Improving comfort in nursing home residents with dementia and pneumonia: Development, implementation and evaluation of a practice guideline for optimal symptom relief

Hertogh, C.M.P.M. [Promotor]Koopmans, R.C.T.M. [Promotor]Vet, H.C.W. de [Promotor]Steen, J.T. van der [Copromotor

Effective combination of liposome-targeted chemotherapy and PD-L1 blockade of murine colon cancer

Therapeutic cancer drug efficacy can be limited by insufficient tumor penetration, rapid clearance, systemic toxicity and (acquired) drug resistance. The poor therapeutic index due to inefficient drug penetration and rapid drug clearance and toxicity can be improved by using a liposomal platform. Drug resistance for instance against pemetrexed, can be reduced by combination with docetaxel. Here, we developed a specific liposomal formulation to simultaneously deliver docetaxel and pemetrexed to enhance efficacy and safety. Hydrophobic docetaxel and hydrophilic pemetrexed were co-encapsulated into pH-sensitive liposomes using a thin-film hydration method with high efficiency. The physicochemical properties, toxicity, and immunological effects of liposomes were examined in vitro. Biodistribution, anti-tumor efficacy, and systemic immune response were evaluated in vivo in combination with PD-L1 immune checkpoint therapy using two murine colon cancer models. In cellular experiments, the liposomes exhibited strong cytotoxicity and induced immunogenic cell death. In vivo, the treatment with the liposome-based drug combination inhibited tumor development and stimulated immune responses. Liposomal encapsulation significantly reduced systemic toxicity compared to the delivery of the free drug. Tumor control was strongly enhanced when combined with anti-PDL1 immunotherapy in immunocompetent mice carrying syngeneic MC38 or CT26 colon tumors. We showed that treatment with liposome-mediated chemotherapy of docetaxel and pemetrexed combined with anti-PD-L1 immunotherapy is a promising strategy for the treatment of colon cancers.Horizon 2020 (H2020

Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case–control study (VeCosCO)

Introduction: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints. To unravel factors associated with persisting complaints, VeCosCO will compare individuals with and without persistent fatigue and cognitive complaints >3 months after infection with SARS-CoV-2. The study consists of two work packages. The first work package aims to (1) investigate the relation between persisting complaints and neuropsychological functioning; (2) determine risk factors and at-risk phenotypes for the development of persistent fatigue and cognitive complaints, including the presence of postexertional malaise and (3) describe consequences of persistent complaints on quality of life, healthcare consumption and physical functioning. The second work package aims to (1) determine the presence of neuroinflammation with [18F]DPA-714 whole-body positron emission tomography (PET) scans in patients with persisting complaints and (2) explore the relationship between (neuro)inflammation and brain structure and functioning measured with MRI. / Methods and analysis: This is a prospective case–control study in participants with and without persistent fatigue and cognitive complaints, >3 months after laboratory-confirmed SARS-CoV-2 infection. Participants will be mainly included from existing COVID-19 cohorts in the Netherlands covering the full spectrum of COVID-19 acute disease severity. Primary outcomes are neuropsychological functioning, postexertional malaise, neuroinflammation measured using [18F]DPA-714 PET, and brain functioning and structure using (f)MRI. / Ethics and dissemination: Work package 1 (NL79575.018.21) and 2 (NL77033.029.21) were approved by the medical ethical review board of the Amsterdam University Medical Centers (The Netherlands). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in peer-reviewed journals and shared with the key population

Comprehensive evaluation of microneedle-based intradermal adalimumab delivery vs. subcutaneous administration: results of a randomized controlled clinical trial

Aims To evaluate feasibility of intradermal (i.d.) adalimumab administration using hollow microneedles, and to compare a single i.d. dose of adalimumab using a hollow microneedle with a single subcutaneous (s.c.) dose using a conventional needle.Methods In this single-centre double-blind, placebo-controlled, double-dummy clinical trial in 24 healthy adults we compared 40 mg adalimumab (0.4 mL) administered i.d. using a hollow microneedle with a s.c. dose using a conventional needle. Primary parameters were pain, acceptability and local tolerability; secondary parameters safety, pharmacokinetics and immunogenicity. We explored usability of optical coherence tomography, clinical photography, thermal imaging, and laser speckle contrast imaging to evaluate skin reaction after i.d. injections. In vitro protein analysis was performed to assess compatibility of adalimumab with the hollow microneedle device.Results While feasible and safe, injection pain of i.d. adalimumab was higher compared to s.c. adalimumab (35.4 vs. 7.9 on a 100-point visual analogue scale). Initial absorption rate and relative bioavailability were higher after i.d. adalimumab (time to maximum plasma concentration = 95 h [47-120]; F-rel = 129% [6.46%]) compared to s.c. adalimumab (time to maximum plasma concentration = 120 h [96-221]). Anti-adalimumab antibodies were detected in 50% and 83% of the subjects after i.d. and s.c. adalimumab, respectively. We observed statistically significantly more erythema and skin perfusion after i.d. adalimumab, compared to s.c. adalimumab and placebo injections (P < .0001). Cytokine secretion after whole blood lipopolysaccharide challenge was comparable between administration routes.Conclusions Intradermal injection of adalimumab using hollowing microneedles was perceived as more painful and less accepted than s.c. administration, but yields a higher relative bioavailability with similar safety and pharmacodynamic effects.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

An inventory of high-risk treatments in beauty salons

Sommige behandelingen in schoonheidssalons brengen risico's met zich mee, waardoor bijvoorbeeld roodheid, zwelling of littekenvorming kan ontstaan. Het is onduidelijk of en hoe vaak dergelijke effecten optreden. Volgens veldpartijen uit de schoonheidsbranche ontstaan risico's vooral door onbekwaam handelen van de behandelaar. Maatregelen om nadelige effecten van risicovolle behandelingen te beperken zouden dan ook vooral gericht moeten zijn op het handelen en/of de opleiding van de behandelaar. Om te kunnen bepalen of maatregelen daadwerkelijk nodig zijn, is het nodig dat nadelige effecten worden gemeld of geregistreerd. Dit blijkt uit een inventarisatie van het RIVM, waarin is bekeken welke behandelingen in schoonheidssalons risicovol zijn en wat de risico's inhouden. De Inspectie Gezondheidszorg en Jeugd (IGJ) wil daar inzicht in krijgen, omdat zij sinds de introductie van de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) in 2016 verantwoordelijk is voor het toezicht op schoonheidssalons. Risicovolle behandelingen in schoonheidssalons zijn behandelingen die door de huid heen gaan of de huid (al dan niet bedoeld) beschadigen, of de samenhang van het huidweefsel verbreken. Voorbeelden zijn behandelingen die huidcellen chemisch (peelings) of mechanisch (zoals microdermabrasie) verwijderen of die door de huid heen gaan (bijvoorbeeld microneedling). De meeste nadelige effecten ontstaan kort na de behandeling (binnen 7 dagen) en houden kort aan (minder dan 7 dagen). Nadelige effecten die langer dan een maand aanhouden zijn bijvoorbeeld littekenvorming en veranderingen in de pigmentatie van de huid, zoals overmatige pigmentvorming. Nadelige effecten die kunnen optreden, zijn in grote lijnen terug te voeren op kenmerken van de behandeling (zoals diepte en frequentie), kenmerken van de cliënt (bijvoorbeeld huidtype), en bekwaamheid van de behandelaar (zoals kennis en ervaring). Het risico van behandelingen hangt grofweg samen met de diepte van de beschadiging van de huid die bij de behandeling wordt aangericht, en de mate van controle die de behandelaar hierover heeft.Some treatments in beauty salons can be associated with risks, causing effects such as redness, swelling or scarring. It is unclear whether and how often such effects occur. According to parties from the beauty sector who are active in the field arise risks largely due to inexpert treatment. Measures for limiting the negative effects of high-risk treatments should therefore primarily be focused on the actions and/or the training of the person giving the treatment. To determine whether measures are actually required, reporting adverse effects is necessary. These are the results from an inventory by the National Institute for Public Health and the Environment. With this inventory has been looked at what treatments at beauty salons could be high-risk and what risks could be involved. The Health and Youth Care Inspectorate wants to gain insight in these risks, as the Inspectorate supervises beauty salons since the introduction of the Healthcare Quality, Complaints and Disputes Act (Wkkgz) in 2016. High-risk treatments in beauty salons are treatments that penetrate the skin or damage the skin (intentionally or otherwise) or that affect the cohesion of the skin tissue. Examples are treatments that remove skin cells chemically (peelings) or mechanically (for example microdermabrasion) or that penetrate the skin (for example microneedling). The majority of adverse effects arise shortly after the treatment (within 7 days) and are transient (for less than 7 days). Adverse effects that persist for longer than one month are for example scarring or changes in skin pigmentation, such as excess pigment production. Negative effects that can occur derive largely from the features of the treatment (such as the depth and frequency), the client (for example their skin type) and the person giving the treatment (such as knowledge and experience). The risk of treatment is roughly correlated to the depth of the damage that is done to the skin during the treatment and the degree of control that the person giving the treatment has over it.Inspectie voor de Gezondheidszorg en Jeugd (IGJ

Een inventarisatie van risicovolle behandelingen in schoonheidssalons

Sommige behandelingen in schoonheidssalons brengen risico's met zich mee, waardoor bijvoorbeeld roodheid, zwelling of littekenvorming kan ontstaan. Het is onduidelijk of en hoe vaak dergelijke effecten optreden. Volgens veldpartijen uit de schoonheidsbranche ontstaan risico's vooral door onbekwaam handelen van de behandelaar. Maatregelen om nadelige effecten van risicovolle behandelingen te beperken zouden dan ook vooral gericht moeten zijn op het handelen en/of de opleiding van de behandelaar. Om te kunnen bepalen of maatregelen daadwerkelijk nodig zijn, is het nodig dat nadelige effecten worden gemeld of geregistreerd. Dit blijkt uit een inventarisatie van het RIVM, waarin is bekeken welke behandelingen in schoonheidssalons risicovol zijn en wat de risico's inhouden. De Inspectie Gezondheidszorg en Jeugd (IGJ) wil daar inzicht in krijgen, omdat zij sinds de introductie van de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) in 2016 verantwoordelijk is voor het toezicht op schoonheidssalons. Risicovolle behandelingen in schoonheidssalons zijn behandelingen die door de huid heen gaan of de huid (al dan niet bedoeld) beschadigen, of de samenhang van het huidweefsel verbreken. Voorbeelden zijn behandelingen die huidcellen chemisch (peelings) of mechanisch (zoals microdermabrasie) verwijderen of die door de huid heen gaan (bijvoorbeeld microneedling). De meeste nadelige effecten ontstaan kort na de behandeling (binnen 7 dagen) en houden kort aan (minder dan 7 dagen). Nadelige effecten die langer dan een maand aanhouden zijn bijvoorbeeld littekenvorming en veranderingen in de pigmentatie van de huid, zoals overmatige pigmentvorming. Nadelige effecten die kunnen optreden, zijn in grote lijnen terug te voeren op kenmerken van de behandeling (zoals diepte en frequentie), kenmerken van de cliënt (bijvoorbeeld huidtype), en bekwaamheid van de behandelaar (zoals kennis en ervaring). Het risico van behandelingen hangt grofweg samen met de diepte van de beschadiging van de huid die bij de behandeling wordt aangericht, en de mate van controle die de behandelaar hierover heeft

De impact van de nieuwe Europese IVD-classificatieregels op de betrokkenheid van notified bodies; Een studie over de in Nederland geregistreerde IVD's

In vitro diagnostics (IVDs) are medical devices for carrying out a test using human specimens such as urine or blood. Examples of these products are pregnancy tests, tests for determining the level of glucose or cholesterol in the blood, and tests that determine the blood group. To ensure that these products are safe and effective in use, the manufacturers must go through a procedure before the IVDs may be sold. The current legislation contains two lists on which IVDs are subdivided into a medium-risk and a high-risk category. IVDs that are not on these lists are automatically classified as low risk. An example of an IVD with high risk is an HIV test, whereas a blood collection tube or a pregnancy test has a low risk. A more stringent market authorisation procedure applies for IVDs with a high risk level and additional approval by an external party, a so-called notified body, is required. For low-risk IVDs, manufacturers may carry out the licensing procedure themselves. This system with lists is no longer sufficient. It has therefore been changed in the new European legislation for IVDs, which comes into effect in 2022. The risk of IVDs is then determined according to rules and subdivided into a cascade of four categories. Examples of factors that determine the risk are severity of the disorder tested for and possible consequences of an incorrect test result. Research carried out by the National Institute for Public Health and the Environment (RIVM) has shown that this means that many more IVDs will end up in a higher risk category (84 instead of 7 percent). This means that the number of IVDs for which the manufacturer requires approval of a notified body in order to obtain market authorization will be much greater.In-vitro diagnostica (IVDs) zijn medische hulpmiddelen om lichaamsmateriaal zoals urine of bloed te testen. Voorbeelden van deze producten zijn zwangerschapstesten, testen om het gehalte van glucose of cholesterol in het bloed te meten en testen die de bloedgroep bepalen. Om te waarborgen dat deze producten veilig en effectief in het gebruik zijn, moeten fabrikanten een procedure doorlopen voordat de IVD's mogen worden verkocht. De huidige wetgeving bevat twee lijsten waarop IVD's zijn onderverdeeld in een 'midden' en een 'hoog' risico. IVD's die niet op deze lijst staan worden automatisch ingeschaald als 'laag' risico. Een voorbeeld van een IVD met een hoog risico is een hiv-test, terwijl een bloedbuisje of zwangerschapstest een laag risico heeft. Voor IVD's met een hoog risico geldt een zwaardere toelatingsprocedure en is een extra goedkeuring door een externe partij, een zogenaamde notified body, nodig. Voor laag risico IVD's mogen fabrikanten zelf de toelatingsprocedure uitvoeren. Dit systeem met lijsten voldoet niet meer. Daarom is het in de nieuwe Europese wetgeving voor IVD's, die in 2022 in werking treedt, veranderd. Het risico van IVD's wordt dan volgens nieuw opgestelde regels bepaald en trapsgewijs in vier klassen onderverdeeld. Factoren die van invloed zijn op het risico zijn bijvoorbeeld de ernst van de aandoening waarop wordt getest en mogelijke gevolgen van een onjuiste testuitslag. Uit onderzoek van het RIVM blijkt dat hierdoor veel meer IVD's in een hogere risicoklasse zullen vallen (84 in plaats van 7 procent). Dat betekent dat het aantal IVD's waarvoor de fabrikant goedkeuring van een notified body nodig heeft om het product op de markt te mogen brengen, veel groter zal zijn.The Dutch Health and Youth Care Inspectorat

The impact of the new European IVD-classification rules on the notified body involvement; a study on the IVDs registered in the Netherlands

In vitro diagnostics (IVDs) are medical devices for carrying out a test using human specimens such as urine or blood. Examples of these products are pregnancy tests, tests for determining the level of glucose or cholesterol in the blood, and tests that determine the blood group. To ensure that these products are safe and effective in use, the manufacturers must go through a procedure before the IVDs may be sold. The current legislation contains two lists on which IVDs are subdivided into a medium-risk and a high-risk category. IVDs that are not on these lists are automatically classified as low risk. An example of an IVD with high risk is an HIV test, whereas a blood collection tube or a pregnancy test has a low risk. A more stringent market authorisation procedure applies for IVDs with a high risk level and additional approval by an external party, a so-called notified body, is required. For low-risk IVDs, manufacturers may carry out the licensing procedure themselves. This system with lists is no longer sufficient. It has therefore been changed in the new European legislation for IVDs, which comes into effect in 2022. The risk of IVDs is then determined according to rules and subdivided into a cascade of four categories. Examples of factors that determine the risk are severity of the disorder tested for and possible consequences of an incorrect test result. Research carried out by the National Institute for Public Health and the Environment (RIVM) has shown that this means that many more IVDs will end up in a higher risk category (84 instead of 7 percent). This means that the number of IVDs for which the manufacturer requires approval of a notified body in order to obtain market authorization will be much greater