Association between smoking and recurrence of venous thromboembolism and bleeding in elderly patients with past acute venous thromboembolism.

BACKGROUND: While the association between smoking and arterial cardiovascular events has been well established, the association between smoking and venous thromboembolism (VTE) remains controversial. OBJECTIVES: To assess the association between smoking and the risk of recurrent VTE and bleeding in patients who have experienced acute VTE. PATIENTS/METHODS: This study is part of a prospective Swiss multicenter cohort that included patients aged ≥65years with acute VTE. Three groups were defined according to smoking status: never, former and current smokers. The primary outcome was the time to a first symptomatic, objectively confirmed VTE recurrence. Secondary outcomes were the time to a first major and clinically relevant non-major bleeding. Associations between smoking status and outcomes were analysed using proportional hazard models for the subdistribution of a competing risk of death. RESULTS: Among 988 analysed patients, 509 (52%) had never smoked, 403 (41%) were former smokers, and 76 (8%) current smokers. After a median follow-up of 29.6months, we observed a VTE recurrence rate of 4.9 (95% confidence interval [CI] 3.7-6.4) per 100 patient-years for never smokers, 6.6 (95% CI 5.1-8.6) for former smokers, and 5.2 (95% CI 2.6-10.5) for current smokers. Compared to never smokers, we found no association between current smoking and VTE recurrence (adjusted sub-hazard ratio [SHR] 1.05, 95% CI 0.49-2.28), major bleeding (adjusted SHR 0.59, 95% CI 0.25-1.39), and clinically relevant non-major bleeding (adjusted SHR 1.21, 95% CI 0.73-2.02). CONCLUSIONS: In this multicentre prospective cohort study, we found no association between smoking status and VTE recurrence or bleeding in elderly patients with VTE

Projected seniority-two orbital optimization of the Antisymmetric Product of one-reference orbital Geminal

We present a new, non-variational orbital-optimization scheme for the Antisymmetric Product of one-reference orbital Geminal wave function. Our approach is motivated by the observation that an orbital-optimized seniority-zero configuration interaction (CI) expansion yields similar results to an orbital-optimized seniority-zero-plus-two CI expansion [J. Chem. Phys., 135, 044119 (2011)]. A numerical analysis is performed for the C$_2$, LiF and CH$_2$ molecules as well as for the symmetric stretching of hypothetical (linear) hydrogen chains. For these test cases, the proposed orbital-optimization protocol yields similar results to its variational orbital optimization counterpart, but prevents symmetry-breaking of molecular orbitals in most cases.Comment: 7 pages, 2 figure

Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women

Objective: To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women. Design and Methods Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up. Results: Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations. Conclusion: Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease

Role of the HIV-1 Reservoir to Maintain Viral Suppression in a Simplified Strategy for the Long-Term Management of HIV-1 Infection (The SIMPL’HIV Trial).

HIV-1 reservoir size and dynamics are promising parameters to ensure the safe prescription of simplified maintenance antiretroviral therapy in chronically HIV-1 infected patients. In the SIMPL’HIV trial, HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained at baseline and week 48 to investigate changes over time and evidence of a predictive relationship to maintain HIV-1 RNA <20 copies/ml. Measurements were available for 175 patients, with no differences observed between treatment strategies. Findings showed that baseline HIV-1 DNA was lower in those with durable HIV-1 RNA <20 copies/ml compared with patients with incomplete viral suppression over 48 weeks

Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood. We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality. We quantified ceDNA by a fluorescent probe, as well as circulating nucleosomes and neutrophil extracellular traps (NETs) by ELISA in plasma from 611 patients aged ≥ 65 years with acute VTE of a prospective cohort study (SWITCO65+). Levels of ceDNA and nucleosomes, but not NETs, correlated with VTE extent. Infectious comorbidities independently increased ceDNA levels in VTE. CeDNA strongly correlated with C-reactive protein and leukocytosis, suggesting an association of ceDNA with inflammation in VTE patients. CeDNA furthermore predicted PE-related and all-cause mortality, but not VTE recurrence, during a 3-year follow-up. Our study suggests that ceDNA levels in VTE patients reflect the degree of inflammation and may serve as a biomarker to stratify VTE patients at risk for mortality

Cognitive Function and Changes in Cognitive Function as Predictors of Incident Cardiovascular Disease: The Women's Health Initiative Memory Study

Background Cognitive impairment and decline may signal the increased risk of incident cardiovascular disease (CVD). We examined associations of global cognitive function, as measured by the Modified Mini-Mental State Examination (3MS) and changes in 3MS over time, with incident CVD, individual CVD outcomes, CVD death, and all-cause mortality. Methods A total of 5,596 women (≥ 60) from the Women's Health Initiative Memory Study free of CVD at baseline were followed for an average of 7.1 years. The 3MS was measured at baseline and annually thereafter. Cox proportional hazards regressions were used to model associations between baseline 3MS and changes in 3MS and time to events. Results In the fully-adjusted models for every 5-point lower baseline 3MS score, the risk was 12% greater for incident CVD, 37% for HF, 35% for CVD death, and 24% for all-cause mortality. No significant relationships were found for coronary heart disease (CHD), angina, stroke/transient ischemic attack (TIA), or coronary revascularization. When change in 3MS was added as a time-varying covariate in the fully-adjusted models, for every 1-point/year greater decline in 3MS, the risk was 4% greater for incident CVD, 10% for CHD, 9% for Stroke/TIA, 17% for CVD death, and 13% for all-cause mortality. Conclusions In older women free of prevalent CVD at baseline, lower baseline global cognitive function or decline in global cognitive function over time, increased risk of incident CVD, CVD death, and all-cause mortality

Long-range corrected DFT calculations of charge-transfer integrals in model metal-free phthalocyanine complexes

An assessment of several widely used exchange--correlation potentials in computing charge-transfer integrals is performed. In particular, we employ the recently proposed Coulomb-attenuated model which was proven by other authors to improve upon conventional functionals in the case of charge-transfer excitations. For further validation, two distinct approaches to compute the property in question are compared for a phthalocyanine dimer