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
Hoogervorst, L.A.; Stijnen, P.; Albini, M.; Janda, N.; Stewardson, A.J.; Patel, K.; ... ; Marang-van de Mheen, P. 2023
Objectives To assess across seven hospitals from six different countries the extent to which the COVID-19 pandemic affected the volumes of orthopaedic hospital admissions and patient outcomes for... Show moreObjectives To assess across seven hospitals from six different countries the extent to which the COVID-19 pandemic affected the volumes of orthopaedic hospital admissions and patient outcomes for non-COVID-19 patients admitted for orthopaedic care.Design A multi-centre interrupted time series (ITS) analysis.Setting Seven hospitals from six countries who collaborated within the Global Health Data@Work collaborative.Participants Non-COVID-19 patients admitted for orthopaedic care during the pre-pandemic (January/2018-February/2020) and COVID-19 pandemic (March/2020-June/2021) period. Admissions were categorised as: (1) acute admissions (lower limb fractures/neck of femur fractures/pathological fractures/joint dislocations/upper limb fractures); (2) subacute admissions (bone cancer); (3) elective admissions (osteoarthritis).Outcome measures Monthly observed versus expected ratios (O/E) were calculated for in-hospital mortality, long (upper-decile) length-of-stay and hospital readmissions, with expected rates calculated based on case-mix. An ITS design was used to estimate the change in level and/or trend of the monthly O/E ratio by comparing the COVID-19 pandemic with the pre-pandemic period.Results 69221 (pre-pandemic) and 22940 (COVID-19 pandemic) non-COVID-19 orthopaedic patient admissions were included. Admission volumes were reduced during the COVID-19 pandemic for all admission categories (range: 33%-45%), with more complex patients treated as shown by higher percentages of patients admitted with >= 1 comorbidity (53.8% versus 49.8%, p<0.001). The COVID-19 pandemic was not associated with significant changes in patient outcomes for most diagnostic groups. Only for patients diagnosed with pathological fractures (pre-pandemic n=1671and pandemic n=749), the COVID-19 pandemic was significantly associated with an immediate mortality reduction (level change of -77.7%, 95%CI -127.9% to -25.7%) and for lower limb fracture patients (pre-pandemic n=9898and pandemic n=3307) with a significantly reduced trend in readmissions (trend change of -6.3% per month, 95%CI -11.0% to -1.6%).Conclusions Acute, subacute, as well as elective orthopaedic hospital admissions volumes were reduced in all global participating hospitals during the COVID-19 pandemic, while overall patient outcomes for most admitted non-COVID-19 patients remained the same despite the strain caused by the surge of COVID-19 patients. Show less
Arend, B.W.H. van der; Bloemhof, M.M.; Schoor, A.G. van der; Zwet, E.W. van; Terwindt, G.M. 2023
BackgroundThis longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination.MethodsWe identified 547 clinically diagnosed... Show moreBackgroundThis longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination.MethodsWe identified 547 clinically diagnosed migraine patients from the Leiden Headache Center who kept a headache E-diary during the COVID-19 pandemic (February 2020 to August 2022). We sent a questionnaire to register their COVID-19 infection and/or vaccination dates. After applying inclusion criteria, n = 59 participants could be included in the infection analysis and n = 147 could be included in the vaccination analysis. Primary outcome was the change in monthly migraine days (MMD) between 1 month prior and 1 month post COVID-19 infection or vaccination. Secondary outcome variables were change in monthly headache days (MHD) and monthly acute medication days (MAMD).ResultsVaccination against COVID-19 was associated with an increase in MMD (1.06; 95% confidence interval [CI] = 0.57–1.55; p < 0.001), MHD (1.52; 95% CI = 0.91–2.14; p < 0.001) and MAMD (0.72; 95% CI = 0.33–1.12; p < 0.001) in the first month post-vaccination. COVID-19 infection solely increased the number of MAMD (1.11; 95% CI = 0.10–1.62; p < 0.027), but no statistically significant differences in MMD or MHD were observed.ConclusionsOur findings imply that vaccination against COVID-19 is associated with an increase in migraine, indicating a possible role of inflammatory mediators in migraine pathophysiology. Show less
Background: Videos have been an important medium for providing health and risk communication to the public during the COVID-19 pandemic. Public health officials, health care professionals, and... Show moreBackground: Videos have been an important medium for providing health and risk communication to the public during the COVID-19 pandemic. Public health officials, health care professionals, and policy makers have used videos to communicate pandemic-related content to large parts of the population. Evidence regarding the outcomes of such communication, along with their determinants, is however limited.Objective: The aim of this study was to test the impact of nonvisual information factors of video communication on 4 outcomes: trust, comprehension, intentions, and behavior.Methods: Twelve short health communication videos related to pandemics were produced and shown to a large sample of participants, applying a randomized controlled between-subjects design. Three factors were included in the creation of the videos: the topic (exponential growth, handwashing, and burden of pandemics on the health care system), the source (expert and nonexpert), and a call to action (present or absent). Participants were randomly assigned to 1 video intervention, and 1194 valid replies were collected. The data were analyzed using factorial ANOVA.Results: The 3 pandemic-related topics did not affect trust, comprehension, intentions, or behavior. Trust was positively influenced by an expert source (2.5%), whereas a nonexpert source instead had a positive effect on the proxy for behavior (5.7%) compared with the expert source. The inclusion of a call to action had a positive effect on both trust (4.1%) and comprehension (15%).Conclusions: Trust and comprehension in pandemic-related video communication can be enhanced by using expert sources and by including a call to action, irrespective of the topic being communicated. Intentions and behavior appear to be affected to a small extent by the 3 factors tested in this study. Show less
IntroductionNanoporous 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 moreIntroductionNanoporous 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.MethodsThis 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 µg 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 S1-specific IgG antibodies 14 days post-vaccination.ResultsIn 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, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA.ConclusionNeedle-free delivery of 20 µg 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. Show less
Oymans, E.J.; Kroon, C.D. de; Bart, J.; Nijman, H.W.; Aa, M.A. van der 2023
Objective: To study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands.Methods: We performed a retrospective... Show moreObjective: To study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands.Methods: We performed a retrospective cohort study using data from the Netherlands Cancer Registry (NCR) on women of 18 years and older diagnosed with invasive endometrial, ovarian, cervical or vulvar cancer in the period 2017-2021. Analyses were stratified for age, socioeconomical status (SES) and region.Results: The incidence rate of gynaecological cancer was 67/100.000 (n = 4832) before (2017-2019) and 68/ 100.000 (n = 4833) during (2020) the COVID-19 pandemic. Comparing the number of diagnoses of the two periods for the four types of cancer separately showed no significant difference. During the first wave of COVID19 (March-June 2020), a clear decrease in number of gynaecological cancer diagnoses was visible (20-34 %). Subsequently, large increases in number of diagnoses were visible (11-29 %). No significant differences in incidence were found between different age groups, SES and regions. In 2021 an increase of 5.9 % in number of diagnoses was seen.Conclusion: In the Netherlands, a clear drop in number of diagnoses was visible for all four types of gynaecological cancers during the first wave, with a subsequent increase in number of diagnoses in the second part of 2020 and in 2021. No differences between SES groups were found. This illustrates good organisation of and access to health care in the Netherlands. Show less
This dissertation aimed to examine the ethnic socialization context in the upbringing of Chinese-Dutch children, specifically three social-contextual factors: parents, children’s books, and the... Show moreThis dissertation aimed to examine the ethnic socialization context in the upbringing of Chinese-Dutch children, specifically three social-contextual factors: parents, children’s books, and the COVID pandemic. Results reveal that Chinese-Dutch children evaluate their ingroup and the White outgroup most positively, followed by the Middle Eastern and North African (MENA) outgroup, and the Black outgroup least positively. Stronger maternal endorsement of multiculturalism is associated with lower child ethnic prejudice (in terms of less ingroup preference). In addition, results demonstrate maternal self-report ethnic-racial socialization strategies and the observed behaviors that reflect color-evasiveness and white normativity. Furthermore, results show an overrepresentation of White authors, illustrators, and characters, and a preference for light skin color in East Asian characters in illustrations in Chinese children’s books, suggesting a form of current postcolonial influences on Chinese children’s literature. Furthermore, results indicate ethnicity-related attitude differences among mothers participating after than before the COVID outbreak, with higher perceived discrimination and stronger ethnic identity. A lower ingroup rejection among Chinese-Dutch children was found in the post-COVID-outbreak group than in the pre-COVID-outbreak group. This dissertation can foster a better understanding of the interethnic relations in the underrepresented Chinese group and elucidate the ethnicity-related consequences of the pandemic in this group. Show less
Koekenbier, E.L.; Fohse, K.; Maat, J.S. van de; Oosterheert, J.J.; Nieuwkoop, C. van; Hoogerwerf, J.J.; ... ; BCG-PRIME Study Grp 2023
ObjectivesTo test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more... Show moreObjectivesTo test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities.MethodsCommunity-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events.ResultsA total of 6112 participants with a median age of 69 years (interquartile range, 65–74) and median of 2 (interquartile range, 1–3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87–1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46–1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35–1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group.Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66–1.28).DiscussionBCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs. Show less
This longitudinal study assessed the impact of the COVID-19 pandemic on children with autism spectrum disorder (ASD; n = 62; M-age = 13 years) by measuring emotional and behavioral problems before... Show moreThis longitudinal study assessed the impact of the COVID-19 pandemic on children with autism spectrum disorder (ASD; n = 62; M-age = 13 years) by measuring emotional and behavioral problems before and during the pandemic, and by comparing this change to a matched sample of children without ASD (n = 213; M-age = 16 years). Moreover, we examined whether indicators of parental well-being promoted resilience of children with ASD. Results showed that the mean change in problems did not differ between children with and without ASD. Importantly, some children showed an increase in problems, while others showed resilience. Parental well-being indicators were not related to resilience among children with ASD. The interindividual variability in responses, particularly among children with ASD, highlights the need for personalized support. Show less
Background In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care... Show moreBackground In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days.Methods This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale.Results In the primary analysis, 587 patients were included (age: 57 [Q1–Q3: 45–68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60–1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42–0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41–1.01, p = 0.05).Conclusion Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508). Show less
Hempenius, M.; Bots, S.H.; Groenwold, R.H.H.; Boer, A. de; Klungel, O.H.; Gardarsdottir, H. 2023
Purpose: During the first waves of the coronavirus pandemic, evidence on potential effective treatments was urgently needed. Results from observational studies on the effectiveness of... Show morePurpose: During the first waves of the coronavirus pandemic, evidence on potential effective treatments was urgently needed. Results from observational studies on the effectiveness of hydroxychloroquine (HCQ) were conflicting, potentially due to biases. We aimed to assess the quality of observational studies on HCQ and its relation to effect sizes.Methods: PubMed was searched on 15 March 2021 for observational studies on the effectiveness of in-hospital use of HCQ in COVID-19 patients, published between 01/01/2020 and 01/03/2021 on. Study quality was assessed using the ROBINS-I tool. Association between study quality and study characteristics (journal ranking, publication date, and time between submission and publication) and differences between effects sizes found in observational studies compared to those found in RCTs, were assessed using Spearman's correlation.Results: Eighteen of the 33 (55%) included observational studies were scored as critical risk of bias, eleven (33%) as serious risk and only four (12%) as moderate risk of bias. Biases were most often scored as critical in the domains related to selection of participants (n = 13, 39%) and bias due to confounding (n = 8, 24%). There were no significant associations found between the study quality and the characteristics nor between the study quality and the effect estimates.Discussion: Overall, the quality of observational HCQ studies was heterogeneous. Synthesis of evidence of effectiveness of HCQ in COVID-19 should focus on RCTs and carefully consider the added value and quality of observational evidence. Show less
BackgroundVolatile organic compounds (VOCs) produced by human cells reflect metabolic and pathophysiological processes which can be detected with the use of electronic nose (eNose) technology.... Show moreBackgroundVolatile organic compounds (VOCs) produced by human cells reflect metabolic and pathophysiological processes which can be detected with the use of electronic nose (eNose) technology. Analysis of exhaled breath may potentially play an important role in diagnosing COVID-19 and stratification of patients based on pulmonary function or chest CT.MethodsBreath profiles of COVID-19 patients were collected with an eNose device (SpiroNose) 3 months after discharge from the Leiden University Medical Centre and matched with breath profiles from healthy individuals for analysis. Principal component analysis was performed with leave-one-out cross validation and visualised with receiver operating characteristics. COVID-19 patients were stratified in subgroups with a normal pulmonary diffusion capacity versus patients with an impaired pulmonary diffusion capacity (DLCOc < 80% of predicted) and in subgroups with a normal chest CT versus patients with COVID-19 related chest CT abnormalities.ResultsThe breath profiles of 135 COVID-19 patients were analysed and matched with 174 healthy controls. The SpiroNose differentiated between COVID-19 after hospitalization and healthy controls with an AUC of 0.893 (95-CI, 0.851-0.934). There was no difference in VOCs patterns in subgroups of COVID-19 patients based on diffusion capacity or chest CT.ConclusionsCOVID-19 patients have a breath profile distinguishable from healthy individuals shortly after hospitalization which can be detected using eNose technology. This may suggest ongoing inflammation or a common repair mechanism. The eNose could not differentiate between subgroups of COVID-19 patients based on pulmonary diffusion capacity or chest CT. Show less
Toes-Zoutendijk, E.; Jonge, L. de; Iersel, C.A. van; Spaander, M.C.W.; Vuuren, A.J. van; Kemenade, F. van; ... ; Lansdorp-Vogelaar, I. 2023
Objective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design:... Show moreObjective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design: All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, 'before', 'during' and 'after' the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. Results: Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.83) and after (OR=0.92) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. Conclusion: The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention. Show less
So, P.; Wierdsma, A.I.; Mulder, C.L.; Vermeiren, R.R.J.M. 2023
Background:There is growing evidence that the COVID-19 pandemic, and its associated social distancing measures, affect adolescents' mental health. We wanted to examine whether and how the number... Show moreBackground:There is growing evidence that the COVID-19 pandemic, and its associated social distancing measures, affect adolescents' mental health. We wanted to examine whether and how the number and characteristics of adolescents' psychiatric emergency presentations have changed throughout the pandemic. Methods: We extracted data from the records of 977 psychiatric emergency consultations of adolescents aged 12- 19 who had been referred to the mobile psychiatric emergency services in Rotterdam, the Netherlands between January 1(st) 2018 and January1(st) 2022. Demographic, contextual, and clinical characteristics were recorded. Time-series-analyses were performed using quasi-Poisson Generalized Linear Model to examine the effect of the first and second COVID-19 lockdown on the number of psychiatric emergency consultations, and to explore differences between boys and girls and internalizing versus externalizing problems. Results: The number of psychiatric emergency consultations regarding adolescents increased over time: from about 13 per month in 2018 to about 29 per month in 2021. During the COVID-19 pandemic, the increase was tempered. In the second wave a pronounced increase of psychiatric emergencies among adolescents with internalizing problems but not with externalizing problems was found. Conclusion: Despite the reported increase of mental health problems in adolescents during the COVID-19 pandemic, we did find a smaller increase in psychiatric emergency consultations in this group then would be expected considering the overall trend. Besides changes in help-seeking and access to care, a possible explanation may be that a calmer, more orderly existence, or more parental supervision led to less psychiatric emergency situations in this age group. In the second wave the number of emergency consultations increased especially among girls with internalizing problems. While there has been a particular fall in emergency referrals of adolescents with externalizing problems since the start of the pandemic it is still too early to know whether this is a structural phenomenon. It would be important to elucidate whether the changes in emergency referrals reflect a true change in prevalence of urgent internalizing and externalizing problems in adolescents during the pandemic or a problem related to access to care. Show less
Background: CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated... Show moreBackground: CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its correlation with respiratory parameters remains unknown. This study aims to assess the association between CT-SS and respiratory outcomes, both in hospital and at three months after hospitalization. Methods: Patients from the COVID-19 High-intensity Immunosuppression in Cytokine storm Syndrome (CHIC) study surviving hospitalization due to COVID-19 associated hyperinflammation were invited for follow-up assessment at three months after hospitalization. Results of CT-SS three months after hospitalization were compared with CT-SS at hospital admission. CT-SS at admission and at 3-months were correlated with respiratory status during hospitalization and with patient reported outcomes as well as pulmonary- and exercise function tests at 3-months after hospitalization. Results: A total of 113 patients were included. Mean CT-SS decreased by 40.4% (SD 27.6) in three months (P < 0.001). CT-SS during hospitalization was higher in patients requiring more oxygen (P < 0.001). CT-SS at 3-months was higher in patients with more dyspnoea (CT-SS 8.31 (3.98) in patients with modified Medical Council Dyspnoea scale (mMRC) 0-2 vs. 11.03 (4.47) in those with mMRC 3-4). CT-SS at 3-months was also higher in patients with a more impaired pulmonary function (7.4 (3.6) in patients with diffusing capacity for carbon monoxide (DLCO) > 80%pred vs. 14.3 (3.2) in those with DLCO < 40%pred, P = 0.002). Conclusion: Patients surviving hospitalization for COVID-19-associated hyperinflammation with higher CT-SS have worse respiratory outcome, both in-hospital and at 3-months after hospitalization. Strict monitoring of patients with high CT-SS is therefore warranted. Show less
CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its... Show moreCT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its correlation with respiratory parameters remains unknown. This study aims to assess the association between CT-SS and respiratory outcomes, both in hospital and at three months after hospitalization.MethodsPatients from the COVID-19 High-intensity Immunosuppression in Cytokine storm Syndrome (CHIC) study surviving hospitalization due to COVID-19 associated hyperinflammation were invited for follow-up assessment at three months after hospitalization. Results of CT-SS three months after hospitalization were compared with CT-SS at hospital admission. CT-SS at admission and at 3-months were correlated with respiratory status during hospitalization and with patient reported outcomes as well as pulmonary- and exercise function tests at 3-months after hospitalization.ResultsA total of 113 patients were included. Mean CT-SS decreased by 40.4% (SD 27.6) in three months (P < 0.001). CT-SS during hospitalization was higher in patients requiring more oxygen (P < 0.001). CT-SS at 3-months was higher in patients with more dyspnoea (CT-SS 8.31 (3.98) in patients with modified Medical Council Dyspnoea scale (mMRC) 0–2 vs. 11.03 (4.47) in those with mMRC 3–4). CT-SS at 3-months was also higher in patients with a more impaired pulmonary function (7.4 (3.6) in patients with diffusing capacity for carbon monoxide (DLCO) > 80%pred vs. 14.3 (3.2) in those with DLCO < 40%pred, P = 0.002).ConclusionPatients surviving hospitalization for COVID-19-associated hyperinflammation with higher CT-SS have worse respiratory outcome, both in-hospital and at 3-months after hospitalization. Strict monitoring of patients with high CT-SS is therefore warranted. Show less
Hilhorst, M.; Bemelman, F.J.; Bruchfeld, A.; Fernandez-Juarez, G.M.; Floege, J.; Frangou, E.; ... ; Immunonephrol Working Grp European 2023
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney... Show moreThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients. Show less
Aims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm... Show moreAims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm syndrome (CSS). Methods: MP pre-treated patients with COVID-19-associated CSS, defined as at least two elevations of C-reactive protein (CRP) >100 mg/L, ferritin >900 mu g/L or D-dimers >1500 mu g/L, received intravenous TCZ (8 mg/kg, max. 800 mg) upon clinical deterioration. A nonlinear-mixed effects model was developed based on TCZ serum concentrations and dosing information. Population pharmacokinetic parameters were estimated and concentration-time profiles were plotted against individual predicted values. Fixed dose simulations were subsequently performed based on the final model. Results:In total 40 patients (mean [SD] age: 62 [12] years, 20% female, body weight: 87 [17] kg) with COVID-19 induced CSS were evaluated on pharmacokinetics and laboratory parameters. A biphasic elimination of TCZ serum concentration was described by a homogeneous population pharmacokinetic model. Serum TCZ concentrations above the 1 mu g/L target saturation threshold were covered for 16 days in all evaluated patients treated with a single dose of 8 mg/kg. In a simulation with TCZ 400 mg fixed dose, this condition of full IL-6 receptor occupancy at minimum serum concentration was also met. Conclusions: A single dose (8 mg/kg, max. 800 mg) is sufficient to cover a period of 16 days of IL-6-mediated hyperinflammation in COVID-19-induced CSS in MP-treated patients. Based on body weight PK simulations, a fixed-dose tocilizumab of 400 mg should be considered to prevent overtreatment, future drug shortage and unnecessary drug expenditure. Show less
