Real-World Persistence and Treatment Interval in Patients with Diabetic Macular Edema Treated with Anti-Vascular Endothelial Growth Factors in the USA.

INTRODUCTION: There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24 months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA. METHODS: This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan® Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6 months prior to their first anti-VEGF treatment and for a duration of at least 24 months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24 months of treatment. Discontinuation rate beyond 24 months and its association with treatment intervals at 24 months was estimated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The overall discontinuation rate among the 1702 eligible patients from 24 to 60 months after treatment initiation was 30%. At 60 months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95% CI 1.43, 2.82], p < 0.001). CONCLUSION: Patients with DME on longer anti-VEGF treatment intervals at 24 months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals.

Anti-Vascular Endothelial Growth Factor Treatment Discontinuation and Interval in Neovascular Age-Related Macular Degeneration in the United States.

PURPOSE: To assess the association between treatment interval and likelihood of anti-vascular endothelial growth factor (anti-VEGF) discontinuation among patients with neovascular age-related macular degeneration (nAMD) in a real-world setting in the United States. DESIGN: Retrospective clinical cohort study. METHODS: Health insurance claims data from the IBM MarketScan Commercial and Medicare Supplemental databases were retrospectively reviewed to identify adults with nAMD who received anti-VEGF for the first time between July 1, 2011, and June 30, 2017. The proportion of discontinued patients was analyzed using Kaplan-Meier curves. Cox proportional hazards models were used to examine the association between treatment intervals at 24 months and anti-VEGF discontinuation. RESULTS: The analysis included 8167 patients on continuous, unilateral anti-VEGF treatment for at least 24 months. Baseline demographics and clinical characteristics were well balanced between treatment interval groups. The overall rate of discontinuation from 24 months until 60 months after treatment initiation was 30.4%. At 60 months, patients on shorter treatment intervals were more likely to remain on treatment than those on longer intervals, ranging from 76.8% (4-week interval group) to 60.6% (>12-week interval group) and corresponding to a 28% lower likelihood (HR [SE] 0.72 [0.12], P < .01) and 55% higher likelihood of discontinuing treatment (HR [SE] 1.55 [0.07], P < .01), respectively, compared with the 8-week group. CONCLUSIONS: nAMD patients on longer anti-VEGF treatment intervals at 24 months had consistently higher discontinuation rates than patients on shorter intervals in the following years. This highlights the need to support and educate patients on long treatment intervals to continue with their treatment.

Histidine methyltransferase SETD3 methylates structurally diverse histidine mimics in actin.

Actin histidine Nτ -methylation by histidine methyltransferase SETD3 plays an important role in human biology and diseases. Here, we report integrated synthetic, biocatalytic, biostructural, and computational analyses on human SETD3-catalyzed methylation of actin peptides possessing histidine and its structurally and chemically diverse mimics. Our enzyme assays supported by biostructural analyses demonstrate that SETD3 has a broader substrate scope beyond histidine, including N-nucleophiles on the aromatic and aliphatic side chains. Quantum mechanical/molecular mechanical molecular dynamics and free-energy simulations provide insight into binding geometries and the free energy barrier for the enzymatic methyl transfer to histidine mimics, further supporting experimental data that histidine is the superior SETD3 substrate over its analogs. This work demonstrates that human SETD3 has a potential to catalyze efficient methylation of several histidine mimics, overall providing mechanistic, biocatalytic, and functional insight into actin histidine methylation by SETD3.

Life events and donor lapse among blood donors in Denmark.

BACKGROUND AND OBJECTIVES: The likelihood of donating blood changes over the life course, with life events shown to influence entry to and exit from the donor population. While these previous findings provide valuable insights for donor management, blood collection agencies need to be cautious about generalizing findings to other countries as blood donor behaviour is context-specific. To examine cross-country variations in donor behaviour, the repeatability of a previous Dutch study on life events and blood donor lapse is examined by using a sample of Danish donors. MATERIALS AND METHODS: Register data from Statistics Denmark was linked to the Scandinavian Donations and Transfusions database (n = 152 887). Logistic regressions were conducted to examine the association between life events in 2009-2012 and blood donor lapse in 2013-2014. RESULTS: Of the total sample, 69 079 (45·2%) donors lapsed. Childbirth and losing a job increased the lapsing risk by 11% and 16%, respectively, while health-related events in the family (i.e. blood transfusion, disease and death) decreased the lapsing risk by 5%, 7% and 9%, respectively. CONCLUSION: Life events are associated with donor lapse of Danish donors. These results are comparable to previous findings from the Netherlands (i.e. childbirth and labour market transitions increased lapsing risk; health-related events decreased lapsing risk), with two thirds of the associations being in the same direction. Differences between study results were mainly related to effect sizes and demographic compositions of the donor pools. We argue contextual factors to be of importance in blood donor studies.

DBDS Genomic Cohort, a prospective and comprehensive resource for integrative and temporal analysis of genetic, environmental and lifestyle factors affecting health of blood donors.

PURPOSE: To establish a cohort that enables identification of genomic factors that influence human health and empower increased blood donor health and safe blood transfusions. Human health is complex and involves several factors, a major one being the genomic aspect. The genomic era has resulted in many consortia encompassing large samples sizes, which has proven successful for identifying genetic factors associated with specific traits. However, it remains a big challenge to establish large cohorts that facilitate studies of the interaction between genetic factors, environmental and life-style factors as these change over the course of life. A major obstacle to such endeavours is that it is difficult to revisit participants to retrieve additional information and obtain longitudinal, consecutive measurements. PARTICIPANTS: Blood donors (n=110 000) have given consent to participate in the Danish Blood Donor Study. The study uses the infrastructure of the Danish blood banks. FINDINGS TO DATE: The cohort comprises extensive phenotype data and whole genome genotyping data. Further, it is possible to retrieve additional phenotype data from national registries as well as from the donors at future visits, including consecutive measurements. FUTURE PLANS: To provide new knowledge on factors influencing our health and thus provide a platform for studying the influence of genomic factors on human health, in particular the interaction between environmental and genetic factors.

A Perceptual Illusion of Empty Space Can Create a Perceptual Illusion of Levitation.

A recent analysis of magic tricks suggests the existence of a perceptual illusion where the space hidden behind an occluding object is experienced as empty in a strangely compelling way. Here, we show that this illusion of absence is not just a trivial consequence of the lack of retinal stimulation but rather the result of an active process of perceptual construction. The results of a simple experiment show that this perceptual illusion of absence can in turn trigger perceptual processes which generate an immediate perceptual impression of levitation via a percept-percept coupling. This suggests that magical illusions of levitation are partially driven by an immediate perceptual impression of floating in thin air. The perceptual mechanisms underlying the illusion of absence are hitherto unknown, but our results provide support for a potential explanation based on the generic view principle.