Levo-α-acetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy.</p> <p>Methods</p> <p>ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines.</p> <p>Results</p> <p>Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1).</p> <p>Conclusions</p> <p>In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.</p

Reliability Of A Novel Intracardiac Electrogram Method For AV And VV Delay Optimization And Comparability To Echocardiography Procedure For Determining Optimal Conduction Delays In CRT Patients

Background: Echocardiography is widely used to optimize CRT programming. A novel intracardiac electrogram method (IEGM) was recently developed as an automated programmer-based method, designed to calculate optimal atrioventricular (AV) and interventricular (VV) delays and provide optimized delay values as an alternative to standard echocardiographic assessment.Objective: This study was aimed at determining the reliability of this new method. Furthermore the comparability of IEGM to existing echocardiographic parameters for determining optimal conduction delays was verified.Methods: Eleven patients (age 62.9± 8.7; 81% male; 73% ischemic), previously implanted with a cardiac resynchronisation therapy defibrillator (CRT-D) underwent both echocardiographic and IEGM-based delay optimization.Results: Applying the IEGM method, concordance of three consecutively performed measurements was found in 3 (27%) patients for AV delay and in 5 (45%) patients for VV delay. Intra-individual variation between three measurements as assessed by the IEGM technique was up to 20 ms (AV: n=6; VV: n=4). E-wave, diastolic filling time and septal-to-lateral wall motion delay emerged as significantly different between the echo and IEGM optimization techniques (p < 0.05). The final AV delay setting was significantly different between both methods (echo: 126.4 ± 29.4 ms, IEGM: 183.6 ± 16.3 ms; p < 0.001; correlation: R = 0.573, p = 0.066). VV delay showed significant differences for optimized delays (echo: 46.4 ± 23.8 ms, IEGM: 10.9 ± 7.0 ms; p <0.01; correlation: R = -0.278, p = 0.407).Conclusion: The automated programmer-based IEGM-based method provides a simple and safe method to perform CRT optimization. However, the reliability of this method appears to be limited. Thus, it remains difficult for the examiner to determine the optimal hemodynamic settings. Additionally, as there was no correlation between the optimal AV- and VV-delays calculated by the IEGM method and the echo optimization, the use of the IEGM method and the comparability to the echo has not been definitely clarified

Challenges in predicting the change in the cumulative exposure of new tobacco and related products based on emissions and toxicity dose–response data

Funding: This work was funded by the Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, the Netherlands. Project number 9.7.1Many novel tobacco products have been developed in recent years. Although many may emit lower levels of several toxicants, their risk in the long term remains unclear. We previously published a method for the exposure assessment of mixtures that can be used to compare the changes in cumulative exposure to carcinogens among tobacco products. While further developing this method by including more carcinogens or to explore its application to non-cancer endpoints, we encountered a lack of data that are required for better-substantiated conclusions regarding differences in exposure between products. In this special communication, we argue the case for more data on adverse health effects, as well as more data on the composition of the emissions from tobacco products. Such information can be used to identify significant changes in relevance to health using the cumulative exposure method with different products and to substantiate regulatory decisions.Publisher PDFPeer reviewe

Антицитрулінові антитіла в діагностиці артритів у дітей

Віходячи з проведеного дослідження, описаного в роботі, можна дійти висновку, що серед дітей із різними формами артритів тільки 4,8% пацієнтів були серопозитивними за РФ, та 23,8% дітей – за рівнем АЦЦП. Прогнастичне значення підвищеного рівня АЦЦП у дітей із РеА полягає в високій вірогідності розвитку ЮРА, що обумовлює більш ретельне їх спостереження із застосуванням індивідуальних схем профілактичного лікування. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/1128

Airborne based spectroscopy of red and far-red sun-induced chlorophyll fluorescence: Implications for improved estimates of gross primary productivity

Remote sensing (RS) approaches commonly applied to constrain estimates of gross primary production (GPP) employ greenness-based vegetation indices derived from surface reflectance data. Such approaches cannot capture dynamic changes of photosynthesis rates as caused by environmental stress. Further, applied vegetation indices are often affected by background reflectance or saturation effects. Sun. induced chlorophyll fluorescence (F) provides the most direct measure of photosynthesis and has been recently proposed as a new RS approach to improve estimates of GPP and tracing plant stress reactions. This work aims to provide further evidence on the complementary information content of F and its relation to changes in photosynthetic activity compared to traditional RS approaches. We use the airborne imaging spectrometer HyPlant to obtain several F products including red fluorescence (F687), far-red fluorescence (F760), F760 yield (F760yield) and the ration between F687 and F760 (Fratio). We calculate several vegetation indices indicative for vegetation greenness. We apply a recently proposed F-based semi-mechanistic approach to improve the forward modeling of GPP using F760 and compare this approach with a traditional one based on vegetation greenness and ground measurements of GPP derived from chamber measurements. In addition, we assess the sensitivity of F760yield and Fratio for environmental stress. Our results show an improved predictive capability of GPP when using F760 compared to greenness-based vegetation indices. F760yield and Fratio show a strong variability in time and between different crop types suffering from different levels of water shortage, indicating a strong sensitivity of F products for plant stress reactions. We conclude that the new RS approach of F provides complements to the set of commonly applies RS: The use of F760 improves constraining estimates of GPP while the ratio of red and far-red F shows large potential for tracking spatio-temporal plant adaptation in response to environmental stress conditions

An application of tomographic PIV to investigate the spray-induced turbulence in a direct-injection engine

Fuel sprays produce high-velocity, jet-like flows that impart turbulence onto the ambient flow field. The spray-induced turbulence augments fuel-air mixing, which has a primary role in controlling pollutant formation and cyclic variability in engines. This paper presents tomographic particle image velocimetry (TPIV) measurements to analyse the 3D spray-induced turbulence during the intake stroke of a direct-injection engine. The spray produces a strong spray-induced jet in the far field, which travels through the cylinder and imparts turbulence onto the surrounding flow. Planar high-speed PIV measurements at 4.8 kHz are combined with TPIV at 3.3 Hz to evaluate spray particle distributions and validate TPIV measurements in the particle-laden flow. An uncertainty analysis is performed to assess the uncertainty associated with vorticity and strain rate components. TPIV analyses quantify the spatial domain of the turbulence in relation to the SIJ and describe how turbulent flow features such as turbulent kinetic energy, strain rate and vorticity evolve into the surrounding flow field. Access to the full tensors facilitate the evaluation of turbulence for individual spray events. TPIV images reveal the presence of strong shear layers (visualized by high S magnitudes) and pockets of elevated vorticity along the immediate boundary of the SIJ. Values are extracted from spatial domains extending in 1mm increments from the SIJ. Turbulence levels are greatest within the 0-1mm region from the SIJ boarder and dissipate with radial distance. Individual strain rate and vorticity components are analyzed in detail to describe the relationship between local strain rates and 3D vortical structures produced within strong shear layers of the SIJ. Analyses are intended to understand the flow features responsible for rapid fuel-air mixing and provide valuable data for the development of numerical models

Computer-Aided Patient-Specific Coronary Artery Graft Design Improvements Using CFD Coupled Shape Optimizer

This study aims to (i) demonstrate the efficacy of a new surgical planning framework for complex cardiovascular reconstructions, (ii) develop a computational fluid dynamics (CFD) coupled multi-dimensional shape optimization method to aid patient-specific coronary artery by-pass graft (CABG) design and, (iii) compare the hemodynamic efficiency of the sequential CABG, i.e., raising a daughter parallel branch from the parent CABG in patient-specific 3D settings. Hemodynamic efficiency of patient-specific complete revascularization scenarios for right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX) bypasses were investigated in comparison to the stenosis condition. Multivariate 2D constraint optimization was applied on the left internal mammary artery (LIMA) graft, which was parameterized based on actual surgical settings extracted from 2D CT slices. The objective function was set to minimize the local variation of wall shear stress (WSS) and other hemodynamic indices (energy dissipation, flow deviation angle, average WSS, and vorticity) that correlate with performance of the graft and risk of re-stenosis at the anastomosis zone. Once the optimized 2D graft shape was obtained, it was translated to 3D using an in-house “sketch-based” interactive anatomical editing tool. The final graft design was evaluated using an experimentally validated second-order non-Newtonian CFD solver incorporating resistance based outlet boundary conditions. 3D patient-specific simulations for the healthy coronary anatomy produced realistic coronary flows. All revascularization techniques restored coronary perfusions to the healthy baseline. Multi-scale evaluation of the optimized LIMA graft enabled significant wall shear stress gradient (WSSG) relief (~34%). In comparison to original LIMA graft, sequential graft also lowered the WSSG by 15% proximal to LAD and diagonal bifurcation. The proposed sketch-based surgical planning paradigm evaluated the selected coronary bypass surgery procedures based on acute hemodynamic readjustments of aorta-CA flow. This methodology may provide a rational to aid surgical decision making in time-critical, patient-specific CA bypass operations before in vivo execution

Effect of Synthetic Dietary Triglycerides: A Novel Research Paradigm for Nutrigenomics

The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-kappaB, RXRs, LXRs, FXR, HNF4alpha, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids in vivo