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"Roukens A H E"
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Unmasking Individual and Institutional HIV Stigma in Hospitals: Perspectives of Dutch Healthcare Providers
by
Stutterheim, S. E
,
van Bruggen, A. W
,
van der Sluis, D
in
Attitudes
,
Cross-sectional studies
,
Data
2024
People with HIV continue to experience HIV stigma. Quantitative data on HIV stigma perpetrated by healthcare providers of hospitals providing HIV care in high-income countries are limited. The aim of this study is to investigate factors associated with HIV stigma in Dutch healthcare settings from the healthcare providers’ perspective. We conducted a cross-sectional study using the questionnaire ‘Measuring HIV Stigma and Discrimination Among Health Facility Staff – Monitoring Tool for Global Indicators’ to assess HIV stigma among healthcare providers (n = 405) in two academic hospitals. Healthcare providers licensed to provide medical care were eligible for inclusion. The primary outcome was the self-reported prevalence of at least one manifestation of HIV stigma measured by six stigma indicators (four individual, two institutional). Secondary outcomes were the prevalence of HIV stigma per indicator, per occupation, per department, and factors associated with individual stigma indicators. HIV stigma was prevalent among 88.1% (95%CI 84.5% − 91.2%) of participants. Stigma was mostly driven by negative attitudes towards people with HIV and worry to acquire HIV. Multivariate analysis showed that several factors were associated with HIV stigma, including younger age, male sex, working at one of the surgical departments, and working as a nurse. Having received any training on HIV stigma and/or discrimination was associated with less HIV stigma among all indicators. In conclusion, HIV stigma is highly prevalent among Dutch healthcare providers. Targeted approaches, including training on HIV stigma and discrimination, are needed to reduce HIV stigma in healthcare and should, among others, focus on younger healthcare providers.
Journal Article
Myocardial function in COVID-19 patients after hospital discharge: a descriptive study comparing the first and second ‘wave’ patients
2022
In hospitalized COVID-19 patients, myocardial injury and echocardiographic abnormalities have been described. The present study investigates cardiac function in COVID-19 patients 6 weeks post-discharge and evaluates its relation to New York Heart Association (NYHA) class. Furthermore cardiac function post-discharge between the first and second wave COVID-19 patients was compared. We evaluated 146 patients at the outpatient clinic of the Leiden University Medical Centre. NYHA class of II or higher was reported by 53% of patients. Transthoracic echocardiography was used to assess cardiac function. Overall, in 27% of patients reduced left ventricular (LV) ejection fraction was observed and in 29% of patients LV global longitudinal strain was impaired (> − 16%). However no differences were observed in these parameters reflecting LV function between the first and second wave patients. Right ventricular (RV) dysfunction as assessed by tricuspid annular systolic planar excursion (< 17 mm) was present in 14% of patients, this was also not different between the first and second wave patients (15% vs. 12%; p = 0.63); similar results were found for RV fraction area change and RV strain. Reduced LV and RV function were not associated with NYHA class. In COVID-19 patients at 6 weeks post-discharge, mild abnormalities in cardiac function were found. However these were not related to NYHA class and there was no difference in cardiac function between the first and second wave patients. Long term symptoms post-COVID might therefore not be explained by mildly abnormal cardiac function.
Journal Article
The Dutch Working Party on Antibiotic Policy (SWAB) Recommendations for the Diagnosis and Management of Febrile Neutropenia in Patients with Cancer
2022
IntroductionThis guideline was written by a multidisciplinary committee with mandated members of the Dutch Society for Infectious Diseases, Dutch Society for Hematology, Dutch Society for Medical Oncology, Dutch Association of Hospital Pharmacists, Dutch Society for Medical Microbiology, and Dutch Society for Pediatrics. The guideline is written for adults and pediatric patients.MethodThe recommendations are based on the answers to nine questions formulated by the guideline committee. To provide evidence-based recommendations we used all relevant clinical guidelines published since 2010 as a source, supplemented with systematic searches and evaluation of the recent literature (2010–2020) and, where necessary, supplemented by expert-based advice.ResultsFor adults the guideline distinguishes between high- and standard-risk neutropenia based on expected duration of neutropenia (> 7 days versus ≤ 7 days). Where possible a distinction has been made between pediatric and adult patients.ConclusionThis guideline was written to aid diagnosis and management of patients with febrile neutropenia due to chemotherapy in the Netherlands. The guideline provides recommendation for children and adults. Adults patient are subdivided as having a standard- or high-risk neutropenic episode based on estimated duration of neutropenia.The most important recommendations are as follows. In adults with high-risk neutropenia (duration of neutropenia > 7 days) and in children with neutropenia, ceftazidime, cefepime, and piperacillin–tazobactam are all first-choice options for empirical antibiotic therapy in case of fever. In adults with standard-risk neutropenia (duration of neutropenia ≤ 7 days) the MASCC score can be used to assess the individual risk of infectious complications. For patients with a low risk of infectious complications (high MASCC score) oral antibiotic therapy in an outpatient setting is recommended. For patients with a high risk of infectious complications (low MASCC score) antibiotic therapy per protocol sepsis of unknown origin is recommended.
Journal Article
AB0668 THE ONSET OF RHEUMATOID ARTHRITIS AFTER COVID-19 – COINCIDENCE OR CONNECTED?
2021
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been suggested to induce autoimmune phenomena. Multiple studies have reported the presence of autoantibodies in patients with COVID-19. Also the presence of anti-citrullinated protein antibodies (ACPA) and flaring of rheumatoid arthritis (RA) after COVID-19 has been described.[1, 2] Furthermore, in rheumatology clinics patients may present with polyarthritis compatible with RA shortly after SARS-CoV-2 infection. However, it is unclear how often ACPA occur after COVID-19 and whether preceding COVID-19 impacts on disease presentation of RA and phenotype of the ACPA response.
This study aims to determine the seroprevalence of ACPA after COVID-19 and to investigate the association between preceding COVID-19 infection and disease presentation of new-onset RA, including clinical phenotype and autoantibody response.
To estimate the prevalence of ACPA after COVID-19 we measured ACPA IgG in samples from 61 patients visiting the specialized post-COVID outpatient clinic of the LUMC 5 weeks after hospitalization, using routine tests or in-house ELISA. Furthermore, we identified 5 patients presenting with polyarthritis compatible with RA after SARS-CoV-2 infection. To study the impact of COVID-19 on disease presentation, we examined clinical phenotype, autoantibody isotype positivity and ACPA IgG variable domain (V-domain) glycosylation of these patients and compared these features to regular RA patients. Autoantibody isotypes, including rheumatoid factor (RF) IgM/IgA, anti-CCP2 IgG/ IgM/IgA and anti-carbamylated protein antibodies (anti-CarP) IgG were measured using in-house ELISA's. The percentage of V-domain glycosylation of purified ACPA IgG was measured with UHPLC.
None of the 61 post-COVID patients tested positive for ACPA 5 weeks after hospitalization, except two patients previously diagnosed with ACPA-positive RA. Thus, we could not observe an increase in ACPA-positivity shortly after COVID-19. Of the 5 patients who developed polyarthritis compatible with RA after SARS-CoV-2 infection, the average age was 63.6 years and 2/5 were female. 4/5 patients had been hospitalized due to severe COVID-19. On average, joint complaints started 6.6 weeks after infection, although two patients reported symptoms before infection. 4/5 patients fulfilled the ACR 2010 criteria for RA. Three patients (patient 1, 4, 5) were phenotypically very similar to regular new-onset RA patients. Patient 3 had a history of seronegative RA and had been in DMARD-free remission for 5 years. She flared 6 weeks after SARS-CoV-2 infection. Patient 2 had a remarkably different presentation. He was admitted with a suspected septic polyarthritis or pneumonia with reactive polyarthritis 6 weeks after COVID-19. ACPA level was low positive. The patient died unexpectedly after two days and autopsy revealed dilating myocarditis of unclear underlying cause. No causative pathogen could be identified.
Previous studies have shown that RA-patients are most often either seronegative or triple-positive for RF, ACPA and anti-CarP antibodies. Autoantibody measurements on sera of the post-COVID polyarthritis patients revealed a similar pattern (Figure 1A) with two patients being completely seronegative, and three patients positive for a range of autoantibodies. In all post-COVID samples, the percentage of ACPA IgG V-domain glycosylation was significantly increased compared to total IgG (Figure 1B), similar as in regular RA.
In conclusion, we found that the seroprevalence of ACPA is not increased post-COVID and that most patients presenting with polyarthritis after COVID-19 resemble regular RA patients, both regarding clinical phenotype and autoantibody characteristics. Although sample size and follow-up was limited, it appears that RA post-COVID may be coincidence rather than connected.
[1]Vlachoyiannopoulos et al. Ann Rheum Dis, 2020.
[2]Perrot et al. The Lancet Rheumatology, 2020.
[Display omitted]
None declared.
Journal Article
Intradermal fractional dose vaccination as a method to vaccinate individuals with suspected allergy to mRNA COVID-19 vaccines
by
Roestenberg, Meta
,
Roukens, Anna H.E.
,
Granger, Alexandra
in
2019-nCoV Vaccine mRNA-1273 - immunology
,
Adult
,
Aged
2024
Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy.
Journal Article
Longitudinal assessment of COVID-19 vaccine immunogenicity in people with HIV stratified by CD4+ T-cell count in the Netherlands: A two-year follow-up study
by
Hensley, Kathryn S.
,
Bogers, Susanne
,
de Vries, Rory D.
in
Adult
,
Antibodies
,
Antibodies, Viral - blood
2025
Although guidelines for COVID-19 additional vaccination strategies generally prioritise people with advanced HIV infection, recommendations vary globally, with some countries recommending an annual vaccination for all people with HIV (PWH), while others restrict this to PWH with a CD4+ T-cell count < 200 cells per µL.
We conducted a prospective cohort study in 448 adult PWH. The primary outcome was the SARS-CoV-2 spike (S1)-specific IgG antibody level at 1, 6, 12, 18, and 24 months after completing a primary COVID-19 vaccination series (two doses of BNT162b2, mRNA-1273, or ChAdOx1-S, or one dose of Ad26.COV2.S). We compared the antibody kinetics over two years between PWH with a baseline CD4+ T-cell count < 200 cells per µL (n = 16) vs. ≥ 200 cells per µL (n = 432) with a mixed-effects model. Secondary outcomes included variables associated with the kinetics of S1-specific antibody levels and the incidence of breakthrough infections.
The median most recent CD4+ T-cell count prior to primary vaccination was 140 (IQR 80-165) in the < 200 cells per µL group, and 688 (IQR 520-899) in the ≥ 200 cells per µL group at the time of primary vaccination. S1-specific antibodies were lower in PWH with a CD4+ T-cell count < 200 vs. ≥ 200 cells per µL during the two-year follow-up, with predicted S1-specific antibody levels of 514 (95% CI 456-578) vs. 2758 (95% CI 1488-5110) BAU per mL at 12 months (p < 0.001) and 839 (95% CI 732-959) vs. 3505 (95% CI 1712-7175) BAU per mL at 24 months (p < 0.001). The overall incidence of SARS-CoV-2 infections was 55% and comparable between groups. A CD4+ T-cell count < 200 cells per µL, higher age, and a vector-based primary vaccination series were negatively associated with S1-specific antibody levels over time.
Long-term humoral responses were lower in PWH with a CD4+ T-cell count < 200 cells per µL compared to those with a CD4+ T-cell count ≥ 200 cells per µL. National COVID-19 vaccine guidelines recommending booster vaccines for all PWH, should therefore specifically emphasise the need for booster vaccines in those with a CD4+ T-cell count < 200 cells per µL. Trial registration: The trial was registered on the International Clinical Trials Platform (registration number: EUCTR2021-001054-57-N).
Journal Article
Comparing the immunogenicity of intradermal and intramuscular vaccination of elderly with BNT162b2 XBB.1.5: An equivalent dose study
by
Diavatopoulos, Dimitri A.
,
Roukens, Anna H.E.
,
van Beek, Lucille F.
in
ACE2
,
Aged
,
Aged, 80 and over
2025
Aging coincides with a decline in immune functioning, whereby elderly become less responsive to vaccination. Alternative vaccination strategies, including administration into the skin, may improve immunogenicity and efficacy. Here, we investigated the immunogenicity of intradermal (ID) administration of a fractional dose of a COVID-19 vaccine in elderly (75 years and older) compared to standard intramuscular (IM) administration of an equivalent dose.
Between November and December 2023, 48 adults aged 75–86 were randomized (1:1:1, n = 16/group) to receive either 20 μg of the BNT162b2 XBB.1.5 vaccine via ID injection, using a microneedle, or 20 μg via IM injection, or the standard 30 μg dose via IM injection (NCT05977127). The primary endpoint was the geometric mean concentration (GMC) of SARS-CoV-2 Spike-specific IgG at day 28 post-vaccination. Secondary endpoints included the serum ACE2 binding inhibition at day 28, as well as incidence of local and systemic adverse events (AEs), recorded during the first 28 days post-vaccination. Exploratory outcomes included longitudinal immunogenicity assessments in serum and nasal mucosal lining fluid, on days 0, 28 and 122 and whole blood transcriptome profiling on day 0 and 1.
At day 28 post-vaccination, no differences were found in serum anti-Spike IgG and ACE2 binding inhibition capacity between all three groups. Longitudinal analysis revealed parallel trends across groups in serum and mucosal IgG, IgA and ACE2 inhibition response. While ID vaccination induced a distinct blood transcriptomic profile compared to IM administration, no specific pathways were found that were differentially regulated. Mild and self-limiting local AEs were observed in all ID vaccinated participants, in contrast to IM vaccinated participants.
No differences were found in antibody level and functionality following ID and IM administration of 20 μg BNT162b2 XBB.1.5 vaccine in elderly, while IM administration was less reactogenic than ID administration.
Journal Article
The promising prospects of a new yellow fever vaccine
2024
Uncontrolled urbanisation, increased population mobility, extreme weather conditions, expansion of the vector Aedes aegypti, and fragmentation of rain forest driving non-human primates—the natural reservoir of yellow fever—into human dwellings all contribute to this risk. [...]a Vero cell-based yellow fever vaccine with a higher viral yield and longer shelf-life is more than welcome and has a high priority on the WHO Vaccines Prequalification Priority List 2024–26. [...]vYFV-247 remained capable of causing visceral and neurological disease in interferon-depleted mice. [...]the same restrictions for use in immunosuppressed individuals will apply for vYFV-247 as for YF-17D. In the phase 1 study by Modjarrad and colleagues, 1 no severe adverse events were observed within the studied dose range with a power to detect at least one severe adverse event in two of five vaccinees if the underlying severe adverse events rate was 1%.
Journal Article
A comparison of two Fendrix hepatitis B vaccination schedules in patients with inflammatory bowel disease
by
Kuiper, Vincent P.
,
van der Plas, Pauline
,
Roestenberg, Meta
in
Allergy and Immunology
,
Antigens
,
Biological products
2022
Systemic immunosuppressive therapy (IS) renders patients with inflammatory bowel disease (IBD) vulnerable to fulminant hepatitis B virus (HBV) infection. Seroprotection against HBV through a full vaccination scheme is preferably obtained before IS is initiated, but often conflicts with the clinical need to initiate therapy rapidly. Consequently, the vast majority of patients will use IS during booster vaccinations. In this retrospective cohort study, we examined the serological response after a modified vaccination schedule which includes an initial double dose of Fendrix in patients with IBD and compared the results with the serological responses of patients with IBD who received the standard schedule. Seroprotection rates were 86.2 % and 88.9 % in the modified and standard schedule groups respectively. One-third of patients obtained seroprotection after only one double dose vaccine. A double dose may be considered in patients with IBD at high short-term risk of HBV infection when a rapid protective response is warranted.
Journal Article