In België is er sinds 2022 veel aandacht voor het ‘no conflict of interest’-principe. Dit principe is neergelegd in artikel 9 bis van de mer-richtlijn en houdt in essentie in dat lidstaten ervoor... Show moreIn België is er sinds 2022 veel aandacht voor het ‘no conflict of interest’-principe. Dit principe is neergelegd in artikel 9 bis van de mer-richtlijn en houdt in essentie in dat lidstaten ervoor moeten zorgen dat de bevoegde instanties hun uit de richtlijn voortvloeiende taken op objectieve wijze vervullen. Als de bevoegde instantie tevens de opdrachtgever is, moet er een passende scheiding worden aangebracht tussen conflicterende functies. De Raad voor Vergunningsbetwistingen (RvVb) oordeelde in het Wasserij-arrest dat dit artikel niet goed in de Vlaamse regelgeving is geïmplementeerd. Op 26 maart 2024 heeft de Belgische Raad van State een prejudiciële vraag gesteld aan het Hof van Justitie over de uitleg die moet worden gegeven aan artikel 9 bis van de richtlijn.Deze ontwikkeling in Vlaanderen is de aanleiding om te kijken hoe Nederland artikel 9 bis heeft geïmplementeerd: zou het Omgevingsbesluit wel de toets van de RvVb doorstaan? Show less
Objectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19... Show moreObjectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19 naive adults aged 18e30 years were recruited from a previous study on primary vaccination regimens that compared 20 mg ID vaccinations with 100 mg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 mg) or the standard-of-care intramuscular (IM) booster dose (50 mg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18e40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. Results: In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150e11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003e6322) BAU/mL; 6629 (4913e8946) BAU/mL; and 5264 (4032e6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Discussion: Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. Show less
Balsby, I.M.; Nielsen, S.M.; Christensen, R.; Henriksen, M.; Dahl, L.U.M.; Berg, J.I.; ... ; Dossing, A. 2024
Objective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically... Show moreObjective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors’ effect was explored in meta-regression and stratified models with pain as the dependent variable. Results: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of −0.51 (95% confidence interval −0.61 to −0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. Conclusion: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO registration ID: CRD42022298984 Show less
Stoelinga, A.E.C.; Biewenga, M.; Drenth, J.P.H.; Verhelst, X.; Meer, A.J.P. van der; Boer, Y.S. de; ... ; Dutch Autoimmune Hepatitis Study 2024
Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA).... Show moreBackground & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Show less
Meer, M.T. van der; Liscio, E.; Jonker, C.M.; Plaat A.; Vossen, P.T.J.M.; Murukannaiah, P.K. 2024
Non-healing wounds represent a substantial medical burden with few effective treatments available. To address this challenge, we developed a novel epidermal wound healing model using suction... Show moreNon-healing wounds represent a substantial medical burden with few effective treatments available. To address this challenge, we developed a novel epidermal wound healing model using suction blisters in healthy volunteers. This model allowed for the comprehensive assessment of wound healing dynamics and the evaluation of INM-755, a topical cream containing cannabinol, as a potential therapeutic agent. Two clinical studies were conducted: an observational study and an interventional study. In both studies, healthy volunteers underwent a suction blister procedure on their lower back, creating open epidermal wounds. Wound healing parameters were assessed using advanced imaging systems. Skin barrier function and perfusion were evaluated through trans epidermal water loss (TEWL) and dynamic optical coherence tomography (D-OCT), respectively. The observational study demonstrated the successful and reproducible Induction of blisters and the removal of epidermal sheet, enabling quantifiable measurements of wound healing parameters over time. Re-epithelialization was observed, revealing recovery of skin barrier function and perfusion. In the interventional study, differences of treatments over time were quantified using the above-described techniques. Despite differences from disease-specific blistering, our developed model provides a valuable platform for studying wound healing mechanisms and assessing novel therapeutic interventions. The sensitivity to treatment effects demonstrated in our study underscores the potential utility of this model in early-phase clinical drug development programs targeting wound healing disorders. Show less
Background Digital health plays a vital role in healthcare services. Governments in many countries, including China, are increasingly advocating for the appropriate use of digital technologies to... Show moreBackground Digital health plays a vital role in healthcare services. Governments in many countries, including China, are increasingly advocating for the appropriate use of digital technologies to address significant health system challenges. It is crucial to incorporate digital health education into the curriculum for future nurses to adapt to the changes in the digital medical system. This study aimed to evaluate the impact of an online Digital Health and Informatics Course in China on the knowledge and comprehension of key digital health and informatics topics, self-assessment of nursing informatics competencies, and satisfaction among undergraduate nursing students. The findings of this study provide recommendations for the design and implementation of future digital health education. Methods This study employed a one-group, quasi-experimental mixed-methods design with pre- and postassessments. The participants received digital health and informatics education through six three-hour online sessions in six interactive days, with online self-learning materials in between. An online quiz and focus group discussions pre- and post the course were designed to evaluate the knowledge and comprehension of key digital health and informatics topics. Also, a validated Chinese version of the Self-assessment of Nursing Informatics Competencies Scale was conducted pre- and post-course to assess self-assessment of nursing informatics competencies. Additionally, all students were invited to participate in an online survey with a performance-focused course evaluation form as well as focus group discussions to gather their feedback on the learning experience and their evaluations of the course. Results A total of 24 undergraduate nursing students were enrolled in the course. All students completed all sessions of this course, resulting in an attendance rate of 100%. Additionally, all students completed both pre- and postassessments. In terms of the knowledge and comprehension of key digital health and informatics topics, scores of the quiz on knowledge assessment improved from the pre-test [mean pretest score: 78.33 (SD 6.005)] to the posttest [mean post-test score: 83.17 (SD 4.86)] upon completion of the course (P<0.001). Also, students acknowledged that the course enhanced their knowledge and comprehension of informatics and digital health, the benefits of (nursing) informatics in clinical practice, and the role of health care professionals in informatics and digital health. In terms of self-assessment of nursing informatics competencies, scores on nursing informatics attitudes demonstrated significant improvement (P<0.001). Furthermore, students reported high satisfaction with various aspects of this course, including the opportunity to explore broad horizons in informatics for future careers, engaging in group discussions, and analyzing case studies on the use of informatics and digital health in clinical practice. Conclusions This Online Digital Health and Informatics education effectively improved undergraduate nursing students’ knowledge and comprehension of the key digital health and informatics topics, nursing informatics attitudes in the self-assessment of nursing informatics competency with high levels of satisfaction. In order to ensure that future education in digital health and informatics for nursing students is in line with the technological advancements in clinical settings, it is necessary to foster collaboration between medical school training and clinical practice. This collaboration should involve the use of clinical examples to illustrate advanced digital health applications and the inclusion of practical exercises on the use of digital health technology in clinical settings. Show less
Synthetic supramolecular polymers and hydrogels in water are emerging as promising biomaterials due to their modularity and intrinsic dynamics. Here, we introduce temperature sensitivity into the... Show moreSynthetic supramolecular polymers and hydrogels in water are emerging as promising biomaterials due to their modularity and intrinsic dynamics. Here, we introduce temperature sensitivity into the nonfunctionalized benzene-1,3,5-tricarboxamide (BTA-EG4) supramolecular system by incorporating a poly(N-isopropylacrylamide)-functionalized (BTA-PNIPAM) moiety, enabling 3D cell encapsulation applications. The viscous and structural properties in the solution state as well as the mechanical and dynamic features in the gel state of BTA-PNIPAM/BTA-EG4 mixtures were investigated and modulated. In the dilute state (c ∼μM), BTA-PNIPAM acted as a chain capper below the cloud point temperature (Tcp = 24 °C) but served as a cross-linker above Tcp. At higher concentrations (c ∼mM), weak or stiff hydrogels were obtained, depending on the BTA-PNIPAM/BTA-EG4 ratio. The mixture with the highest BTA-PNIPAM ratio was ∼100 times stiffer and ∼10 times less dynamic than BTA-EG4 hydrogel. Facile cell encapsulation in 3D was realized by leveraging the temperature-sensitive sol-gel transition, opening opportunities for utilizing this hydrogel as an extracellular matrix mimic. Show less
Central Asia is highly vulnerable to the impacts of climate change. There is, however, a lack of research on how local businesses, political elites and the general public perceive the need for... Show moreCentral Asia is highly vulnerable to the impacts of climate change. There is, however, a lack of research on how local businesses, political elites and the general public perceive the need for comprehensive greening initiatives to address its consequences. To account for the material and ideational factors influencing clean energy transition in Central Asian petrostates, I offer an alternative analytic framework that I call ‘contrasting adaptation’. I argue that the energy transition has resulted in two contradictory responses at multiple levels of political governance: a formal response that is broadly supportive of new ‘green’ identities and policies, and an informal response that seeks to delay plans to decarbonize local business models and continues to prioritize ‘old’ oil and gas activities through new transnational networks. Drawing on a model of actor interactions at different levels of climate governance, I examine ‘contrasting adaptation’ – its constituent policies and discourse – to provide a better theorized framework for understanding climate politics in Central Asia. I use comparative analysis of the climate policies of Kazakhstan and Uzbekistan, the two Central Asian petrostates that pledged to carbon neutrality, informed by documentary and textual sources, and discourse analysis. Show less
