Denktank Overlijdensschade: nieuwe richting benadering en berekening overlijdensschade

De denktank overlijdensschade is ontstaan, omdat de rekenmethodiek voor overlijdensschade niet uit te leggen is aan nabestaanden en geen recht doet aan de maatschappelijke ontwikkelingen. Diverse professionals besloten niet langer slechts te ageren tegen de bestaande situatie, maar er werkelijk wat aan te doen. Dit heeft geresulteerd in een conceptnotitie ‘Nieuwe richting benadering en berekening overlijdensschade’. In dit artikel wordt deze notitie kort besproken

Notitie Denktank Overlijdensschade. Nieuwe richting benadering en berekening overlijdensschade

In 2009 is een werkgroep onder de naam Denktank Overlijdensschade gestart met het bestuderen van een ander, aan de huidige tijd aangepast model voor de berekening van overlijdensschade. Doelstelling was te komen tot een, ook voor nabestaanden, transparantie systematiek welke recht doet aan de vorderingsgerechtigdheid van de nabestaanden. In 2014 heeft de Denktank Overlijdensschade haar werkzaamheden voltooid met het opleveren van een nieuwe rekenmethodiek. In deze Notitie wordt beschreven hoe de Denktank tot deze nieuwe benadering van het berekenen van overlijdensschade is gekomen, welke onderzoeken daaraan ten grondslag liggen en wat de uiteindelijke rekenregel is, die nu voorgesteld wordt. Kern van de nieuwe methodiek is het uitgangspunt dat het gezin als economische eenheid wordt beschouwd, voor én na het overlijden

Calsequestrin as a risk factor in Graves’ hyperthyroidism and Graves’ ophthalmopathy patients

Background: The pathogenesis of Graves’ ophthalmopathy (GO), Graves’ hyperthyroidism (GH) and the mechanisms for its link to thyroid autoimmunity are poorly understood. Our research focuses on the role of the skeletal muscle calcium binding protein calsequestrin (CASQ1) in thyroid. We measured the concentration of the CASQ1 protein correlating levels with parameters of the eye signs, CASQ1 antibody levels and CASQ1 gene polymorphism rs3838284. Methods: CASQ1 protein was measured by quantitative Western Blotting. The protein concentrations were expressed as pmol/mg total protein by reference to CASQ1 standards. Results: Western blot analysis showed the presence of two forms of CASQ1 in the thyroid. The mean concentration of CASQ1 protein was significantly reduced in patients with Graves’ disease, compared to thyroid from control subjects with multi-nodular goitre or thyroid cancer. Although in patients with GO it was lower than that, compared with patients with GH this difference was not significant. Reduced CASQ1 in Graves’ thyroid correlated with the homozygous genotype of the rs3838284 CASQ1 polymorphism. Conclusions: Decreased CASQ1 in the thyroid of patients with Graves’ disease compared to thyroid from control subjects is not explained but may reflect consumption of the protein during an autoimmune reaction against CASQ1 in the thyroid

Healthcare costs of metastatic cutaneous melanoma in the era of immunotherapeutic and targeted drugs

Immunotherapeutic and targeted drugs improved survival of patients with metastatic melanoma. There is, however, a lack of evidence regarding their healthcare costs in clinical practice. The aim of our study was to provide insight into real-world healthcare costs of patients with metastatic cutaneous melanoma. Data were obtained from the Dutch Melanoma Treatment Registry for patients who were registered between July 2012 and December 2018. Mean total/monthly costs per patient were reported for all patients, patients who did not receive systemic therapy, and patients who received systemic therapy. Furthermore, mean episode/monthly costs per line of therapy and drug were reported for patients who received systemic therapy. Mean total/monthly costs were € 89,240/€ 6809: € 7988/€ 2483 for patients who did not receive systemic therapy (n = 784) and € 105,078/€ 7652 for patients who received systemic therapy (n = 4022). Mean episode/monthly costs were the highest for nivolumab plus ipilimumab (€ 79,675/€ 16,976), ipilimumab monotherapy (€ 79,110/€ 17,252), and dabrafenib plus trametinib (€ 77,053/€ 12,015). Dacarbazine yielded the lowest mean episode/monthly costs (€ 6564/€ 2027). Our study showed that immunotherapeutic and targeted drugs had a large impact on real-world healthcare costs. As new drugs continue entering the treatment landscape for (metastatic) melanoma, it remains crucial to monitor whether the benefits of these drugs outweigh their costs

Optimisations and challenges involved in the creation of various bioluminescent and fluorescent influenza a virus strains for in vitro and in vivo applications

Bioluminescent and fluorescent influenza A viruses offer new opportunities to study influenza virus replication, tropism and pathogenesis. To date, several influenza A reporter viruses have been described. These strategies typically focused on a single reporter gene (either bioluminescent or fluorescent) in a single virus backbone. However, whilst bioluminescence is suited to in vivo imaging, fluorescent viruses are more appropriate for microscopy. Therefore, the idea l reporter virus varies depending on the experiment in question, and it is important that any reporter virus strategy can be adapted accordingly. Herein, a strategy was developed to create five different reporter viruses in a single virus backbone. Specifically, enhanced green fluorescent protein (eGFP), far-red fluorescent protein (fRFP), near-infrared fluorescent protein (iRFP), Gaussia luciferase (gLUC) and firefly luciferase (fLUC) were inserted into the PA gene segment of A/PR/8/34 (H1N1). This study provides a comprehensive characterisation of the effects of different reporter genes on influenza virus replication and reporter activity. In vivo reporter gene expression, in lung tissues, was only detected for eGFP, fRFP and gLUC expressing viruses. In vitro, the eGFP-expressing virus displayed the best reporter stability and could be used for correlative light electron microscopy (CLEM). This strategy was then used to create eGFP-expressing viruses consisting entirely of pandemic H1N1, highly pathogenic avian influenza (HPAI) H5N1 and H7N9. The HPAI H5N1 eGFP-expressing virus infected mice and reporter gene expression was detected, in lung tissues, in vivo. Thus, this study provides new tools and insights for the creation of bioluminescent and fluorescent influenza A reporter viruses. Copyright

Lower risk of severe checkpoint inhibitor toxicity in more advanced disease

Background Immune checkpoint inhibitor (ICI) can cause severe and sometimes fatal immune-related adverse events (irAEs). Since these irAEs mimick immunological disease, a female predominance has been speculated on. Nevertheless, no demographic or tumour-related factors associated with an increased risk of irAEs have been identified until now. Methods Risk ratios of severe (grade ≥3) irAEs for age, sex, WHO performance status, number of comorbidities, stage of disease, number of metastases and serum lactate dehydrogenases (LDH) were estimated using data from anti-PD1-treated patients with advanced melanoma in the prospective nationwide Dutch Melanoma Treatment Registry. Results 111 (11%) out of 819 anti-programmed cell death 1 treated patients experienced severe irAEs. Patients with non-lung visceral metastases (stage IV M1c or higher) less often experienced severe irAEs (11%) compared with patients with only lung and/or lymph node/soft tissue involvement (stage IV M1b or lower; 19%; adjusted risk ratio (RR adj) 0.63; 95% CI 0.41 to 0.94). Patients with LDH of more than two times upper limit of normal had a non-significantly lower risk of developing severe irAEs than those with normal LDH (RR adj 0.65; 95% CI 0.20 to 2.13). None of the other variables were associated with severe irAEs. Conclusion In patients with melanoma, more advanced disease is associated with a lower rate of severe irAEs. No association with sex was found