Danish study of Non-Invasive Testing in Coronary Artery Disease 3 (Dan-NICAD 3):study design of a controlled study on optimal diagnostic strategy

Introduction Current guideline recommend functional imaging for myocardial ischaemia if coronary CT angiography (CTA) has shown coronary artery disease (CAD) of uncertain functional significance. However, diagnostic accuracy of selective myocardial perfusion imaging after coronary CTA is currently unclear. The Danish study of Non-Invasive testing in Coronary Artery Disease 3 trial is designed to evaluate head to head the diagnostic accuracy of myocardial perfusion imaging with positron emission tomography (PET) using the tracers 82Rubidium (82Rb-PET) compared with oxygen-15 labelled water PET (15O-water-PET) in patients with symptoms of obstructive CAD and a coronary CT scan with suspected obstructive CAD.Methods and analysis This prospective, multicentre, cross-sectional study will include approximately 1000 symptomatic patients without previous CAD. Patients are included after referral to coronary CTA. All patients undergo a structured interview and blood is sampled for genetic and proteomic analysis and a coronary CTA. Patients with possible obstructive CAD at coronary CTA are examined with both 82Rb-PET, 15O-water-PET and invasive coronary angiography with three-vessel fractional flow reserve and thermodilution measurements of coronary flow reserve. After enrolment, patients are followed with Seattle Angina Questionnaires and follow-up PET scans in patients with an initially abnormal PET scan and for cardiovascular events in 10 years.Ethics and dissemination Ethical approval was obtained from Danish regional committee on health research ethics. Written informed consent will be provided by all study participants. Results of this study will be disseminated via articles in international peer-reviewed journal.Trial registration number NCT04707859

Frequency and characteristics of immune-related thyroid adverse events in patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors: a national cohort study

PURPOSE: Immune-related thyroid adverse events (irTAEs) occur frequently following immune checkpoint inhibitor (ICI) therapy. The purpose of this study is to provide knowledge about the incidence, clinical timeline characteristics, associated factors of irTAEs, and potential impact on treatment efficacy in patients with melanoma receiving adjuvant ICI therapy.METHODS: A national multicenter retrospective cohort study of patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors between November 2018 and December 2020. Data were extracted from the Danish Metastatic Melanoma Database. The irTAEs were defined as two consecutive abnormal TSH values and subdivided into transient or persistent.RESULTS: Of 454 patients, 99 developed an irTAE (21.8%), of these were 46 transient (46.5%) and 53 persistent (53.5%). Median time to transient and persistent irTAE was 55 and 44 days, respectively (p = 0.57). A hyperthyroid phase followed by hypothyroidism was seen in 73.6% of persistent irTAEs, whereas 87% of transient irTAEs developed an isolated hypo- or hyperthyroid phase. Multiple variable analysis demonstrated an association between irTAE and female sex (HR 2.45; 95% CI 1.63-3.70; p &lt; 0.001), but no association with recurrence-free survival (HR 0.86; 95% CI 0.50-1.48; p = 0.587) or overall survival (HR 1.05; 95% CI 0.52-2.12, p = 0.891).CONCLUSIONS: IrTAE is a common side effect to PD-1 inhibitors primarily occurring within the first 3 months, with a high risk of persistency. Female sex is a strong predictive factor. IrTAE was not associated with improved clinical outcome.</p

National nitrogen budget for Denmark (excel-file 125 kB)

A nitrogen (N) budget for Denmark has been developed for the years 1990 to 2010, describing the inputs and outputs at the national scale and the internal flows between relevant sectors of the economy. Satisfactorily closing the N budgets for some sectors of the economy was not possible, due to missing or contradictory information. The budgets were nevertheless considered sufficiently reliable to quantify the major flows. Agriculture was responsible for the majority of inputs, though fisheries and energy generation also made significant contributions. Agriculture was the main source of N input to the aquatic environment, whereas agriculture, energy generation and transport all contributed to emissions of reactive N gases to the atmosphere. Significant reductions in inputs of reactive N have been achieved during the 20 years, mainly by restricting the use of N for crop production and improving livestock feeding. This reduction has helped reduce nitrate leaching by about half. Measures to limit ammonia emissions from agriculture and mono-nitrogen oxides (NOx) emissions from energy generation and transport, has reduced gaseous emissions of reactive N. Much N flows through the food and feed processing industries and there is a cascade of N through the consumer to solid and liquid waste management systems. The budget was used to frame a discussion of the potential for further reductions in losses of reactive N to the environment. These will include increasing the recycling of N between economic sectors, increasing the need for the assessment of knock-on effects of interventions within the context of the national N cycle