289 research outputs found

    Leray and LANS-α\alpha modeling of turbulent mixing

    Get PDF
    Mathematical regularisation of the nonlinear terms in the Navier-Stokes equations provides a systematic approach to deriving subgrid closures for numerical simulations of turbulent flow. By construction, these subgrid closures imply existence and uniqueness of strong solutions to the corresponding modelled system of equations. We will consider the large eddy interpretation of two such mathematical regularisation principles, i.e., Leray and LANSα-\alpha regularisation. The Leray principle introduces a {\bfi smoothed transport velocity} as part of the regularised convective nonlinearity. The LANSα-\alpha principle extends the Leray formulation in a natural way in which a {\bfi filtered Kelvin circulation theorem}, incorporating the smoothed transport velocity, is explicitly satisfied. These regularisation principles give rise to implied subgrid closures which will be applied in large eddy simulation of turbulent mixing. Comparison with filtered direct numerical simulation data, and with predictions obtained from popular dynamic eddy-viscosity modelling, shows that these mathematical regularisation models are considerably more accurate, at a lower computational cost.Comment: 42 pages, 12 figure

    Overdracht van lood, cadmium, kwik en arseen van diervoeders naar dierlijke produkten van mestlammeren

    Get PDF
    In samemo1erking met het IVVO te Lelystad werd nagegaan wat het effekt bij mestlammeren was van toediening van zware metalen via het voer op het gehalte van deze metalen in een aantal dierlijke produkten. Lood, cadmium, kwik en arseen werden toegediend in de vorm van oplosbare verbindingen of zoals ze voorkomen in haven- en rioolslib. De toegediende hoeveelheden bedroegen voor lood, cadmium, kwik en arseen respektievelijk 10, 2, 0,1 en 2 mg/kg droge stof

    De uitscheiding van anorganisch bromide, na orale dosering, in melk van lakterende koeien

    Get PDF
    Doel is het vaststellen van de overdracht van anorganisch bromide van voer naar melk om normen in veevoedergrondstoffen en dierlijke produkten op elkaar af te stemmen

    Reported Challenges in Health Technology Assessment of Complex Health Technologies

    Get PDF
    Objectives: With complex health technologies entering the market, methods for health technology assessment (HTA) may require changes. This study aimed to identify challenges in HTA of complex health technologies.  Methods: A survey was sent to European HTA organizations participating in European Network for HTA (EUnetHTA). The survey contained open questions and used predefined potentially complex health technologies and 7 case studies to identify types of complex health technologies and challenges faced during HTA. The survey was validated, tested for reliability by an expert panel, and pilot tested before dissemination.  Results: A total of 22 HTA organizations completed the survey (67%). Advanced therapeutic medicinal products (ATMPs) and histology-independent therapies were considered most challenging based on the predefined complex health technologies and case studies. For the case studies, more than half of the reported challenges were “methodological,” equal in relative effectiveness assessments as in cost-effectiveness assessments. Through the open questions, we found that most of these challenges actually rooted in data unavailability. Data were reported as “absent,” “insufficient,” “immature,” or “low quality” by 18 of 20 organizations (90%), in particular data on quality of life. Policy and organizational challenges and challenges because of societal or political pressure were reported by 8 (40%) and 4 organizations (20%), respectively. Modeling issues were reported least often (n = 2, 4%).  Conclusions: Most challenges in HTA of complex health technologies root in data insufficiencies rather than in the complexity of health technologies itself. As the number of complex technologies grows, the urgency for new methods and policies to guide HTA decision making increases

    When Reality Does Not Meet Expectations-Experiences and Perceived Attitudes of Dutch Stakeholders Regarding Payment and Reimbursement Models for High-Priced Hospital Drugs

    Get PDF
    This study aimed to identify the current experiences with and future preferences for payment and reimbursement models for high-priced hospital therapies in the Netherlands, where the main barriers lie and assess how policy structures facilitate these models. A questionnaire was sent out to Dutch stakeholders (in)directly involved in payment and reimbursement agreements. The survey contained statements assessed with Likert scales, rankings and open questions. The results were analyzed using descriptive statistics. Thirty-nine stakeholders (out of 100) (in)directly involved with reimbursement decision-making completed the survey. Our inquiry showed that currently financial-based reimbursement models are applied most, especially discounts were perceived best due to their simplicity. For the future, outcome-based reimbursement models were preferred, particularly pay-for-outcome models. The main stated challenge for implementation was generating evidence in practice. According to the respondents, upfront payments are currently implemented most often, whereas delayed payment models are preferred to be applied more frequently in the future. Particularly payment-at-outcome-achieved models are preferred; however, they were stated as administratively challenging to arrange. The respondents were moderately satisfied with the payment and reimbursement system in the Netherlands, arguing that the transparency of the final agreements and mutual trust could be improved. These insights can provide stakeholders with future direction when negotiating and implementing innovative reimbursement and payment models. Attention should be paid to the main barriers that are currently perceived as hindering a more frequent implementation of the preferred models and how national policy structures can facilitate a successful implementation

    Adverse Events to SARS-CoV-2 (COVID-19) Vaccines and Policy Considerations that Inform the Funding of Safety Surveillance in Low- and Middle-Income Countries: A Mixed Methods Study

    Get PDF
    Introduction/Objective: Rapid global approval of coronavirus disease 2019 (COVID-19) vaccines and concurrent introduction in high-income countries and low- and middle-income countries (LMIC) highlights the importance of equitable safety surveillance of adverse events following immunization (AEFIs). We profiled AEFIs to COVID-19 vaccines, explored reporting differences between Africa and the rest of the world (RoW), and analyzed policy considerations that inform strengthening of safety surveillance in LMICs. Methods: Using a convergent mixed-methods design we compared the rate and profile of COVID-19 vaccines’ AEFIs reported to VigiBase by Africa versus the RoW, and interviewed policymakers to elicit considerations that inform the funding of safety surveillance in LMICs. Results: With 87,351 out of 14,671,586 AEFIs, Africa had the second-lowest crude number and a reporting rate of 180 adverse events (AEs) per million administered doses. Serious AEs (SAEs) were 27.0%. Death accounted for about 10.0% of SAEs. Significant differences were found in reporting by gender, age group, and SAEs between Africa and the RoW. AstraZeneca and Pfizer BioNTech vaccines were associated with a high absolute number of AEFIs for Africa and RoW; Sputnik V contributed a considerably high rate of AEs per 1 million administered doses. Funding decisions for safety surveillance in LMICs were not based on explicit policies but on country priorities, perceived utility of data, and practical implementation issues. Conclusion: African countries reported fewer AEFIs relative to the RoW. To enhance Africa’s contribution to the global knowledge on COVID-19 vaccine safety, governments must explicitly consider safety monitoring as a priority, and funding organizations need to systematically and continuously support these programs

    Real World Data in Health Technology Assessment of Complex Health Technologies

    Get PDF
    The available evidence on relative effectiveness and risks of new health technologies is often limited at the time of health technology assessment (HTA). Additionally, a wide variety in real-world data (RWD) policies exist among HTA organizations. This study assessed which challenges, related to the increasingly complex nature of new health technologies, make the acceptance of RWD most likely. A questionnaire was disseminated among 33 EUnetHTA member HTA organizations. The questions focused on accepted data sources, circumstances that allowed for RWD acceptance and barriers to acceptance. The questionnaire was validated and tested for reliability by an expert panel, and pilot-tested before dissemination via LimeSurvey. Twenty-two HTA organizations completed the questionnaire (67%). All reported accepting randomized clinical trials. The most accepted RWD source were patient registries (19/22, 86%), the least accepted were editorials and expert opinions (8/22, 36%). With orphan treatments or companion diagnostics, organizations tended to be most likely to accept RWD sources, 4.3-3.2 on a 5-point Likert scale, respectively. Additional circumstances were reported to accept RWD (e.g., a high disease burden). The two most important barriers to accepting RWD were lacking necessary RWD sources and existing policy structures. European HTA organizations seem positive toward the (wider) use of RWD in HTA of complex therapies. Expanding the use of patient registries could be potentially useful, as a large share of the organizations already accepts this source. However, many barriers still exist to the widespread use of RWD. Our results can be used to prioritize circumstances in which RWD might be accepted

    Decision making under uncertainty: comparing regulatory and health technology assessment reviews of medicines in the United States and Europe

    Get PDF
    Assessments of clinical evidence vary between regulators and health technology assessment bodies, but precise differences remain unclear. To compare uncertainties raised on the clinical evidence of approved drugs, we analyzed assessments of regulators and health technology assessment (HTA) bodies in the United States and Europe. We found that US and European regulators report uncertainties related to safety for almost all drugs (85–94%), whereas HTA bodies reported these less (53–59%). By contrast, HTA bodies raised uncertainties related to effects against relevant comparators for almost all drugs (88–100%), whereas this was infrequently addressed by regulators (12–32%). Regulators as well as HTA bodies reported uncertainties related to the patient population for 60–95% of drugs. The patterns of regulator-HTA misalignment were comparable between the United States and Europe. Our results indicate that increased coordination between these complementary organizations is necessary to facilitate the collection of necessary evidence in an efficient and timely manner
    corecore