51628 research outputs found
Sort by
Evaluation of NanoLuc substrates for bioluminescence imaging of transferred cells in mice
Get PDFNanoLuc luciferase recently gained popularity due to its small size and superior bioluminescence performance. For in vivo imaging applications, NanoLuc has been limited by its substrate furimazine, which has low solubility and bioavailability. Herein, we compared the performances of recently reported NanoLuc luciferase substrates for in vivo imaging in mice. Two substrates with improved aqueous solubility, hydrofurimazine and fluorofurimazine, were evaluated along with three stabilized O-acetylated furimazine analogues, the hikarazines. All 5 analogues, when tested in vitro, displayed greater signal intensity and reaction duration, in comparison to the standard NanoLuc substrate, furimazine. The two best-performing analogues from the in vitro study were selected for further in vivo testing. The NanoLuc/fluorofurimazine pair demonstrated the highest bioluminescence intensity, post intravenous administration. It was found to be around 9-fold brighter compared to the NanoLuc/furimazine and 11-fold more intense than the NanoLuc/hikarazine-003 pair, with an average of 3-fold higher light emission when the substrate was injected intraperitoneally, in a subcutaneous model. Excitingly, despite the fact that NanoLuc/fluorofurimazine emits mostly blue light, we prove that cells trapped in mice lungs vasculature could be visualised via the NanoLuc/fluorofurimazine pair and compare the results to the AkaLuc/AkaLumine system. Therefore, among the tested analogues, fluorofurimazine enables higher substrate loading and improved optical imaging sensitivity in small animals, upgrading the use of NanoLuc derived bioluminescent systems for deep tissue imaging
Changes in hospital variation in the probability of receiving treatment with curative intent for esophageal and gastric cancer
Get PDFBackground: Previous studies describe a large variation in the proportion of patients undergoing treatment with curative intent for esophageal (EC) and gastric cancer (GC). Since centralization of surgical care was initiated and more awareness regarding hospital practice variation was potentially present, we hypothesized that hospital practice variation for potentially curable EC and GC patients changed over time. Methods: Patients with potentially curable EC (n = 10,115) or GC (n = 3988) diagnosed between 2012–2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to analyze the differences in the probability of treatment with curative intent between hospitals of diagnosis over time, comparing 2012−2014 with 2015−2017. Relative survival (RS) between hospitals with different probabilities of treatment with curative intent were compared. Results: The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis for EC was 45–95 % in 2012−2014 and 54–89 % in 2015−2017, and for GC 52–100 % and 45–100 %. The adjusted variation declined for EC with Odds Ratios ranging from 0.50 to 1.72 between centers in the first period to 0.70–1.44 in the second period (p < 0.001) and did not change for GC (Odds Ratios ranging from 0.78 to 1.23 to 0.82–1.23, (p = 1.00)). A higher probability of treatment with curative intent was associated with a better survival for both malignancies. Conclusion: Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC. A low probability of receiving curative treatment remained associated with worse survival
"Care is not care if it isn't person-centred": A content analysis of how Person-Centred Care is expressed on Twitter
Get PDFBackground: Person-Centred Care (PCC) has been the subject of growing interest in recent decades. Even though there is no conceptual consensus regarding PCC, many health-care institutions have implemented elements into their care. Objective: This study aimed to investigate the PCC topics presented by different stakeholder groups on Twitter and to explore the perceptions of PCC within the content of the tweets. Method: Tweets with mentions of PCC in various translations were collected through a Twitter Application Programming Interface in October 2019. The tweets were analysed using quantitative and qualitative content analysis. Results: Five stakeholder groups and ten topics were identified within 1540 tweets. The results showed that the PCC content focused on providing information and opinions rather than expressing experiences of PCC in practice. Qualitative content analysis of 428 selected tweets revealed content on a vision that all care should be person-centred but that the realization of that vision was more complicated. Conclusions: Twitter has shown to be a quick and non-intrusive data collection tool for uncovering stakeholders' expressions concerning PCC. The PCC content revealed that stakeholders feel a need to 'educate' others about their perception of PCC when experiences and real-life applications are missing. More action should be taken for the implementation of PCC rather than circulating PCC vision without operationalization in care. Public Contribution: The public provided the data through their posts on Twitter, and it is their perception of PCC that is studied here
Remote consultations in paediatric urology–Not just for pandemics?
No full textAlthough some centres have successfully integrated remote clinics into their paediatric urological practice, for many, remote clinics have developed due to the COVID-19 pandemic. One UK-based institution has integrated remote clinics in their practice for over two years and has developed guidelines considering which conditions may be suitable for remote consultations. These guidelines have been appraised by the European Association of Urology Young Academic Urologists paediatric working group. Through practical experience and anticipated difficulties, we have discussed considerations that paediatric urology departments should ponder when integrating remote clinics into their practice as we move forward from the pandemic
The optimal HPV-screening protocol in Eastern-Europe: The example of Slovenia
Get PDFObjective: Eastern European countries are contemplating to introduce the high-risk Human Papillomavirus (HPV)-test as the primary screening test for their cervical cancer screening programme, but its optimal protocol is yet unknown. The aim of this study was to compare the costs, effects and cost-effectiveness of different primary HPV-screening protocols in Eastern Europe, using Slovenia as an example and with respect of local preferences for screening. Methods: We evaluated 968 HPV-screening protocols, which varied by screening ages, triage tests (i.e. cytology, repeat HPV and/or genotyping) and strategy for women under 35 years old, using the microsimulation model MISCAN-Cervix. Results: Within the subset of strategies that would be acceptable for Slovenian women, the optimal HPV-screening protocol is to start with two cytology tests at age 25 and 28 and switch to 5-yearly HPV screening from age 30 to 65. When also other protocols were considered, the optimal screening strategy would be 5-yearly HPV screening from age 30 to 65 only, improving the cost-effectiveness with 5%. Adding genotyping in the triage algorithm consistently improved cost-effectiveness. Sensitivity analyses showed the robustness of the results for other situations in Eastern Europe. Conclusions: Despite differences in cervical cancer epidemiology between Eastern and Western European regions where HPV screening was evaluated, the optimal screening protocol was found to be very similar. Furthermore, strategies that were considered socially acceptable to the population were found to be almost as cost-effective as less acceptable strategies and can therefore be considered a viable alternative to prevent opportunistic screening
Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? – A preclinical assessment in vitro and in vivo
Get PDFBackground: Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They are virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced by proteasome inhibitors such as bortezomib. Methods and results: In this study, we assessed several combined treatment modalities in vitro and in vivo. By cell-based functional analyses, in a 3D in ovo and an orthotopic mouse model, we demonstrated sensitizing effects of bortezomib combined with cisplatin, radiation and peptide receptor radionuclide therapy (PRRT). By gene expression profiling and western blot, we explored the underlying mechanisms, which resulted in an impaired DNA damage repair. Therapy-induced DNA damage triggered extrinsic proapoptotic signaling as well as the induction of cell cycle arrest, leading to a decreased vital tumor volume and altered tissue composition shown by magnetic resonance imaging and F-18-FDG-PET in vivo, however with no significant additional benefit related to PRRT alone. Conclusions: We demonstrated that bortezomib has short-term sensitizing effects when combined with DNA damaging therapy by interfering with DNA repair in vitro and in ovo. Nevertheless, due to high tumor heterogeneity after PRRT in long-term observations, we were not able to prove a therapeutic advantage of bortezomib-combined PRRT in an in vivo mouse model
What works better for preference elicitation among older people? Cognitive burden of discrete choice experiment and case 2 best-worst scaling in an online setting
Get PDFTo appropriately weight dimensions of quality of life instruments for health economic evaluations, population and patient preferences need to be elicited. Two commonly used elicitation methods for this purpose are discrete choice experiments (DCE) and case 2 best-worst scaling (BWS). These methods differ in terms of their cognitive burden, which is especially relevant when eliciting preferences among older people. Using a randomised experiment with respondents from an online panel, this paper examines the cognitive burden associated with colour-coded and level overlapped DCE, colour-coded BWS, and ‘standard’ BWS choice tasks in a complex health state valuation setting. Our sample included 469 individuals aged 65 and above. Based on both revealed and stated cognitive burden, we found that the DCE tasks were less cognitively burdensome than case 2 BWS. Colour coding case 2 BWS cannot be recommended as its effect on cognitive burden was less clear and the colour coding lead to undesired choice heuristics. Our results have implications for future health state valuations of complex quality of life instruments and at least serve as an example of assessing cognitive burden associated with different types of choice experiments
Conditional relative survival among patients with follicular lymphoma: a population-based study in the Netherlands
Get PDFGuillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study
Get PDFObjective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil. Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids. Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently. Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS