Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration : A Novel Regression Analysis to Capture the Bilateral Nature of the Disease

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited

Functional evolution of nuclear structure

The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis

The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-016-0367-9">https://link.springer.com/article/10.1007/s12325-016-0367-9</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Nuclear actin: ancient clue to evolution in eukaryotes?

Until recently it was widely accepted that the dynamic cytoskeletal matrix is exclusive to the cytoplasm of eukaryotes, evolving before the emergence of the cell nucleus to enable phagocytosis, cell motility and the sophisticated functioning of the endomembrane system within the cytosol. The discovery of the existence of a prokaryotic cytoskeleton has changed this picture significantly. As a result, the idea has taken shape that the appearance of actin occurred in the very first cell; therefore, the emergence of microfilaments precedes that of the eukaryotic cytoskeleton. The discovery of nuclear actin opened new perspective on the field, suggesting that the nuclear activities of actin reflect the functions of primordial actin-like proteins. In this paper, we review the recent literature to explore the evolutionary origin of nuclear actin. We conclude that both ancient and eukaryotic features of the actin world can be detected in the nucleus today, which supports the idea that the cytoskeleton attained significant eukaryotic innovations before the tandem evolution of the cytoskeleton and nucleus occurred