Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Association between vitamin D supplementation and severity of tuberculosis in wild boar and red deer

Tuberculosis (TB) is a chronic disease affecting humans and other mammal species. Severity of TB caused by Mycobacterium tuberculosis in humans seems to be influenced by nutritional factors like vitamin D3 intake. However, this relationship has been scarcely studied in cattle and other mammals infected with Mycobacterium bovis. The aim of this work was to assess if wildlife reservoirs of M. bovis show different levels of TB severity depending on the level of vitamin D found in serum after supplementation with vitamin D3. Forty hunted wildlife mammals were included in this study: 20 wild boar and 20 red deer. Ten wild boar and ten red deer had been supplemented with a vitamin D3-enriched food, whereas the remaining animals had received no supplementation. TB diagnosis was carried out in each animal based on microbiological isolation of M. bovis. Animals infected with M. bovis were then classified as animals with localized or generalized TB depending on the location and dissemination of the lesions. Furthermore, serum levels of vitamin D2 and D3 were determined in each animal to evaluate differences not only between supplemented and non-supplemented animals but also between those with localized and generalized TB. Levels of vitamin D3 found in both, supplemented wild boar and red deer, were significantly higher than those found in the non-supplemented animals. Interestingly, higher levels of vitamin D3 were observed in animals suffering localized TB when compared to animals with generalized TB suggesting that vitamin D3 concentration correlates negatively with TB severity in these wildlife reservoirs

Association between vitamin D supplementation and severity of tuberculosis in wild boar and red deer

Tuberculosis (TB) is a chronic disease affecting humans and other mammal species. Severity of TB caused by Mycobacterium tuberculosis in humans seems to be influenced by nutritional factors like vitamin D3 intake. However, this relationship has been scarcely studied in cattle and other mammals infected with Mycobacterium bovis. The aim of this work was to assess if wildlife reservoirs of M. bovis show different levels of TB severity depending on the level of vitamin D found in serum after supplementation with vitamin D3. Forty hunted wildlife mammals were included in this study: 20 wild boar and 20 red deer. Ten wild boar and ten red deer had been supplemented with a vitamin D3-enriched food, whereas the remaining animals had received no supplementation. TB diagnosis was carried out in each animal based on microbiological isolation of M. bovis. Animals infected with M. bovis were then classified as animals with localized or generalized TB depending on the location and dissemination of the lesions. Furthermore, serum levels of vitamin D2 and D3 were determined in each animal to evaluate differences not only between supplemented and non-supplemented animals but also between those with localized and generalized TB. Levels of vitamin D3 found in both, supplemented wild boar and red deer, were significantly higher than those found in the non-supplemented animals. Interestingly, higher levels of vitamin D3 were observed in animals suffering localized TB when compared to animals with generalized TB suggesting that vitamin D3 concentration correlates negatively with TB severity in these wildlife reservoirs

The effect of oral vaccination with Mycobacterium bovis BCG on the development of tuberculosis in captive European badgers (Meles meles)

The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a ten-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a ten-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease

Clinical features and natural history of PRKAG2 Variant Cardiac Glycogenosis

BACKGROUND PRKAG2 gene variants cause a syndrome characterized by cardiomyopathy, conduction disease, and ventricular pre-excitation. Only a small number of cases have been reported to date, and the natural history of the disease is poorly understood. OBJECTIVES The aim of this study was to describe phenotype and natural history of PRKAG2 variants in a large multicenter European cohort. METHODS Clinical, electrocardiographic, and echocardiographic data from 90 subjects with PRKAG2 variants (53% men; median age 33 years; interquartile range [IQR]: 15 to 50 years) recruited from 27 centers were retrospectively studied. RESULTS At first evaluation, 93% of patients were in New York Heart Association functional class I or II. Maximum left ventricular wall thickness was 18 +/- 8 mm, and left ventricular ejection fraction was 61 +/- 12%. Left ventricular hypertrophy (LVH) was present in 60 subjects (67%) at baseline. Thirty patients (33%) had ventricular pre-excitation or had undergone accessory pathway ablation; 17 (19%) had pacemakers (median age at implantation 36 years; IQR: 27 to 46 years), and 16 (18%) had atrial fibrillation (median age 43 years; IQR: 31 to 54 years). After a median follow-up period of 6 years (IQR: 2.3 to 13.9 years), 71% of subjects had LVH, 29% had AF, 21% required de novo pacemakers (median age at implantation 37 years; IQR: 29 to 48 years), 14% required admission for heart failure, 8% experienced sudden cardiac death or equivalent, 4% required heart transplantation, and 13% died. CONCLUSIONS PRKAG2 syndrome is a progressive cardiomyopathy characterized by high rates of atrial fibrillation, conduction disease, advanced heart failure, and life-threatening arrhythmias. Classical features of pre-excitation and severe LVH are not uniformly present, and diagnosis should be considered in patients with LVH who develop atrial fibrillation or require permanent pacemakers at a young age. (c) 2020 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission [PI17/01941, AC16/0014, PI17/01690, PI18/01582, PT17/0015/0043]ERA-CVD Joint Transnational Call 2016 (GENPROVIC)DETECTIN-HF project (ERA-CVD framework)Wellcome TrustWellcome TrustEuropean Commission [107469/Z/15/, HICF-R6-373]National Institute for Health Research (NIHR) Royal Brompton Cardiovascular Biomedical Research UnitNIHR Imperial Biomedical Research CentreDepartment of Health, United Kingdom [HICF-R6-373]British Heart FoundationBritish Heart Foundation [SP/10/10/28431]Obra Social La Caixa FoundationLa Caixa Foundation [100010434]Fundacio Privada Daniel Bravo AndreuInstituto de Salud Carlos III - Plan Estatal de I.D.I. 2013-2016, European Regional Development Fund ("A Way of Making Europe")Spanish Ministry of Economy and Competitiveness - Plan Estatal de I.D.I. 2013-2016, European Regional Development Fund ("A Way of Making Europe")Medical Research Council Clinical Academic Research Partnership AwardUCL Hospitals NIHR Biomedical Research CentreFondazione per la Ricerca Ospedale MaggioreNIHR Great Ormond Street Hospital Biomedical Research Centreinfo:eu-repo/semantics/publishedVersio