Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

<p>Abstract</p> <p>Background</p> <p>Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs.</p> <p>Methods</p> <p>This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation.</p> <p>Results</p> <p>For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks.</p> <p>Conclusions</p> <p>For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide additional, complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies.</p

Spectroscopy of formaldehyde in the 30140-30790cm^-1 range

Room-temperature absorption spectroscopy of formaldehyde has been performed in the 30140-30790cm^-1 range. Using tunable ultraviolet continuous-wave laser light, individual rotational lines are well resolved in the Doppler-broadened spectrum. Making use of genetic algorithms, the main features of the spectrum are reproduced. Spectral data is made available as Supporting Information

Design and Key Features of the PIAAC Survey of Adults

This chapter gives an overview of the most important features of the Programme for the International Assessment of Adult Competencies (PIAAC) survey as it pertains to two main goals. First, only a well-designed survey will lead to accurate and comparable test scores across different countries and languages both within and across assessment cycles. Second, only an understanding of its complex survey design will lead to proper use of the PIAAC data in secondary analyses and meaningful interpretation of results by psychometricians, data analysts, scientists, and policymakers. The chapter begins with a brief introduction to the PIAAC survey followed by an overview of the background questionnaire and the cognitive measures. The cognitive measures are then compared to what was assessed in previous international adult surveys. Key features of the assessment design are discussed followed by a section describing what could be done to improve future PIAAC cycles

Emerging Pharmacotherapies for Adult Patients with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) treatment regimes are amongst the longest, most intensive and complex used in hematooncology. Despite this, while treatment of pediatric ALL is a success story, we are far from being able to ensure a durable response in adult ALL. This is not due to failure of induction therapy as a complete remission (CR) is achieved in over 90% of patients. However the challenge remains in ensuring a sustained remission. Furthermore in the face of relapsed disease, salvage therapies currently offer a poor chance of a good outcome. This article reviews the novel agents which show the most promise in the treatment of adult ALL

Final Report for DOE Project: Portal Web Services: Support of DOE SciDAC Collaboratories

Grid portals provide the scientific community with familiar and simplified interfaces to the Grid and Grid services, and it is important to deploy grid portals onto the SciDAC grids and collaboratories. The goal of this project is the research, development and deployment of interoperable portal and web services that can be used on SciDAC National Collaboratory grids. This project has four primary task areas: development of portal systems; management of data collections; DOE science application integration; and development of web and grid services in support of the above activities

Impact of polystyrene microplastics on Daphnia magna mortality and reproduction in relation to food availability

Microplastics (MPs) in the environment continue to be a growing area of concern in terms of acute and chronic impacts on aquatic life. Whilst increasing numbers of studies are providing important insights into microparticle behaviour and impacts in the marine environment, a paucity of information exists regarding the freshwater environment. This study focusses on the uptake, retention and the impact of 2µm polystyrene MPs in the freshwater cladoceran Daphnia magna in relation to food intake (algae Chlorella vulgaris), with MP size chosen to approximately match the cell size of the algae. Daphnia were exposed to varied concentrations of MPs and algae. When exposed to a single concentration of MPs Daphnia almost immediately ingested them in large quantities. However, the presence of algae, even at low concentrations, had a significant negative impact on MP uptake that was not in proportion to relative availability. As MP concentrations increased, intake did not if algae were present, even at higher concentrations of MPs. This suggests that Daphnia are selectively avoiding ingesting plastics. Adult Daphnia exposed to MPs for 21 days showed mortality after 7 days of exposure in all treatments compared to the control. However significant differences were all related to algal concentration rather than to MP concentration. This suggests that where ample food is present, MPs have little effect on adults. There was also no impact on their reproduction. The neonate toxicity test confirmed previous results that mortality and reproduction was linked to availability of food rather than MP concentrations. This would make sense in light of our suggestion that Daphnia are selectively avoiding ingesting microplastics

Degeneracy: a link between evolvability, robustness and complexity in biological systems

A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology. This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present evidence that degeneracy is a fundamental source of robustness, it is intimately tied to multi-scaled complexity, and it establishes conditions that are necessary for system evolvability

Efecto del SASP de células tumorales sobre monocitos y macrófagos

67 p.El cáncer gástrico es un adenocarcinoma que se diferencia según su histología en intestinal que afecta principalmente a hombres y difuso que afecta más a jóvenes, es una patología con elevada incidencia en nuestro país, que comienza como un cuadro de gastritis y termina como cáncer invasivo mortal. Nuestro sistema inmune detecta células tumorales e incluso las puede eliminar, pero existen ocasiones donde se suprime el sistema inmune, ya que la carcinogénesis altera el genoma y mecanismo celulares, por lo que se pierda la capacidad de respuesta antitumoral o su eliminación tumoral respectivamente. La senescencia es la pérdida irreversible de la capacidad proliferativa de células que se mantienen en un estado metabólicamente activo, es inducida por el acortamiento de los telómeros o por respuesta al estrés. Estas células presentan cambios morfológicos, aumento de ciertas proteínas, como la p16INK4a que es usado como marcador de senescencia celular. También producen fenotipo secretor asociado a senescencia (SASP, senescent-associated secretory phenotype), que es un conjunto de factores de señalización solubles o proteínicos y componentes insolubles o no proteínicos; las células que pertenecen a este fenotipo estimulan la eliminación de células envejecidas o bien, mantienen, incluso exacerban el estado senescente. Los macrófagos son células del sistema fagocítico mononuclear (SFM), forman parte de la inmunidad innato. Su polarización ocurre durante la inflamación, esta puede ser hacia M1 (microbicida) o M2 (antiinflamatorio) dependiendo de la cantidad y el tiempo que se expongan a las citocinas y los factores que se activen. El efecto pleiotropico y las características del microambiente tumoral son cruciales para la proliferación de los macrófagos asociados a tumor y su fenotipo en senescencia