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A dynamic STIRPAT model used in the current study is based on panel data from the eight most populous countries from 1975 to 2020, revealing the nonlinear effects of urbanization routes (percentage of total urbanization, percentage of small cities and percentage of large cities) on carbon dioxide (CO2) emissions. Using "Dynamic Display Unrelated Regression (DSUR)" and "Fully Modified Ordinary Least Squares (FMOLS)" regressions, the outcomes reflect that percentage of total urbanization and percentage of small cities have an incremental influence on carbon dioxide emissions. However, square percentage of small cities and square percentage of total urbanization have significant adverse effects on carbon dioxide (CO2) emissions. The positive relationship between the percentage of small cities, percentage of total urbanization and CO2 emissions and the negative relationship between the square percentage of small cities, square percentage of total urbanization and CO2 emissions legitimize the inverted U-shaped EKC hypothesis. The impact of the percentage of large cities on carbon dioxide emissions is significantly negative, while the impact of the square percentage of large cities on carbon dioxide emissions is significantly positive, validating a U-shaped EKC hypothesis. The incremental effect of percentage of small cities and percentage of total urbanization on long-term environmental degradation can provide support for ecological modernization theory. Energy intensity, Gross Domestic Product (GDP), industrial growth and transport infrastructure stimulate long-term CO2 emissions. Country-level findings from the AMG estimator support a U-shaped link between the percentage of small cities and CO2 emissions for each country in the entire panel except the United States. In addition, the Dumitrescu and Hulin causality tests yield a two-way causality between emission of carbon dioxide and squared percentage of total urbanization, between the percentage of the large cities and emission of carbon dioxide, and between energy intensity and emission of carbon dioxide. This study proposes renewable energy options and green city-friendly technologies to improve the environmental quality of urban areas. [ABSTRACT FROM AUTHOR]

Aims Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods and results Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy and safety of lasmiditan for acute treatment of migraine in patients using migraine preventive medications. Background: While lasmiditan has been proven to be an effective acute treatment for migraine, its effectiveness has not been examined when used concurrently with migraine preventives. Methods: SAMURAI and SPARTAN were similarly designed, double-blind, phase 3, placebo-controlled studies of patients 18 years or older with 3 to 8 migraine attacks per month. Patients were randomized to treat a migraine attack with oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Migraine preventives were allowed as long as doses were stable for 3 months prior to screening and were unchanged during the study. Preventive medications with established or probable efficacy, as recommended by the American Academy of Neurology, the American Headache Society, and the European Headache Federation, plus botulinum toxin type A and candesartan, were included. Within the subgroups of patients using and not using preventive therapies, lasmiditan and placebo groups were analyzed for the outcome of pain-free at 2 h and other efficacy outcomes. The subgroups of patients using and not using preventive therapies were compared and interaction p-values were calculated for safety and efficacy outcomes. Results: In these trials, 698 of 3981 patients (17.5%) used migraine preventive treatments. Among patients using preventives, all lasmiditan doses resulted in significantly more patients being pain-free at 2 h, compared to placebo (p < 0.05). Primary efficacy outcome (pain-free at 2 h), key secondary outcome (most bothersome symptom-free at 2 h) and all other efficacy outcomes were not significantly different between patients using or not using migraine preventives (all interaction p-values ≥0.1). Rates of adverse events were similar for patients using and not using preventive medications. Conclusions: Lasmiditan was more effective than placebo for the acute treatment of migraine in patients concurrently using migraine preventive medications. Lasmiditan efficacy and safety measures were similar for patients using and not using preventive medications. Trial registration: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Registered 18 March 2015. [ABSTRACT FROM AUTHOR]