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Menstrual products:culprits or bystanders in endometriosis and adenomyosis pathogenesis?
No full textProducts that may reduce menstrual flow from the endometrial cavity to the vagina (i.e. tampons and menstrual cups) could facilitate retrograde menstruation and the spillage of blood into the myometrium, two mechanisms which could be major determinants in endometriosis and adenomyosis pathogenesis. The aim of this narrative review is to summarize the evidence regarding the mechanical role menstrual products may have in the pathogenesis of these two conditions. Evidence in this regard is inconclusive. While Darrow and colleagues observed that 14 or more years of tampon use were associated with endometriosis (OR 3.6; 95% CI, 1.04–13.5); in Meaddough and colleagues’ retrospective study, the percentage of women using pads only was significantly higher among those with endometriosis than among those without the condition (31% vs 22%). Three further groups failed to find an association between endometriosis/adenomyosis and any type of menstrual product. The only case that may be considered as a sort of proof-of-concept of the association between products potentially reducing anterograde menstrual flow and endometriosis was reported by Spechler and colleagues, who described the case of a 41 year-old who developed endometriosis after having used a menstrual cup on a regular basis. However, the number of studies on the subject is scarce, study populations are exiguous and a greater attention to temporality of endometriosis onset in relation to when women started habitually using a specific menstrual product is needed. Confounding variables including type and quantity of endocrine disruptors contained in menstrual products should also be addressed. At the present moment, no recommendation can be provided on the safety of one type of menstrual product compared to another.</p
HIV-1 Integrase T218I/S Polymorphisms Do Not Reduce HIV-1 Integrase Inhibitors' Phenotypic Susceptibility
No full textThe recently Food and Drug Administration (FDA)-approved cabotegravir (CAB) has demonstrated efficacy as an antiretroviral agent for HIV treatment and prevention, becoming an important tool to stop the epidemic in the United States of America (USA). However, the effectiveness of CAB can be compromised by the presence of specific integrase natural polymorphisms, including T97A, L74M, M50I, S119P, and E157Q, particularly when coupled with the primary drug-resistance mutations G140S and Q148H. CAB's recent approval as a pre-exposure prophylaxis (PrEP) may increase the number of individuals taking CAB, which, at the same time, could increase the number of epidemiological implications. In this context, where resistance mutations, natural polymorphisms, and the lack of drug-susceptibility studies prevail, it becomes imperative to comprehensively investigate concerns related to the use of CAB. We used molecular and cell-based assays to assess the impact of T218I and T218S in the context of major resistance mutations G140S/Q148H on infectivity, integration, and resistance to CAB. Our findings revealed that T218I and T218S, either individually or in combination with G140S/Q148H, did not significantly affect infectivity, integration, or resistance to CAB. Notably, these polymorphisms also exhibited neutrality concerning other widely used integrase inhibitors, namely raltegravir, elvitegravir, and dolutegravir. Thus, our study suggests that the T218I and T218S natural polymorphisms are unlikely to undermine the effectiveness of CAB as a treatment and PrEP strategy
Citizen satisfaction with arm's length bodies in local government:expert insights on policy and practice
No full textPurpose: The purpose of this study is to investigate the application of citizen satisfaction (CS) as a tool for measuring performance by arm's length bodies (ALBs) in local governments across eleven countries, addressing central questions about its functionality and influencing factors. Design/methodology/approach: We employ a hybrid inductive-deductive explorative study design, characterized by an iterative interpretative approach guided by sensitizing concepts. Expert interviews are analyzed through template analysis and cover eleven countries where ALBs are present due to decentralization and outsourcing. Findings: Our study uncovers limited real-world applications of CS in evaluating public service delivery by ALBs. Expert interviews reveal insights into factors potentially influencing CS use, such as the level of autonomy of local governments, state traditions and austerity measures. A research agenda is formulated for further investigation. Originality/value: Contributing to the CS debate, our study focuses on its application in evaluating public service delivery by ALBs. The explorative design, expert opinions and theoretical foundations enhance understanding, offering insights into factors potentially shaping CS use in this context. The study proposes a research agenda, propelling further investigations into this underexplored, yet emerging, area.</p
Quality of reporting of pre-recorded music interventions in surgical patients ‐ A systematic review
Get PDFBackground: Perioperative music interventions are promising, with substantial beneficial effects on patients. However, adequate reporting is crucial for interpreting the outcomes and implementing the interventions. Our objective is to analyze the reporting quality of perioperative music interventions and to provide recommendations and a research agenda for future trials. Material and methods: This study utilized data from a systematic review, that was conducted as part of a separate previous analysis by Geensen, Dirven et al. For this analysis, a PROSPERO registration (CRD42023427138) was formalized. The Template for intervention Description and Replication (TiDieR) checklist was adapted and used. Nineteen intervention items were assessed, categorized in the aim, the core and the implementation. Results: Due to narrowed inclusion criteria, ten music intervention studies were included. None of the studies completely reported all intervention items. The reporting of core intervention items were poorly described. Complete description of implementation items, such as fidelity and modifications, was scarce. Conclusions: Perioperative music studies often lack the complete reporting of essential intervention items. This hinders replicability, generalization of the results and might contribute to research waste. We recommend adequate reporting in future studies to avoid these problems, by using our adapted TIDieR checklist.</p
From preferences to policy:Essays in political economy
No full textPublic spending is an essential tool of the state to improve the welfare of citizens. How public money is spent matters for the well-being of both current and future generations. The goal of this thesis is to contribute to understanding differences in spending patterns across countries, electoral systems, and economic situations. In doing so, I study three distinct cases along the path from preference formation to the implementation of public policy. First, who makes policy determines what policy is chosen. Therefore, I study the role that electoral competition plays in the selection of politicians using data from U.S. congressional elections. Second, I study the role that public attitudes have directly on policy choice. Particularly, I focus on the effect of trust in politicians for the propensity to provide public goods. I show that politicians who represent areas with less trust in politics are less likely to work on topics relating to public goods. Finally, it is vital to understand the way that preferences are formed and how external shocks can affect them. I contribute to this question with a case study on refugee influx in the Netherlands in 2015. I show that voters closely exposed to refugees are more likely to discuss religious minorities online as well as vote for anti-immigration parties
Type of D-dimer assay determines the diagnostic yield of computed tomography in patients suspected for pulmonary embolism
Get PDFBackground: Pulmonary embolism (PE) is a life-threatening condition with high morbidity and mortality. The diagnosis of PE is challenging due to nonspecific symptoms, making reliable diagnostic tools essential. This study addresses the clinical impact of interassay variability in D-dimer measurements on the utilization and diagnostic yield of computed tomography pulmonary angiography (CTPA). Objectives: To investigate the effect of different D-dimer assays on the decision to perform CTPA and the subsequent diagnostic yield in patients with suspected PE. Methods: This retrospective, multicenter cohort study analyzed data from 3 teaching hospitals in the southwest region of the Netherlands, covering the years 2018, 2019, 2022, and 2023. The study included data from 40,096 clinically requested D-dimer results and 11,372 CTPA records of patients with suspected PE. The D-dimer assays used were the Roche Tina-quant and Siemens INNOVANCE. Results: The study found significant differences in CTPA utilization and diagnostic yield based on the D-dimer assay used. In 2018 to 2019, hospitals using the Roche Tina-quant assay ordered 21% fewer CTPA scans and had a 9% higher positivity rate compared with those using the Siemens INNOVANCE assay. Conclusion: The findings highlight the necessity for assay-specific cutoff values or, ideally, the standardization of the D-dimer assay to optimize the accuracy and efficiency of PE diagnosis. This study demonstrates that the choice of D-dimer assay significantly influences the clinical management of suspected PE, affecting both the number of CTPA scans performed and the positivity rate of these scans. Implementing assay-specific cutoff values or standardization of the D-dimer assay could reduce unnecessary CTPA scans, minimize patient exposure to radiation, and lower healthcare costs. These results advocate enhanced collaboration between clinicians and laboratory specialists to accurately interpret D-dimer results within the context of the specific assay used. Future research should validate these findings in prospective studies and explore standardized protocols that account for interassay variability.</p
High-risk percutaneous coronary intervention in patients with reduced left ventricular ejection fraction deemed not suitable for surgical revascularisation. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the ESC Working Group on Cardiovascular Surgery
No full textThis clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions was developed in association with the European Society of Cardiology Working Group on Cardiovascular Surgery. It aims to define procedural and contemporary technical requirements that may improve the efficacy and safety of percutaneous coronary intervention (PCI), both in the acute phase and at long-term follow-up, in a high-risk cohort of patients on optimal medical therapy when clinical and anatomical high-risk criteria are present that entail unacceptable surgical risks, precluding the feasibility of coronary artery bypass grafting (CABG). This document pertains to patients with surgical contraindication according to the Heart Team, in whom medical therapy has failed (e.g., residual symptoms), and for whom the Heart Team estimates that revascularisation may have a prognostic benefit (e.g., left main, last remaining vessel, multivessel disease with large areas of ischaemia); however, there is a lack of data regarding the size of this patient population. This document aims to guide interventional cardiologists on how to proceed with PCI in such high-risk patients with reduced left ventricular ejection fraction after the decision of the Heart Team is made that CABG − which overall is the guideline-recommended option for revascularisation in these patients − is not an option and that PCI may be beneficial for the patient. Importantly, when a high-risk PCI is planned, a multidisciplinary decision by interventional cardiologists, cardiac surgeons, anaesthetists and noninvasive physicians with expertise in heart failure management and intensive care should be agreed upon after careful consideration of the possible undesirable consequences of PCI, including futility, similar to the approach for structural interventions.</p
Duration of Time Intervals for Risk Minimization Measure Effectiveness Studies
Get PDFInsights into the time needed for evaluation of risk minimization measures' (RMMs) effectiveness might identify areas for improvement. We assessed the duration of time intervals between regulatory milestones for RMM effectiveness studies assessed by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA). We included completed RMM effectiveness post-authorization safety studies (PASSs) assessed by PRAC between 2016 and 2022. Regulatory documents submitted by marketing authorization holders and assessment reports were extracted from non-public EMA databases. To calculate the duration of time intervals, we collected the dates of study request, protocol assessment start, protocol approval, study start, final study report assessment start, and final study report PRAC outcome. We identified 98 PASSs. The median duration from study request to final study report PRAC outcome was 52 months (Q1–Q3: 40–70). The median duration from study request to study start was 21 months (Q1–Q3: 15–30; n = 95) and from study start to final study report assessment start was 21 months (Q1–Q3: 13–36; n = 95). The final study report assessment often comprised <6 months (median: 4; Q1–Q3: 1–6). For PASSs with a PRAC-approved protocol (n = 80, 81.6%), the median duration of protocol assessment was 7 months (Q1–Q3: 4–10). Concluding, the median duration from study request to RMM effectiveness PASS completion exceeded 4 years. Next to the study conduct duration, the period from study request until study start was the most time-consuming. The duration of this period might be minimized by improved guidance on RMM effectiveness PASSs and encouraging timely protocol submission.</p
Voorbij de system-level bureaucratie:Over datastromen, algoritmes en inclusieve AI in de databureaucratie
No full textAround the turn of the century, government digitalization mostly consisted of the automation of relatively simple bureaucratic procedures and the digitalization of organizations’ client databases. In this article, we argue that the ‘system-level bureaucracy’ has been surpassed by the emergence of information infrastructures, in which (big) data is shared among a wide variety of organizations, and the increased use of machine learning algorithms to assist administrative decision-making. We call this the ‘data-bureaucracy’. Rather than mere technical innovations developed to improve government efficiency, these developments have profound consequences for the way government organizations use public and private data, organize decision-making processes, and can be held accountable for their actions and decisions by citizens. We speak of the emergence of a ‘coding elite’ – data professionals that design concrete AI-applications and, in doing so, make (implicit) trade-offs between relevant public values beyond political and public scrutiny. In order to recover public value deliberation in algorithmic governance, we argue for the importance of inclusive design processes of AI-applications and develop a concrete framework for realizing such processes (‘inclusive AI’)
Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia:Phase 2 Part B Study
Get PDFCurrent treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017–004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.</p