Packer M, Bristow MR, Cohn JN, et al. Int. For primary prevention, anticoagulants can substantially reduce risk of thromboembolism. Several studies have performed propensity score analysis in order to increase the comparability of patient characteristics between digoxin-treated and untreated patients. On the other hand, other analyses have reported different results [10-12]. Fisher LD, Lin DY. MacLeod-Glover N., Mink M., Yarema M., Chuang R. Digoxin toxicity: Case for retiring its use in elderly patients? This activity . Whitbeck M.G., Charnigo R.J., Khairy P., et al. Patients with tissue valve or mitral valve repair can still be considered for DOAC. In addition, recent reports suggest increased mortality in patients with atrial fibrillation without . After a very sophisticated analysis, they showed a significant dose-response curve between serum digoxin levels and mortality: for each 0.5-ng/mL increase in the former, there was a 19% increase in mortality. A nationwide population-based cohort study. An official website of the United States government. sharing sensitive information, make sure youre on a federal government site. Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors. See NHSGGC guidelines on StaffNet. A proposal for new clinical concepts in the management of atrial fibrillation. Before 2012 Oct;105(10):507-16. doi: 10.1016/j.acvd.2012.06.004. Freitas CS, Lage DP, Oliveira-da-Silva JA, Costa RR, Mendona DVC, Martins VT, Reis TAR, Antinarelli LMR, Machado AS, Tavares GSV, Ramos FF, Brito RCF, Ludolf F, Chvez-Fumagalli MA, Roatt BM, Ramos GS, Munkert J, Ottoni FM, Campana PRV, Duarte MC, Gonalves DU, Coimbra ES, Braga FC, Pdua RM, Coelho EAF. Since its isolation in the 1930s, digoxin has played a pivotal role in the treatment of cardiac conditions including heart failure and supraventricular tachyarrhythmias. Li S-J, Sartipy U, Lund LH, et al. (22). A resting 12-lead ECG confirms diagnosis, shows the ventricular rate, may indicate presence of structural heart disease. In the last two decades, several studies have correlated therapeutic use of digoxin with increased mortality. Rohde L.E.P., Montera M.W., Bocchi E.A., et al. However, the Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient versus Strict Rate Control II (RACE II) study showed that, compared with strict rate control, lenient rate control was not inferior in terms of preventing major clinical events. -, Hallberg P., Lindbck J., Lindahl B., Stenestrand U., Melhus H. Digoxin and mortality in atrial fibrillation: A prospective cohort study. Prognostic significance of resting heart rate and use of -blockers in atrial fibrillation and sinus rhythm in patients with heart failure and reduced ejection fraction: findings from the Swedish Heart Failure Registry. II diretrizes brasileiras de fibrilao atrial. Eur J Clin Pharmacol. Doses may need to be reduced in some patients who have either low body weight (60kg), renal impairment or age 80 years and another risk factor. Digoxin and mortality in atrial fibrillation: a prospective cohort study. Gheorghiade M., Fonarow G.C., van Veldhuisen D.J., et al. Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation. Camm AJ, Al-Khatib SM, Calkins H, et al. Although current U.S. [44] and European guidelines [45] do not specifically recommend measuring serum digoxin levels in patients with AF, it will not come as a surprise to us if they include such procedure in their next updates. Based on values and preferences, rate control therapy most often includes a beta-blocker, but should be individualised on the basis of the type and severity of underlying structural heart disease, the activity level of the patient and other individual considerations. Sophie Rushton-Smith (Medlink Healthcare Communications Ltd) provided editorial assistance with editing the final version and was funded by the authors. Study design: Ferrari F; Data collection: Ferrari F, Stein R; Analysis and interpretation of data, manuscript writing: Ferrari F, Santander IRMF, Stein R; Critical review of the manuscript for important intellectual content: Stein R. Hospital de Clnicas de Porto Alegre Research and Event Incentive Fund (FIPE-HCPA), Brazilian Research Council (CNPq). eCollection 2022. This regime involves 2mg being given daily for 2 weeks with once weekly monitoring. For an overview of the management of AF Persistent see above under 'Therapeutic', and for Recent Onset AF and Flutter see here. The primary goals of rate control are to improve symptoms and prevent deterioration of cardiac function associated with excessively rapid ventricular rates during AF. Vhody smoothies zvisia od toho, o do nich dte. Al-Zakwani et al. Epub 2021 Jul 3. An ancillary trial included 988 patients with preserved ventricular function (i.e., ejection fraction greater than 45 percent). Cardiac glycosidesincluding digoxinhave been used for centuries to treat patients with heart disease, including those with atrial fibrillation. Lopes R.D., Rordorf R., De Ferrari G.M., et al. Differential effects of carvedilol and metoprolol succinate on plasma norepinephrine release and peak exercise heart rate in subjects with chronic heart failure. Wasserstrom JA, Aistrup GL. Camm AJ, Kirchhof P, Lip GYH, et al. Vamos M, Erath JW, Hohnloser SH. For choice see guidance above. Withering W. An account of the foxglove and some of its medical uses, with practical remarks on dropsy, and other diseases. [52] From an ethical perspective, it might be difficult today to carry out a large randomised trial with digoxin for rate control, as there are other adequate treatments. Cautions include: recurrent falls e.g. For many years, digitalis has been widely used in the treatment of heart failure (HF), owing to its cardiotonic and neurohormonal effects and atrial fibrillation (AF), due to its parasympathomimetic effect on AV node (Table 2) ().The increased contractility of the heart result in increased cardiac output and a subsequent reduction of ventricular filling pressure, which favors patients with HF. The results of this analysis suggest that beta-blockers are unlikely to be harmful for AF patients with HF and reduced EF, but the prognostic benefits of beta-blockers have consequently been questioned for patients with HF and AF. Recommendations for the use of digoxin in the clinical management of atrial fibrillation by different societies. Adding aspirin to warfarin in AF does not reduce the risk of stroke (except with prosthetic heart valves) but substantially increases the risk of bleeding. Received 2015 Dec 5; Accepted 2016 Jan 21. Hohnloser SH, Halperin JL, Camm AJ, et al. However, the unique pharmacokinetic properties, electrolyte-dependent effects, and P-glycoprotein drug interactions influence the clinical use of digoxin. Rate control in atrial fibrillation: choice of treatment and assessment of efficacy. analysed the influence of HR (measured by the 6-minute walk test [6MWT] and 24-hour Holter monitoring) on QoL in 89 patients with chronic AF. Thus, the prevailing concept of AF mechanism focuses on the interdependence of triggers and substrate, and monophasic atrial potentials recordings illustrate differences between normal myocardial properties and AF substrate, also for new-onset episodes. INTRODUCTION Cardiac glycosides have important positive inotropic, neurohormonal, and electrophysiologic actions, which are the basis for its use in two clinical situations: heart failure due to systolic dysfunction, and in certain supraventricular tachyarrhythmias. Digoxin is mainly given to elderly AF patients with HF and impaired LV function. Although this study included a large number of patients, it was performed in an intensive care setting, which makes it difficult to translate the results into other clinical settings. Digoxin comes from the foxgloves plant known as Digitalis lanata. Unauthorized use of these marks is strictly prohibited. The purpose of this document is to update the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" S1.3-1 (2014 AF Guideline) in areas for which new evidence has emerged since its publication. FOIA Washam J.B., Stevens S.R., Lokhnygina Y., et al. Role of digoxin in atrial fibrillation. Lindenfeld J., Albert N.M., Boehmer J.P., et al. Please enable it to take advantage of the complete set of features! 2022 Jun 2;13:902459. doi: 10.3389/fphar.2022.902459. Large randomised multicentre studies are currently ongoing to address these important questions.[1,2]. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. Lip GHY et al. Hyperkalemia complicating digoxin toxicity in a patient with renal failure. In the past, adequate heart rate control had been empirically defined as <80 beats per minute (bpm) at rest. Electrophysiological and electrocardiographic effects of digoxin. 2 Yet, digoxin does have a role and remains one of the treatment options, as an adjunct to . Increasing the force of heart contractions: Digoxin inhibits certain pumps in the cardiac cell membranes, reducing the movement of sodium from the inside of cells to the outside of cells. In another setting, including patients with end-stage renal disease on hemodialysis, there was an increased risk of overall mortality with concomitant digoxin therapy. Advanced age is not a contraindication to anticoagulation. Even with sophisticated statistical techniques, it may be challenging to fully adjust for disease severity and the indication for treatment as assessed by the provider. The chemical formula of digoxin is C41 H64 O14. 2020 Dec 22;324(24):2497-2508. doi: 10.1001/jama.2020.23138. Urgent anticoagulation required use the Age-adjusted warfarin induction regimen and cover with enoxaparin(see NHSGGC StaffNet / Clinical Info / Clinical Guidelines Directory and search for 'warfarin induction protocols'). About 80% of an oral digoxin dose is absorbed, especially in the proximal small intestine [21]. The parasympathomimetic activity makes digoxin a reasonable option for controlling ventricular rate in atrial fibrillation (AF). Guidelines for the management of atrial fibrillation: The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Friberg L, Hammar N, Rosenqvist M. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF). Study Design Randomized Un programa que dej de tener gracia cuando se. [3,4,19] Based on the highest level of evidence, beta-blockers are strongly recommended in clinical European and US guidelines for the management of HF and reduced EF. Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction. The onset of action occurs 30 minutes to 2 hours after oral ingestion and 15 to 30 minutes after intravenous administration [20]. Similarly, the compliance with digoxin or beta-blocker therapy, and whether it relates to clinical events, should be better characterised in future analyses. The .gov means its official. Ahmed A, Bourge RC, Fonarow GC, et al. Wang ZQ, Zhang R, Chen MT, Wang QS, Zhang Y, Huang XH, Wang J, Yan JH, Li YG. Federal government websites often end in .gov or .mil. 08/29/2020 References Contribution To Literature: The RATE-AF trial showed that digoxin was associated with symptom improvement and reduction in NT-proBNP compared with a beta-blocker. Careers. Inclusion in an NLM database does not imply endorsement of, or agreement with, 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. sharing sensitive information, make sure youre on a federal As a library, NLM provides access to scientific literature. With the increase of the vagal tone, the release of norepinephrine from the sympathetic terminals is expected to be inhibited by the interaction between the sympathetic and parasympathetic nervous systems [18]. Finally, HR is difficult to fully describe in any analysis with AF patients and presents a field of investigation. [7] By contrast, only limited observational data are available from everyday clinical practice regarding the events and possible benefits associated with beta-blocker use in patients with AF and HF. Digoxin: clinical highlights: A review of digoxin and its use in contemporary medicine. Scalese M.J., Salvatore D.J. [35] Whether digoxin significantly affects prognosis and mortality in AF associated with HF is poorly known. It is hoped that this standardization of care will result in improved patient Electrophysiological and electrocardiographic effects of, Electrophysiological and electrocardiographic effects of digoxin. Federal government websites often end in .gov or .mil. Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF), with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. Kirchhof P, Breithardt G, Camm AJ, et al. Digoxin has been used for more than 200 years in the treatment of patients with Heart Failure (HF) [1]. Please enable it to take advantage of the complete set of features! For example, a recent analysis of AF patients, including individuals with and without HF, found no association between digoxin treatment and mortality, even after adjustment for confounding factors with different models and propensity scores [29]. Although it is no longer considered a first-line agent for heart rate control in AF [35], it is still an attractive option, since it has no negative inotropic effects [36]. [16] The evidence to support the benefit of HR reduction in improving quality of life and symptoms also remains limited. Unable to load your collection due to an error, Unable to load your delegates due to an error. McMurray JJV, Adamopoulos S, Anker SD, et al. Vittorio TJ, Zolty R, Kasper ME, et al. the contents by NLM or the National Institutes of Health. National Library of Medicine Patients withheart failure should be started on digoxin or beta-blocker as appropriate and follow the NHSGGC Heart Failure guideline. No such difference was seen in patients with HF. Digoxin use was associated with a 17% increase in the relative risk of all-cause mortality (hazard ratio: 1.17, p<0.01). It should be noted that the dosage in obese individuals should be based on lean body mass since the distribution of the drug into adipose tissue is minimal [20]. Gheorghiade M, Hall VB, Jacobsen G, et al. doi: 10.1007/s00228-007-0346-9. It is also indicated in the treatment of pre-eclampsia, eclampsia, and other plant-derived cardiac glycoside poisonings. In contrast, in a retrospective analysis of a large cohort (n = 122,465, with 28,679 of these on digoxin), Turakhia et al. In: eTG complete [Internet]. Sethy et al. Atrial fibrillation: Rate control for atrial fibrillation. Keywords: [27] More specifically, treatment effect, judged by reduction in all-cause mortality, seemed to be less in 3066 patients with AF (hazard ratio 0.97, 95 % CI [0.831.14]) than in the 13,946 patients not in AF (hazard ratio 0.73, 95 % CI [0.670.80]). Fauchier L, Grimard C, Pierre B, et al. Owing to its negative chronotropic activity, digoxin is still commonly used for heart rate control in patients with AF or HF, particularly in those who do not achieve their heart rate target or who are unable to tolerate -blocker therapy. [43] Digoxin use was there assessed at a fixed time point only, at the time of randomisation. More gastrointestinal bleeding with dabigatran and rivaroxaban, especially in the elderly. Benefits of prescribing low-dose digoxin in atrial fibrillation. For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the Guidelines see European Digoxin-associated mortality: A systematic review and meta-analysis of the literature. It bears noting that, as early as 1997, the DIG study showed that serum concentrations equal to or greater than 1.2 ng/ml were associated with a 56% increase in the risk of death when compared to patients who were not taking the drug [13]. Banning abortions disproportionately impacts poor women and women of color. The authors declare no conflict of interest, financial or otherwise. [8] Among patients with both AF and HF with systolic dysfunction, only a few trials have specifically investigated the use of adding a beta-blocker to digoxin or the opposite. doi: 10.4330/wjc.v7.i11.808. Batch CBD Full-Spectrum Gummies. . Accessibility Dorian P, Connors SP. An official website of the United States government. When reading the available literature, the clinical cardiologist should take into account that all analyses that found an increased risk of adverse outcomes with the use of digoxin were based on observational studies or post-hoc analyses of RCTs, which may limit the quality of the evidence. The parasympathomimetic activity makes digoxin a reasonable option for controlling ventricular rate in atrial fibrillation (AF). These findings corroborate the data described above [39], indicating the importance of maintaining digoxin levels below 1 ng/mL [40]. The effect of digoxin on mortality and morbidity in patients with heart failure. Careers. Minimum evaluation: 1. [49,50] Another major limitation in the article by Whitbeck et al. government site. NICE CKS Atrial fibrillation Digoxin Atrial fibrillation: Digoxin Last revised in August 2022 What are the contraindications and cautions of digoxin? Photo: Andreas Neumann. Drug information provided by: . [17] Today, it is recommended that treatment for rate control of persistent or permanent AF should aim for a resting HR of <100 bpm. Includes dosages for Congestive Heart Failure and Atrial Fibrillation; plus renal, liver and dialysis adjustments. FOIA N.B. Does digoxin increase the risk of ischemic stroke and mortality in atrial fibrillation? Many contraindications to warfarin also apply to the newer agents. N.B. 8600 Rockville Pike 8600 Rockville Pike In a sub-analysis of the AFFIRM study [30], which included more than 4,000 patients with AF who were at high risk for stroke, digoxin was also associated with an expressive increase in mortality, even after controlling for comorbidities and propensity scores, regardless of gender and the presence or absence of underlying HF. Over the years, digoxin has played a prominent role, but today it is viewed with suspicion by many cardiologists. Remember: DOACS are indicated only in those patients who have non-valvular AF; not those with mitral stenosis or a mechanical valve. Digitalis use in contemporary clinical practice: Refitting the foxglove. Relieve symptoms often only rate control required; diuretic may also be needed (often only on temporary basis). This was consistent across all subgroups and was independent of drug adherence, renal dysfunction, HF, or concomitant therapy with beta-blockers or amiodarone. It can be used in combination with a beta-blocker or rate-limiting CCB when control of the ventricular rate is difficult. N.B. The .gov means its official. Liver enzymes if alcohol abuse is suspected. Drug Saf. National Library of Medicine Effects of discontinuation of digoxin. (A higher resolution / colour version of this figure is available in the electronic copy of the article). [Digoxin and atrial fibrillation in 2016]. Allen L.A., Fonarow G.C., Simon D.N., et al. [3134] There remain significant knowledge gaps about how digitalis works and how it should be used in the modern treatment of AF. Freeman J.V., Reynolds K., Fang M., et al. Greenblatt D.J., Duhme D.W., Koch-Weser J. In these patients, regardless of systolic dysfunction, both digoxin and beta-blockers reduce the ventricular rate and both may improve symptoms. Department of Cardiology, Trousseau University Hospital and Faculty of Medicine,, University Franois Rabelais, Tours, France. Anderson JL, Halperin JL, Albert NM, et al. As a consequence, the intracellular Na+ concentration increases, facilitating the entry of Ca2+ into the cell, which increases cardiac inotropism [15, 16]. 2017;30(4):434440. Patients without contraindications to anticoagulant therapy. [5557] In the AFFIRM trial, an SDC 1.0 ng/ ml was encouraged and higher doses of digoxin were used to meet the stringent rate control requirement (resting HR of <80 bpm and exercise heart rate <110 bpm), which might not be the case in everyday clinical practice. Before Identify concomitant left ventricular (LV) systolic dysfunction and heart failure. The https:// ensures that you are connecting to the Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF), with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. Description: The goal of the trial was to evaluate digoxin compared with beta-blocker among patients with permanent atrial fibrillation. Anticoagulation not urgent consider a slower regime such as low-slow-start warfarin. -, Scalese M.J., Salvatore D.J. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5 ng/ml increase (p = 0.0010); these results . (A higher resolution / colour version of, MeSH Bethesda, MD 20894, Web Policies Freitas CS, Oliveira-da-Silva JA, Lage DP, Costa RR, Mendona DVC, Martins VT, Reis TAR, Antinarelli LMR, Machado AS, Tavares GSV, Ramos FF, Coelho VTS, Brito RCF, Ludolf F, Chvez-Fumagalli MA, Roatt BM, Ramos GS, Munkert J, Ottoni FM, Campana PRV, Humbert MV, Coimbra ES, Braga FC, Pdua RM, Coelho EAF. As an aside, the main current indications for the therapeutic use of digoxin by different societies [35, 44-46] are detailed in Table 11. [42] In this study, digoxin was used as a time-dependent covariate in a Cox proportional hazard model. 2015 Sep;66(3):270-5. doi: 10.1097/FJC.0000000000000274. Would you like email updates of new search results? Adapted with permission from the American College of Chest Physicians. Beta-blockers must be initiated under direction of a hospital physician. In vitro and in vivo antileishmanial activity of -acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. [41] When these and other differences in patient characteristics were accounted for, digoxin use appeared to be neutral for long-term mortality in patients with AF. J. Clin. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Detailed Digoxin dosage information for adults and children. Sethi N.J., Nielsen E.E., Safi S., Feinberg J., Gluud C., Jakobsen J.C. Digoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. In AF, beta-blockers are preferred as a rate-control agent in patients after myocardial infarction and in patients with congestive heart failure. [9,10] In these studies, no comparison was made between beta-blockers alone versus digoxin alone, or the combination. In patients with 'lone' AF, i.e. If still symptomatic, aim for lower rate, <80bpm. Precautions. Digoxin comes as a tablet, injection, and liquid. Digoxin: in the cross hairs again. Akera T, Baskin SI, Tobin T, et al. Renard D., Rubli E., Voide N., Borruat F.X., Rothuizen L.E. whether LV systolic dysfunction / hypertrophy) and therefore helps identify need for anticoagulation. Van Gelder IC, Groenveld HF, Crijns HJGM, et al. Al-Zakwani I., Panduranga P., Zubaid M., et al. In this review, we explored the therapeutic use of digoxin in the context of AF, discussed mortality data by means of critical analysis in the light of the best available evidence, and position ourselves in relation to more rigorous control of serum levels of this drug in daily practice. Increased mortality among patients taking digoxin--analysis from the AFFIRM study. Napumpujte ho antioxidantmi a vitamnmi! He armed himself with a balaclava, latex gloves, condoms and Viagra pills and posed as a cab driver in a Mercedes to roam the streets of Brighton, East Sussex. Hallberg P., Lindbck J., Lindahl B., Stenestrand U., Melhus H. Digoxin and mortality in atrial fibrillation: A prospective cohort study. DOACs are only indicated as an alternative to warfarin in non-valvular atrial fibrillation patients, and should not be used as an alternative to warfarin in patients with prosthetic valves. 2021;28:38. doi: 10.1051/parasite/2021036. Digoxin and risk of death in adults with atrial fibrillation: The ATRIA-CVRN study. Arch Cardiovasc Dis. In addition, we will describe the mechanisms of action and pharmacology of digoxin, its main indications, and possible pathways that lead to greater risks of adverse effects. Effects of digoxin at low serum concentrations on mortality and hospitalization in heart failure: a propensity-matched study of the DIG trial. Bethesda, MD 20894, Web Policies Digitalis: new actions for an old drug. Inclusion in an NLM database does not imply endorsement of, or agreement with, Optimal management of concomitant cardiovascular disease. Clipboard, Search History, and several other advanced features are temporarily unavailable. Beta-blockers are currently a cornerstone in the treatment of patients with HF and reduced EF. The https:// ensures that you are connecting to the [6] Furthermore, digoxin does not improve survival of patients with HF who are in sinus rhythm,[7] and long-term therapy with digoxin has been suggested to be a risk factor for death in patients with AF without HF. In a scenario that is poor in well-designed evidence (i.e. January CT, Wann LS, Alpert JS, et al. At first, the dose is usually 10 to 15 micrograms (mcg) per kilogram (kg) of body weight. Details available on NHSGGC StaffNet / Clinical Info / Clinical Guidelines Directory and search for 'warfarin induction protocol for out-patients'. These CBD candies offer a simple and flexible . Besides that, initiating digoxin in patients with AF was significantly associated with an increased risk of HF hospitalization, primarily among patients with previous HF. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial. However, such studies have po [9] found that the use of this drug in Middle Eastern patients with AF but without HF was associated with long-term mortality. It is essential for doctors to use the appropriate scientific evidence and to fully analyze the risk-effectiveness balance. Turakhia M.P., Santangeli P., Winkelmayer W.C., et al. Patients with AF and a previous stroke or transient ischaemic attack (TIA) have an absolute risk of a further stroke of the order of 1012% per annum and an absolute benefit of approximately 80 fewer strokes per 1000 patient years of treatment. Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial. Recent studies have focused on the prognostic nature of AF and HF with systolic dysfunction and the questionable use of digoxin and beta-blocker therapy when these conditions coexist. Jaber J, Cirenza C, Jaber J, et al. The site is secure. 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