Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

A risk score for iliofemoral patients with deep vein thrombosis

Objective: Deep vein thrombosis (DVT) is a common condition with a high risk of post-thrombotic morbidity, especially in patients with a proximal thrombus. Successful iliofemoral clot removal has been shown to decrease the severity of postthrombotic syndrome. It is assumed that earlier thrombus lysis is associated with a better outcome. Generally, the earlier IFDVT is confirmed, the earlier thrombus lysis could be performed. D-Dimer levels and Wells score are currently used to assess the preduplex probability for DVT; however, some studies indicate that the D-dimer value varies depending on the thrombus extent and localization. Using D-dimer and other risk factors might facilitate development of a model selecting those with an increased risk of IFDVT that might benefit from early referral for additional analysis and adjunctive iliofemoral thrombectomy.Methods: All consecutive adult patients from a retrospective cohort of STAR diagnostic center (primary care) in Rotterdam suspected of having DVT between September 2004 and August 2016 were assessed for this retrospective study. The diagnostic workup for DVT including Wells score and D-dimer were performed as well as complete duplex ultrasound examination. Patients with objective evidence of DVT were categorized according to thrombus localization using the Lower Extremity Thrombolysis classification. Logistic regression analysis was done for a model predicting IFDVT. The cutoff value of the model was determined using a receiver operating characteristic curve.Results: A total of 3381 patients were eligible for study recruitment, of whom 489 (14.5%) had confirmed DVT. We developed a multivariate model (sensitivity of 77% and specificity of 82%; area under the curve, 0.90; 0.86-0.93) based on D-dimer, Wells score, age, and anticoagulation use, which is able to distinguish IFDVT patients from all patients suspected of DVT.Conclusions: This multivariate model adequately distinguishes IFDVT among all suspected DVT patients. Practically, this model could give each patient a preduplex risk score, which could be used to prioritize suspected IFDVT patients for an immediate imaging test to confirm or exclude IFDVT. Further validation studies are needed to confirm potential of this prediction model for IFDVT

Non-coding RNAs related to angiogenesis in gynecological cancer

Gynecological cancer affects the female reproductive system, including ovarian, uterine, endometrial, cervical, vulvar, and vaginal tumors. Non-coding RNAs (ncRNAs), and in particular microRNAs, function as regulatory molecules, which can control gene expression in a post-transcriptional manner. Normal physiological processes like cellular proliferation, differentiation, and apoptosis, and pathological processes such as oncogenesis and metastasis are regulated by microRNAs. Numerous reports have shown a direct role of microRNAs in the modulation of angiogenesis in gynecological cancer, via targeting pro-angiogenic factors and signaling pathways. Understanding the molecular mechanism involved in the regulation of angiogenesis by microRNAs may lead to new treatment options. Recently the regulatory role of some long non-coding RNAs in gynecological cancer has also been explored, but the information on this function is more limited. The aim of this article is to explore the pathways responsible for angiogenesis, and to what extent ncRNAs may be employed as biomarkers or therapeutic targets in gynecological cancer. © 2021 Elsevier Inc

Impact of substrate on magnetic phase coexistence in bicritical Sm0.53Sr0.47MnO3 thin films

Sm0.53Sr0.47MnO3 thin films were deposited on single crystal LaAlO3 (LAO/(001)) and SrTiO3 (STO/(001)) substrates by DC magnetron sputtering. The theta-2 theta and omega-2 theta scans show that these films have very good crystallinity and the films on LAO and STO are under compressive and tensile strain, respectively. The films on LAO and STO substrates show ferromagnetic (insulator-metal) transition at T-C similar to 126 K (at T-IM similar to 128 K) and 120 K (T-IM similar to 117 K), respectively. The magnetic state at T < T-C is akin to cluster glass, which is formed by the presence of charge ordered-antiferromagnetic clusters in the ferromagnetic matrix. Huge drop in the resistivity at T-IM and the associated hysteresis with respect to cooling and warming cycles reveal the bicritical and the first order nature of phase transition, which is also confirmed by the Banerjee criterion. The differences and similarities in the functional properties of films are explained in terms of substrate modified magnetic phase coexistence