Aims Various drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VTNF... Show moreAims Various drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VTNF). Dihydropyridines block L-type calcium channels, but their association with OHCA risk is unknown. We aimed to study whether nifedipine and/or amlodipine, often-used dihydropyridines, are associated with increased OHCA risk, and how these drugs impact on cardiac electrophysiology.Methods and results We conducted a case-control study with VT/VF-documented OHCA cases with presumed cardiac cause from ongoing population-based OHCA registries in the Netherlands and Denmark, and age/sex/index date-matched nonOHCA controls (Netherlands: PHARMO Database Network, Denmark: Danish Civil Registration System). We included 2503 OHCA cases, 10 543 non-OHCA controls in Netherlands, and 8101 OHCA cases, 40 505 nonOHCA controls in Denmark. To examine drug effects on cardiac electrophysiology, we performed single-cell patch-clamp studies in human-induced pluripotent stem cell-derived cardiomyocytes. Use of high-dose nifedipine (>= 60 mg/day), but not low-dose nifedipine (<60 mg/day) or amlodipine (any-dose), was associated with higher OHCA risk than non-use of dihydropyridines [Netherlands: adjusted odds ratios (ORadj) 1.45 (95% confidence interval 1.02-2.07), Denmark: 1.96 (1.18-3.25)] or use of amlodipine [Netherlands: 2.31 (1.54-3.47), Denmark: 2.20 (1.32-3.67)]. Out-of-hospital cardiac arrest risk of (high-dose) nifedipine use was not further increased in patients using nitrates, or with a history of ischaemic heart disease. Nifedipine and amlodipine blocked L-type calcium channels at similar concentrations, but, at clinically used concentrations, nifedipine caused more L-type calcium current block, resulting in more action potential shortening.Conclusion High-dose nifedipine, but not low-dose nifedipine or any-dose amlodipine, is associated with increased OHCA risk in the general population. Careful titration of nifedipine dose should be considered. Show less
Glas, N. de; Bastiaannet, E.; Boer, A. de; Siesling, S.; Liefers, G.J.; Portielje, J. 2019
PurposeThe number of older patients with breast cancer is rapidly increasing. A previous study showed that between 1990 and 2005, the survival of older patients with breast cancer did not improve... Show morePurposeThe number of older patients with breast cancer is rapidly increasing. A previous study showed that between 1990 and 2005, the survival of older patients with breast cancer did not improve in contrast to younger patients. In recent years, scientific evidence in the older age group has increased and specific guidelines for older women with breast cancer have been developed. The aim of this study was to assess changes in survival outcomes of older patients with breast cancer.Patients and methodsAll patients with breast cancer between 2000 and 2017 were included from the Netherlands cancer registry. We assessed changes in treatments using logistic regression. We calculated changes in relative survival as proxy for breast cancer mortality, stratified by age and stage.ResultsWe included 239,992 patients. Relative survival improved for patients<65 for all stages. In patients aged 65-75 years, relative survival did not improve in stage I-II but did improve in stage III breast cancer (RER 0.98, 95% CI 0.96-1.00, p=0.046). Concurrently, prescription of systemic treatments increased. In patients>75, relative survival did not improve in patients with stage I/II or stage III disease, nor did treatment strategies change.ConclusionsThis study shows that relative survival of patients aged 65-75 years with advanced breast cancer has improved, and concurrently, prescription of systemic treatment increased. To improve survival of patients >75 as well, future studies should focus on individualizing treatments based on concomitant comorbidity, geriatric parameters and the risk of competing mortality and toxicity of treatments. Show less
Pouwels, S.; Boer, A. de; Javaid, M.K.; Hilton-Jones, D.; Verschuuren, J.; Cooper, C.; ... ; Vries, F. de 2013
