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

Prevalence and progression of diabetic nephropathy in South Asian, white European and African Caribbean people with type 2 diabetes: A systematic review and meta-analysis

AIMS: To conduct a systematic review and meta-analysis of published observational evidence to assess the difference in the prevalence and progression of diabetic nephropathy, and the development of end-stage renal disease (ESRD) in people from three different ethnic groups with type 2 diabetes (T2DM). MATERIALS AND METHODS: Relevant studies were identified in a literature search of MEDLINE, EMBASE and reference lists of relevant studies published up to May 2018. We decided a priori that there were no differences in the prevalence and progression of diabetic nephropathy, and the development of ESRD in the three ethnicities with T2DM. Pooled relative risks of microalbuminuria by ethnicity were estimated by fitting three random effects meta-analyses models. A narrative synthesis of the nephropathy progression in the studies was carried out. The review was registered in PROSPERO (CRD42018107350). RESULTS: Thirty-two studies with data on 153 827 unique participants were eligible for inclusion in the review. The pooled prevalence ratio of microalbuminuria in South Asian compared with white European participants was 1.14 (95% confidence interval [CI] 0.99, 1.32; P = 0.065), while for African Caribbean vs South Asian participants the pooled prevalence ratio was 1.08 (95% CI 0.93, 1.24; P = 0.327). Results for renal decline were inconsistent, with preponderance towards a high rate of disease progression in South Asian compared with white participants. The estimated pooled incidence rate ratio (IRR) for ESRD was significantly higher in African Caribbean vs white European participants: 2.75 (95% CI 2.01, 3.48; P < 0.001). CONCLUSION: The results of this review did not show a significant link between ethnicity (South Asian, white European and African Caribbean) and the prevalence of microalbuminuria; however, the IRR for ESRD in African Caribbean compared with white European participants was significantly higher. Further research is needed to explore the potential non-albuminuric pathways of progression to ESRD

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 &gt;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 &gt;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 &gt;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 &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;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

Is the relationship between common mental disorder and adiposity bidirectional? Prospective analyses of a UK general population-based study

The direction of the association between mental health and adiposity is poorly understood. Our objective was to empirically examine this link in a UK study. This is a prospective cohort study of 3 388 people (men) aged >= 18 years at study induction who participated in both the UK Health and Lifestyle Survey at baseline (HALS-1, 1984/1985) and the re-survey (HALS-2, 1991/1992). At both survey examinations, body mass index, waist circumference and self-reported common mental disorder (the 30-item General Health Questionnaire, GHQ) were measured. Logistic regression models were used to compute odds ratios (OR) and accompanying 95% confidence intervals (CI) for the associations between (1) baseline common mental disorder (QHQ score > 4) and subsequent general and abdominal obesity and (2) baseline general and abdominal obesity and re-survey common mental disorders. After controlling for a range of covariates, participants with common mental disorder at baseline experienced greater odds of subsequently becoming overweight (women, OR: 1.30, 1.03 - 1.64; men, 1.05, 0.81 -1.38) and obese (women, 1.26, 0.82 - 1.94; men, OR: 2.10, 1.23 - 3.55) than those who were free of common mental disorder. Similarly, having baseline common mental health disorder was also related to a greater risk of developing moderate (1.57, 1.21 - 2.04) and severe (1.48, 1.09 - 2.01) abdominal obesity (women only). Baseline general or abdominal obesity was not associated with the risk of future common mental disorder. These findings of the present study suggest that the direction of association between common mental disorders and adiposity is from common mental disorder to increased future risk of adiposity as opposed to the converse

Electronic and NLO Performances of Benzohydrazide Derivatives: DFT Investigation and (RDG, AIM) Analysis

International audienceDFT calculations of ground-state hydrazine and benzohydrazide derivatives were performed by using hybrid functional B3LYP and CAMB3LYP with 6–31G (d, p) as basis set. The electric dipole moment (μ), polarizability (α) and molecular first hyperpolarizability (β) were characterized in these compounds. The HOMO–LUMO energy gaps and the global chemical reactivity descriptors were computed by B3LYP and CAMB3LYP using 6–31G (d,p), while the excitation energies have determined by time dependent DFT (TDDFT). Besides, the stability and charge delocalization were studied by natural bond orbital analysis. Topological analyses such as atom in molecule (AIM), natural bonding orbital (NBO) and molecular electrostatic potential (MEP) have used to compute intermolecular interactions and in particular hydrogen bonds. The obtained first-order hyperpolarizabilities in the range of 1.5 × 10−30 to 30.2 × 10−30 esu revealed that the hydrazine and benzohydrazide derivatives have better NLO properties. The low-energy gap of 3.53 eV generates an intramolecular charge transfer, leading to the enhancement of the NLO activity in these compounds

Reactive hypoglycaemia during the OGTT after gestational diabetes mellitus: Metabolic implications and evolution.

Gestational diabetes (GDM) presents an increased cardio-metabolic risk and is diagnosed with an oral glucose tolerance test (OGTT). Reactive hypoglycaemia (RH) during the OGTT in pregnancy is associated with adverse outcomes. Although postpartum OGTT after GDM is recommended, the occurrence and implications of RH are unknown. We investigated the prevalence, metabolic implications and longitudinal evolution of RH at 6-8 weeks postpartum in women with a history of GDM. Between 2011 and 2021, we consecutively followed 1237 women with previous GDM undergoing an OGTT at 6-8 weeks postpartum. RH was defined as 2-h glucose &lt;3.9 mmoL/L after the OGTT. Metabolic outcomes were compared in women with and without RH (RH+/RH-). We also included a subcohort of 191 women with data on insulin sensitivity/secretion indices (MATSUDA, HOMA-IR, insulin-adjusted-secretion ISSI-2). The postpartum prevalence of RH was 12%. RH+ women had a more favourable metabolic profile including a 2-5-times lower prevalence of glucose intolerance and metabolic syndrome at 6-8 weeks postpartum compared to RH- (all p ≤ 0.034). In the subcohort, women with RH+ had higher insulin sensitivity, higher ISSI-2 and an earlier glucose peak after OGTT (p ≤ 0.049) compared to RH- women at the same time point. Insulin resistance increased and ISSI-2 decreased over the first year postpartum in both groups. These changes were associated with a 50% reduction in overall RH prevalence at 1-year postpartum. Some of the favourable profiles of RH+ persisted at 1-year postpartum, without group differences in the longitudinal metabolic changes. At 6-8 weeks postpartum, RH was frequent in women after GDM and associated with a better metabolic profile including increased insulin sensitivity and higher insulin-adjusted-secretory capacity. RH might be a marker of favourable metabolic prognosis in women with a history of GDM

The annual cycle of Saharan populations of Locusta migratoria cinerascens (Orthoptera: Acrididae: Oedipodinae) in Algeria

Chantier qualité GAUntil recently, the Algerian populations of Locusta migratoria cinerascens were considered as sedentary and solitarious. In the Central Sahara and bordering areas, the extension of pivot-irrigated areas since 1980, has resulted in the creation of biotopes favourable to the reproduction of this acridid, particularly in the cereal crops of the Adrar and Ouargla regions. From analysis of the archives of the National Institute of plant Protection, and our personal work carried out from 1995 to 2004, we can provide new information on the life cycle of L. m. cinerascens. We show that, in the cereal crops of the regions studied, there are three generations of this acridid per annum: the first one developing on corn in the spring, until the harvest; the second a spring-summer generation in market gardens in the vicinity of wheat stubble, or in early-growth Sorghum crops, and a third, summer-autumn generation, that develops on summer cereal crops and probably over-winters as diapausing adults until the following February.Jusqu’à une période récente, les populations algériennes de Locusta migratoria cinerascens étaient considérées comme sédentaires et solitaires. Au Sahara central et dans les régions limitrophes, l’intensification des périmètres irrigués sous pivot depuis les années 1980, ont entraîné la création de biotopes favorables à la reproduction de cet acridien, particulièrement dans les périmètres céréaliers à Adrar et Ouargla. L’analyse des archives de l’Institut National de la Protection des Plantes et de nos travaux personnels entre 1995 et 2004 nous ont permis de relever certains points originaux sur le cycle biologique de L. m. cinerascens. Dans les zones anthropisées des régions d’étude, nous argumentons que le cycle de cet acridien pourrait présenter une succession de 3 générations : une première génération printanière qui se développe sur les blés jusqu’aux moissons, une seconde printano-estivale étant dans les maraîchages avoisinant les chaumes de blé ou dans les pivots de Sorgho au début du développement des plants, et une troisième estivo-automnale établie sur les céréales d’été et susceptible d’hiverner probablement à l’état d’adultes diapausants jusqu’au mois de février suivant