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Type-2 Biomarkers, Asthma Diagnosis and Lung Function Impairment in the General Population
No full textInstruments to measure nurses' intention-to-stay in the profession:A systematic literature review
No full textIntroduction:There is a large and increasing shortage of nursing staff. To alleviate this problem, healthcare systems should prioritize healthcare interventions that improve nurse retention over healthcare interventions that reduce it or leave it unchanged. One way to do so is to evaluate interventions on their anticipated impact on nurse intention-to-stay, which is an important precursor of retention. An overview of available instruments to quantify nurse intention-to-stay is lacking, resulting in researchers re-inventing the wheel. This review aims to fill this gap. Methods:A systematic literature search was performed in the databases Medline ALL via Ovid, Embase.com, Web of Science Core Collection, CINAHL Plus, PsycINFO, the Cochrane Central Register of Controlled Trials via Wiley, and Google Scholar (200 highest-ranked references only). The search string consisted of terms and associated synonyms for 1) nursing staff, 2) personnel intent to stay/leave, and 3) surveys. Articles were included when there was a quantitative method mentioned for measuring the intention of nurses to stay or quit nursing and/or their job/position/organization. Information was extracted on the year of publication, study design, study population, number of participants, instrument used for measuring intention-to-stay, and whether the instrument was focused on leaving the job, organization, or profession. In addition, we checked whether the instrument was used to evaluate the (expected or realized) impact of an intervention and if an association was determined between intention-to-stay (measured through the instrument) and retention. The protocol was not registered.Results:967 articles fulfilled our inclusion criteria, most of which were published in recent years. A total of 485 instruments were found. Nine regularly used instruments were identified, differing in their respective popularity over time, their size, the population for which they were developed and the strength of their link to actual retention. Notably, compared with the large body of literature on nurse intention-to-stay generally, the number of studies specifically measuring the impact of an intervention on nurse intention-to-stay is limited (n=20). Most of these intervention studies focused on changes in nurse training/mentorship or mental health support.Discussion & conclusion:Many different instruments exist to measure nurses' intention-to-stay. To add to our identified instruments, a comparative study is needed to identify which instrument offers the strongest predictive value for nurse retention. The absence of studies specifically evaluating the impact of interventions on nurses' intention-to-stay creates a critical gap in understanding how health interventions influence retention. Funding Dutch Research Council, 406.XS.04.151.</p
Debiasing entrepreneurial careers:A field experiment on female role model effects on entrepreneurial self-efficacy and early-stage career choices
No full textWomen remain underrepresented not only as founders but also as employees – or “joiners” – in young and small firms, limiting their exposure to entrepreneurial environments that often serve as critical pathways to venture creation. To address this gap, we investigate whether introducing female entrepreneur role models in educational settings can shape young women's entrepreneurial self-efficacy and early career choices. Drawing on role congruity theory and social cognitive career theory (SCCT), we conducted a field experiment involving over 430 university students and 98 early-stage entrepreneurs. Using a pre-test/post-test design and longitudinal tracking of early career choices, we explore the causal effects of exogenously assigned female role models on students' decisions to join a young or small firm. We find that exposure to social interactions with female entrepreneurs significantly boosts female students' entrepreneurial self-efficacy. More importantly, women who were paired with a female entrepreneur were over 10% more likely to join a young firm after graduation compared to those assigned to a male entrepreneur. Mediation analysis confirms that entrepreneurial self-efficacy is a key mechanism linking exposure to same-sex role models with women's decision to join a young firm. These findings highlight the potential of targeted role model interventions to reduce gender disparities in entrepreneurial entry pathways and expand the diversity of entrepreneurial ecosystems.</p
Methodological challenges in Dutch HTA of non-oncological orphan drugs:a retrospective analysis and price comparison using different pricing models
No full textBackground: Cost-effectiveness analyses can have limited informative value for pricing and reimbursement decisions for orphan drugs. In cases where cost-effectiveness cannot be reliably assessed or achieved, value-based pricing principles may not be applicable. As a result, alternative pricing models have been proposed. It remains unclear how these alternative approaches compare to one another and to traditional value-based pricing. This study aims to explore and compare these pricing models in the context of orphan drugs. Methods: All cost-effectiveness assessments of non-oncological orphan drugs published by the Dutch National Health Care Institute between 2015 and 2024 were analyzed to identify methodological challenges and recommended value-based price estimates. For each treatment, prices were also estimated using a cost-plus pricing model and a discounted cash flow model. These estimates were then compared to value-based prices and public list prices.Results: Cost-effectiveness assessments of 13 different therapies were found, 12 of which provide information for determining a value-based price. All assessment reports cite major uncertainties or unresolved issues in one or more of the following areas: (1) lack of a suitable comparator, (2) sub-optimal disease understanding, (3) limited evidence to inform models, (4) effect uncertainty and (5) flawed QoL measurement. Only one single treatment was found to be cost-effective at the appropriate threshold. Value-based prices were found to fall below, within or above the price ranges of the two alternative models. Conclusion: Challenges cited in literature are present in Dutch assessments of the cost-effectiveness of orphan drugs. Although these issues cause considerable uncertainty, they did not negate CEA’s ability to inform decision-making. Still, orphan drugs tend to be far from cost-effective, providing a challenge for patient access that is both timely and financially feasible. Alternative models like cost-plus pricing and discounted cash flow tend to generate even lower price estimates and rely on considerable assumptions, making them unlikely to offer a viable solution in their current state.</p
Head-to-head comparison of [<sup>177</sup>Lu]Lu-FAP-2286 and [<sup>161</sup>Tb]Tb-FAP-2286 efficacy in a PDAC mouse model
No full textBackground: Terbium-161 (Tb-161) emits internal conversion and Auger electrons, in addition to beta-minus radiation, which might be of added benefit for targeted radionuclide therapy (TRT) compared to Lutetium-177 (Lu-177). We extensively compared Lu-177 and Tb-161 for fibroblast activation protein (FAP)- TRT in a preclinical setting. To study this, FAP-2286 was labeled with Lu-177 and Tb-161 and characterized in vitro on FAP-expressing cells and ex vivo using patient tumor samples. Moreover, in vivo studies (i.e. biodistribution and efficacy) were performed using a clinically representative pancreatic ductal adenocarcinoma (PDAC) mouse model. Biodistribution was performed 1, 4, 24, and 48 h post injection of 5 MBq/500 pmol [177Lu]Lu-FAP-2286 or [161Tb]Tb-FAP-2286. Subsequently, animals were treated with 4 × 40 MBq/500 pmol [177Lu]Lu-FAP-2286 or [161Tb]Tb-FAP-2286 and with alternating doses of 2 × 40 MBq/500 pmol of each radiopharmaceutical. Results: No difference in [177Lu]Lu-FAP-2286 and [161Tb]Tb-FAP-2286 uptake was observed in the cell models. In vivo studies did not show a survival benefit of 4 × 40 MBq/500 pmol [177Lu]Lu-FAP-2286 or [161Tb]Tb-FAP-2286, while Kaplan-Meier analyses demonstrated a modest prolonged survival after tandem therapy in mice that first received [177Lu]Lu-FAP-2286 followed by [161Tb]Tb-FAP-2286. Dosimetry calculations based on autoradiography studies on patient tumor samples showed that even with lower binding, a higher absorbed dose to the tumor can be accomplished with [161Tb]Tb-FAP-2286. Conclusions: In our in vitro and in vivo studies, [177Lu]Lu-FAP-2286 and [161Tb]Tb-FAP-2286 demonstrated similar behavior. In the applied PDAC mouse model, FAP-TRT showed limited therapeutic efficacy, most likely due to the limited radiopharmaceutical uptake observed in the tumors. This hampered determination of a potential benefit of either radioisotope for FAP-TRT. Of note, a modest response was observed in the tandem therapy group that first received [177Lu]Lu-FAP-2286, followed by [161Tb]Tb-FAP-2286.</p
Innovations to detect complications cfter heart- and lung transplantation
No full textOverall, the aim of this thesis was to investigate novel innovations to detect complications a er heart and lung transplantation. Part I is the general introduction of this thesis and focusses on the current state of eNose technology in the eld of pulmonary medicine (Chapter 1). Part II explores the application of exhaled breath analysis using eNose technology for detecting complications following transplantation. Chapter 2 investigates the potential of eNose technology in lung transplantation. Chapter 3 examines whether eNose technology can di erentiate between complications, particularly acute cellular rejection and infection in lung transplant recipients. Chapter 4 assesses its accuracy in detecting chronic lung allogra dysfunction. Chapter 5 evaluates its potential for therapeutic drug monitoring of Tacrolimus trough levels. Chapter 6 explores the ability of eNose technology to detect bacterial colonization of the lung allogra . Finally, Chapter 7 investigates its use in identifying heart transplant recipients at risk for impaired glucose tolerance. Part III focuses on the exploration of home monitoring. Chapter 8 evaluates a home monitoring application for lung transplantation follow–up. Overall, the aim of this thesis was to investigate novel innovations to detect complications a er heart and lung transplantation. Part I is the general introduction of this thesis and focusses on the current state of eNose technology in the eld of pulmonary medicine (Chapter 1). Part II explores the application of exhaled breath analysis using eNose technology for detecting complications following transplantation. Chapter 2 investigates the potential of eNose technology in lung transplantation. Chapter 3 examines whether eNose technology can di erentiate between complications, particularly acute cellular rejection and infection in lung transplant recipients. Chapter 4 assesses its accuracy in detecting chronic lung allogra dysfunction. Chapter 5 evaluates its potential for therapeutic drug monitoring of Tacrolimus trough levels. Chapter 6 explores the ability of eNose technology to detect bacterial colonization of the lung allogra . Finally, Chapter 7 investigates its use in identifying heart transplant recipients at risk for impaired glucose tolerance. Part III focuses on the exploration of home monitoring. Chapter 8 evaluates a home monitoring application for lung transplantation follow–up. Overall, the aim of this thesis was to investigate novel innovations to detect complications a er heart and lung transplantation. Part I is the general introduction of this thesis and focusses on the current state of eNose technology in the eld of pulmonary medicine (Chapter 1). Part II explores the application of exhaled breath analysis using eNose technology for detecting complications following transplantation. Chapter 2 investigates the potential of eNose technology in lung transplantation. Chapter 3 examines whether eNose technology can di erentiate between complications, particularly acute cellular rejection and infection in lung transplant recipients. Chapter 4 assesses its accuracy in detecting chronic lung allogra dysfunction. Chapter 5 evaluates its potential for therapeutic drug monitoring of Tacrolimus trough levels. Chapter 6 explores the ability of eNose technology to detect bacterial colonization of the lung allogra . Finally, Chapter 7 investigates its use in identifying heart transplant recipients at risk for impaired glucose tolerance. Part III focuses on the exploration of home monitoring. Chapter 8 evaluates a home monitoring application for lung transplantation follow–up. Part IV comprises the general discussion, which examines the key ndings and challenges of this thesis. It also explores their implications for future research and potential integration into routine clinical practice
No Evidence of Microsatellite Instability in Head and Neck Squamous Cell Carcinoma of Non-Smokers and Non-Drinkers
No full textIntroduction: While the prevalence of microsatellite instability (MSI) is low in the whole head and neck squamous cell carcinoma (HNSCC) population, it has been suggested to be more prominent in tumors of non-smokers. Therefore, the goal of this study was to determine the presence of MSI in a cohort of well-defined HNSCC of non-smokers and non-drinkers (NSND). Methods: Clinical characteristics and tumor tissue of 119 NSND with HNSCC were retrospectively collected and analyzed for MLH1, PMS2, MSH2, and MSH6 protein expression on tissue microarrays (TMA). In case of negative staining for one of these mismatch repair proteins in the TMA cores, immunohistochemistry (IHC) was repeated on a whole slide section and additional molecular analyses were performed using polymerase chain reaction (PCR) and quantitative PCR (qPCR). Results: Two cases showed dubious loss of MSH2 expression, one of these with concurrent dubious loss of MSH6 on the TMA. However, MSH2 and MSH6 expression was retained on whole slide sections and PCR and qPCR analyses did not show any mutations, compatible with a microsatellite stable result. Conclusion: This study shows no single case with MSI in the NSND subgroup of HNSCC. Although a deficient DNA mismatch repair system is a predictive biomarker for response to immune checkpoint inhibitors, we found no evidence to support routine analysis of MSI in HNSCC, also not in the subgroup of NSND.</p
Breast Cancer-Related Lymphedema (BCRL):Comprehensive Characterization of Patients Seeking Microsurgical Treatment
No full textBackground: Accurate characterization of the breast cancer-related lymphedema (BCLR) population is essential to understand its pathophysiology and develop predictive models for identifying at-risk patients and implementing tailored preventive microsurgical strategies. Key factors influencing BCRL severity and progression remain unclear. This study characterizes patients with BCRL seeking microsurgical treatment and evaluates the impact of oncological treatment intensity on lymphedema severity and progression. Methods: This cohort study was conducted at an outpatient tertiary lymphedema clinic between 2017 and 2023. BCRL severity was assessed at intake by a lymphedema-specialized plastic surgeon using International Society of Lymphology staging and indocyanine green lymphography with near-infrared fluorescence imaging (ICG-NIFI). Data were collected during scheduled medical evaluations and analyzed retrospectively. Exploratory analysis investigated associations between oncological treatment intensity and BCRL severity and progression. Results: A total of 163 consecutive female patients with BCRL were included. Lymphedema severity varied significantly, with no consistent link between severity and time since onset. A significant association was found between axillary lymph node dissection (ALND) and ICG-NIFI stages (p<0.001). However, no significant associations were found between oncological treatment intensity—surgery, radiotherapy, systemic treatment—and BCRL severity and progression. Analyses further revealed associations between lymphedema severity, body mass index, postmenopausal status, and clinical course. Conclusion: This study provides a comprehensive profile of patients with BCRL seeking microsurgical treatment, revealing variable lymphedema progression patterns. Oncological treatment intensity did not appear to influence BCRL severity or progression, suggesting that these may depend more on biological predisposition. These findings enhance BCRL understanding and highlight the importance of precise patient characterization, laying the foundation for targeted, individually tailored preventive microsurgical interventions.</p
No longitudinal association between hearing loss and Alzheimer’s disease pathology
No full textIntroduction Hearing loss (HL) is a potential risk factor for Alzheimer’s disease (AD), with animal studies suggesting a bidirectional relationship. This study examines whether HL links to changes in AD pathology and, whether AD biomarkers relate to subsequent HL progression. Methods Baseline Aβ42/Aβ40 and p-tau217 were measured using single-molecule arrays in 474 participants of the Rotterdam Study (mean age=62.37) between 2010-2016. HL was defined as the better-ear’s pure-tone threshold average. After seven years, participants underwent amyloid PET; HL and p-tau217 were reassessed two years after PET. Results Baseline HL was not associated with amyloid PET positivity, Aβ42/Aβ40, or longitudinally with p-tau217. Likewise, HL progression did not predict PET outcomes. APOE4 carriership did not modify associations with Aβ PET. Similarly, baseline plasma biomarkers were also unrelated to longitudinal HL changes. Conclusion No bidirectional association was observed between HL and AD pathology, suggesting that HL may contribute to dementia through other pathways.</p