Clinical and economic impact of non-adherence in COPD:A systematic review

BACKGROUND: Medication for Chronic Obstructive Pulmonary Disease (COPD) has shown to substantially reduce symptoms and slow progression of disease. However, non-adherence to medication is common and associated with worsened clinical and economic outcomes. OBJECTIVE: The objective of this study was to perform a systematic review of published literature to assess the impact of non-adherence to COPD medication on clinical and economic outcomes. METHODS: A search in PubMed and Web of Science databases was conducted of original studies published from database inception to 2012. Studies must report on the association between adherence to COPD medication and outcomes, published in English in peer-reviewed journals and full texts needed to be available. RESULTS: Twelve full articles were included in the review. Most studies were retrospective database studies. Seven studies reported on the association between adherence and clinical outcomes, two on mortality, three on costs, four on quality of life and one on work productivity. Results indicated a clear association between adherence and both clinical and economic outcomes. Evidence from studies revealed increased hospitalizations, mortality, quality of life and loss of productivity among non-adherent patients. CONCLUSION: This review revealed a clear association between non-adherence to COPD medication and worsened clinical and economic outcomes making non-adherent patients a priority for cost-effective interventions.</p

Elbow Joint Loads during Simulated Activities of Daily Living:Implications for Formulating Recommendations after Total Elbow Arthroplasty.

Background: Overloading of the elbow joint prosthesis following total elbow arthroplasty can lead to implant failure. Joint moments during daily activities are not well-contextualized for a prosthesis' failure limits and the effect of the current postoperative instruction on elbow joint loading is unclear. This study investigates the difference in elbow joint moments between simulated daily tasks and between flexion-extension, pronation-supination, varus-valgus movement directions. Additionally, the effect of the current postoperative instruction on elbow joint load is examined.Methods: Nine healthy participants (age 45.8 ± 17 years, 3 males) performed eight tasks; driving a car, opening a door, rising from chair, lifting, sliding, combing hair, drinking, emptying cup, without and with the instruction "not lifting more than 1 kg". Upper limb kinematics and hand contact forces were measured. Elbow joint angles and net moments were analyzed using inverse dynamic analysis, where the net moments are estimated from movement data and external forces.Results: Peak elbow joint moments differed significantly between tasks (p &lt; 0.01) and movement directions (p &lt; 0.01). The most and least demanding tasks were, rising from a chair (13.4 Nm extension, 5.0 Nm supination, 15.2 Nm valgus) and sliding (4.3 Nm flexion, 1.7 Nm supination, 2.6 Nm varus). Net moments were significantly reduced after instruction only in the chair task (p &lt; 0.01).Conclusion: This study analyzed elbow joint moments in different directions during daily tasks. The outcomes question whether postoperative instruction can lead to decreasing elbow loads. Future research might focus on reducing elbow loads in the flexion-extension and varus-valgus directions.<br/

Identification of plastic constitutive parameters at large deformations from three dimensional displacement fields

The aim of this paper is to provide a general procedure to extract the constitutive parameters of a plasticity model starting from displacement measurements and using the Virtual Fields Method. This is a classical inverse problem which has been already investigated in the literature, however several new features are developed here. First of all the procedure applies to a general three-dimensional displacement field which leads to large plastic deformations, no assumptions are made such as plane stress or plane strain although only pressure-independent plasticity is considered. Moreover the equilibrium equation is written in terms of the deviatoric stress tensor that can be directly computed from the strain field without iterations. Thanks to this, the identification routine is much faster compared to other inverse methods such as finite element updating. The proposed method can be a valid tool to study complex phenomena which involve severe plastic deformation and where the state of stress is completely triaxial, e.g. strain localization or necking occurrence. The procedure has been validated using a three dimensional displacement field obtained from a simulated experiment. The main potentialities as well as a first sensitivity study on the influence of measurement errors are illustrated

Opening of endothelial cell–cell contacts due to sonoporation

Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell interaction using the Brandaris 128 ultra-high-speed camera (up to 25 Mfps) coupled to a custom-built Nikon confocal microscope, to visualize both microbubble oscillation and the cellular response. Sonoporation and opening of cell-cell contacts by single αVβ3-targeted microbubbles (n = 152) was monitored up to 4 min after ultrasound insonification (2 MHz, 100–400 kPa, 10 cycles). Sonoporation occurred when microbubble excursion amplitudes exceeded 0.7 μm. Quantification of the influx of the fluorescent model drug propidium iodide upon sonoporation showed that the size of the created pore increased for larger microbubble excursion amplitudes. Microbubble-mediated opening of cell-cell contacts occurred as a cellular response upon sonoporation and did not correlate with the microbubble excursion amplitude itself. The initial integrity of the cell-cell contacts affected the susceptibly to drug delivery, since cell-cell contacts opened more often when cells were only partially attached to their neighbors (48%) than when fully attached (14%). The drug delivery outcomes were independent of nonlinear microbubble behavior, microbubble location, and cell size. In conclusion, by studying the microbubble–cell interaction at nanosecond and nanometer resolution the relationship between drug delivery pathways and their underlying mechanisms was further unraveled. These novel insights will aid the development of safe and efficient microbubble-mediated drug delivery

High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles

Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble–cell interaction remains poorly understood. Because intracellular calcium (Cai 2+) is a key cellular regulator, unraveling the Cai 2+ fluctuations caused by an oscillating microbubble provides crucial insight into the underlying bio-effects. Therefore, we developed an optical imaging system at nanometer and nanosecond resolution that can resolve Cai 2+ fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Cai 2+ uptake profiles upon sonoporation of endothelial cells, which strongly correlated with the microbubble oscillation amplitude, severity of sonoporation and opening of cell–cell contacts. We found a narrow operating range for viable drug delivery without lethal cell damage. Moreover, adjacent cells were affected by a calcium wave propagating at 15 μm/s. With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Cai 2+ fluctuations, providing new insight into the microbubble–cell interaction to aid clinical translation

Resonances in a spring-pendulum: algorithms for equivariant singularity theory

A spring-pendulum in resonance is a time-independent Hamiltonian model system for formal reduction to one degree of freedom, where some symmetry (reversibility) is maintained. The reduction is handled by equivariant singularity theory with a distinguished parameter, yielding an integrable approximation of the Poincaré map. This makes a concise description of certain bifurcations possible. The computation of reparametrizations from normal form to the actual system is performed by Gröbner basis techniques.

Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase

BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons

Inertial Sensor-Based Motion Tracking in Football with Movement Intensity Quantification

Inertial sensor-based measurements of lower body kinematics in football players may improve physical load estimates during training sessions and matches. However, the validity of inertial-based motion analysis systems is specific to both the type of movement and the intensity at which movements are executed. Importantly, such a system should be relatively simple, so it can easily be used in daily practice. This paper introduces an easy-to-use inertial-based motion analysis system and evaluates its validity using an optoelectronic motion analysis system as a gold standard. The system was validated in 11 football players for six different football specific movements that were executed at low, medium, and maximal intensity. Across all movements and intensities, the root mean square differences (means ± SD) for knee and hip flexion/extension angles were 5.3° ± 3.4° and 8.0° ± 3.5°, respectively, illustrating good validity with the gold standard. In addition, mean absolute flexion/extension angular velocities significantly differed between the three movement intensities. These results show the potential to use the inertial based motion analysis system in football practice to obtain lower body kinematics and to quantify movement intensity, which both may improve currently used physical load estimates of the players