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Background and objectivesAnemia management changed substantially among dialysis patients in the United States around the time of implementation of the new Centers for Medicare & Medicaid Services bundled payment system and erythropoiesis-stimulating agent (ESA) label change in 2011. Among these, average ferritin levels increased dramatically and have remained high since; this study sought to gain understanding of this sustained rise in ferritin levels.Design, setting, participants, & measurementsTrends in mean ferritin, hemoglobin, IV iron dose, and ESA dose from 2009 to 2013 were examined in 9735 patients from 91 United States Dialysis Outcomes and Practice Patterns Study facilities. Linear mixed models were used to assess the extent to which intravenous (IV) iron and ESA dose accounted for patients' changes in ferritin over time.ResultsMean ESA dose and hemoglobin levels declined throughout the study. Mean IV iron dose increased from 210 mg/mo in 2009-2010 to a peak of 280 mg/mo in 2011, then declined back to 200 mg/mo and remained stable from 2012 to 2013. Mean ferritin increased from 601 ng/ml in the third quarter of 2009 to 887 ng/ml in the first quarter of 2012; models suggest that higher IV iron dosing was a primary determinant during 2011, but lower ESA doses contributed to the sustained high ferritin levels thereafter. In a subset of 17 facilities that decreased IV iron dose in 2011, mean ferritin rose by 120 ng/ml to 764 ng/ml, which appeared to be primarily due to ESA reduction. Together, changes in IV iron and ESA doses accounted for 46% of the increase in ferritin over the study period.ConclusionsIn contrast to expectations, the rise in average IV iron dose did not persist beyond 2011. The sustained rise in ferritin levels in United States dialysis patients after policy changes in 2011, to average levels well in excess of 800 ng/ml, appeared to be partly due to reductions in ESA dosing and not solely IV iron dosing practices. The effect of these changes in ferritin on health outcomes requires further investigation.

The UV absorption spectrum of all-trans-octatetraene is reinvestigated theoretically, focussing on the strongly dipole-allowed 1 A g – 1 B u transition. The dynamical calculations rely on ab initio multistate CASPT2 (MS-CASPT2) computations of the underlying potential energy surfaces and coupling elements, and the multiconfiguration time-dependent Hartree (MCTDH) method for solving the time-dependent Schrödinger equation for the nuclear motion. The vibronic structure of the absorption band near 2700 Å is well reproduced, better than ever before by a purely ab initio approach. The C–C single bond and C = C double bond stretching modes dominate the vibrational structure of the transition. While the latter resembles nearly harmonic motion on weakly coupled potential energy surfaces, the time-dependent calculations reveal a subpicosecond electronic population transfer from the 1 B u state to the lower-lying 2 A g state proceeding on a time scale of ∼ 50 fs . The details of this internal conversion process and its relation to the conical intersection between the two excited states are discussed, paying particular attention to the impact of the 1 B u – 2 A g energy gap on the dynamics. [ABSTRACT FROM AUTHOR]

Purpose: Mortality among first-year hemodialysis (HD) patients remains unacceptably high. To address this problem, we estimate the proportions of early HD deaths that are potentially preventable by modifying known risk factors., Methods: We included 15,891 HD patients (within 60 days of starting HD) from 21 countries in the Dialysis Outcomes and Practice Patterns Study (1996-2015), a prospective cohort study. Using Cox regression adjusted for potential confounders, we estimated the fraction of first-year deaths attributable to one or more of twelve modifiable risk factors (the population attributable fraction, AF) identified from the published literature by comparing predicted survival based on risk factors observed vs counterfactually set to reference levels., Results: The highest AFs were for catheter use (22%), albumin <3.5 g/dL (19%), and creatinine <6 mg/dL (12%). AFs were 5%-9% for no pre-HD nephrology care, no residual urine volume, systolic blood pressure <130 or ≥160 mm Hg, phosphorus <3.5 or ≥5.5 mg/dL, hemoglobin <10 or ≥12 g/dL, and white blood cell count >10,000/μL. AFs for ferritin, calcium, and PTH were <3%. Overall, 65% (95% CI: 59%-71%) of deaths were attributable to these 12 risk factors. Additionally, the AF for C-reactive protein >10 mg/L was 21% in facilities where it was routinely measured., Conclusion: A substantial proportion of first-year HD deaths could be prevented by successfully modifying a few risk factors. Highest priorities should be decreasing catheter use and limiting malnutrition/inflammation whenever possible., Competing Interests: Friedrich K Port has a consultancy contract with Arbor Research Collaborative for Health. Hal Morgenstern is consultant at Arbor Research Collaborative for Health. Takeshi Hasagawa has consulted for Kyowa Hakko Kirin, received research funding from JSPS KAKENHI (Grant Number 15K00877) and received speaker honoraria from Kyowa Hakko Kirin, Chugai Pharmaceutical, Torii Pharmaceutical, and Daiichi-Sankyo Pharmaceutical. Raymond Vanholder has received travel support and speaker’s honoraria from B. Braun and Nikisho. Michel Jadoul has served as a consultant for Astellas, MSD, Vifor Fresenius Medical Care Renal Pharma, received grant/research support from Amgen, Astra-Zeneca, Janssen-Cilag, MSD, Otsuka, Roche, been a speaker for AbbVie, Amgen, Menarini, MSD, Vifor Fresenius Medical Care Renal Pharma, received travel compensation from Amgen; all monies paid to institution including non-financial support from Sanofi-Genzyme, outside the submitted work. Elke Schaeffner reports speaker honorarium from Fresenius Medical Care, Fresenius Kabi, Siemens healthineers and grants from E.N.D.I foundation and DDnÄ, outside the submitted work. Angelo Karaboyas, Bruce M. Robinson, Ronald L Pisoni, Brian A. Bieber are employees of Arbor Research Collaborative for Health, which administers the DOPPS. Angelo Karaboyas reports grants from Akebia Therapeutics, Amgen, AstraZeneca, Bard Peripheral Vascular, Baxter Healthcare, Bayer Yakuhin, Chugai Pharmaceutical, Fresenius Medical Care Asia-Pacific, Japanese Society for Peritoneal Dialysis, JMS Co, Kidney Research UK, Kidney Foundation Japan, Kissei Pharmaceutical Co, Kyowa Kirin Co, MEDICE Arzneimittel Pütter GmbH & Co KG, Nikkiso, ONO Pharmaceutical Co, Sanofi-Aventis Deutschland GmbH, Terumo Corporation, Torii Pharmaceutical Co, Vifor-Fresenius Medical Care Renal Pharma Ltd, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2020 Karaboyas et al.)