Anticholinergic Exposure in a Cohort of Adults Aged 80 years and Over

Anticholinergics are frequently prescribed for older adults and can lead to adverse drug events. The novel MARANTE (Muscarinic Acetylcholinergic Receptor ANTagonist Exposure) scale measures the anticholinergic exposure by incorporating potency and dosages of each medication into its calculations. The aims were to assess prevalence and intensity of the anticholinergic exposure in a longitudinal cohort study of community‐dwelling patients aged 80 years and over (n = 503) and to study the impact on mortality and hospitalization. Chronic medication use at baseline (November 2008–September 2009) was entered and codified with the Anatomical Therapeutic Chemical classification. Time‐to‐event analysis until first hospitalization or death was performed at 18 months after inclusion, using Kaplan–Meier curves. Cox regression was performed to control for covariates. Mean age was 84 years (range 80–102), and mean number of medications was 5 (range 0–16). Prevalence of anticholinergic use was 31.8%, with 9% taking ≥2 anticholinergics (range 0–4). Main indications for anticholinergics were depression, pain and gastric dysfunction. Female gender, the level of multi‐morbidity and the number of medications were associated with anticholinergic use. Mortality and hospitalization rate were 8.9% and 31.0%, respectively. After adjustment for the level of multi‐morbidity and medication intake, multi‐variable analysis showed increased risks of mortality (HR 2.3, 95% CI: 1.07–4.78) and hospitalization (HR 1.7; 95% CI: 1.13–2.59) in those with high anticholinergic exposure. The longitudinal study among Belgian community‐dwelling oldest old demonstrated great anticholinergic exposure, which was associated with increased risk of mortality and hospitalization after 18 months.     

Comparison of Timed Automata with Discrete Event Simulation for Modeling of Biomarker-Based Treatment Decisions: An Illustration for Metastatic Castration-Resistant Prostate Cancer

Background

With the advent of personalized medicine, the field of health economic modeling is being challenged and the use of patient-level dynamic modeling techniques might be required.

Constrained Optimization Methods in Health Services Research—An Introduction: Report 1 of the ISPOR Optimization Methods Emerging Good Practices Task Force

Providing health services with the greatest possible value to patients and society given the constraints imposed by patient characteristics, health care system characteristics, budgets, and so forth relies heavily on the design of structures and processes. Such problems are complex and require a rigorous and systematic approach to identify the best solution. Constrained optimization is a set of methods designed to identify efficiently and systematically the best solution (the optimal solution) to a problem characterized by a number of potential solutions in the presence of identified constraints. This report identifies 1) key concepts and the main steps in building an optimization model; 2) the types of problems for which optimal solutions can be determined in real-world health applications; and 3) the appropriate optimization methods for these problems. We first present a simple graphical model based on the treatment of “regular” and “severe” patients, which maximizes the overall health benefit subject to time and budget constraints. We then relate it back to how optimization is relevant in health services research for addressing present day challenges. We also explain how these mathematical optimization methods relate to simulation methods, to standard health economic analysis techniques, and to the emergent fields of analytics and machine learning.     

Comparison of characteristics of dopamine uptake and mazindol binding in mouse striatum

Summary Biochemical and pharmacological studies suggest that the binding of [³H]mazindol is functionally related to the dopamine uptake carrier complex in rodent striatum. In order to study further the relationship between the substrate recognition site for dopamine uptake and the high-affinity binding site for mazindol the uptake of [³H]dopamine and the binding of [³H]mazindol was studied in BALB/cBy mouse striatum in various buffers (Tris, HEPES, bicarbonate-phosphate). Kinetic analysis showed that theK _d, of the binding of [³H]mazindol and theK _m of the uptake of [³Mdopamine was changed by different sodium concentrations and/or by the presence of Tris, while theB _max, and theV _max remained essentially the same. However, the shape of the Na⁺ dependency curves was not the same for mazindol binding and dopamine uptake in the various buffers. The inhibitory effect of other cations such as K⁺ and Tris was also different on binding and uptake under similar experimental circumstances. Dopamine did not slow down the dissociation of mazindol from its site and this effect was not sodium-sensitive. These complexities can be accomodated by a model that involves overlapping sites for mazindol and dopamine on the dopamine uptake carrier complex, and translocation -reorientation steps.Abbreviations K _d dissociation rate constant - HEPES N-2hydroxyethyl-piperazine-N-2-ethanesulfonic acid - Km half-saturating concentration for uptake - B _max maximal binding capacity - V _max maximal initial uptake rate - k _–1 dissociation rate constant - IC₅₀ concentration of inhibitor causing 50% inhibition - DA 3,4dihydroxyphenylethylamine (dopamine) On leave from the Institute of Experimental Medicine, H-1450, Budapest, P.O.B. 67, Hungary. Send offprint request to I. Zimányi at her present address     

Brain vein disorders in newborn infants

The brain veins of infants are in a complex phase of remodelling in the perinatal period. Magnetic resonance venography and susceptibility‐weighted imaging, together with high‐resolution Doppler ultrasound, have provided new tools to aid study of venous developmental anatomy and disease. This review aims to provide a comprehensive background of vein development and perinatal venous lesions in preterm and term‐born infants, and to encourage further research in both the fetus and the newborn infant, with the aim of preventing or mitigating parenchymal injury related to diseases involving veins.     

Soft like velvet and shiny like satin: Perceptual material signatures of fabrics depicted in 17th century paintings

Dutch 17^th century painters were masters in depicting materials and their properties in a convincing way. Here, we studied the perception of the material signatures and key image features of different depicted fabrics, like satin and velvet. We also tested whether the perception of fabrics depicted in paintings related to local or global cues, by cropping the stimuli. In Experiment 1, roughness, warmth, softness, heaviness, hairiness, and shininess were rated for the stimuli shown either full figure or cropped. In the full figure, all attributes except shininess were rated higher for velvet, whereas shininess was rated higher for satin. This distinction was less clear in the cropped condition, and some properties were perceived significantly different between the two conditions. In Experiment 2 we tested whether this difference was due to the choice of the cropped area. On the basis of the results of Experiment 1, shininess and softness were rated for multiple crops from each fabric. Most crops from the same fabric differed significantly in shininess, but not in softness perception. Perceived shininess correlated positively with the mean luminance of the crops and the highlights’ coverage. Experiment 1 showed that painted velvet and satin triggered distinct perceptions, indicative of robust material signatures of the two fabrics. The results of Experiment 2 suggest that the presence of local image cues affects the perception of optical properties like shininess, but not mechanical properties such as softness.