Cost-utility analysis of a structured medication review compared to usual care in Parkinson's disease.

PURPOSE: For controlling symptoms in Parkinson's disease (PD) together with treating additional comorbidities, patients often face complex medication regimens, with suboptimal adherence, drug-related problems, and diminished therapy efficacy as a common consequence. A medication review could potentially tackle these issues, among others by optimizing drug treatment. Even if no change in clinical outcomes is observed, this intervention might decrease health care costs by reducing drug-related problems and hospital admissions. This study aimed to gain more insight in the health benefits and costs of a structured medication review (SMR) in PD. METHODS: A cost-utility analysis was performed, based on a multicenter randomized controlled trial with 202 PD patients with polypharmacy. The intervention group received an SMR, whereas the control group received usual care. The intervention effect after 6 months of follow-up was presented as incremental quality-adjusted life years (QALY) using the EQ-5D-5L questionnaire. Costs were based on real-world data. Missing data was imputed using multiple imputation techniques. Bootstrapping was used to estimate the uncertainty in all health and economic outcomes. RESULTS: The QALY gain in the intervention group compared to the control group was - 0.011 (95% CI - 0.043; 0.020). Incremental costs were €433 (95% CI - 873; 1687). When adapting a willingness-to-pay threshold of €20,000/QALY and €80,000/QALY, the probability of SMRs being cost-effective was 18% and 30%, respectively. CONCLUSION: A community pharmacist-led SMR in PD patients in the current setting shows no apparent benefit and is not cost-effective after 6 months, compared to usual care. TRIAL REGISTRATION: Netherlands Trial Register, NL4360. Registered 17 March 2014.

Huygens' inspired multi-pendulum setups: Experiments and stability analysis.

This paper examines synchronization of a set of metronomes placed on a lightweight foam platform. Two configurations of the set of metronomes are considered: a row setup containing one-dimensional coupling and a cross setup containing two-dimensional coupling. Depending on the configuration and coupling between the metronomes, i.e., the platform parameters, in- and/or anti-phase synchronized behavior is observed in the experiments. To explain this behavior, mathematical models of a metronome and experimental setups have been derived and used in a local stability analysis. It is numerically and experimentally demonstrated that varying the coupling parameters for both configurations has a significant influence on the stability of the synchronized solutions.

Network synchronization of time-delayed coupled nonlinear systems using predictor-based diffusive dynamic couplings.

We study the problem of controlled network synchronization of coupled semipassive systems in the case when the outputs (the coupling variables) and the inputs are subject to constant time-delay (as it is often the case in a networked context). Predictor-based dynamic output feedback controllers are proposed to interconnect the systems on a given network. Using Lyapunov-Krasovskii functional and the notion of semipassivity, we prove that under some mild assumptions, the solutions of the interconnected systems are globally ultimately bounded. Sufficient conditions on the systems to be interconnected, on the network topology, on the coupling dynamics, and on the time-delays that guarantee global state synchronization are derived. A local analysis is provided in which we compare the performance of our predictor-based control scheme against the existing static diffusive couplings available in the literature. We show (locally) that the time-delay that can be induced to the network may be increased by including the predictors in the loop. The results are illustrated by computer simulations of coupled Hindmarsh-Rose neurons.

Synchronization of weakly nonlinear oscillators with Huygens' coupling.

In this paper, the occurrence of synchronization in pairs of weakly nonlinear self-sustained oscillators that interact via Huygens' coupling, i.e., a suspended rigid bar, is treated. In the analysis, a generalized version of the classical Huygens' experiment of synchronization of two coupled pendulum clocks is considered, in which the clocks are replaced by arbitrary self-sustained oscillators. Sufficient conditions for the existence and stability of synchronous solutions in the coupled system are derived by using the Poincaré method. The obtained results are supported by computer simulations and experiments conducted on a dedicated experimental platform. It is demonstrated that the mass of the coupling bar is an important parameter with respect to the limit synchronous behaviour in the oscillators.

Multidisciplinary decision-making in older patients with cancer, does it differ from younger patients?

BACKGROUND: In order to tailor treatment to the individual patient, it is important to take the patients context and preferences into account, especially for older patients. We assessed the quality of information used in the decision-making process in different oncological MDTs and compared this for older (≥70 years) and younger patients. PATIENTS AND METHODS: Cross-sectional observations of oncological MDTs were performed, using an observation tool in a University Hospital. Primary outcome measures were quality of input of information into the discussion for older and younger patients. Secondary outcomes were the contribution of different team members, discussion time for each case and whether or not a treatment decision was formulated. RESULTS: Five-hundred and three cases were observed. The median patient age was 63 year, 32% were ≥70. In both age groups quality of patient-centered information (psychosocial information and patient's view) was poor. There was no difference in quality of information between older and younger patients, only for comorbidities the quality of information for older patients was better. There was no significant difference in the contributions by team members, discussion time (median 3.54 min) or number of decision reached (87.5%). CONCLUSION: For both age groups, we observed a lack of patient-centered information. The only difference between the age groups was for information on comorbidities. There were also no differences in contributions by different team members, case discussion time or number of decisions. Decision-making in the observed oncological MDTs was mostly based on medical technical information.

Enhancing master-slave synchronization: The effect of using a dynamic coupling.

This paper introduces a modified master-slave synchronization scheme for dynamical systems. In contrast to the standard configuration, the slave system does not receive any driving signal from the master, but rather the interaction is through a linear dynamical system. The key feature of the proposed coupling scheme is that it induces synchronization in certain systems that cannot be synchronized when using the classical static interconnection. Likewise, the dynamic coupling achieves synchronization for arbitrarily large coupling strength values in certain systems for which the classical configuration is applicable only within a narrow interval of coupling strength values. The performance of the synchronization scheme is illustrated in pairs of identical chaotic and mechanical oscillators.

An observational study of pre-operative transcranial Doppler examinations to predict cerebral hyperperfusion following carotid endarterectomies.

The objective of this observational study was to determine whether pre-operative transcranial Doppler measurements could identify patients at risk for early cerebral hyperperfusion following carotid endarterectomies. Fifty-five patients (mean age 64.4 years) with symptomatic internal carotid artery stenosis were included. Pre-operative transcranial Doppler measurements included middle cerebral artery blood flow velocities at normocapnia, pulsatility indices and estimation of the cerebro-vascular reserve capacity ipsilateral to the internal carotid artery stenosis. The percentage change in blood flow velocities before and at the end of the procedure was calculated. Early cerebral hyperperfusion was defined as an increase of mean blood flow velocity of more than 100% at the end of the carotid endarterectomy. Early cerebral hyperperfusion was observed in 9.2%. Cerebral hyperperfusion was seen in patients with a subtotal carotid artery stenosis in combination with reduced pre-operative blood flow velocity and pulsatility. The post-operative stroke incidence in patients with an early cerebral hyperperfusion was tenfold higher compared to patients who did not experience early hyperperfusion. A prospective clinical trial is warranted to determine whether transcranial Doppler parameters can be used to indicate patients at risk for reperfusion strokes following carotid endarterectomies.

Network complexity and synchronous behavior--an experimental approach.

We discuss synchronization in networks of Hindmarsh-Rose neurons that are interconnected via gap junctions, also known as electrical synapses. We present theoretical results for interactions without time-delay. These results are supported by experiments with a setup consisting of sixteen electronic equivalents of the Hindmarsh-Rose neuron. We show experimental results of networks where time-delay on the interaction is taken into account. We discuss in particular the influence of the network topology on the synchronization.