Rationale and design of the IRON-AF study: a double-blind, randomised, placebo-controlled study to assess the effect of intravenous ferric carboxymaltose in patients with atrial fibrillation and iron deficiency

Introduction: Atrial fibrillation (AF) is associated with significantly impaired quality-of-life. Iron deficiency (ID) is prevalent in patients with AF. Correction of ID in other patient populations with intravenous iron supplementation has been shown to be a safe, convenient and effective way of improving exercise tolerance, fatigue and quality-of-life. The IRON-AF (Effect of Iron Repletion in Atrial Fibrillation) study is designed to assess the effect of iron repletion with intravenous ferric carboxymaltose in patients with AF and ID. Methods and Analysis: The IRON-AF study is a double-blind, randomised controlled trial that will recruit at least 84 patients with AF and ID. Patients will be randomised to receive infusions of either ferric carboxymaltose or placebo, given in repletion and then maintenance doses. The study will have follow-up visits at weeks 4, 8 and 12. The primary endpoint is change in peak oxygen uptake from baseline to week 12, as measured by cardiopulmonary exercise testing (CPET) on a cycle ergometer. Secondary endpoints include changes in quality-of-life and AF disease burden scores, blood parameters, other CPET parameters, transthoracic echocardiogram parameters, 6-minute walk test distance, 7-day Holter/Event monitor burden of AF, health resource utilisation and mortality. Ethics and dissemination: The study protocol has been approved by the Central Adelaide Local Health Network Human Research Ethics Committee, Australia. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.Samuel J Tu, Adrian D Elliott, Nicole Hanna-Rivero, Celine Gallagher, Ricardo S Mishima, Ellen Lyrtzis, Danielle Wlochowicz, Nicholas AR Clarke, Kurt C Roberts-Thomson, Michael B Stokes, Mehrdad Emami, Dennis H Lau, Prashanthan Sanders, Christopher X Won

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Anemia and iron deficiency in patients with atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions.Nicole Hanna, Rivero, Samuel J. Tu, Adrian D. Elliott, Bradley M. Pitman, Celine Gallagher, Dennis H. Lau, Prashanthan Sanders, and Christopher X. Won

Associations of anaemia with stroke, bleeding, and mortality in atrial fibrillation: a systematic review and meta-analysis

BACKGROUND: Anaemia frequently co-exists with atrial fibrillation (AF) and has been variably associated with worse outcomes. We performed a systematic review and meta-analysis to comprehensively assess the effect of anaemia on mortality, stroke/systemic thromboembolism and bleeding events in patients with AF. METHODS: MEDLINE and Embase were searched from inception until May 2020. Studies examining associations of anaemia with the above outcomes in AF patients were included, and maximally adjusted hazard ratios (HRs) meta-analysed. PROSPERO registration number CRD42020171113. RESULTS: Twenty-eight studies involving 365,484 patients (41% female, mean age 74.7 years) were included. The average study follow-up ranged from 0.2 to 4.0 years, and prevalence of anaemia was 16%. Anaemia was associated with a 78% increase in all-cause mortality (HR 1.78, 95% CI 1.44-2.20), 60% increase in cardiovascular mortality (HR 1.60, 95% CI 1.17-2.19), 134% increase in non-cardiovascular mortality (HR 2.34, 95% CI 1.58-3.47) 15% increase in stroke/systemic thromboembolism (HR 1.15, 95% CI 1.01-1.31), 78% increase in major bleeding (HR 1.78, 95% CI 1.54-2.05), and 77% increase in gastrointestinal bleeding (HR 1.77, 95% CI 1.23-2.55). Sensitivity analyses including studies that reported odds ratios did not result in any material change. CONCLUSION: Anaemia is a frequently observed comorbidity in patients with AF, and is associated with an increased risk of all-cause, cardiovascular and non-cardiovascular mortality, stroke/systemic thromboembolism, and major and gastrointestinal bleeding. Future studies are required to explore the causes of anaemia in AF, and whether investigation and treatment may be clinically beneficial in affected individuals. This article is protected by copyright. All rights reserved.Samuel J. Tu, Nicole Hanna‐Rivero, Adrian D. Elliott, Nicholas Clarke, Sonia Huang, Bradley M. Pitman … et al

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer

Available online 29 April 2022Abstract not availableHidde M. Kroon, Lotje A. Hoogervorst, Nicole Hanna-Rivero, Luke Traeger, Nagendra N. Dudi-Venkata, Sergei Bedrikovetski, Miranda Kusters, George J. Chang, Michelle L. Thomas, Tarik Sammou

Trends in the use, complications and costs of permanent pacemakers in Australia: a nationwide study from 2008-2017

OBJECTIVE: To characterise contemporary pacemaker procedure trends. METHODS: Nationwide analysis of pacemaker procedures and costs between 2008-2017 in Australia. The main outcome measures were total, age- and gender-specific implant, replacement and complication rates and costs. RESULTS: Pacemaker implants increased from 12,153 to 17,862. Implantation rates rose from 55.3 to 72.6 per 100,000, a 2.8% annual increase (incidence rate ratio [IRR] 1.028; 95% CI, 1.02-1.04; p<0.001). Pacemaker implants in the 80+ age group were 17.37-times higher than the <50 group (95% CI 16.24-18.59; p<0.001), and in males were 1.48-times higher than in females (95% CI 1.42-1.55; p<0.001). However, there were similar increases according to age (p = 0.10) and gender (p = 0.68) over the study period. Left ventricular lead rates were stable (IRR 0.995; 95% CI 0.98-1.01; p = 0.53). Generator replacements decreased from 20.5 to 18.3 per 100,000 (IRR 0.975; 95% CI 0.97-0.98; p<0.001). Although procedures for generator-related complications were stable (IRR 0.995; 95% CI 0.98-1.01; p = 0.54), those for lead-related complications decreased (IRR 0.985; 95% CI 0.98-0.99; p<0.001). Rates for all pacemaker procedures were consistently greater in males (p<0.001). Although annual costs of all pacemaker procedures increased from $178 million to$329 million, inflation-adjusted costs were more stable, rising from $294 million to$329 million. CONCLUSIONS: Increasing demand for pacemaker implants is driven by the ageing population and rising rates across all ages, while replacement and complication procedure rates appeared more stable. Males have consistently greater pacemaker procedure rates than females. Our findings have significant clinical and public health implications for healthcare resource planning. This article is protected by copyright. All rights reserved.Samuel Westaway, Elsbeth Nye, Celine Gallagher, Samuel J. Tu, Nicholas Clarke, Nicole Hanna-Rivero ... et al

Predictors of anticoagulation use in indigenous and non-indigenous Australians with atrial fibrillation

OBJECTIVE:Prior studies have demonstrated that anticoagulation underutilisation for atrial fibrillation (AF) and elevated stroke risk is common. However, there is little data on factors associated with appropriate anticoagulation, particularly in Indigenous Australians who face a disproportionate burden of AF and stroke. We thus sought to determine factors associated with anticoagulation use in Australians with AF. DESIGN:Administrative, clinical, prescriptive and laboratory data were linked and aggregated over a 12-year period. SETTING:Single tertiary teaching hospital. PARTICIPANTS:19,305 (98%) and 308 (2%) consecutive non-Indigenous and Indigenous Australians with AF identified from administrative databases. MAIN OUTCOME MEASURES:Associations of anticoagulation use according to ethnicity. RESULTS:Significant independent predictors of anticoagulation use included hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.17-1.34; p<0.001), diabetes (OR 1.14, 95% CI 1.05-1.24; p=0.002), heart failure (OR 1.54 95% CI 1.43-1.66; p<0.001) and prior stroke or transient ischaemic attack (OR 2.07, 95% CI 1.84-2.33; p<0.001). In contrast, increasing age (OR 0.99, 95% CI 0.98-0.99; p<0.001), female gender (OR 0.88, 95% CI 0.82-0.93; p<0.001), and vascular disease (OR 0.72, 95% CI 0.64-0.80; p<0.001) were significant predictors of no anticoagulation. Hypertension was associated with less anticoagulation use in Indigenous compared to non-Indigenous Australians (p=0.02). CONCLUSIONS:Anticoagulation for AF was suboptimal in both Indigenous and non-Indigenous Australians. Older age, female gender, and comorbid vascular disease were found to be negatively associated with anticoagulation. Importantly, hypertension may also be under-recognised as a stroke risk factor in Indigenous Australians. Future efforts to encourage anticoagulation use in accordance with guideline recommendations is likely to reduce the burden of AF-related stroke in both Indigenous and non-Indigenous populations.Simon Rocheleau, Celine Gallagher, Bradley M. Pitman, Samuel J. Tu, Nicole Hanna-Rivero, Nicholas Clarke ... et al