The sense of safety and security of older people is a widely acknowledged action domain for policy and practice in age-friendly cities. Despite an extensive body of knowledge on the matter, the... Show moreThe sense of safety and security of older people is a widely acknowledged action domain for policy and practice in age-friendly cities. Despite an extensive body of knowledge on the matter, the theory is fragmented, and a classification is lacking. Therefore, this study investigated how older people experience the sense of safety and security in an age-friendly city. A total of four focus group sessions were organised in The Hague comprising 38 older people. Based on the outcomes of the sessions, the sense of safety and security was classified into two main domains: a sense of safety and security impacted by intentional acts and negligence (for instance, burglary and violence), and a sense of safety and security impacted by non-intentional acts (for instance, incidents, making mistakes online). Both domains manifest into three separate contexts, namely the home environment, the outdoor environment and traffic and the digital environment. In the discussions with older people on these derived domains, ideas for potential improvements and priorities were also explored, which included access to information on what older people can do themselves to improve their sense of safety and security, the enforcement of rules, and continuous efforts to develop digital skills to improve safety online. Show less
Dijk, M. van; Brakenhoff, S.M.; Isfordink, C.J.; Cheng, W.H.; Blokzijl, H.; Boland, G.; ... ; Knegt, R.J. de 2021
Background: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is... Show moreBackground: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to harvest detailed data on the Dutch HCV epidemic. This study aims to provide a well-supported timeline towards HCV elimination in The Netherlands. Methods: A previously published Markov model was used, adopting published data and unpublished CELINE project data. Two main scenarios were devised. In the Status Quo scenario, 2020 diagnosis and treatment levels remained constant in subsequent years. In the Gradual Decline scenario, an annual decrease of 10% in both diagnoses and treatments was implemented, starting in 2020. WHO incidence target was disregarded, due to low HCV incidence in The Netherlands (& LE;5 per 100,000). Results: Following the Status Quo and Gradual Decline scenarios, The Netherlands would meet WHO's elimination targets by 2027 and 2032, respectively. From 2015 to 2030, liver-related mortality would be reduced by 97% in the Status Quo and 93% in the Gradual Decline scenario. Compared to the Status Quo scenario, the Gradual Decline scenario would result in 12 excess cases of decompensated cirrhosis, 18 excess cases of hepatocellular carcinoma, and 20 excess cases of liver-related death from 2020-2030. Conclusions: The Netherlands is on track to reach HCV elimination by 2030. However, it is vital that HCV elimination remains high on the agenda to ensure adequate numbers of patients are being diagnosed and treated. Show less
Suleimanova, A.; Talanov, M.; Maagdenberg, A.M.J.M. van den; Giniatullin, R. 2021
Familial hemiplegic migraine type 3 (FHM3) is caused by gain-of-function mutations in the SCN1A gene that encodes the alpha 1 subunit of voltage-gated Na(V)1.1 sodium channels. The high level of... Show moreFamilial hemiplegic migraine type 3 (FHM3) is caused by gain-of-function mutations in the SCN1A gene that encodes the alpha 1 subunit of voltage-gated Na(V)1.1 sodium channels. The high level of expression of Na(V)1.1 channels in peripheral trigeminal neurons may lead to abnormal nociceptive signaling thus contributing to migraine pain. Na(V)1.1 dysfunction is relevant also for other neurological disorders, foremost epilepsy and stroke that are comorbid with migraine. Here we used computer modeling to test the functional role of FHM3-mutated Na(V)1.1 channels in mechanisms of trigeminal pain. The activation of A delta-fibers was studied for two algogens, ATP and 5-HT, operating through P2X3 and 5-HT3 receptors, respectively, at trigeminal nerve terminals. In WT A delta-fibers of meningeal afferents, Na(V)1.1 channels efficiently participate in spike generation induced by ATP and 5-HT supported by Na(V)1.6 channels. Of the various FHM3 mutations tested, the L263V missense mutation, with a longer activation state and lower activation voltage, resulted in the most pronounced spiking activity. In contrast, mutations that result in a loss of Na(V)1.1 function largely reduced firing of trigeminal nerve fibers. The combined activation of P2X3 and 5-HT3 receptors and branching of nerve fibers resulted in very prolonged and high-frequency spiking activity in the mutants compared to WT. We identified, in silico, key determinants of long-lasting nociceptive activity in FHM3-mutated A delta-fibers that naturally express P2X3 and 5-HT3 receptors and suggest mutant-specific correction options. Modeled trigeminal nerve firing was significantly higher for FHM3 mutations, compared to WT, suggesting that pronounced nociceptive signaling may contribute to migraine pain. Show less
Timp, J.F.; Lijfering, W.M.; Rosendaal, F.R.; Cessie, S. le; Cannegieter, S.C. 2019
Study Design.A retrospective cohort study.Objective.The aim of this study was to assess and compare the predictive accuracy of six models designed to estimate survival of patients suffering from... Show moreStudy Design.A retrospective cohort study.Objective.The aim of this study was to assess and compare the predictive accuracy of six models designed to estimate survival of patients suffering from spinal bone metastases Just (SBMs).Summary of Background Data.On the basis of the estimated survival of patients with SBM, extent of treatment can be adjusted. To aid clinicians in the difficult task of assessing probability of survival, prognostic scoring systems have been developed by Tomita, Tokuhashi, Van der Linden, Bauer, Rades, and Bollen.Methods.All patients who were treated for SBM between 2000 and 2010 were included in this international, multicenter, retrospective study (n=1379). Medical records were reviewed for all items needed to use the scoring systems. Survival time was calculated as the difference between start of treatment for SBM and date of death. Survival curves were estimated using the Kaplan-Meier method and accuracy was assessed with the c-statistic. Survival rates of the worst prognostic groups were evaluated at 4 months.Results.Median follow-up was 6.7 years [95% confidence interval (95% CI) 5.6-7.7] with a minimum of 2.3 years and a maximum of 12.3 years. The overall median survival was 5.1 months (95% CI 4.6-5.6). The most common primary tumors were breast (n=388, 28%), lung (n=318, 23%), and prostate cancer (n=259, 19%). The Tokuhashi, Bauer, Tomita, and Van der Linden models performed similar with a c-statistic of 0.64 to 0.66 and a 4-month accuracy of 62% to 65%. The Rades model (c-statistic 0.44) and Bollen model (c-statistic 0.70) had a 4-month accuracy of 69% and 75%, respectively.Conclusion.The Bollen model performs better than the other models. However, improvements are still warranted to increase the accuracy.Level of Evidence: 3 Show less
