Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears

We analyzed cycles with periods, τ, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the τ range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) τ of 1.39 years; the 95% confidence interval (CI) of the τ extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a τ and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's τ overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a τ of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a τ with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly τ and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The τs are only candidate transyears; the 95% CIs of their τs overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's τ no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a τ between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities. © 2005 Elsevier SAS. All rights reserved

C. Mendel's Legacy

This paper reviews the development of chronobiology, the science (logos) of life (bios) in time (chronos), and of chronomics, against the background of Mendel's contributions far beyond genetics. In keeping with Mendel the meteorologist, we document for rhythms that light and food are not the only external switches. The "master switch", light, can be overridden more often and more critically than we visualize by feeding (3) or by a magnetic storm (4). Very important hypothalamic "oscillators" (5) are not the only internal mechanism of rhythms. Time structures, chronomes, reside in every biological unit, pro- or eukaryote, Figure 2 (6; cf. 5, 7). Chronomes in us have a strong genetic component which, in turn, entered the genome in response to environmental chronomes, explored meteorologically by Mendel. The more remote environmental origin of rhythms and their less remote genetic aspect both qualify biological chronomes as the legacy of Mendel the meteorologist as well as the geneticist. Our continued resonance with the environment renders an exophased endocycling even more interesting. The need for coordinated physical and biological monitoring, the topic of a project on The BIOsphere and the COSmos, briefly BIOCOS, to complement genomics, can also be viewed as the legacy of Mendel the meteorologist/cartographer. Some of Mendel's meteorological data were meta-chrono-analyzed. Mendel himself published more often on meteorology than on what became genetics. His legacies of paraphernalia are those of a meteorologist. Despite failing his examination for certification as a regular teacher in 1850 -- his lowest marks were in biology and geology (!) -- and although he reportedly never passed his teacher's license examination, Mendel started the science that distinguished the rules of dominant vs. recessive behavior and eventually led to the cloning of organisms and the debate about stem cells, again raising the question "What is life?" (1, 8, 9). Mendel is the de facto teacher par excellence of this generation of genomics, proteomics and nanochemistry by virtue of what became not only genetics but also chronomics in Brno. Our advocacy of education in instrumented self-help for chronobiologic literacy includes genetics and ecology, and qualifies as Mendelian. Chronobiologic literacy in everyday health care serves for the quantification of normalcy. By resolving chronomes in the normal range, we act positively rather than defining health negatively and only qualitatively (as the absence of disease, i.e., of deviations outside that range) summarized as % morbidity and % mortality only for a population, not for the individual. From these several viewpoints that have as a common denominator focus upon the usual, we view Johann Gregor Mendel as a chronobiologist. We view chronobiology in a broad perspective of its now thoroughly documented roots in our genes and via our genome in the cosmoi, as they were when and where life began and as they changed from then to now. Evolution, ecology, genetics and chemistry, the legacies of Darwin, Haeckel, Mendel and Lavoisier respectively, and their transdisciplinary fusion by Brückner, Egeson, Norman Lockyer, W.J.S. Lockyer, Chizhevsky and Vernadsky in the spirit of Dokuchaev, like everything else, occur in time. They are part and parcel of chronobiology and of a much broader temporal perspective from chronomics, an overdue transdisciplinary cartography of the as-yet unknown

Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears

We analyzed cycles with periods, τ, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the τ range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) τ of 1.39 years; the 95% confidence interval (CI) of the τ extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a τ and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's τ overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a τ of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a τ with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly τ and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The τs are only candidate transyears; the 95% CIs of their τs overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's τ no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a τ between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities. © 2005 Elsevier SAS. All rights reserved

Unseen space weather also relates to cardiac events

[No abstract available

Unseen space weather also relates to cardiac events

[No abstract available