Objectives Dry powder inhalers (DPIs) and soft mist inhalers have a substantially lower global warming potential than pressurised metered-dose inhalers (pMDIs). To help mitigate climate change, we... Show moreObjectives Dry powder inhalers (DPIs) and soft mist inhalers have a substantially lower global warming potential than pressurised metered-dose inhalers (pMDIs). To help mitigate climate change, we assessed the potential emission reduction in CO2 equivalents when replacing pMDIs by non-propellant inhalers (NPIs) in Dutch respiratory healthcare and estimated the associated cost. Design We performed a descriptive analysis of prescription data from two national databases of two independent governmental bodies. First, we calculated the number of patients with chronic obstructive pulmonary disease (COPD) and asthma that were using inhalation medication (2020). Second, we calculated the number and total of daily defined doses of pMDIs and NPIs including DPIs and soft mist inhalers, as well as the number of dispensed spacers per patient (2020). Third, we estimated the potential emission reduction in CO2 equivalents if 70% of patients would switch from using pMDIs to using NPIs. Fourth, we performed a budget impact analysis. Setting Dutch respiratory healthcare. Primary and secondary outcome measures The carbon footprint of current inhalation medication and the environmental and financial impact of replacing pMDIs with NPIs. Results In 2020, 1.4 million patients used inhalers for COPD or asthma treatment. A total of 364 million defined daily doses from inhalers were dispensed of which 49.6% were dispensed through pMDIs. We estimated that this could be reduced by 70% which would lead to an annual reduction in greenhouse gas emission of 63 million kg.CO2 equivalents saving at best EUR 49.1 million per year. Conclusions In the Netherlands, substitution of pMDIs to NPIs for eligible patients is theoretically safe and in accordance with medical guidelines, while reducing greenhouse gas emission by 63 million kg.CO2 equivalents on average and saving at best EUR 49.1 million per year. This study confirms the potential climate and economic benefit of delivering a more eco-friendly respiratory care. Show less
Background Proton magnetic resonance spectroscopy (H-1-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in... Show moreBackground Proton magnetic resonance spectroscopy (H-1-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking.Purpose To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized H-1-MRS.Study type Test-retest repeatability and measurement validation study.Subjects Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy.Field Strength/Sequence Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T.Assessment Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the H-1-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo H-1-MRS measurements against biochemical assays in myocardial tissue from the same subjects.Statistical Tests Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between H-1-MRS measurements and biochemical assay was tested with regression analyses.Results The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% +/- 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% +/- 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with H-1-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05.Data Conclusion We validated the use of localized H-1-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy.Level of Evidence 2Technical Efficacy Stage 2 Show less
Aims/hypothesis The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. Methods This study is a pre-specified... Show moreAims/hypothesis The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. Methods This study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m(2)) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported. Results The trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (n = 23) vs placebo (n = 26) significantly reduced body weight (liraglutide 98.4 +/- 13.8 kg to 94.3 +/- 14.9 kg; placebo 94.5 +/- 13.1 kg to 93.9 +/- 13.2 kg; estimated treatment effect -4.5 [95% CI -6.4, -2.6] kg). HbA(1c) declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 +/- 11.5 mmol/mol to 55.0 +/- 13.2 mmol/mol [8.4 +/- 1.1% to 7.3 +/- 1.2%]; placebo 64.7 +/- 10.2 mmol/mol to 56.9 +/- 6.9 mmol/mol [8.2 +/- 1.0% to 7.5 +/- 0.7%]; estimated treatment effect -2.9 [95% CI -8.1, 2.3] mmol/mol or -0.3 [95% CI -0.8, 0.2]%). VAT did not change significantly between groups (liraglutide 207 +/- 87 cm(2) to 203 +/- 88 cm(2); placebo 204 +/- 63 cm(2) to 200 +/- 55 cm(2); estimated treatment effect -7 [95% CI -24, 10] cm(2)), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 +/- 142 cm(2) to 339 +/- 131 cm(2); placebo 329 +/- 107 cm(2) to 333 +/- 125 cm(2); estimated treatment effect -29 [95% CI -51, -8] cm(2)). Epicardial fat did not change significantly between groups (liraglutide 8.9 +/- 4.3 cm(2) to 9.1 +/- 4.7 cm(2); placebo 9.6 +/- 4.1 cm(2) to 9.6 +/- 4.6 cm(2); estimated treatment effect 0.2 [95% CI -1.5, 1.8] cm(2)). Change in HTGC was not different between groups (liraglutide 18.1 +/- 11.2% to 12.0 +/- 7.7%; placebo 18.4 +/- 9.4% to 14.7 +/- 10.0%; estimated treatment effect -2.1 [95% CI -5.3, 1.0]%). MTGC was not different after treatment with liraglutide (1.5 +/- 0.6% to 1.2 +/- 0.6%) vs placebo (1.3 +/- 0.5% to 1.2 +/- 0.6%), with an estimated treatment effect of -0.1 (95% CI -0.4, 0.2)%. There were no adjudicated serious adverse events. Conclusions/interpretation Compared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study. Funding This study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark). Show less
Background The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic... Show moreBackground The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans. Methods T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (H-1-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model. Results A total of 131 individuals were included (54 South Asians [50.1 +/- 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 +/- 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [- 0.20 (- 0.36; - 0.03), P = 0.021] and Europeans [- 0.20 (- 0.36; - 0.04), P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30), P < 0.001] (P for interaction by ethnicity = 0.005) with a lower extracellular volume fraction [- 1.9% (- 3.4; - 0.4), P = 0.013] (P for interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84), P = 0.001] (P for interaction = 0.002) than their control group. Conclusions Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required. Show less
The aim of this thesis was to develop advanced body MR techniques that can contribute to the knowledge of the metabolic syndrome (MetS). Such techniques are important since the incidence of... Show moreThe aim of this thesis was to develop advanced body MR techniques that can contribute to the knowledge of the metabolic syndrome (MetS). Such techniques are important since the incidence of the metabolic syndrome is reaching pandemic proportions. We looked In the first part of this thesis, consisting of chapters 2, 3 and 4, new techniques for body MR were developed. Firstly high dielectric passive shimming was developed and applied on liver imaging to increase image quality. Furthermore, the required power was reduced by applying the passive shimming method. Secondly MR spectroscopy was optimized to reliably measure lipid levels in the heart and kidney. By looking at the various parameters and optimizing them individually very high measurement reproducibility was reached. Even though MR spectroscopy is a great tool for studying MetS the complexity of the technique hampers broad application therefore, extra emphasis was placed on the ease of use of the developed protocol. In the second part of the thesis the previously mentioned methods were applied in a more clinical setting. Show less
Jonker, J.T.; Heer, P. de; Engelse, M.A.; Rossenberg, E.H. van; Klessens, C.Q.F.; Baelde, H.J.; ... ; Vries, A.P.J. de 2018
The current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell... Show moreThe current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell motility (non-receptor protein tyrosin adesion kinases, FAK, Src and paxillin, Apoptosis (caspase-3 activity and M30 expression) and regulation of cell growth (COX-2 expression). In addition the use of selective COX-2 inhibitors for the treatment of colorectal cancer liver metastases is investigated and discussed. The main outcomes of the thesis are that combined FAK/Src immunohistochemical expression is predictive of tumor recurrence in colorectal cancer, but is not overexpressed in liver metastases. Increased tumor cell apoptosis can have a positive or a negative impact on survival and local recurrence, depending on the location of the tumor in the large bowel . In rectal cancer caspase-3 activity can be used to preoperatively select patients who will not benefit from radiation therapy. COX-2 expression in rectal cancer is only of prognostic significance in irradiated rectal cancer patients, not in non-irradiated. Liver metastases in an animal model show deminished growth in the abcence of COX-2 expression and prostaglandin production. Show less
