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    Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure ( FAIR ‐ HF2 ‐ DZHK05 ) trial: Baseline characteristics and comparison to other relevant clinical trials

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    Aims Prior randomized trials have reported conflicting evidence regarding the efficacy of intravenous (IV) iron in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID). Methods and results FAIR‐HF2 is a double‐blind, randomized, controlled trial evaluating the efficacy of IV ferric carboxymaltose in patients with HFrEF and ID. We report the baseline characteristics of enrolled patients and compare them with other major trials of IV iron in HFrEF (FAIR‐HF, CONFIRM‐HF, AFFIRM‐AHF, IRONMAN, and HEART‐FID). A total of 1105 patients were randomized between March 2017 and November 2023. Most patients were men (67%) and median age was 72 (interquartile range [IQR] 63–79) years. More than one‐third had a heart failure hospitalization within the preceding 12 months (36%), and 53% were hospitalized at randomization. Common comorbidities included hypertension (79%), coronary artery disease (74%), dyslipidaemia (67%), and diabetes (46%). The median left ventricular ejection fraction was 58% (IQR 42–77) and mean estimated glomerular filtration rate was 58 (IQR 42–77) ml/min/1.73 m 2 . A total of 1064 (96%) patients were on renin–angiotensin system inhibitors (angiotensin receptor–neprilysin inhibitors [ARNI] 38%), 1016 (92%) on beta‐blockers, and 779 (71%) on mineralocorticoid receptor antagonists; and 261 (24%) of patients were on sodium–glucose cotransporter 2 (SGLT2) inhibitors, which is much higher than prior trials. A higher proportion of patients had ischaemic HFrEF (78%) compared to preceding trials. The baseline median haemoglobin (g/dl) was 12.7 (IQR 11.8–13.4), median serum ferritin (μg/dl) was 63 (IQR 36–90), and median transferrin saturation (%) was 16.5 (IQR 11.8–22.9), resembling that of other trials. The mean 6‐min walk distance at enrolment was 314 ± 118 m. Conclusion The FAIR‐HF2 trial represents a contemporary cohort of patients with baseline characteristics mostly similar to prior trial populations. Use of SGLT2 inhibitors and ARNI in FAIR‐HF2 was higher than in prior trials. Clinical Trial Registration: ClinicalTrials.gov ID NCT03036462

    Rationale and design of the FAIR ‐ HF 2‐ DZHK 05 trial: Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure

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    Abstract Aims While it is widely accepted that intravenous (IV) iron improves functional capacity, symptoms, and cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) diagnosed with iron deficiency (ID), three recently published cardiovascular outcome trials (AFFIRM‐AHF, IRONMAN and HEART‐FID) of IV iron supplementation in HF failed to demonstrate a significant benefit on their respective primary endpoints. Dosing of IV iron after the initial correction of baseline ID – by design or as a result of trial circumstances – was relatively low (i.e. 1000 mg/year). The second objective of the study is to create prospective evidence for patients fulfilling the new definition of ID for patients with HF, i.e. for those with a transferrin saturation 16 mg/dl or serum ferritin >800 ng/ml are met on repeat visits. The trial will evaluate three primary hypotheses: (i) time to first event of cardiovascular death or hospitalization for HF, (ii) the rate of total (first and recurrent) HF hospitalizations (both analysed in the full study population), and (iii) the time to first event of cardiovascular death or hospitalization for HF in patients with a transferrin saturation <20% at baseline. The familywise type I error rate across the three primary endpoint hypotheses will be controlled using the Hochberg procedure (alpha 0.05). Conclusion The FAIR‐HF2 will evaluate the efficacy of FCM in patients with HFrEF in improving cardiovascular outcomes by utilizing a more aggressive approach towards iron supplementation ensuring prevention of transitional ID after initial repletion targets have been met

    Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer

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    Abstract Background Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. Objectives We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. Methods We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height 2 (women,  61 g/m 2 ; men,  74 g/m 2 ) and by presence of wasting syndrome with unintentional weight loss (BMI < 24 kg/m 2 and weight loss ≥ 5% in the prior 12 months). Repeat echocardiograms were obtained usually within 3–6 months for 85 patients. Results Patients in the lowest LVmass/height 2 tertile had higher plasma GH (median (IQR) for 1 st , 2 nd , and 3 rd tertile women, 1.8 (0.9–4.2), 0.8 (0.2–2.2), 0.5 (0.3–1.6) ng/mL, p  = 0.029; men, 2.1 (0.8–3.2), 0.6 (0.1–1.7), 0.7 (0.2–1.9) ng/mL, p  = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48–116), 72 (48–95), 49 (35–76) ng/mL, p  = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p  = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p  = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r  =  − 0.591, p  < 0.001; men, r  =  − 0.575, p  < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up ( r  =  − 0.318, p  = 0.003). Conclusion In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associated with a decrease in relative LVmass during follow-up. Graphical abstractDeutsches Zentrum für Herz-Kreislaufforschung http://dx.doi.org/10.13039/100010447Charité - Universitätsmedizin Berlin http://dx.doi.org/10.13039/50110000283

    Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency

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    Uncertainty remains about the effect of intravenous (i.v.) iron on outcomes for heart failure (HF) with iron deficiency. In the present study, we summarize the efficacy and safety of i.v. iron from six trials (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID and FAIR-HF2), including 7,175 patients. In comparison to prior analyses, this meta-analysis added new data from FAIR-HF2, used a harmonized and robust Bayesian approach and included individual participant data from five trials. Patients assigned to i.v. iron, compared with those assigned to placebo, had lower rates for the composite endpoint of recurrent HF hospitalizations and cardiovascular mortality at 12 months (risk ratio (RR) = 0.72 (95% confidence interval (CI) = 0.55-0.89)) and for the complete length of follow-up (RR = 0.81 (95% CI = 0.63-0.97)). Each component of the primary endpoint contributed to the beneficial effect of i.v. iron at both 12 months and the complete length of follow-up: recurrent HF hospitalizations (RR = 0.69 (95% CI = 0.48-0.88) and RR = 0.78 (95% CI = 0.55-0.98), respectively) and cardiovascular mortality (hazard ratio (HR) = 0.80 (95% CI = 0.61-1.03) and HR = 0.87 (95% CI = 0.73-1.04), respectively). All-cause mortality at 12 months and for the complete length of follow-up (HR = 0.82 (95% CI = 0.65-1.03)) and HR = 0.92 (95% CI = 0.80-1.07), respectively, indicated the overall safety of i.v. iron treatment. Treatment effects were greatest in the first year after randomization when the doses of i.v. iron provided are highest. These findings suggest that treating iron deficiency in patients with HF significantly reduces cardiovascular events and also suggests further investigation of optimal dosing of i.v. iron

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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