Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update

Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients. Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during a routine therapeutic drug monitoring protocol. Model building and validation were performed using NONMEM 7.2 (ICON plc), Xpose4 and Perl-speaks-to-NONMEM. The final pop-PK model was a one-compartment first-order elimination model, with a 2.7% IIV for drug clearance (Cl), influence of creatinine clearance on drug clearance and of sex on distribution volume. After model validation, we simulated 10,000 patients with the Monte-Carlo method to predict the efficacy and tolerability of different daptomycin daily dosages. For the most common 6 mg/kg daily dose, the simulated probability of overcoming the toxic minimum concentration (24.3 mg/L) was 14.8% and the efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S. aureus, S. pneumoniae and E. faecium was 95.77%, 99.99% and 68%, respectively. According to the model-informed precision dosing paradigm, pharmacokinetic models such as ours could help clinicians to perform patient-tailored antimicrobial dosing and maximize the odds of therapy success without neglecting toxicity risk

Influences of Human Cognition and Visual Behavior on Password Strength during Picture Password Composition

Visual attention, search, processing and comprehension are important cognitive tasks during a graphical password com-position activity. Aiming to shed light on whether individual differences on visual behavior affect the strength of the created passwords, we conducted an eye-tracking study (N=36) and adopted an accredited cognitive style theory to interpret the results. The analysis revealed that users with different cognitive styles followed different patterns of visual behavior which affected the strength of the created passwords. Motivated, by the results of the first study, we introduced adaptive characteristics to the user authentication mechanism, aiming to assist specific cognitive style user groups to create more secure passwords, and conducted a second study with a new sample (N=40) to test the adaptive characteristics. Results strengthen our assumptions that adaptive mechanisms based on users’ differences in cognitive and visual behavior uncover a new perspective for improving the password’s strength within graphical user authentication realms

Insight into contact force local impedance technology for predicting effective pulmonary vein isolation

BackgroundHighly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have the potential to act as a reliable predictor of the durability of the lesions created.ObjectiveWe aimed to collect data on the procedural parameters affecting LI-guided ablation in a large multicenter registry.MethodsA total of 212 consecutive patients enrolled in the CHARISMA registry and undergoing their first pulmonary vein (PV) isolation for paroxysmal and persistent AF were included.ResultsIn all, 13,891 radiofrequency (RF) applications of ≥3 s duration were assessed. The first-pass PV isolation rate was 93.3%. A total of 80 PV gaps were detected. At successful ablation spots, baseline LI and absolute LI drop were larger than at PV gap spots (161.4 ± 19 Ω vs. 153.0 ± 13 Ω, p < 0.0001 for baseline LI; 22.1 ± 9 Ω vs. 14.4 ± 5 Ω, p < 0.0001 for LI drop). On the basis of Receiver operating characteristic curve analysis, the ideal LI drop, which predicted successful ablation, was >21 Ω at anterior sites and >18 Ω at posterior sites. There was a non-linear association between the magnitude of LI drop and contact-force (CF) (r = 0.14, 95% CI: 0.13–0.16, p < 0.0001) whereas both CF and LI drop were inversely related with delivery time (DT) (−0.22, −0.23 to −0.20, p < 0.0001 for CF; −0.27, −0.29 to −0.26, p < 0.0001 for LI drop).ConclusionAn LI drop >21 Ω at anterior sites and >18 Ω at posterior sites predicts successful ablation. A higher CF was associated with an increased likelihood of ideal LI drop. The combination of good CF and adequate LI drop allows a significant reduction in RF DT.Clinical trial registrationhttp://clinicaltrials.gov/, identifier: NCT03793998

Effective Percutaneous Repositioning of an Active Fixation ICD Lead

We report a case of effective trans catheter repositioning of an ICD lead that was displaced during a trans venous extraction procedure of another malfunctioning ICD lead. This original technique was effective also in screwing-in the active fixation tip of the lead. Skilled operators could take into account this technique to avoid the re-opening of the device pocket, when dealing with specific situations at high risk of infection.</p

Large, single-center experience in transvenous coronary sinus lead extraction: procedural outcomes and predictors for mechanical dilatation

Background: The aim of this study was to evaluate procedural outcomes of coronary sinus (CS) lead extraction, focusing on predictors and need for mechanical dilatation (MD) in the event that manual traction (MT) is ineffective.Methods: The study assessed results in 145 consecutive patients (age 69 +/- 10 years; 121 men)-a total of 147 CS pacing leads-who underwent transvenous CS lead removal between January 2000 and March 2010.Results: All leads but one (99%) (implantation time 29 +/- 25 months) were successfully removed. MT was effective in 103 (70%), and MD was necessary in the remaining 44 (30%) procedures. In multivariate analyses, unipolar design (odds ratio [OR] 3.22, 95% confidence interval [CI] 1.43-7.7; P = 0.005) and noninfective indication (OR 4.8, 95% CI 1.8-13, P = 0.002) were independent predictors for MD (P &lt; 0.0001), with a predictive trend for prior cardiac surgery (OR 2.2, 95% CI 0.98-5.26; P = 0.06). Five (3.4%) complex procedures required a transfemoral vein approach (TFA) or repeat procedure. No deaths occurred, and there was one major complication (0.7%), cardiac tamponade, after MT. No complication predictors were identified.Conclusions: CS leads were safely and effectively removed in nearly all patients, and 70% were removed with MT alone; 30% required MD. Preoperative predictors suggesting the need for MD or TFA were noninfective indication and unipolar lead design. Complications were rare, and there was no predictable pattern among MT or MD removal techniques. (PACE 2012; 35:215-222

Transvenous Removal of Pacing and Implantable Cardiac Defibrillating Leads using Single Sheath Mechanical Dilatation and Multiple Venous Approaches

Introduction Device related complications are raising the need for transvenous lead removal (TLR). Transvenous extraction of pacing (PL) and defibrillating leads (DL) is a highly effective technique. The aim of this chapter is to describe an 18 year single-center experience in pacing and defibrillating leads removal using an effective and safe modified mechanical dilatation technique. Methods We developed a single mechanical dilating sheath extraction technique with multiple venous entry site approaches. We performed a venous entry site approach (VEA) in cases of exposed leads, and an alternative transvenous femoral approach (TFA) combined with an internal transjugular approach (ITA) in the presence of very tight binding sites causing failure of VEA extraction or in cases of free-floating leads. Results From January 1997 to December 2014, we managed 2250 consecutive patients (1718 men, mean age 65.3 years) with 4114 leads (mean pacing period 71.8 months, range 1-576). PL were 3228 (1582 ventricular, 1391 atrial, 355 coronary sinus leads), DL were 786 (765 ventricular, 6 atrial, 15 superior vena cava leads). Removal was attempted in 4105 leads, since the technique was not applicable in 9 PL. Among these, 4019 leads were completely removed (97.9%), 44 (1.1%) partially removed, and 42 (1.0%) not removed. Among 4020 exposed leads, 625 were removed by manual traction (15.5%), 2998 by mechanical dilatation using the venous entry site (74.6%), 32 by femoral approach (FA) (0.8%), and 279 by ITA. Major complications occurred in 13 cases (0.6%): cardiac tamponade (12 cases, 2 deaths), hemotorax (1 death). Conclusion Mechanical single sheath extraction technique with multiple venous entry site approaches is effective, safe and has a good cost effective profile for pacing and ICD leads removal. TLR through the ITA increases the effectiveness and safety of the procedure in case of challenging leads

Leadless cardiac pacemaker implant in a patient with two deep brain stimulators: a peaceful cohabitation beyond prejudices

Leadless cardiac pacemaker implant in a patient with two deep brain stimulators: A peaceful cohabitation beyond prejudices