The studies described in this thesis investigate the effects of different pharmacotherapieson antinociception and ventilatory control. Additionally, inherent variabilities in patient phenotypes... Show moreThe studies described in this thesis investigate the effects of different pharmacotherapieson antinociception and ventilatory control. Additionally, inherent variabilities in patient phenotypes within the population were assessed to gain a deeper understanding of the individual effects of analgesics and the ventilatory effects of disease, particularly type 2 diabetes mellitus (T2DM). Show less
Proteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by... Show moreProteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by revisiting elements previously considered essential, investigating known pathways, and identifying new players in the field of proteinuria. First, a zebrafish embryo model for developing new therapeutic options for the rare but devastating disease of nephropathic cystinosis is presented. The studies presented in thesis also investigate loss of heparan sulphate glycosaminoglycans in a zebrafish embryo model and in multiple osteochondroma patients. These studies show that loss of heparan sulphate glycosaminoglycans does not always lead to proteinuria. Next, dynamin is described as a promising potential therapeutic target for treating proteinuria. The final study introduces transmembrane protein 14A as an essential factor in maintaining glomerular filtration barrier function. Overall, these studies contribute to elucidating the pathways to proteinuria in the hope to keep advancing the field towards targeted treatment of proteinuria for the benefit of our patients. Show less
The aim of the thesis was to contribute to a better understanding of the influence of differences in implant design and surgical techniques on the migration of total knee arthroplasties (TKAs) and,... Show moreThe aim of the thesis was to contribute to a better understanding of the influence of differences in implant design and surgical techniques on the migration of total knee arthroplasties (TKAs) and, more broadly, the effect of using Radiostereometric Analysis (RSA) and other markers to detect early loosening. In this thesis, we compared various types of TKAs in different randomized controlled trials. Additionally, we investigated whether the positioning of TKAs relative to the patient's specific leg axis (e.g., neutral, varus, or valgus alignment) affects the stability of the prosthesis. We also analyzed, by combining registry data with data from a meta-analysis, whether TKAs evaluated with migration analysis (radiostereometric analysis; RSA) yield better results than TKAs that have not been previously examined with RSA. Finally, we conducted a systematic review to explore whether there are markers that can indicate loosening/failure of a prosthesis. Show less
Creutzig, F.; Simoes, S. G.; Leipold, S.; Berrill, P.; Azevedo, I.; Edelenbosch, O.; ... ; Wilson, C. 2024
As fossil fuels are phased out in favour of renewable energy, electric cars and other low-carbon technologies, the future clean energy system is likely to require less overall mining than the... Show moreAs fossil fuels are phased out in favour of renewable energy, electric cars and other low-carbon technologies, the future clean energy system is likely to require less overall mining than the current fossil-fuelled system. However, material extraction and waste flows, new infrastructure development, land-use change, and the provision of new types of goods and services associated with decarbonization will produce social and environmental pressures at localized to regional scales. Demand-side solutions can achieve the important outcome of reducing both the scale of the climate challenge and material resource requirements. Interdisciplinary systems modelling and analysis are needed to identify opportunities and trade-offs for demand-led mitigation strategies that explicitly consider planetary boundaries associated with Earth’s material resources. Show less
Hoffman, C.M.; Versluis, A.; Chirila, S.; Kirenga, B.J.; Khan, A.; Saeed, S.; ... ; Kleij, M.J.J.R. van der 2024
The FRESHAIR4Life study aims to reduce the non-communicable disease (NCD) burden by implementing preventive interventions targeting adolescents’ exposure to tobacco use and air pollution (AP)... Show moreThe FRESHAIR4Life study aims to reduce the non-communicable disease (NCD) burden by implementing preventive interventions targeting adolescents’ exposure to tobacco use and air pollution (AP) worldwide. This paper presents the FRESHAIR4Life methodology and initial rapid review results. The rapid review, using various databases and PubMed, aimed to guide decision-making on risk factor focus, target areas, and populations. It showed variable NCD mortality rates related to tobacco use and AP across the participating countries, with tobacco as the main risk factor in the Kyrgyz Republic, Greece, and Romania, and AP prevailing in Pakistan and Uganda. Adolescent exposure levels, sources, and correlates varied. The study will continue with an in-depth situational analysis to guide the selection, adaptation, and integration of evidence-based interventions into the FRESHAIR4Life prevention package. This package will be implemented, evaluated, assessed for cost-effectiveness, and iteratively refined. The research places a strong emphasis on co-creation, capacity building, and comprehensive communication and dissemination. Show less
Oratie uitgesproken door Prof. Dr. Suzan Verberne bij de aanvaarding van het ambt van hoogleraar Natural Language Processing aan de Universiteit Leiden op maandag 3 juni 2024_______________________... Show moreOratie uitgesproken door Prof. Dr. Suzan Verberne bij de aanvaarding van het ambt van hoogleraar Natural Language Processing aan de Universiteit Leiden op maandag 3 juni 2024____________________________________________________________Text also in English : Is the search engine of the future a chatbot? Show less
Simonse, O.; Dijk, W. van; Dillen, L.F. van; Dijk, E. van 2024
The subjective experience of financial stress has profound implications for well-being, health, cognitive performance, and decision-making. In a sample of Dutch households (N = 1114), we studied... Show moreThe subjective experience of financial stress has profound implications for well-being, health, cognitive performance, and decision-making. In a sample of Dutch households (N = 1114), we studied the association of five economic factors - income, saving, debts, income volatility, and employment - with a four-factor measure of financial stress: 1) an appraisal of insufficient financial resources, 2) an appraisal of lack of control over one's financial situation, 3) financial worries and rumination, and 4) a short-term focus. This enabled us to examine the economic factors' relative contributions to predicting5 financial stress. We found that the combination of economic factors predicted financial stress better than income alone. Particularly, buffer savings had a large contribution to predicting financial stress. The number of debts had a smaller relative contribution to predicting financial stress, whereas we did not find support for debt amount as a predictor of financial stress. Employment was negatively associated with financial stress, but only for households with the lowest incomes. We found no support for income volatility predicting financial stress. These results imply that research and policy on financial stress should have a broader scope than income alone and should take a more integrative approach to households' financial situation, considering savings, number of debts, and unemployment. Show less
Objectives: Troponin I has been suggested as a more specific diagnostic biomarker for myocardial involvement in systemic sclerosis than the frequently used troponin T. The aim of this study is to... Show moreObjectives: Troponin I has been suggested as a more specific diagnostic biomarker for myocardial involvement in systemic sclerosis than the frequently used troponin T. The aim of this study is to evaluate the additive value of troponin I to detect myocardial involvement in systemic sclerosis. To this end, we evaluated the association between troponin I levels and myocardial involvement in systemic sclerosis patients. Methods: A cross-sectional observational study was performed, including 20 healthy controls and four groups of each 20 systemic sclerosis patients from the Leiden Combined Care in Systemic Sclerosis cohort: (1) patients with myocardial involvement, (2) patients with myositis, (3) patients with elevated troponin T and creatine kinase levels but without organ involvement, and (4) patients without any signs of organ involvement. Troponin I levels were measured using enzyme-linked immunosorbent assay. Troponin I levels were compared between the different groups using the Mann–Whitney U and Kruskal–Wallis tests. Results: The mean age of the 80 included patients was 56 years; 61% of the study population was female. Troponin I levels were not significantly different between patients with and without myocardial involvement (2.7 (0.5–15.3) vs 1.2 (0.1–6.6) ng/L; p=0.117). Systemic sclerosis patients were more often positive for troponin I than healthy controls (70.0% vs 30.0%; p=0.001). Conclusion: Elevated troponin I was not of additional value to diagnose myocardial involvement in systemic sclerosis patients. Show less
Background: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To... Show moreBackground: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To investigate measures related to staff during the COVID-19 pandemic, staff perspectives of important measures and the involvement of staff in deciding on these measures. Design: A qualitative study. Setting(s): We analysed minutes of nursing home outbreak teams in the Netherlands and conducted group meetings with Dutch nursing home staff in different positions, prioritizing measures and discussing staff' involvement in deciding on the measures. Participants were recruited purposefully. Participants: The minutes of 41 nursing home organizations were collected during March-November, 2020. Four group meetings were organized in the same period, each with 5 to 7 participants, resulting in 23 participants. Methods: The meeting minutes were analysed using qualitative content analysis, whereas reflexive thematic analysis was used for the group meeting data. The group meetings were conducted online and structured by the Nominal Group Technique to discuss the importance of measures for staff. Results: Measures implemented for staff focused on prevention of COVID-19 transmission, (suspension of) educational activities, testing, additional tasks and staffing capacity, promoting wellbeing, and other means of support. The implemented measures overlapped with the measures considered important by staff. In addition, staff considered measures on decision-making support and communication to be important. Staff prioritized the measures in the group meetings because they affected their well-being, workforce scheduling, decision-making, or infection prevention. Furthermore, the group meetings revealed that decision-making shifted from mainly implementing national measures to more context-adjusted decision-making in the staff's or clients' situations. Conclusions: We showed that although nursing home staff were not always involved in decisionmaking during the first COVID-19 wave, there was overlap between the measures implemented by the organizations and measures considered important by staff. We suggest that organizations Show less
This article studies the use of the Bare Aorist in the Berber variety of Figuig, an oasis at the border of Morocco and Algeria. Like elsewhere in Berber, the Bare Aorist isused as a form that is... Show moreThis article studies the use of the Bare Aorist in the Berber variety of Figuig, an oasis at the border of Morocco and Algeria. Like elsewhere in Berber, the Bare Aorist isused as a form that is neutral as to aspect, whose interpretation is provided by context. It is shown that the major types of occurrence that were established for other varieties (Mauri2017) are also represented in Figuig Bare Aorists. Framed Aorists are found in main clauses that are preceded by a temporal/aspectual clause that provides the framing for its aspectual interpretation. With Chained Aorists, the framing is provided by verbs in preceding main clauses. It is shown, however, that Chained Aorists are subtly different in Figuig from the way they have been described for other varieties, as they mainly occur to express continuity at points where such a continuity is less expected. Show less
Nanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken... Show moreNanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken embryos. We injected the embryos in the vitelline vein at stages 18–19. We injected polystyrene nanoparticles (PS-NPs) tagged with europium- or fluorescence. Their biodistribution was tracked using inductively-coupled plasma mass spectrometry on tissue lysates, paraffin histology, and vibratome sections analysed by machine learning algorithms. PS-NPs were found at high levels in the heart, liver and kidneys. Furthermore, PS-NPs crossed the endocardium of the heart at sites of epithelial-mesenchymal transformation; they also crossed the liver endothelium. Finally, we detected PS-NPs in the allantoic fluid, consistent with their being excreted by the kidneys. Our study shows the power of the chicken embryo model for analysing the biodistribution of nanoplastics in embryos. Such experiments are difficult or impossible in mammalian embryos. These findings are a major advance in our understanding of the biodistribution and tissue-specific accumulation of PS-NPs in developing animals. Show less
Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward... Show moreIndividuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (atrisk carriers) using of a one-time questionnaire. A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46–63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22–32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children’s cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options. Show less
Predicting the development of rheumatoid arthritis (RA) in an early stage through magnetic resonance imaging (MRI) can initiate timely treatment and improve long-term patient outcomes. Although... Show morePredicting the development of rheumatoid arthritis (RA) in an early stage through magnetic resonance imaging (MRI) can initiate timely treatment and improve long-term patient outcomes. Although manual prediction is time-consuming and requires expert knowledge, automatic RA prediction has not been fully investigated. While standard models fail to achieve acceptable performance, we present a consistency-based deep learning framework to classify and predict RA automatically and precisely, including an output-standardized model, customized self-supervised pretraining and a loss function that is based on label consistency between original and augmented inputs. For training and evaluation, we used a database, containing 5945 MRI scans of carpal, metacarpophalangeal (MCP), and metatarsophalangeal (MTP) joints, from 2151 subjects obtained over a period of ten years. Four (three classification- and one prediction-) tasks were defined to distinguish two patient groups (with recent-onset arthritis and clinically suspect arthralgia) from healthy controls and RA from other arthritis patients within the recent-onset arthritis group, and predict RA development in a period of two years within the clinically suspect arthralgia group. The proposed method was evaluated with the area under the receiver operating curve (AUROC) on a separate test set, achieving mean AUROCs of 83.6%, 83.3%, and 69.7% in the three classification tasks, and 67.8% in the prediction task. This proves the existence of early signs of RA in MRI and the potential of a consistency-based deep learning model to detect these early signs and predict RA Show less
BackgroundWhen research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus among interested stakeholders. In these processes, the... Show moreBackgroundWhen research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus among interested stakeholders. In these processes, the knowledge, experience, and expertise of health professionals, researchers, policymakers, and the public are systematically collected and synthesised to reach agreed clinical recommendations and/or priorities. However, despite the influence of consensus exercises, the methods used to achieve agreement are often poorly reported. The ACCORD (ACcurate COnsensus Reporting Document) guideline was developed to help report any consensus methods used in biomedical research, regardless of the health field, techniques used, or application. This explanatory document facilitates the use of the ACCORD checklist.Methods and findingsThis paper was built collaboratively based on classic and contemporary literature on consensus methods and publications reporting their use. For each ACCORD checklist item, this explanation and elaboration document unpacks the pieces of information that should be reported and provides a rationale on why it is essential to describe them in detail. Furthermore, this document offers a glossary of terms used in consensus exercises to clarify the meaning of common terms used across consensus methods, to promote uniformity, and to support understanding for consumers who read consensus statements, position statements, or clinical practice guidelines (CPGs). The items are followed by examples of reporting items from the ACCORD guideline, in text, tables, and figures.ConclusionsThe ACCORD materials—including the reporting guideline and this explanation and elaboration document—can be used by anyone reporting a consensus exercise used in the context of health research. As a reporting guideline, ACCORD helps researchers to be transparent about the materials, resources (both human and financial), and procedures used in their investigations so readers can judge the trustworthiness and applicability of their results/recommendations. Show less
Rede uitgesproken door Prof. dr. Anton Jan van Zonneveld ter gelegenheid van zijn afscheid als hoogleraarNierziekten, in het bijzonder de experimentele vasculaire geneeskunde aan de Universiteit... Show moreRede uitgesproken door Prof. dr. Anton Jan van Zonneveld ter gelegenheid van zijn afscheid als hoogleraarNierziekten, in het bijzonder de experimentele vasculaire geneeskunde aan de Universiteit Leiden op vrijdag 31 mei 2024 Show less
Background: The risk of urinary tract infections (UTIs) is increased by unnecessary placement and prolonged use of urinary catheters. Aim: To assess whether inappropriate use of catheters and... Show moreBackground: The risk of urinary tract infections (UTIs) is increased by unnecessary placement and prolonged use of urinary catheters. Aim: To assess whether inappropriate use of catheters and catheter-associated UTI were reduced through patient participation. Methods: In this multicentre, interrupted time-series and before-and-after study, we implemented a patient-centred app which provides catheter advice for patients, together with clinical lessons, feedback via e-mails and support rounds for staff members. Data on catheter use and infections were collected during a six-month baseline and a six-month intervention period on 13 wards in four hospitals in the Netherlands. Dutch Trial Register: NL7178. Findings: Between June 25th, 2018 and August 1st, 2019, 6556 patients were included in 24 point-prevalence surveys, 3285 (50%) at baseline and 3271 (50%) during the intervention. During the intervention 249 app users and a median of seven new app users per week were registered (interquartile range: 5.5e13.0). At baseline, inappropriate catheter use was registered for 175 (21.9%) out of 798 catheters, compared to 55 (7.0%) out of 786 during the intervention. Time-series analysis showed a non-significant decrease of inappropriate use of 5.8% (95% confidence interval: e3.76 to 15.45; P ¼ 0.219), with an odds ratio of 0.27 (0.19e0.37; P < 0.001). Catheter-associated UTI decreased by 3.0% (1.3e4.6; P ¼ 0.001), with odds ratio 0.541 (0.408e0.716; P < 0.001). Show less
Beek, S.H. van de; Erdal, A.; Husebo, B.S.; Vislapuu, M.; Achterberg, W.P.; Caljouw, M.A.A. 2024
Objective: This study aims to identify whether pain and dementia-related behavior are associated withdifferent types of activities in nursing home residents, controlled for dementia severity.Design... Show moreObjective: This study aims to identify whether pain and dementia-related behavior are associated withdifferent types of activities in nursing home residents, controlled for dementia severity.Design: Cross-sectional baseline data from the multicomponent cluster randomized controlled COSMOS trial (acronymfor Communication, Systematic pain treatment,Medication review, Organization of activities, and Safety).Setting and Participants: A total of 723 patients from 33 Norwegian nursing homes with 67 units(clusters). Participants aged >= 65 years, with a life expectancy of >6 months, and with valid data onactivity were eligible for inclusion.Methods: Activity was operationalized in time (hours per week) and type (cognitive, social, physical, andno activity). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), painwith the Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2), and behaviorwith the Neuropsychiatric Inventory Nursing Home version (NPI-NH). Analyses were performed usinglinear and logistic regression. Sensitivity analyses for dementia severity were performed to account foreffect modification.Results: A total of 289 participants were included (mean age 86.2 [SD 7.6]; 74% female). A higher painscore was associated with less time spent on activity in participants with severe dementia (estimate0.897, P = .043). A higher score for the NPI-NH mood cluster (depression and anxiety) was associatedwith a higher likelihood of participation in cognitive activities (odds ratio [OR], 1.073; P ¼ .039). Apathy(OR, 0.884; P = .041) and lack of inhibition (OR, 0.904; P = .042) were associated with a lower likelihoodof participation in social activities as well as no engagement in activities (apathy OR, 0.880; P = .042; lackof inhibition OR, 0.894; P = .034).Conclusion and Implications: Pain and dementia-related behavior may influence the participation inactivities in the nursing home. There is an urgent need to investigate what type of activity stimulatespeople in different stages of dementia. Show less
