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BACKGROUND: Messenger RNA (mRNA) vaccines provide robust protection against SARS-CoV-2 in healthy individuals. However, immunity after vaccination of patients with multiple sclerosis (MS) treated with ocrelizumab (OCR), a B cell-depleting anti-CD20 monoclonal antibody, is not yet fully understood. METHODS: In this study, deep immune profiling techniques were employed to investigate the immune response induced by SARS-CoV-2 mRNA vaccines in untreated patients with MS (n=21), OCR-treated patients with MS (n=57) and healthy individuals (n=30). RESULTS: Among OCR-treated patients with MS, 63% did not produce detectable levels of antibodies (non-seroconverted), and those who did have lower spike receptor-binding domain-specific IgG responses compared with healthy individuals and untreated patients with MS. Before vaccination, no discernible immunological differences were observed between non-seroconverted and seroconverted OCR-treated patients with MS. However, non-seroconverted patients received overall more OCR infusions, had shorter intervals since their last OCR infusion and displayed higher OCR serum concentrations at the time of their initial vaccination. Following two vaccinations, non-seroconverted patients displayed smaller B cell compartments but instead exhibited more robust activation of general CD4+ and CD8+ T cell compartments, as indicated by upregulation of CD38 and HLA-DR surface expression, when compared with seroconverted patients. CONCLUSION: These findings highlight the importance of optimising treatment regimens when scheduling SARS-CoV-2 vaccination for OCR-treated patients with MS to maximise their humoral and cellular immune responses. This study provides valuable insights for optimising vaccination strategies in OCR-treated patients with MS, including the identification of CD38 and HLA-DR as potential markers to explore vaccine efficacy in non-seroconverting OCR-treated patients with MS.

Background: The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL-4-signaling along the T helper 2-axis may be instrumental in IgG4 class switching. Recently, repeated SARS-CoV-2 mRNA vaccination has been linked to IgG4 skewing. Although widely used immunosuppressive drugs have been shown to only moderately affect humoral responses to SARS-CoV-2 mRNA vaccination, the effect on IgG4 switching has not been investigated. Methods: Here we study the impact of such immunosuppressive drugs, including the IL-4 receptor-blocking antibody dupilumab, on IgG4 skewing upon repeated SARS-CoV-2 mRNA vaccination. Receptor-binding domain (RBD) specific antibody responses were longitudinally measured in 600 individuals, including patients with immune-mediated inflammatory diseases treated with a TNF inhibitor (TNFi) and/or methotrexate (MTX), dupilumab, and healthy/untreated controls, after repeated mRNA vaccination. Results: We observed a substantial increase in the proportion of RBD-specific IgG4 antibodies (median 21%) in healthy/untreated controls after third vaccination. This IgG4 skewing was profoundly reduced in dupilumab-treated patients (<1%). Unexpectedly, an equally strong suppression of IgG4 skewing was observed in TNFi-treated patients (<1%), whereas MTX caused a modest reduction (7%). RBD-specific total IgG levels were hardly affected by these immunosuppressive drugs. Minimal skewing was observed, when primary vaccination was adenoviral vector-based. Conclusions: Our results imply a critical role for IL-4/IL-13 as well as TNF in vivo IgG4 class switching. These novel findings advance our understanding of IgG4 class switch dynamics, and may benefit humoral tolerance induction strategies, treatment of IgG4 pathologies and mRNA vaccine optimization.

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Item does not contain fulltext, BACKGROUND: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. METHODS: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed

Contains fulltext : 251778.pdf (Publisher’s version ) (Open Access), BACKGROUND: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. METHODS: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result. FINDINGS: In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls. INTERPRETATION: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.

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Contains fulltext : 251778.pdf (Publisher’s version ) (Open Access), BACKGROUND: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. METHODS: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result. FINDINGS: In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls. INTERPRETATION: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.

Item does not contain fulltext, BACKGROUND: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. METHODS: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed

BACKGROUND: Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants. METHODS: The dynamics of cellular immune reactivation upon vaccination of SARS-CoV-2 experienced MS patients treated with the humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) and RA patients treated with methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry of whole blood samples upon vaccination with the SARS-CoV-2 mRNA-1273 (Moderna) vaccine. Longitudinal B and T cell immune responses were compared to SARS-CoV-2 experienced healthy controls (HCs) before and 7 days after the first and second vaccination. RESULTS: OCR-treated MS patients exhibit a preserved recall response of CD8+ T central memory cells following first vaccination compared to HCs and a similar CD4+ circulating T follicular helper 1 and T helper 1 dynamics, whereas humoral and B cell responses were strongly impaired resulting in absence of SARS-CoV-2-specific humoral immunity. MTX treatment significantly delayed antibody levels and B reactivation following the first vaccination, including sustained inhibition of overall reactivation marker dynamics of the responding CD4+ and CD8+ T cells. CONCLUSIONS: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients may still benefit from vaccination by inducing a broad CD8+ T cell response which has been associated with milder disease outcome. The delayed vaccine-induced IgG kinetics in RA-MTX patients indicate an increased risk after the first vaccination, which might require additional shielding or alternative strategies such as treatment inte

Objectives: The Person-centered Care (PCC) philosophy emphasizes close care relationships to enable care professionals to recognize the needs of nursing home residents with dementia. This study explored how care professionals make sense of resident behavior with regard to intimacy and sexuality. Methods: 26 nursing home care professionals (15 Nurses, 9 Health Care Professionals and 2 Managers) completed in-depth interviews that were subjected to an Interpretative Phenomenological Analysis (IPA). Results: Three thematic layers were identified. 1. Care Professionals pursue a “true” understanding of intimate and sexual behavior that underpins a resident’s expression. 2. When care professionals feel the need to protect themselves, they can reframe a specific care relation in order to continue care. 3. The social context around the resident, from family to professionals (i.e. peers), influences interpretation of behavior and, consequently, the provision of care. Conclusions: Intimate and sexual expressions of residents can put care relations under pressure. Care relations that lack professional distance may compromise care professionals’ judgments, impede their natural boundaries and decrease their well-being. Clinical implications: Along with implementing PCC principles, organizations should empower staff to develop, discuss and include self-reflection skills and personal boundaries within their work.

Research aim When aging in place, social networks are sources of support and contribute to wellbeing of olderadults. As social networks change, especially when accompanied by health decline, older adults’sources of support change and their wellbeing is challenged. Previous studies predominantly use quantitative measures to examine how older adults’ social networks change. Therefore, we explored social network change qualitatively, examining the impact of social network change on older adults’ lives and how older adults experience social network change and health decline. Additionally, we perceive that home care nurses could benefit from the implementation of our results in their practice, although in literature numerous studies mention a ‘research-to-practice gap’ in healthcare. Therefore, we designed a study to develop an intervention for home care nurses, using previously mentioned results and making an extra effort to bridge the research-to-practice gap. Methods In four rounds, we follow the sequential steps of Intervention Mapping (IM) to develop an intervention for home care nurses to reduce the impact of social network change on older adults who are aging in place. Round 1 is concerned with creating a logic model of the problem and of the change that is intended. Round 1 will be based on results of our previous studies on experiences of older adults and input of home care nurses. Round 2 is concerned with choosing change methods and applications. Round 1 and 2 will be executed by a project group of home care nurses, implementation specialists and a researcher. In round 3 we will hold three co-creation sessions with home care nurses to develop the intervention materials. Round 4 contains the making of an implementation and evaluation plan. After finishing every round, a group of experts (home care teams, managers and health insurance buyers) will be consulted for feedback on the intermediate results and to reach consensus on the definitive resu

Light therapy for older persons with dementia is often administered with light boxes, even though indoor ambient light may more comfortably support the diverse lighting needs of this population. Our objective is to investigate the influence of indoor daylight and lighting on the health of older adults with dementia living in long-term care facilities. A systematic literature search was performed within PubMed, CINAHL, PsycINFO, Web of Science and Scopus databases. The included articles (n=37) were published from 1991 to 2020. These articles researched the influence of existing and changed indoor light conditions on health and resulted in seven categories of health outcomes. Although no conclusive evidence was found to support the ability of indoor light to decrease challenging behaviors or improve circadian rhythms, findings of two studies indicate that exposure to (very) cool light of moderate intensity diminished agitation. Promising effects of indoor light were to reduce depressive symptoms and facilitate spatial orientation. Furthermore, there were indications that indoor light improved one’s quality of life. Despite interventions with dynamic lighting having yielded little evidence of its efficacy, its potential has been insufficiently researched among this study population. This review provides a clear and comprehensive description of the impact of diverse indoor light conditions on the health of older adults with dementia living in long-term care facilities. Variation was seen in terms of research methods, (the description of) light conditions, and participants’ characteristics (types and severity of dementia), thus confounding the reliability of the findings. The authors recommend further research to corroborate the beneficial effects of indoor light on depression and to clarify its role in supporting everyday activities of this population. An implication for practice in long-term care facilities is raising the awareness of the increased lighting needs of ag

This study is on the effects of spousal loss among older adults who continue to live independently after bereavement. Little longitudinal studies focus on this group, which is of special interest, since in many countries, care policy and system reform are aimed at increasing independent living among older adults. Using longitudinal data from a Dutch public data repository, we investigate the effects of spousal loss on psychological well-being, perceived quality of life, and (indication of) yearly health-care costs. Of the respondents who had a spouse and were living independently (N = 9,400) at baseline, the majority had not lost their spouse after 12 months (T12, n = 9,150), but 2.7% (n = 250) had lost their spouse and still lived independently. We compared both groups using multivariate regression (ordinary least squares) analyses. The results show that spousal loss significantly lowers scores on psychological well-being and perceived quality of life, but we found no effect on health-care costs.

De Academische Werkplaats Ouderen van Tranzo/Tilburg University deed een snelle literatuurstudie. Het doel was om te onderzoeken wat we kunnen leren van andere crisissen of rampen wereldwijd om de zorg voor Nederlandse ouderen in het verpleeghuis tijdens de uitbraak van COVID-19 zo optimaal mogelijk te houden. De literatuurstudie is gepubliceerd in het Tijdschrift voor Gerontologie en Geriatrie (TGG) https://tvgg.nl/artikelen/covid-19-vpz/. Wij delen de belangrijkste tips met je

De Academische Werkplaats Ouderen van Tranzo/Tilburg University deed een snelle literatuurstudie. Het doel was om te onderzoeken wat we kunnen leren van andere crisissen of rampen wereldwijd om de zorg voor Nederlandse ouderen in het verpleeghuis tijdens de uitbraak van COVID-19 zo optimaal mogelijk te houden. De literatuurstudie is gepubliceerd in het Tijdschrift voor Gerontologie en Geriatrie (TGG) https://tvgg.nl/artikelen/covid-19-vpz/. Wij delen de belangrijkste tips met je!

Long-term care for older adults is in transition. Organizations offering long-term care for older adults are expected to provide person-centered care (PCC) in a complex context, with older adults aging in place and participating in society for as long as possible, staff shortages and the slow adoption of technological solutions. To address these challenges, these organizations increasingly use scientific knowledge to evaluate and innovate long-term care. This paper describes how co-creation, in the sense of close, intensive, and equivalent collaboration between science, care practice, and education, is a key factor in the success of improving long-term care for older adults. Such co-creation is central in the Academic Collaborative Center (ACC) Older Adults of Tilburg University. In this ACC, Tilburg University has joined forces with ten organizations that provide care for older adults and CZ zorgkantoor to create both scientific knowledge and societal impact in order to improve the quality of person-centered care for older adults. In the Netherlands, a “zorgkantoor” arranges long-term (residential) care on behalf of the national government. A zorgkantoor makes agreements on cost and quality with care providers and helps people that are in need of care to decide what the best possible option in their situation is. The CZ zorgkantoor arranges the long-term (residential) care in the south and southwest of the Netherlands. This paper describes how we create scientific knowledge to contribute to the knowledge base of PCC for older adults by conducting social scientific research in which the perspectives of older adults are central. Subsequently, we show how we create societal impact by facilitating and stimulating the use of our scientific knowledge in daily care practice. In the closing section, our ambitions for the future are discussed.

Doel: Het doel van het huidige onderzoek was om van twee verschillende zorgconcepten in kaart tebrengen hoe zij mensgerichte zorg in de praktijk hebben vormgegeven. Uit de literatuur blijken verschillende elementen belangrijk in het bieden van mensgerichte zorg aan mensen met dementie in zorglocaties, waaronder het behouden van de autonomie, het afstemmen van de zorg op de belevingswereld van de persoon met dementie, het betrekken van naasten in de zorg en het bieden van een fysieke omgeving die mensgerichte zorg faciliteert. In het kader van het huidige onderzoek werd bestudeerd hoe deze elementen in de praktijk zijn gebracht door twee zorglocaties die langdurige zorg bieden aan mensen met dementie. De zorglocaties betroffen De Wever, locatie Satijnhof en De Leyhoeve, locatie Tilburg, beiden gevestigd in Tilburg. In het huidige onderzoek trachtten we antwoord te geven op onderstaande onderzoeksvragen: 1. In hoeverre voldoet de fysieke omgeving aan voorwaarden om mensgerichte zorg te realiseren? 2. Welke attitudes hebben medewerkers over mantelzorgverlening? 3. In welke mate bieden medewerkers mensgerichte zorg? 4. In welke mate wordt mantelzorg verleend en ervaren naasten een rol in de zorg voor de bewoner? 5. Hoe komt autonomie van bewoners tot uitdrukking in het dagelijks leven? Methode: Verschillende meetinstrumenten zijn geselecteerd voor het beantwoorden van de onderzoeksvragen. Middels observaties is in kaart gebracht in hoeverre de fysieke omgeving voldeed aan voorwaarden om mensgerichte zorg te realiseren en daarmee bijdroeg aan het welzijn van de bewoners. Tevens zijn twee vragenlijsten afgenomen: één bij medewerkers en één bij naasten van bewoners. Middels de vragenlijst voor medewerkers is onderzocht in welke mate mensgerichte zorg geboden werd en wat de attitudes van medewerkers waren over mantelzorgverlening. Middels de vragenlijst voor naasten van bewoners is de mate van mantelzorgverlening onderzocht en de a

Social networks are sources of support and contribute to the well-being of older adults who are ageing in place. As social networks change, especially when accompanied by health decline, older adults' sources of support change and their well-being is challenged. Previous studies predominantly used quantitative measures to examine how older adults' social networks change. Alternatively, this study explores the impact of changing social networks on older adults' lives by examining their personal experiences. We held four focus groups, two with a total of 14 older adults who are ageing in place and receiving home care and two with a total of 20 home-care nurses from different regions and organisations in the Netherlands. Subsequently, an expert team of home-care professionals and managers discussed and verified the results. Procedures for grounded theory building were used for analysis. We revealed four themes of high-impact experiences: (a) struggling with illness/death of the spouse; (b) working out a changing relationship with (grand)children; (c) regretting the loss of people they have known for so long and (d) feeling dependent and stressed when helpers enter the network. Also, network dynamics were found to follow three consecutive stages: (a) awareness of social network change; (b) surprise when social network change actually occurs and (c) acceptance and adjusting to new circumstances. Together, the four themes of experiences and three stages of network change form an integrative model of the role of social network dynamics for older adults' lives when ageing in place.