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Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis.Methods and Results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67-0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71-0.89], the LWYY method (RR 0.78, 95% CI 0.68-0.90), and the joint frailty model (HR 0.75, 95% CI 0.66-0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar.Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied. [ABSTRACT FROM AUTHOR]

Aims: Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes.Methods and Results: ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril. At baseline, 1944 (27.7%) patients had diabetes. Median follow-up was shorter in patients with diabetes compared with those without (24 months vs. 46 months). Among patients with diabetes, the primary endpoint of cardiovascular death or hospitalization for heart failure occurred in 216 patients (33.1%) in the enalapril group (reference), 172 (27.4%) in the aliskiren group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67-1.00; P = 0.053], and 196 (29.5%) in the combination group (HR 0.86, 95% CI 0.71-1.04; P = 0.13). The effects of the treatments studied did not differ significantly compared with patients without diabetes. In patients with diabetes, aliskiren monotherapy was associated with a lower risk of symptomatic hypotension compared to enalapril [42 (6.7%) vs. 65 (10.0%); P = 0.04], whereas other adverse events were generally balanced between the three groups.Conclusion: In patients with HFrEF and diabetes, there was no signal of harm and a trend towards benefit when direct renin inhibition monotherapy was compared with an angiotensin-converting enzyme inhibitor, whereas combined aliskiren and enalapril treatment led to more adverse events with no improvement in outcomes. Treatment effects did not differ in patients with diabetes compared with those without. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658. [ABSTRACT FROM AUTHOR]

The Cover Feature shows how sunlight can convert a dihydroazulene derivative into a high‐energy vinyl-heptafulvene isomer, which in the dark returns to the original isomer, at the same time releasing the energy as heat. By introducing electron‐withdrawing groups (EWGs), the half‐life for the back‐reaction is significantly prolonged without compromising the energy density of the system, which is a key step towards using the couple as a molecular solar thermal energy storage system for light‐harvesting during daytime and heat release during nighttime. More information can be found in the Full Paper by M. Jevric, K. V. Mikkelsen, M. B. Nielsen et al. [ABSTRACT FROM AUTHOR]

The demand for organic food products, including tomatoes (Solanum lycopersicum , L. 1753), is growing. Heated greenhouse production is well described through life cycle assessment (LCA), but inventories reflecting organic production conditions are inadequate or missing. At the same time, energy systems in Europe are changing, which is expected to have a considerable impact on the emissions from the energy intensive greenhouse production. Thus, this study is assessing the current environmental impacts using LCA of an organic tomato production in a heated greenhouse, and estimate the expected changes to impacts due to changes in energy supply. The assessment is based on activity data from a commercial greenhouse production. Current organic tomato production where plants are transplanted into the greenhouse in the late winter has impacts of 1.06 kg CO 2 eq., 7.22 × 10−4 N eq., 3.49 × 10−5 kg Sb eq., and result in 3.12 kg C deficit from land use while consuming 24.58 MJ of energy per kg organic tomato. The impacts from earlier started tomato cultures are higher, as increased yield does not remedy increased energy use. The result from current production shows that direct energy consumption is responsible for the main impact on climate change (78%), cumulative energy demand (75%), marine eutrophication (56%) and land use (62%). However, expected future changes in the energy system towards 2030 are likely to reduce life cycle environmental impacts considerably (reduction potential for climate change impact: 69%, cumulative energy demand: 48%, eutrophication potential: 47%, mineral, fossil and renewable resource depletion: 4%, land use: 48%) as intensity of the energy supply changes. Mitigation options such as increased energy efficiency, alternative heat sources and agronomic management decisions are further discussed. [Display omitted] • Environmental LCA of two tomato production strategies in a heated greenhouse. • Carbon footprint of 3.72 and 1.06 kg CO 2 e of early- and late-started cultures. • Direct energy input was determined as the main hotspot of environmental impacts. • Climate impact in 2030 modeled based on planned changes in the energy system. • Expected energy composition in 2030 reduce environmental impacts considerably. [ABSTRACT FROM AUTHOR]

BACKGROUND Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography- guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P=0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography- guided PCI group. CONCLUSIONS Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. [ABSTRACT FROM AUTHOR]

Background: In 2004 the Danish parliament repenalised possession of illicit drugs for personal use after it had been depenalised for 35 years. This article analyses the introduction of a more repressive drug policy in Denmark by studying how drug use and drug users were problematized in two key government whitepapers and how this problematization articulated a more general problematisation of 'a culture of intoxication' among young Danes. The analysis also shows how the policy change involved a change of governmentality away from a welfarist and towards a neo-liberal governmentality. The analysis particularly focuses on the implications of these problematisations for the constitution of young drug users a 'governable subjects'.Methods: The article takes its inspiration from research that has applied governmentality theory to analyse drug policy and particularly how the governmentalities that drug policies articulate involve different subjectifications of drug users. Within this overall framework the article also takes inspiration from Carol Bacchi's post-structural approach to policy analysis to show the assumptions about young people, drugs and how to govern them before and after the policy change.Results: The new drug policy articulated new ways of problematising drug use and the young drug user. Drug use was no longer defined as more or less socially conditioned but as an individual choice made by a rational actor. Punishment for violating the drug legislation should make the drug user responsible for his or her transgressions and deter others from making similar transgressions.Conclusion: Research has shown that neo-liberal discourses can lead to more empowering and harm reduction oriented drug policies. This is not the case in Denmark. Here neo-liberal discourses led to a more repressive drug policy. Briefly accounting for some of the lived effects of the new drug policy, the article shows how socially disadvantaged parts of the Danish population bears the burden on the more punitive drug policy. This more repressive drug policy goes against the trend in several other European countries that have become less repressive. However, even if Danish drug policy has become more repressive, the legal measures taken against drug users in Denmark are still fairly 'mild' compared with the legal measures taken against drug users in other countries. [ABSTRACT FROM AUTHOR]

Background: Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia.Methods: This was an observational, retrospective, longitudinal cohort study.Results: The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C-index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD.Conclusions: This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD. [ABSTRACT FROM AUTHOR]