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Point of view:Challenges in implementation of new immunotherapies for Alzheimer's disease
No full textThe advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists. Additionally, there are logistical concerns related to infrastructure, as well as cost-effectiveness and reimbursement issues. This article brings together insights from a diverse group of international researchers and dementia experts and outlines the potential challenges and opportunities, urging all stakeholders to prepare for the introduction of DMTs. We emphasize the need to develop appropriate use criteria, including patient characteristics, specifically for the European healthcare system, to ensure that treatments are administered to the most suitable patients. It is crucial to improve the skills and knowledge of physicians to accurately interpret biomarker results, share decision-making with patients, recognize treatment-related side effects, and monitor long-term treatment. We advocate for investment in patient registries and unbiased follow-up studies to better understand treatment effectiveness, evaluate treatment-related side effects, and optimize long-term treatment. Utilizing amyloid-targeting therapies as a starting point for combination therapies should also be a priority
Changing meat on the plate:an interdisciplinary examination of meat alternatives
Get PDFWe face significant challenges, such as climate change, that demand a more sustainable food system. An important aspect of this is the transition from animal-based to plant-based foods. In her research, Linsay Ketelings addresses three key questions: (i) what exactly do we mean by meat alternatives, (ii) how do consumers perceive these products, particularly in terms of health and nutritional value, and (iii) to what extent do the names of meat alternatives cause confusion among consumers, producers, and policymakers? A clear definition of meat alternatives is crucial to ensure that everyone – from researchers to retailers – has the same understanding. This requires attention to aspects such as production methods, taste, nutritional value, sustainability, and consumer perception. The research shows that consumers generally assess the nutritional value of meat alternatives quite well. However, they sometimes overestimate health benefits or protein content, particularly when claims like “high in protein” are present. Additionally, names such as "vegetarian sausage" can confuse some people about the product's category. These insights underline the importance of clear regulations and accurate information. They provide guidance for producers, policymakers, and consumers to work together towards a more sustainable diet
Have a little faith:Validating student voices in vocational education
Get PDFInvolving students in shaping their own education allows for more suitable education, more engagement and motivation, and increased relevance and quality of education. However, student perspectives have been marginalised in teaching and learning. The aim of this thesis is to contribute to a better, healthier and more promising position for vocational education students by promoting student voice activities, in particular by involving students in organising, designing and delivering citizenship education classes for their peers. This thesis is centred around three research questions: 1) Who are these VET students and what makes them tick? 2) What kind of beliefs and expectations do these students have about themselves and how are they perceived by those around them? 3) How do these beliefs and expectations influence their participation in citizenship education development
Constructing Chinese Firms as Development Catalysts:State-Firm Public Diplomacy Collaboration in Kenya
No full textThe debate surrounding China's public diplomacy in Africa highlights how the state coordinates and leverages Chinese actors, including firms, to advance diplomatic objectives. However, this article questions the notion of unidirectional state dominance by exploring the intricate interactions between the Chinese state and firms around promoting and publicizing corporate social responsibility (CSR), which is conceptualized as a public diplomacy tool of corporations to engage with the foreign public. Using the lens of public diplomacy, the author examines the unconventional state-firm interplay in the symbolic domain, shedding light on practices of China's expansion in Africa. Through two empirical cases, the author demonstrates the interdependence and collaboration between the Chinese state and firms, revealing their divided interests and contested cooperative efforts to enact public diplomacy in Kenya
The Association Between Trajectories of Self-reported Psychotic Experiences and Continuity of Mental Health Care in a Longitudinal Cohort of Adolescents and Young Adults
No full textBackground and Hypothesis Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition to AMHS and mental health outcomes.Study Design In this prospective cohort study, interviews and questionnaires were used to assess PE, mental health, and service use in 763 child and adolescent mental health service users reaching their service's upper age limit in 8 European countries. Trajectories of self-reported PE (3 items) from baseline to 24-month follow-up were determined using growth mixture modeling (GMM). Associations were assessed with auxiliary variables and using mixed models. Study results. At baseline, 56.7% of YP reported PE. GMM identified 5 trajectories over 24 months: medium increasing (5.2%), medium stable (11.7%), medium decreasing (6.5%), high decreasing (4.2%), and low stable (72.4%). PE trajectories were not associated with continuity of specialist care or transition to AMHS. Overall, YP with PE reported more mental health problems at baseline. Persistence of PE or an increase was associated with poorer outcomes at follow-up.Conclusions PE are common among CAMHS users when reaching the upper age limit of CAMHS. Persistence or an increase of PE was associated with poorer mental health outcomes, poorer prognosis, and impaired functioning, but were less discriminative for continuity of care
Joint Trajectories of Performance-Based and Self-Reported Physical Functioning in Older Adults:A 20-Year Longitudinal Study in the Netherlands
No full textBackground: The well-known disablement process has been conceptualized as a series of transitions between progressive states of functional decline. We studied joint patterns of change within disablement states defined as walking speed, grip strength, and self-reported disability. Methods: 1702 participants aged 65 and over were included from the Longitudinal Aging Study Amsterdam, spanning seven waves over 20 years (1996–2016). Group-based multi-trajectory modeling yielded trajectory clusters (TCs) of different patterns of change, further characterized by baseline sociodemographic characteristics, physical and cognitive health, and survival rate. Results: Five TCs were identified, distinguished by increasing baseline age. Walking speed and disability showed generally concomitant trajectories. Women had poorer trajectories in grip strength than men, but not in walking speed and disability. Poor physical health distinguished especially the poorest, and cognitive impairment distinguished especially the one-before-poorest from the better TCs. Discussion: The findings suggest that the disablement states are not generally distinct or sequential
Diffusion-derived intravoxel-incoherent motion anisotropy relates to CSF and blood flow
No full textThis study investigates the feasibility of multi-b-value, multi-directional diffusion MRI for assessing the anisotropy of the cerebral pseudo-diffusion (D*)-tensor. We examine D*-tensor's potential to (1) reflect CSF and blood flow, and (2) detect microvascular architectural alterations in cerebral small vessel disease (cSVD) and aging. Methods: Multi-b-value diffusion MRI was acquired in 32 gradient directions for 11 healthy volunteers, and in six directions for 29 patients with cSVD and 14 controls at 3 T. A physics-informed neural network was used to estimate intravoxel incoherent motion (IVIM)–DTI model parameters, including the parenchymal slow diffusion (D-)tensor and the pseudo-diffusion (D*)-tensor, from which the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were derived. Comparisons of D*-tensor metrics were made between lateral, third, and fourth ventricles and between the middle cerebral arteries and superior sagittal sinus. Group differences in D*-tensor metrics in normal-appearing white matter were analyzed using multivariable linear regression, correcting for age and sex. Results: D*-anisotropy aligned well with CSF flow and arterial blood flow. FA(D*), MD(D*), AD(D*), and RD(D*) were highest in the third, moderate in the fourth, and lowest in the lateral ventricles. The arteries showed higher MD(D*), AD(D*), and RD(D*) than the sagittal sinus. Higher FA(D*) in the normal-appearing white matter was related to cSVD diagnosis and older age, suggesting microvascular architecture alterations. Conclusion: Multi-b-value, multi-directional diffusion analysis using the IVIM–DTI model enables assessment of the cerebral microstructure, fluid flow, and microvascular architecture, providing information on neurodegeneration, glymphatic waste clearance, and the vasculature in one measurement.</p
Percutaneous coronary intervention with drug-eluting stents versus coronary bypass surgery for coronary artery disease:a Bayesian perspective
No full textObjectives: Coronary revascularization is frequently performed for coronary artery disease (CAD). This study aims to assess the totality of randomized evidence comparing percutaneous coronary intervention with drug-eluting stents (DES-PCI) with coronary artery bypass grafting (CABG) for CAD. Methods: A systematic search was applied to 3 electronic databases, including randomized trials comparing DES-PCI with CABG for CAD with 5-year follow-up. A Bayesian hierarchical meta-analytic model was applied. The primary outcome was all-cause mortality at 5 years; secondary outcomes were stroke, myocardial infarction, and repeat revascularization. End points were reported in median relative risks (RRs) and absolute risk differences, with 95% credible intervals (CrIs). Kaplan-Meier curves were used to reconstruct individual patient data. Results: Six studies comprising 8269 patients (DES-PCI, n = 4134; CABG, n = 4135) were included. All-cause mortality at 5 years was increased with DES-PCI (median RR, 1.23; 95% CrI, 1.01-1.45), with a median absolute risk difference of +2.3% (95% CrI, 0.1%-4.5%). For stroke, myocardial infarction, and repeat revascularization, the median RRs were 0.79 (95% CrI, 0.54-1.25), 1.84 (95% CrI, 1.23-2.75), and 1.80 (95% CrI, 1.51-2.16) for DES-PCI, respectively. In a sample of 1000 patients undergoing DES-PCI instead of CABG for CAD, a median of 23 additional deaths, 46 myocardial infarctions, and 85 repeat revascularizations occurred at 5 years, whereas 10 strokes were prevented. Conclusions: The current data suggest a clinically relevant benefit of CABG over DES-PCI at 5 years in terms of mortality, myocardial infarction, and repeat revascularization, despite an increased risk of stroke. These findings may guide the heart-team and the shared decision-making process.</p
An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting
No full textObjective: Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department. Methods: We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centres. We analysed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or other. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine. Results: The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI: 92.3, 98.3), while the accuracy for classification of MSU using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI: 87.9, 95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI: 82.7, 92.2). The model was able to discriminate between pathological crystals, artifacts and other particles such as microplastics. Conclusion: We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.</p