiplatelets to OAC. Five patients experienced a stroke or TIA (median time to event 1.2 months), of which one patient died. Three of the patients with stroke or TIA had AF detected prior to the recurrent event. Conclusion: Continuous monitoring with an ILR in patients with cryptogenic stroke of TIA detects a high proportion of AF; this can be attributed to longer continuous monitoring in this study. These patients have high CHADS2/CHA2DS2VASc scores; documenting AF in these cases may therefore be clinically relevant in order to decide appropriate treatment

Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices)

Objective: The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. Background: Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. Design, setting, and patients A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. Results: During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3–14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22–3.64, P = 0.008). Conclusions: Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment

Stimulation of the intra-cardiac vagal nerves innervating the AV-node to control ventricular rate during AF: specificity, parameter optimization and chronic use up to 3 months

Stimulation of the intra-cardiac vagal nerves innervating the AV-node (AVNS) is a promising approach to slow down ventricular rate (VR) during atrial fibrillation (AF). Our purpose was to demonstrate that effects on R-R-interval during stable AF can be maintained for several months once optimized and that AVNS affects specifically the nerves innervating the AV-node. Our study included both an acute and chronic phase. Fifteen goats were implanted with a pacemaker connected to an atrial and ventricular lead and a neurostimulator connected to an atrial lead placed at a certain septal site, to induce an AV prolongation. In the chronic experiments (n = 9), after assessment of optimal AVNS parameters, the effect of continuous AVNS on VR was studied during stable AF for up to 3 months. The mechanism of AVNS was studied using atropine and esmolol. Next, the effects of AVNS during the atrial refractory period on electrophysiological and hemodynamic parameters were investigated acutely (n = 7). The maximal effect was found at a stimulation frequency of 40 Hz, and increased with increasing pulse width (at lower voltages) and increasing voltage. After 0, 1, and 3 months of AVNS during stable AF, AVNS decreased average VR, respectively, 55% (n = 9), 48% (n = 8), and 28% (n = 6). The AVNS effect appeared to be dominantly parasympathetic. AVNS did not influence (1) the sinus node, (2) the refractory period of the atrial, ventricular tissue, and His and (3) hemodynamic parameters. AVNS is efficient in reducing ventricular rate for at least 3 months using optimized parameters and specifically affects the parasympathetic nerves innervating the AV-node

Patient attitudes towards chemotherapy and survival: A prospective observational study in advanced non-small cell lung cancer

WOS: 000272370400017PubMed ID: 19264374This multicenter, non-interventional, prospective, observational study aimed to determine whether patients' attitude to chemotherapy is an independent prognostic factor for survival in patients with advanced non-small cell lung cancer (NSCLC) who are treated with gemcitabine-platinum. Chemonaive patients (n = 1895) with stage IIIB or IV NSCLC not amenable to curative surgery or radiotherapy were treated with a combination of gemcitabine plus cisplatin/carboplatin and followed for a maximum of 18 months. Patients' attitude to treatment was measured on a 5-point scale and responses were used to assign patients to one of the three need categories: A, maximum extension of survival with the acceptance of high toxicity (60.0% of patients); B, maximum extension of survival only if coupled with normal lifestyle (26.1%); C, relief of symptoms (13.8%). Median survival varied significantly among the need categories (A = 13.00 months, B = 15.70 months, C = 15.33 months; log-rank test P=0.0415). Patient attitude to treatment (need categories) was not a significant prognostic factor for survival after adjusting for known prognostic factors (P=0.0503). After adjusting for baseline differences, patients in this study had a significantly lower risk of death than patients in three randomized trials (hazard ratio 0.879; 95% confidence interval: 0.775, 0.998; P=0.0458). In conclusion, in this observational study, patient attitude to chemotherapy was not an independent prognostic factor of survival. (C) 2009 Elsevier Ireland Ltd. All rights reserved.Eli Lilly and CompanyEli Lilly; Indianapolis, INWe acknowledge and thank all the clinicians involved in this study. This study was sponsored by Eli Lilly and Company, Indianapolis, IN. In compliance with the Uniform Requirements for Manuscripts, established by the International Committee of Medical journal Editors, the sponsor of this study did not impose any impediment, directly or indirectly, on the publication of the study's results. Eligible authors from the sponsoring company worked with their co-authors to design the study, to collect, analyze and interpret the data and to prepare and make the decision to submit the manuscript. All authors acknowledge the independent medical writing assistance provided by ProScribe Medical Communications (www.proscribe.com.au), funded by Eli Lilly and Company. ProScribe's services complied with international guidelines for Good Publication Practice

Timing of Dose Relative to Sexual Intercourse Attempt in Previous Sildenafil Citrate Users Treated with Tadalafil: A Geographical Comparison from a Single Arm, Open-Label Study

Introduction. Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. Aim. To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Methods. Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of >= 6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Main Outcomes Measures. Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. Results. A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. Conclusion. Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use. Rubio-Aurioles E, Glina S, Abdo CHN, Hernandez-Serrano R, Rampazzo C, Sotomayor M, West TM, Gallagher GL, and Lenero E. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: A geographical comparison from a single arm, open-label study. J Sex Med 2009;6:2836-2850