One-Year Mortality After Intensification of Outpatient Diuretic Therapy

One-Year Mortality After Intensification of Outpatient Diuretic Therapy

Background The increased mortality after hospitalization for decompensated heart failure (HF), where diuretics are usually intensified. It is not clear how risk is affected after the intensification outpatient diuretic therapy for HF.

Methods and Results From the national administrative registers, we identified all patients diagnosed with HF Denmark 2001-2016 and received an angiotensin-converting enzyme inhibitors / angiotensin receptor blockers and β-blockers within 120 days. Next follow-up tracked events progressive intensification diuretic and HF hospitalization. Intensification of events defined as a new addition or doubling of the loop diuretics or thiazide diuretics increase the loop. This event is included in the multivariable Cox regression models, calculating the danger of death one year after each year since inclusion.

Patients with intensification events or hospitalizations set risk-adjusted with two control HF nonworsened and 1 year absolute risk of death was calculated using Kaplan-Meier estimates. We included 74 990 patients, their average age was 71 years, and 36% are women. Intensification of events associated with a significantly increased mortality at any time during follow-up. one-year mortality was 18.0% after the intensification, 22.6% after HF hospitalization, and 10.4% for the control fits nicely.

In multivariable Cox models adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for death of 1 year after the intensification of events was 1.75 (95% CI, 1.66 to 1 , 85), and it was 2.28 (95% CI, 2.16 to 2.41) after HF hospitalization. Conclusion In a nationwide cohort of patients with HF, outpatient intensification events associated with almost 2-fold risk of mortality over the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in an outpatient setting is a signal to review and intensify its efforts to improve HF outcomes.

 One-Year Mortality After Intensification of Outpatient Diuretic Therapy
One-Year Mortality After Intensification of Outpatient Diuretic Therapy

Perfusion approach an alternative to intensification of Virus-Like Particle Production in HEK293 Culture

Virus-like particles (VLP) has gained interest over the last year as the format of a recombinant vaccine, because they produce a strong immune response and the storage and distribution of present advantages over conventional vaccines. Therefore, VLP vaccine is being considered as a potential candidate for several diseases. One of the requirements for further clinical testing they are scalable and platform development process for the production of cell-based viral particles.

In this work, methods of gene expression extended (EGE), which consists in the replacement of the media that successive combined with retransfections cells, successfully optimized and transferred to the perfusion bioreactor operation. An optimization process using design of experiments (DoE) was conducted to obtain the optimal value for the current retransfection, a certain degree of perfusion cell (CSPR) and the concentration of transfected DNA, increasing 86.7% as previously reported in HEK293 EGE protocol.

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In addition, it has been successfully applied in 1.5L bioreactor using the ATF as a cell retention system reaches a concentration of 6.8 · 1010 VLP / mL. VLP interaction with hollow fiber ATF studied through confocal microscopy, field emission scanning electron microscope, and nanoparticle tracking analysis for designing bioprocess able to separate monomer and unassembled Gag VLP concentrate in one step.

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