Background: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To... Show moreBackground: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To investigate measures related to staff during the COVID-19 pandemic, staff perspectives of important measures and the involvement of staff in deciding on these measures. Design: A qualitative study. Setting(s): We analysed minutes of nursing home outbreak teams in the Netherlands and conducted group meetings with Dutch nursing home staff in different positions, prioritizing measures and discussing staff' involvement in deciding on the measures. Participants were recruited purposefully. Participants: The minutes of 41 nursing home organizations were collected during March-November, 2020. Four group meetings were organized in the same period, each with 5 to 7 participants, resulting in 23 participants. Methods: The meeting minutes were analysed using qualitative content analysis, whereas reflexive thematic analysis was used for the group meeting data. The group meetings were conducted online and structured by the Nominal Group Technique to discuss the importance of measures for staff. Results: Measures implemented for staff focused on prevention of COVID-19 transmission, (suspension of) educational activities, testing, additional tasks and staffing capacity, promoting wellbeing, and other means of support. The implemented measures overlapped with the measures considered important by staff. In addition, staff considered measures on decision-making support and communication to be important. Staff prioritized the measures in the group meetings because they affected their well-being, workforce scheduling, decision-making, or infection prevention. Furthermore, the group meetings revealed that decision-making shifted from mainly implementing national measures to more context-adjusted decision-making in the staff's or clients' situations. Conclusions: We showed that although nursing home staff were not always involved in decisionmaking during the first COVID-19 wave, there was overlap between the measures implemented by the organizations and measures considered important by staff. We suggest that organizations Show less
For decades, public health experts and journalists worldwide warned about a viral pandemic capable of causing illness and loss of life. Previous outbreaks of SARS, Ebola, and MERS highlighted this... Show moreFor decades, public health experts and journalists worldwide warned about a viral pandemic capable of causing illness and loss of life. Previous outbreaks of SARS, Ebola, and MERS highlighted this threat, which occupied top positions in risk assessments globally. Yet even with knowledge and precedent, the COVID-19 pandemic caught the world off guard. It revealed a world inadequately prepared and plunged societies into a state of disruption, with over 7 million deaths reported to the World Health Organization by April 2024. How did this tragedy foretold take the world by such surprise? In The COVID-19 Intelligence Failure: Why Warning Was Not Enough, Erik J. Dahl explores this question from the vantage point of the United States.In his book, Dahl, who is highly regarded for his expertise on intelligence failures, analyzes past and present intelligence efforts to underline the shortcomings and successes of the U.S. intelligence community's anticipation of the pandemic, comparing the anticipation and response to COVID-19 with historical failed warnings, such as those preceding 9/11 and Pearl Harbor. Show less
Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
The outbreaks of AIDS and COVID-19 showed clearly how infectious viruses can influence people’s lives. Investigating the changes in the host metabolism may provide a paradigm shift to consider... Show moreThe outbreaks of AIDS and COVID-19 showed clearly how infectious viruses can influence people’s lives. Investigating the changes in the host metabolism may provide a paradigm shift to consider immune-metabolic interactions as therapeutic targets. The aim of this thesis is to examine the interplay between the immune system and metabolism during viral infections, such as HIV and coronavirus. These investigations will utilize metabolomic and lipidomic mass spectrometry techniques to gain a comprehensive understanding of the metabolic changes that occur during viral infections. To enhance the coverage of the lipidome, a new method will be developed. Show less
Lopuhaä, B.V.; Guzel, C.; Lee, A. van der; Bosch, T.P.P. van den; Kemenade, F.J. van; Huisman, M.; ... ; Thüsen, J.H. von der 2024
AimsCOVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed... Show moreAimsCOVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue.MethodsLiquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls.ResultsCompared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins.ConclusionsThe decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.A decrease in platelet activation pathways in COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. In situ thrombi show upregulation of SARS-CoV-2 pathogenesis proteins compared to thromboemboli, underscoring the significance of in situ pulmonary thrombosis in COVID-19. image Show less
Wolfkamp, W.; Meijer, J.; Hoeve, J.C. van; Erning, F. van; Geus-Oei, L.F. de; Hingh, I. de; ... ; Siesling, S. 2024
Background: In the Netherlands, the COVID-19 pandemic resulted in a temporary halt of population screening for cancer and limited hospital capacity for non-COVID care. We aimed to investigate the... Show moreBackground: In the Netherlands, the COVID-19 pandemic resulted in a temporary halt of population screening for cancer and limited hospital capacity for non-COVID care. We aimed to investigate the impact of the pandemic on the in-hospital diagnostic pathway of breast cancer (BC) and colorectal cancer (CRC).Methods: 71,159 BC and 48,900 CRC patients were selected from the Netherlands Cancer Registry. Patients, diagnosed between January 2020 and July 2021, were divided into six periods and compared to the average of patients diagnosed in the same periods in 2017-2019. Diagnostic procedures performed were analysed using logistic regression. Lead time of the diagnostic pathway was analysed using Cox regression. Analyses were stratified for cancer type and corrected for age, sex (only CRC), stage and region.Results: For BC, less mammograms were performed during the first recovery period in 2020. More PET-CTs were performed during the first peak, first recovery and third peak period. For CRC, less ultrasounds and more CT scans and MRIs were performed during the first peak. Lead time decreased the most during the first peak by 2 days (BC) and 8 days (CRC). Significantly fewer patients, mainly in lower stages, were diagnosed with BC (-47%) and CRC (-36%) during the first peak.Conclusion: Significant impact of the COVID-19 pandemic was found on the diagnostic pathway, mainly during the first peak. In 2021, care returned to the same standards as before the pandemic. Long-term effects on patient outcomes are not known yet and will be the subject of future research. Show less
The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic... Show moreThe emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease prevention and treatment. As science and technology advance, the availability and diversity of observational and experimental data related to these biological processes continue to grow. In this thesis, we integrate multisource data with dynamic modeling to investigate the biological mechanisms of Notch signaling in biological development and to develop prevention and control strategies for infectious diseases. Show less
Kidney transplant recipients (KTRs) elicit an impaired immune response after COVID-19 vaccination; however, the exact clinical impact remains unclear. We therefore analyse the relationship between... Show moreKidney transplant recipients (KTRs) elicit an impaired immune response after COVID-19 vaccination; however, the exact clinical impact remains unclear. We therefore analyse the relationship between antibody levels after vaccination and the risk of COVID-19 in a large cohort of KTRs. All KTRs living in the Netherlands were invited to send a blood sample 28 days after their second COVID-19 vaccination for measurement of their IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD IgG). Information on COVID-19 was collected from the moment the blood sample was obtained until 6 months thereafter. Multivariable Cox and logistic regression analyses were performed to analyse which factors affected the occurrence and severity (i.e., hospitalization and/or death) of COVID-19. In total, 12,159 KTRs were approached, of whom 2885 were included in the analyses. Among those, 1578 (54.7%) became seropositive (i.e., anti-RBD IgG level >50 BAU/mL). Seropositivity was associated with a lower risk for COVID-19, also after adjusting for multiple confounders, including socio-economic status and adherence to COVID-19 restrictions (HR 0.37 (0.19-0.47), p = 0.005). When studied on a continuous scale, we observed a log-linear relationship between antibody level and the risk for COVID-19 (HR 0.52 (0.31-0.89), p = 0.02). Similar results were found for COVID-19 severity. In conclusion, antibody level after COVID-19 vaccination is associated in a log-linear manner with the occurrence and severity of COVID-19 in KTRs. This implies that if future vaccinations are indicated, the aim should be to reach for as high an antibody level as possible and not only seropositivity to protect this vulnerable patient group from disease. Show less
Many COVID-19 survivors have post-COVID-19 conditions, and females are at a higher risk. We sought to determine (1) how protein levels change from acute to post-COVID-19 conditions, (2) whether... Show moreMany COVID-19 survivors have post-COVID-19 conditions, and females are at a higher risk. We sought to determine (1) how protein levels change from acute to post-COVID-19 conditions, (2) whether females have a plasma protein signature different from that of males, and (3) which biological pathways are associated with COVID-19 when compared to restrictive lung disease. We measured protein levels in 74 patients on the day of admission and at 3 and 6 months after diagnosis. We determined protein concentrations by multiple reaction monitoring (MRM) using a panel of 269 heavy-labeled peptides. The predicted forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were measured by routine pulmonary function testing. Proteins associated with six key lipid-related pathways increased from admission to 3 and 6 months; conversely, proteins related to innate immune responses and vasoconstriction-related proteins decreased. Multiple biological functions were regulated differentially between females and males. Concentrations of eight proteins were associated with FVC, %, and they together had c-statistics of 0.751 (CI:0.732-0.779); similarly, concentrations of five proteins had c-statistics of 0.707 (CI:0.676-0.737) for DLCO, %. Lipid biology may drive evolution from acute to post-COVID-19 conditions, while activation of innate immunity and vascular regulation pathways decreased over that period. (ProteomeXchange identifiers: PXD041762, PXD029437) Show less
Pulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades,... Show morePulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades, diagnosing PE is still a difficult process due to the non-specific symptoms, which can frequently overlap with symptoms of other cardiopulmonary diseases. Currently recommended diagnostic strategies for suspected acute PE consist of standardized assessment of the clinical pre-test probability (CPTP) using validated clinical decision rules (CDRs) and D-dimer testing. PE is considered safely ruled out in patients with a non-high CPTP and a normal D-dimer test. Imaging tests as computed tomography pulmonary angiography (CTPA) are required in the case of a high CPTP and/or abnormal D-dimer test to confirm the diagnosis. The first part of this thesis describes the challenges of diagnosing PE in general and in specific clinically relevant patient subgroups. Moreover, this part evaluates the diagnostic performance of non-invasive diagnostic strategies for suspected PE in specific relevant patient subgroups. The second part of this thesis focuses on venous thrombotic complications in hospitalized patients with COVID-19. Show less
By examining the iconised photographs of the COVID-19 pandemic, published under the heading of The Great Empty by the New York Times in March 2020, this article explores the aesthetic operations... Show more By examining the iconised photographs of the COVID-19 pandemic, published under the heading of The Great Empty by the New York Times in March 2020, this article explores the aesthetic operations and ethical implications of representing anxiety through photographing desolate landscapes. To do so, it situates these images within the genre of late photography, also known as aftermath photography, to discuss how emptiness can function as a surrogate for anxiety. First, by foregrounding the unique temporality of the landscape genre in photography, it examines the aesthetic dimension of seeing deserted places in photographs. By shifting its focus from the image to its caption, it then discusses how the caption of such photographs can interpolate an ethical dimension onto them. Finally, by drawing on Giorgio Agamben’s philosophy of “gesture,” the article puts forward that the combination of aestheticized photographs with ethicised captions in The Great Empty expresses anxiety as a mode of gesturality: a sui generis communicational mode that simultaneously galvanizes and paralyzes the viewer. Show less
Bazdar, S.; Berg, S. van den; Rutjes, N.W.; Bloemsma, L.D.; Downward, G.S.; Weger, L.A. de; ... ; Kapitein, B. 2023
BackgroundThe incidence of severe asthma exacerbations (SAE) requiring a pediatric intensive care unit (PICU) admission during the coronavirus disease 2019 (COVID-19) pandemic (and its association... Show moreBackgroundThe incidence of severe asthma exacerbations (SAE) requiring a pediatric intensive care unit (PICU) admission during the coronavirus disease 2019 (COVID-19) pandemic (and its association with public restrictions) is largely unknown. We examined the trend of SAE requiring PICU admission before, during, and after COVID-19 restrictions in Amsterdam, the Netherlands, and its relationship with features such as environmental triggers and changes in COVID-19 restriction measures.MethodsIn this single-center, retrospective cohort study, all PICU admissions of children aged >= 2 years for severe asthma at the Amsterdam UMC between 2018 and 2022 were included. The concentrations of ambient fine particulate matter (PM2.5) and pollen were obtained from official monitoring stations.ResultsBetween January 2018 and December 2022, 228 children were admitted to the PICU of the Amsterdam UMC for SAE. While we observed a decrease in admissions during periods of more stringent restriction, there was an increase in the PICU admission rate for SAE in some periods following the lifting of restrictions. In particular, following the COVID-19 restrictions in 2021, we observed a peak incidence of admissions from August to November, which was higher than any other peak during the indicated years. No association with air pollution or pollen was observed.ConclusionWe hypothesize that an increase in clinically diagnosed viral infections after lockdown periods was the reason for the altered incidence of SAE at the PICU in late 2021, rather than air pollution and pollen concentrations. Show less
In dit onderzoek hebben we de rol van thromboinflammatie onderzocht in verschillende hoog-risico populaties, zoals mensen met type 2 diabetes mellitus (T2DM) en patiënten met ernstige COVID-19, als... Show moreIn dit onderzoek hebben we de rol van thromboinflammatie onderzocht in verschillende hoog-risico populaties, zoals mensen met type 2 diabetes mellitus (T2DM) en patiënten met ernstige COVID-19, als ook naar verhoogd risico bij vrouwen in de Nederlandse samenleving. Thromboinflammatie is de verbinding tussen de gelijktijdige activatie van de stollingsroute en immuunrespons welke een belangrijke trigger vormt voor bloedvat schade, prominent in microvasculaire gezondheid. Als eerste laten we zien dat er genderspecifieke associaties zijn tussen het activatie potentieel van de stollingsroute en microvasculaire gezondheid met betrekking tot eventueel ontwikkelen van hartfalen. Het mechanisme van T2DM progressie varieert bij verschillende etniciteiten en we hebben aangetoond dat veranderingen in cholesterol functie (HDL) en lipiden profiel in het bloed een van de onderliggende mechanismen kunnen zijn die leiden tot versnelde ziekte progressie bij Zuid-Aziaten van Nederlandse afkomst met T2DM in vergelijk met Nederlandse blanke Europeanen met T2DM. Met nieuwe geavanceerde technieken vonden we ook dat bij patiënten met ernstige COVID-19 factoren in het bloed aanwezig zijn die schade aan de kleine bloedvaten en verhoogde stollingsactiviteit teweegbrengen. Ook bij deze patiënten zagen we dat veranderingen in HDL compositie een belangrijke rol in de ernst van de ziekte speelt. Samen geven de resultaten het belang aan van thromboinflammatie in verhoogd-risico populaties in versneld ontwikkelen van hartfalen, T2DM en COVID-19. Het onderzoek laat de noodzaak zien van vroege detectie in het proces, waarbij vroegtijdige interventies kunnen lijden tot preventie of het beter managen van het thromboinflammatoire ziekteproces.*************************************************************************In this study, we investigated the role of thromboinflammation in various high-risk populations, including individuals with type 2 diabetes mellitus (T2DM) and patients with severe COVID-19, as well as the increased risk in women in Dutch society. Thromboinflammation refers to the simultaneous activation of the clotting pathway and immune response, which is a significant trigger for vascular damage, particularly in microvascular health.Firstly, we demonstrated sex-specific associations between coagulation parameters and microvascular health. The mechanism of T2DM progression varies among different ethnicities, and we found that changes in cholesterol function (HDL) and lipid profiles in the blood could be underlying mechanisms leading to accelerated disease progression in South Asians of Dutch descent with T2DM compared to Dutch white Caucasian with T2DM.Using advanced techniques, we also identified factors in the blood of patients with severe COVID-19 that contribute to small blood vessel damage and increased clotting activity. We observed that changes in HDL composition played an important role in the severity of the disease in these patients.Overall, our results highlight the importance of thromboinflammation in high-risk populations in the accelerated development of heart failure, T2DM, and COVID-19. The research emphasizes the need for early detection in the process, where timely interventions can lead to prevention or better management of the thromboinflammatory disease process. Show less
ObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient... Show moreObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic.MethodsThis study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models.Results1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves.ConclusionDelirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave. Show less
Aims The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to allocation of healthcare resources. Yet the impact of COVID-19 on... Show moreAims The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to allocation of healthcare resources. Yet the impact of COVID-19 on diabetes outpatients has not been extensively evaluated. This study aimed to assess the effect of the COVID-19 pandemic on diagnostics and intermediate outcomes of outpatient diabetes care pre- and during COVID.Methods This observational cohort study included 8,442 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2019 and 2021. A mixed-effects regression analysis was used to examine differences in target achievement of HbA1c, BMI, blood pressure, LDL-cholesterol, eGFR, and the difference in mean HbA1c between 2019 and 2020 among n = 1,426 outpatients who visited in both years. Analyses were adjusted for age, sex, and BMI.Results A 22.7% (21.6-23.8%, p < 0.001) decline in outpatient volume was observed during the pandemic (2020). BMI, lipid spectrum, kidney function, and HbA1c were assessed less frequently in 2020 than in 2019. In 2020, compared to 2019, the median HbA1c level increased by 2.2% (1.0 mmol/mol, p = 0.035) and the percentages of patients with known HbA1C meeting targets below 10, 8, 7% (86, 64, and 53 mmol/mol) decreased by 0.5%, 1.7% and 1.4%, respectively. Target blood pressure <= 130/80 mmHg was achieved more often in 2020 (15.0% versus 18.3%, p = 0.018), while HbA1c <= 86 mmol/mol was achieved less (89.3% versus 87.1%, p = 0.001), among diabetes outpatients seen in both 2019 and 2020. In patients visiting both years, HbA1c was 2.3% (1.9 mmol/l, 95% CI 1.2-2.5, p < 0.001) lower during the pandemic than in the prepandemic (2019).Conclusions The COVID pandemic was associated with a marked reduction in patient volume in diabetes outpatient care among five hospitals. Among patients who received outpatient care both before and during the pandemic period, HbA1c control and blood pressure control enhanced during the pandemic. Re-evaluation of current diabetes outpatient care organization is warranted to ensure optimal diabetes care in future times. Show less
Leegwater, E.; Dol, L.; Benard, M.R.; Roelofsen, E.E.; Delfos, N.M.; Feltz, M. van der; ... ; Nieuwkoop, C. van 2023
IntroductionRemdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to... Show moreIntroductionRemdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir.MethodsThis was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration.ResultsOf 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79–1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48–1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07–7.56).ConclusionRemdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation. Show less
The treatment of community-acquired pneumonia (CAP) is based on early diagnosis and swift initiation of appropriate antibiotic treatment. Despite effective treatment, CAP is still one of the... Show moreThe treatment of community-acquired pneumonia (CAP) is based on early diagnosis and swift initiation of appropriate antibiotic treatment. Despite effective treatment, CAP is still one of the leading causes of morbidity and mortality due to infectious diseases worldwide. This thesis aimed to identify strategies to optimise the treatment of hospitalised CAP patients outside an intensive care unit (ICU) setting with a focus on corticosteroid treatment. First, this thesis focused on the question whether oral adjunctive corticosteroid treatment improves outcomes in hospitalised CAP patients and tries to identify a subgroup of CAP patients, based on inflammatory status at admission, in whom the beneficial effects of adjunctive corticosteroid treatment outweigh the disadvantages associated with corticosteroid use. Next, this thesis investigated whether obesity and overweight are associated with worse clinical outcomes in a population of hospitalised COVID-19 patients who were all treated with the recommended 6 mg dexamethasone dose. Last, this thesis focused on optimising antibiotic treatment by exploring whether extensive microbiological testing facilitates early antibiotic alterations in CAP patients. Show less
Introduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher... Show moreIntroduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA.Methods: This study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 & mu;g mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1specific IgG antibodies 14 days post-vaccination.Results: In April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599-1,689), 3,855 (2,800-5,306), and 3,513 (2,554-4,833) at day 1, 15 and 29, respectively). In addition, SARSCoV-2-specific T cell responses were lower after ID vaccination through npMNA.Conclusion: Needle-free delivery of 20 & mu;g mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Clinical trial registry (on ClinicalTrial.gov): NCT05315362. Show less
