Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS: The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. CONCLUSIONS: This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.

Complement activation in polycystic ovary syndrome occurs in the postprandial and fasted state and is influenced by obesity and insulin sensitivity.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with metabolic risk. Complement proteins regulate inflammation and lipid clearance but their role in PCOS-associated metabolic risk is unclear. We sought to establish whether the complement system is activated in PCOS in the fasting and postprandial state. DESIGN: Case-control study. PATIENTS: Fasting complement levels were measured in 84 women with PCOS and 95 healthy controls. Complement activation post-oral fat tolerance test (OFTT) was compared in 40 additional subjects (20 PCOS, 20 controls). MEASUREMENTS: Activation pathway (C3, C4, C3a(desArg), factor B, factor H, properdin, Factor D) and terminal pathway (C5, C5a, terminal complement complex [TCC]) proteins were measured by commercial or in-house assays. RESULTS: Fasting C3, C3a(desArg) and TCC concentrations were increased in insulin-resistant (adjusted differences: C3 0.13 g/L [95%CI 0-0.25]; C3a(desArg) 319.2 ng/mL [19.5-619]; TCC 0.66 µg/mL [0.04-1.28]) but not in insulin-sensitive women with PCOS. C3 and factor H levels increased with obesity. Post-OFTT, C3 and C4 levels increased to a similar extent in PCOS subjects and controls, whist factor H levels increased more in women with PCOS compared to controls (adjusted differences (area under the curve): 12 167 µg min/mL [4942-19 392]), particularly in the presence of concomitant obesity. CONCLUSIONS: Activation and terminal complement pathway components are elevated in patients with PCOS, especially in the presence of insulin resistance and obesity.

An improved cell-permeable fluorogenic substrate as the basis for a highly sensitive test for NAD(P)H quinone oxidoreductase 1 (NQO1) in living cells.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme upregulated in response to oxidative stress and in some cancers. Its upregulation by compounds has been used as an indicator of their potential anti-cancer properties. In this study we have designed, produced and tested a fluorogenic coumarin conjugate which selectively releases highly fluorescent 4-methylumbelliferone (4-MU) in the presence of NQO1. It was found that measuring 4-MU release rapidly and specifically quantitated NQO1 levels in vitro and in live cells. Both the substrate and its products freely perfused through cell membranes and were non-toxic. The substrate was very specific with low background, and the assay itself could be done in less than 10minutes. This is the first assay to allow the quantitation of NQO1 in live cells which can then be retained for further experiments.