The use of clonidine in elderly patients with delirium; pharmacokinetics and hemodynamic responses

Background The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is an RCT investigating the effect of clonidine in medical patients > 65 years with delirium. To assess the dosage regimen and safety measures of this study protocol, we measured the plasma concentrations and hemodynamic effects of clonidine in the first 20 patients. Methods Patients were randomised to clonidine (n = 10) or placebo (n = 10). The treatment group was given a loading dose (75μg every 3rd hour up to a maximum of 4 doses) to reach steady state, and further 75μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days. Blood pressure (BP) and heart rate (HR) were measured just before every dose. If the systolic BP was < 100 mmHg or HR < 50 beats per minute the next dose was omitted. Plasma concentrations of clonidine were measured 3 h after each drug intake on day 1, just before intake (day 2 and at steady state day 4–6) and 3 h after intake at steady state (Cmax). Our estimated pre-specified plasma concentration target range was 0.3–0.7μg/L. Results 3 h after the first dose of 75μg clonidine, plasma concentration levels rose to median 0.35 (range 0.24–0.40)μg/L. Median trough concentration (C0) at day 2 was 0.70 (0.47–0.96)μg/L. At steady state, median C0 was 0.47 (0.36–0.76)μg/L, rising to Cmax 0.74 (0.56–0.95)μg/L 3 h post dose. A significant haemodynamic change from baseline was only found at a few time-points during the loading doses within the clonidine group. There was however extensive individual BP and HR variation in both the clonidine and placebo groups, and when comparing the change scores (delta values) between the clonidine and the placebo groups, there were no significant differences. Conclusions The plasma concentration of clonidine was at the higher end of the estimated therapeutic range. Hemodynamic changes during clonidine treatment were as expected, with trends towards lower blood pressure and heart rate in patients treated with clonidine, but with dose adjustments based on SBP this protocol appears safe. Trial registration ClinicalTrials.gov NCT01956604, 09.25.2013. EudraCT Number: 2013–000815-26, 03.18.2013. Enrolment of first participant: 04.24.2014

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents

Modulational instability, solitons and beam propagation in spatially nonlocal nonlinear media

We present an overview of recent advances in the understanding of optical beams in nonlinear media with a spatially nonlocal nonlinear response. We discuss the impact of nonlocality on the modulational instability of plane waves, the collapse of finite-size beams, and the formation and interaction of spatial solitons.Comment: Review article, will be published in Journal of Optics B, special issue on Optical Solitons, 6 figure

Collapse arrest and soliton stabilization in nonlocal nonlinear media

We investigate the properties of localized waves in systems governed by nonlocal nonlinear Schrodinger type equations. We prove rigorously by bounding the Hamiltonian that nonlocality of the nonlinearity prevents collapse in, e.g., Bose-Einstein condensates and optical Kerr media in all physical dimensions. The nonlocal nonlinear response must be symmetric, but can be of completely arbitrary shape. We use variational techniques to find the soliton solutions and illustrate the stabilizing effect of nonlocality.Comment: 4 pages with 3 figure

Dissipative Dynamics of Collisionless Nonlinear Alfven Wave Trains

The nonlinear dynamics of collisionless Alfven trains, including resonant particle effects is studied using the kinetic nonlinear Schroedinger (KNLS) equation model. Numerical solutions of the KNLS reveal the dynamics of Alfven waves to be sensitive to the sense of polarization as well as the angle of propagation with respect to the ambient magnetic field. The combined effects of both wave nonlinearity and Landau damping result in the evolutionary formation of stationaryOA S- and arc-polarized directional and rotational discontinuities. These waveforms are freqently observed in the interplanetary plasma.Comment: REVTeX, 6 pages (including 5 figures). This and other papers may be found at http://sdphpd.ucsd.edu/~medvedev/papers.htm

Two dimensional modulational instability in photorefractive media

We study theoretically and experimentally the modulational instability of broad optical beams in photorefractive nonlinear media. We demonstrate the impact of the anisotropy of the nonlinearity on the growth rate of periodic perturbations. Our findings are confirmed by experimental measurements in a strontium barium niobate photorefractive crystal.Comment: 8 figure

A global map of hemispheric influenza vaccine recommendations based on local patterns of viral circulation

Both the Northern and the Southern Hemisphere annual WHO influenza vaccine recommendations are designed to ensure vaccine delivery before the winter-time peak of viral circulation in each hemisphere. However, influenza seasonal patterns are highly diverse in tropical countries and may be out of phase with the WHO recommendations for their respective hemisphere. We modelled the peak timing of influenza activity for 125 countries using laboratory-based surveillance data from the WHO’s FLUNET database and compared it with the influenza hemispheric recommendations in place. Influenza vaccine recommendations for respectively 25% and 39% of the Northern and Southern Hemisphere countries were out of phase with peak influenza circulation in their corresponding hemisphere (62% and 53%, respectively, when the analysis was limited to the 52 countries in the tropical belt). These results indicate that routine influenza immunization efforts should be closely tailored to local patterns of viral circulation, rather than a country’s hemispheric position

The significance of lifeworld and the case of hospice

Questions on what it means to live and die well are raised and discussed in the hospice movement. A phenomenological lifeworld perspective may help professionals to be aware of meaningful and important dimensions in the lives of persons close to death. Lifeworld is not an abstract philosophical term, but rather the opposite. Lifeworld is about everyday, common life in all its aspects. In the writings of Cicely Saunders, known as the founder of the modern hospice movement, facets of lifeworld are presented as important elements in caring for dying patients. Palliative care and palliative medicine today are, in many ways, replacing hospices. This represents not only a change in name, but also in the main focus. Hospice care was originally very much about providing support and comfort for, and interactions with the patients. Improved medical knowledge today means improved symptomatic palliation, but also time and resources spent in other ways than before. Observations from a Nordic hospice ward indicate that seriously ill and dying persons spend much time on their own. Different aspects of lifeworld and intersubjectivity in the dying persons’ room is presented and discussed