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Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.
Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates.
Agitation is a common symptom in schizophrenia and bipolar mania, causing marked distress and posing considerable risks for patients. Intramuscular formulations of psychotropic medication can provide a fast acting treatment of severe agitation in patients with acute episodes of schizophrenia or mania. As effective as these treatments are, particular antipsychotics can be associated with a heightened risk of dystonia and related Extrapyramidal Symptoms (EPS). Patients presenting to emergency care settings are also likely to have coexisting intoxications and medical conditions that may contribute to this risk.
The aim of this observational prospective study was to document the safety and effectiveness of all IM psychotropic drugs during the 24 hours following an initial injection in acutely agitated patients suffering from schizophrenia or bipolar disorder under naturalistic conditions.
Two-hundred-thirty-two (232) participating investigator sites (12 European countries) observed 1940 patients (mean age: 39 y, 42% female, 66% schizophrenia diagnosis). The primary endpoint was the occurrence of extrapyramidal symptoms (EPS), further endpoints were clinical severity measured by PANSS-EC and CGI-S. A total of 1311 (68%) patients received a monotherapy injection at baseline. Within 24 hours after the first injection, 190 (10%) of all 1940 patients experienced EPS. All intramuscular psychotropic drugs were shown to be effective in reducing measures of acute agitation.
This study provides favourable results on EPS related adverse events and effectiveness of intramuscular psychotropic medication for the management of acute agitation in patients within a naturalistic setting during the first 24 hours of treatment.
This naturalistic, observational pan-European study assessed the safety and early effectiveness of intramuscular (IM) psychotropic treatments in patients with acute agitation suffering from schizophrenia or bipolar mania. One thousand nine hundred and forty of 1945 patients completed the 24-hour observation period after initial IM treatment. Patients from 12 European countries were included (mean age 39 years; 58% male, 66% schizophrenia). IM treatment was at the physician's discretion. The primary objective was to describe the acute tolerability of IM psychotropic therapies in clinical practice, with particular emphasis on EPS. At baseline, 68% of the patients received IM monotherapy, with IM olanzapine most commonly prescribed (36%). During the first 24hours, 190 (9.8%) patients experienced EPS. The occurrence of EPS was statistically significantly lower in patients treated with IM olanzapine compared to those treated with other IM psychotropic medications (mainly typical antipsychotics and benzodiazepines): acute dystonia: 1.1%, 95% CI 0.5–2.3 and 2.9%, CI 2.0–4.0; akathisia: 2.3%, CI 1.3–3.7 and 5.5%, CI 4.3–6.9; Parkinsonism: 2.9%, CI 1.8–4.4 and 7.8%, CI 6.4–9.4, respectively. Anticholinergic treatment was given to 12% IM olanzapine versus 31% non-olanzapine treated patients. Acute agitation after 24hours was reduced by 1.68 (95% CI 1.46–1.91) points on the Clinical Global Impression of Severity (CGI-S) in IM olanzapine patients and 1.51 (95% CI 1.30–1.73) points in non-olanzapine patients. Additional psychotropic medication was required for 90% of the patients during the first 24hours of treatment. Results provide naturalistic evidence for low EPS rates and improvement of agitation with IM psychotropic medications during acute states of patients suffering from acute mania or schizophrenia.
There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders.
The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models.
Current combined MDD [β = 0.29, 95% confidence interval (CI) 0.03–0.55] and current atypical MDD (β = 0.32, 95% CI 0.10–0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up.
The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.
The reorientation phenomenon of a single red blood cell during sedimentation is simulated using the boundary element method. The cell settles downwards due to a density difference between the internal and external fluids, and it changes orientation toward a vertical orientation regardless of Bond number or viscosity ratio. The reorientation phenomenon is explained by a shape asymmetry caused by the gravitational driving force, and the shape asymmetry increases almost linearly with the Bond number. When velocities are normalised by the driving force, settling/drifting velocities are weak functions of the Bond number and the viscosity ratio, while the angular velocity of the reorientation drastically changes with these parameters: the angular velocity is smaller for lower Bond number or higher viscosity ratio. As a consequence, trajectories of the sedimentation are also affected by the angular velocity, and blood cells with slower reorientation travel longer distances in the drifting direction. We also explain the mechanism of the reorientation using an asymmetric dumbbell. From the analysis, we show that the magnitude of the angular velocity is explained by two main factors: the shape asymmetry and the instantaneous orientation angle.
Patients with psychosis display the so-called ‘Jumping to Conclusions’ bias (JTC) – a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in ‘at-risk mental state’ (ARMS) patients, specifically in ARMS samples fulfilling ‘ultra-high risk’ (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups.
In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument – Adult Version (SPI-A).
The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement.
Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.
Feedback provided by relativistic jets may be effective in shaping the galaxy luminosity function. The quenching mode (quasar mode) at redshifts ~2-3 potentially disperses gas in star-forming galaxies. The maintenance mode (radio mode) heats the gas in galaxy clusters counteracting cooling flows. A number of authors have examined the effect of relativistic jets in dispersing clouds in the kpc-scale inhomogeneous interstellar medium of evolving galaxies. We have also investigated a particular case of maintenance-mode feedback in our simulation of the iconic radio galaxy / cooling flow cluster Hydra A. Modelling of the knots produced by the jets in the inner 10 kpc provides an estimate of 0.8 – 0.9 c for the velocities of the jets in agreement with other velocity estimates for FR1 jets. The addition of jet precession provides realistic simulations of the morphology of the Hydra A radio source and raises interesting questions as to the role of black hole and disk precession, in general, in galaxy formation.
In this chapter, we present a comprehensive framework for tackling the classical problem of face recognition, based on theory and algorithms from sparse representation. Despite intense interest in the past several decades, traditional pattern recognition theory still stops short of providing a satisfactory solution capable of recognizing human faces in the presence of real-world nuisances such as occlusion and variabilities in pose and illumination. Our new approach, called sparse representation-based classification (SRC), is motivated by a very natural notion of sparsity, namely, one should always try to explain a query image using a small number of training images from a single subject category. This sparse representation is sought via ℓ1 minimization. We show how this core idea can be generalized and extended to account for various physical variabilities encountered in face recognition. The end result of our investigation is a full-fledged practical system aimed at security and access control applications. The system is capable of accurately recognizing subjects out of a database of several hundred subjects with state-of-the-art accuracy.
Automatic face recognition is a classical problem in the computer vision community. The community's sustained interest in this problem is mainly due to two reasons. First, in face recognition, we encounter many of the common variabilities that plague vision systems in general: illumination, occlusion, pose, and misalignment. Inspired by the good performance of humans in recognizing familiar faces , we have reason to believe that effective automatic face recognition is possible, and that the quest to achieve this will tell us something about visual recognition in general.
The significance of the potential impacts of microbial activity on the transport properties of host rocks for geological repositories is an area of active research. Most recent work has focused on granitic environments. This paper describes pilot studies investigating changes in transport properties that are produced by microbial activity in sedimentary rock environments in northern Japan. For the first time, these short experiments (39 days maximum) have shown that the denitrifying bacteria, Pseudomonas denitrificans, can survive and thrive when injected into flow-through column experiments containing fractured diatomaceous mudstone and synthetic groundwater under pressurized conditions. Although there were few significant changes in the fluid chemistry, changes in the permeability of the biotic column, which can be explained by the observed biofilm formation, were quantitatively monitored. These same methodologies could also be adapted to obtain information from cores originating from a variety of geological environments including oil reservoirs, aquifers and toxic waste disposal sites to provide an understanding of the impact of microbial activity on the transport of a range of solutes, such as groundwater contaminants and gases (e.g. injected carbon dioxide).
Large-scale graphene sheets were grown on thin nickel film coated Si substrates using a reliable and repeatable thermal Chemical Vapor Deposition (CVD) technique. The graphene films were then transferred onto a SiO2 coated Si wafer to fabricate a 5 mm x 5 mm resistive sensor structure. Raman spectroscopy analysis confirmed the existence of graphene. Preliminary sensing results were demonstrated by the detection of hazardous gases such as NO2 and MMH (mono-methyl hydrazine). Characterization of the device channel resistivity (switching response) was conducted as a function of the analyte type and concentration. The sensor response indicates a charge transfer mechanism between the analytes and graphene.
Narrow-Line Seyfert 1 (NLS1) class of active galactic nuclei (AGNs) is generally radio-quiet, but a small percent of them are radio-loud. The recent discovery by Fermi/LAT of high-energy γ-ray emission from 4 NLS1s proved the existence of relativistic jets in these systems. It is therefore important to study this new class of γ-ray emitting AGNs. Here we report preliminary results about the observations of the July 2010 γ-ray outburst of PMN J0948+0022, when the source flux exceeded for the first time 10−6 ph cm−2 s−1 (E > 100 MeV).
Quantum Dots (QDs) bound to gold nanoparticles have shown photoluminescence (PL) quenching dependent on distance between the two particles. The incident light from the QD couples to plasmon excitation of the metal when the frequencies of the light and the surface plasmon resonance (SPR) coincide, leading to a reduction in emitted PL in the system. The quenching effect of gold nanoparticles on QDs was used to study protein-protein interactions with the potential for drug screening applications. CdTe and CdHgTe QDs with emission wavelengths from 500˜900nm were synthesized and gold nanospheres and nanorods with controlled absorption in the visible and near-infrared (NIR) wavelength regions were prepared. The PL quenching of QD-Protein-Protein-Au complexes was studied as a function of Au concentration, QD size and protein type. A quenching efficiency of up to 90% was observed. The QD-Au complexes were also studied for electric potential sensing. The surface of the QDs was negatively charged due to thiol ligands capping. By applying a positive potential on the gold or gold nanoparticle attached substrate, the local electric field between the substrate and the statically charged QDs would pull the QDs closer to the gold surface and quench the QD PL. PL quenching of QD with Au was studied as a function of electric signal and QD type. In this methodology, electric signals were effectively converted to optical signals.