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Aims To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit. Methods In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression. Results The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was −12% (25th to 75th percentile: −48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: −40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints). Conclusions The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm. [ABSTRACT FROM AUTHOR]

Aims of the Study: To obtain predictions for the course of the COVID-19 pandemic in Germany using the modified Bateman SIZ model and input variables based on the status quo in July 2020. To predict the effect of a change in t α on the course of the pandemic. To evaluate the robustness and sensitivity of the model in response to a change in the input parameters., Materials and Methods: Start parameters for the modified Bateman SIZ model were obtained from observational data published by the Robert-Koch-Institute in Berlin for the period June 1 to July 13, 2020. The robustness and sensitivity of the model were determined by changing the input parameter for the doubling-time (t α ) by ± 5% and ± 10%., Results: The predictions show that small changes, ± 5%, in the doubling-time, t α for the rate of increase in the number of new infections, can have a major effect, both positive and negative, on the course of the pandemic. The model predicted that the number of persons infected with the virus would reach 1 million within 8 years. A 5% longer t α would reduce the number of infected persons by ~ 75%. In contrast, a 5% shorter doubling-time would increase the number of infections over 8 years to ~ 9 million when the number of infectious persons would exceed 100,000 at the end of 2022. The pandemic is predicted to have disappeared by the end of 2024., Discussion: Predictions for the course of the COVID-19 pandemic in Germany based on the status quo up to July 13, 2020 have been obtained using the modified Bateman SIZ model. There are several important assumptions necessary to apply the model and thus the results must be interpreted with caution. The model, previously used to predict the course of the COVID-19 pandemic in the city of Heidelberg (pop. 166,000) gives comparable predictive data for the whole of Germany (pop. 83 million) and thus appears to be both sensitive and robust., Conclusion: Since a shorter doubling-time for the number of infectious persons by only 5% would result in a major clinical emergency, interventional measures such as vaccination are urgently needed. Taking into consideration that a SARS-CoV-2 vaccine is not yet available and the efficacy of the Corona-Warn-App has yet to be shown, a relaxation in the lockdown conditions in Germany in 2020 appears premature.

Aims of the Study: Published data show that the current progression of the COVID-19 pandemic in Heidelberg, Germany, despite the current lockdown, could continue into 2021 and become more severe. We have used the modified Bateman SIZ algorithm to predict the effects of interventional measures to control the COVID-19 pandemic., Materials and Methods: Model parameters, e.g., doubling time and rate of decrease in the number of infectious persons were obtained from published reports. Predictions were made for the status quo on June 1, 2020, and for interventional measures obtained for 4 scenarios. These included vaccination of the whole population using a SARS-CoV-2 vaccine having an efficacy of 50% and 100%, mass-testing for COVID-19 coronavirus and application of the Corona-Warn-App., Results: The principle findings were 1) without new measures to control the pandemic, the daily number of infectious persons could reach a peak of > 4,500 daily within 18 months when > 67,000 persons would have been infected. This could be prevented by using a vaccine with 50% efficacy which was almost equally effective as a vaccine with 100% efficacy. Application of the Corona-Warn-App was the most effective method and more effective than testing for COVID-19. The methodology used has been described in detail to enable other researchers to apply the modified Bateman SIZ model to obtain predictions for COVID-19 outbreaks in other regions. Application of the model has been verified by independent investigators using different commercial software packages., Conclusion: The modified Bateman SIZ model has been verified and used to predict the course of the COVID-19 pandemic in Heidelberg. Lockdown measures alone are insufficient to control the pandemic during 2021. Vaccination, diagnostic tests, and use of the Corona-Warn-App with quarantine could successfully control the spread of the coronavirus infection in the community. The Corona-Warn-App applied correctly may be the most effective. The model showed that vaccination with 50% efficacy is almost as effective as vaccination with 100% efficacy.

Background: Patients with impaired glucose tolerance have an elevated risk of cardiovascular (CV) death; however, the causes and risk factors associated with non-CV deaths are poorly understood., Methods: The NAVIGATOR trial enrolled 9,306 participants with impaired glucose tolerance and CV disease or at high CV risk, with a median follow-up of 6.4years. Using this population, we identified (1) the proportion of deaths attributed to CV, non-CV, and unknown causes, and (2) the risk factors associated with non-CV death., Results: During the NAVIGATOR trial follow-up, 622 patients died. Investigators reported 244 (39.2%) CV deaths, 313 (50.3%) non-CV deaths, and 65 (10.5%) deaths of unknown cause. Myocardial infarction was the leading cause of investigator-reported death (57/622 [9.2%]). Among non-CV deaths, the most commonly identified cause related to malignancy (177/313 [56.5%]). Using adjudicated causes of death, Cox proportional hazard models identified 3 independent prognostic markers that increased the risk of non-CV death: history of non-melanoma skin cancer (hazard ratio 2.67 [95% CI 1.65-4.33]; P<.0001), white blood cell count (1 unit >5000/mm 3 ; 1.10 [1.02-1.18]; P=.011), and serum potassium levels (per 1mmol/L above any value; 1.67 [1.302.15]; P<.0001)., Conclusions: Despite the high baseline CV risk among patients in the NAVIGATOR trial, the most common cause of death was non-CV. The high burden of non-CV death in this population has potential implications for future CV event-driven trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear., Methods: Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1β, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-γ (IFN-γ), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1β (MIP-1β) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels., Results: The presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-α, IL-6, IL-1β) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-γ) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas., Conclusions: These findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.