A high-volume study on the impact of diabetes mellitus on clinical outcomes after surgical and percutaneous cardiac interventions.

BACKGROUND: Type I and type II diabetes mellitus (DM) patients have a higher prevalence of cardiovascular diseases, as well as a higher mortality risk of cardiovascular diseases and interventions. This study provides an update on the impact of DM on clinical outcomes, including mortality, complications and reinterventions, using data on percutaneous and surgical cardiac interventions in the Netherlands. METHODS: This is a retrospective, nearby nationwide study using real-world observational data registered by the Netherlands Heart Registration (NHR) between 2015 and 2020. Patients treated for combined or isolated coronary artery disease (CAD) and aortic valve disease (AVD) were studied. Bivariate analyses and multivariate logistic regression models were used to evaluate the association between DM and clinical outcomes both unadjusted and adjusted for baseline characteristics. RESULTS: 241,360 patients underwent the following interventions; percutaneous coronary intervention(N = 177,556), coronary artery bypass grafting(N = 39,069), transcatheter aortic valve implantation(N = 11,819), aortic valve replacement(N = 8,028) and combined CABG and AVR(N = 4,888). The incidence of DM type I and II was 21.1%, 26.7%, 17.8%, 27.6% and 27% respectively. For all procedures, there are statistically significant differences between patients living with and without diabetes, adjusted for baseline characteristics, at the expense of patients with diabetes for 30-days mortality after PCI (OR = 1.68; p <.001); 120-days mortality after CABG (OR = 1.35; p <.001), AVR (OR = 1.5; p <.03) and CABG + AVR (OR = 1.42; p =.02); and 1-year mortality after CABG (OR = 1.43; p <.001), TAVI (OR = 1.21; p =.01) and PCI (OR = 1.68; p <.001). CONCLUSION: Patients with DM remain to have unfavourable outcomes compared to nondiabetic patients which calls for a critical reappraisal of existing care pathways aimed at diabetic patients within the cardiovascular field.

Study protocol of the GRoningen early-PD Ambroxol treatment (GREAT) trial: a randomized, double-blind, placebo-controlled, single center trial with ambroxol in Parkinson patients with a GBA mutation.

BACKGROUND: To date, no disease modifying therapies are available for Parkinson's disease (PD). Since PD is the second most prevalent neurodegenerative disorder, there is a high demand for such therapies. Both environmental and genetic risk factors play an important role in the etiology and progression of PD. The most common genetic risk factor for PD is a mutation in the GBA1(GBA)-gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). The mucolytic ambroxol is a repurposed drug, which has shown the property to upregulate GCase activity in-vitro and in-vivo. Ambroxol therefore has the potency to become a disease modifying therapy in PD, which was the reason to design this randomized controlled trial with ambroxol in PD patients. METHODS: This trial is a single-center, double-blind, randomized, placebo-controlled study, including 80 PD patients with a GBA mutation, receiving either ambroxol 1800 mg/day or placebo for 48 weeks. The primary outcome measure is the Unified Parkinson's Disease Rating Scale motor subscore (part III) of the Movement Disorder Society (MDS-UPDRSIII) in the practically defined off-state at 60 weeks (after a 12-week washout period). Secondary outcomes include a 3,4-dihydroxy-6-18F-fluoro-I-phenylalanine ([18F]FDOPA) PET-scan of the brain, Magnetic Resonance Imaging (with resting state f-MRI and Diffusion Tensor Imaging), GCase activity, both intra- and extracellularly, sphingolipid profiles in plasma, Montreal Cognitive Assessment (MoCA), quality of life (QoL) measured by the Parkinson's Disease Questionnaire (PDQ-39) and the Non-Motor Symptom Scale (NMSS) questionnaire. DISCUSSION: Ambroxol up to 1200 mg/day has shown effects on human cerebrospinal fluid endpoints, which supports at least passage of the blood-brain-barrier. The dose titration in this trial up to 1800 mg/day will reveal if this dose level is safe and also effective in modifying the course of the disease. TRIAL REGISTRATION: NCT05830396. Registration date: March 20, 2023.

Assessing the impacts of citizen-led policies on emissions, air quality and health.

Air pollution is a global challenge, and especially urban areas are particularly affected by acute episodes. Traditional approaches used to mitigate air pollution primarily consider the technical aspects of the problem but not the role of citizen behaviour and day-to-day practices. ClairCity, a Horizon 2020 funded project, created an impact assessment framework considering the role of citizen behaviour to create future scenarios, aiming to improve urban environments and the wellbeing and health of its inhabitants. This framework was applied to six pilot cases: Bristol, Amsterdam, Ljubljana, Sosnowiec, Aveiro Region and Liguria Region, considering three-time horizons: 2025, 2035 and 2050. The scenarios approach includes the Business As Usual (BAU) scenario and a Final Unified Policy Scenarios (FUPS) established by citizens, decision-makers, local planners and stakeholders based on data collected through a citizen and stakeholder co-creation process. Therefore, this paper aims to present the ClairCity outcomes, analysing the quantified impacts of selected measures in terms of emissions, air quality, population exposure, and health. Each case study has established a particular set of measures with different levels of ambition, therefore different levels of success were achieved towards the control and mitigation of their specific air pollution problems. The transport sector was the most addressed by the measures showing substantial improvements for NO2, already with the BAU scenarios, and overall, even better results when applying the citizen-led FUPS scenarios. In some cases, due to a lack of ambition for the residential and commercial sector, the results were not sufficient to fulfil the WHO guidelines. Overall, it was found in all cities that the co-created scenarios would lead to environmental improvements in terms of air quality and citizens' health compared to the baseline year of 2015. However, in some cases, the health impacts were lower than air quality due to the implementation of the measures not affecting the most densely populated areas. Benefits from the FUPS comparing to the BAU scenario were found to be highest in Amsterdam and Bristol, with further NO2 and PM10 emission reductions around 10%-16% by 2025 and 19%-28% by 2050, compared to BAU.