As cousins, we discovered a treasure trove of family papers, revealing the intricate relationship between precarity and privilege of our family from Salonica navigating the post-Ottoman transition.... Show moreAs cousins, we discovered a treasure trove of family papers, revealing the intricate relationship between precarity and privilege of our family from Salonica navigating the post-Ottoman transition. Recognising the potential of family history to provide a more intimate and complex historiography, this article offers our initial study of these family papers. By highlighting the challenges posed by the scarcity of such documents in Middle Eastern studies, emphasising women’s roles in preserving family memory and focussing on the interplay between personal and political domains, we identify the preparation of a family tree as a gendered and socioeconomic project of preserving the past and shaping the present. By tracing our family's origins, including unsettling discoveries, we address matters of identity and memory before embarking on our analysis. By reconstructing the biographies of two generations, we characterise the family’s socioeconomic struggle to sustain their precarious privilege amid shifting frontiers and along their journey from Ottoman Salonica to Kemalist Turkey. Ultimately, this article underscores the significance of family history as a transnational, intergenerational, intersectional and social history that enriches our understanding of the post-Ottoman transition through the lives of ordinary (and some extraordinary) Ottomans. Show less
The goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and N-acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the... Show moreThe goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and N-acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the model to optimize dosing regimens of cotrimoxazole for Pneumocystis jirovecii pneumonia and in patients with renal insufficiency or with continuous renal replacement therapy (CRRT). This was a retrospective multicenter observational cohort study based on therapeutic drug monitoring (TDM) data from hospitalized patients treated with cotrimoxazole. We developed two population pharmacokinetic (POPPK) models: a model of trimethoprim and an integrated model with both sulfamethoxazole and N-acetyl sulfamethoxazole concentrations. Monte Carlo simulations were performed to determine the optimal dosing regimen. A total of 348 measurements from 168 patients were available. The estimated glomerular filtration rate (eGFR) and CRRT were included as covariates on the clearance of all three compounds. Cotrimoxazole TID 1,920 mg and b.i.d. 2,400 mg led to sufficient exposure for infections with P. jirovecii in patients without renal insufficiency. To reach equivalent exposure, a dose reduction of 33.3% is needed in patients with an eGFR of 10 mL/minute/1.73 m2 and of 16.7% for an eGFR of 30 mL/minute/1.73 m2. N-acetyl sulfamethoxazole accumulates in patients with a reduced eGFR. CRRT increased the clearance of sulfamethoxazole, but not trimethoprim or N-acetyl sulfamethoxazole, compared with the median clearance in the population. Doubling the sulfamethoxazole dose is needed for patients on CRRT to reach equivalent exposure. Show less
Wastewater-based epidemiological surveillance at municipal wastewater treatment plants has proven to play an important role in COVID-19 surveillance. Considering international passenger hubs... Show moreWastewater-based epidemiological surveillance at municipal wastewater treatment plants has proven to play an important role in COVID-19 surveillance. Considering international passenger hubs contribute extensively to global transmission of viruses, wastewater surveillance at this type of location may be of added value as well. The aim of this study is to explore the potential of long-term wastewater surveillance at a large passenger hub as an additional tool for public health surveillance during different stages of a pandemic. Here, we present an analysis of SARS-CoV-2 viral loads in airport wastewater by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) from the beginning of the COVID-19 pandemic in Feb 2020, and an analysis of SARS-CoV-2 variants by whole-genome next-generation sequencing from Sep 2020, both until Sep 2022, in the Netherlands. Results are contextualized using (inter)national measures and data sources such as passenger numbers, clinical surveillance data and national wastewater surveillance data. Our findings show that wastewater surveillance was possible throughout the study period, irrespective of measures, as viral loads were detected and quantified in 98.6 % (273/277) of samples. Emergence of SARS-CoV-2 variants, identified in 91.0 % (161/177) of sequenced samples, coincided with increases in viral loads. Furthermore, trends in viral load and variant detection in airport wastewater closely followed, and in some cases preceded, trends in national daily average viral load in wastewater and variants detected in clinical surveillance. Wastewater-based epidemiology at a large international airport is a valuable addition to classical COVID-19 surveillance and the developed expertise can be applied in pandemic preparedness plans for other (emerging) pathogens in the future. Show less
As China’s internet has matured, from its initial web-based origins through innovative ‘2.0’ and ‘3.0’ innovations, so too have the community sentiments that criss-cross the People’s Republic of... Show moreAs China’s internet has matured, from its initial web-based origins through innovative ‘2.0’ and ‘3.0’ innovations, so too have the community sentiments that criss-cross the People’s Republic of China’s networked society. A perennial issue has been the question of how Chinese nationhood has been constructed and reproduced through digital technologies and how the evolving affordances of internet technology have contributed to China’s many nationalisms. This short essay reflects on this history. It discusses how early internet forums and blogs allowed users to coordinate their sense of Chineseness, how these processes later changed when communication moved to widely adopted microblogging platforms and what we can expect of the future, as China’s media environments shift their focus towards short-messaging applications and video-sharing platforms. What will happen to Chinese nationalisms as China’s platformisation enters its next phases? Show less
Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current... Show moreTuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants - CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB. In vitro in human dendritic cells (DCs), the adjuvanted formulation induced a significant increase in the production of (innate) cytokines and chemokines compared to the liposome without additional adjuvants. In vivo, the new vaccine administrated subcutaneously significantly reduced Mycobacterium tuberculosis (Mtb) bacterial load in the lungs and spleens of mice, significantly outperforming results from mice vaccinated with the antigen mixed with adjuvants without liposomes. In-depth analysis underpinned the vaccine's effectiveness in terms of its capacity to induce polyfunctional CD4+ and CD8+ T-cell responses, both considered essential for controlling Mtb infection. Also noteworthy was the differential abundance of various CD69+ B-cell subpopulations, which included IL17-A-producing B cells. The vaccine stimulated robust antigen-specific antibody titers, further extending its potential as a novel protective agent against TB. Show less
Tan, N.H.; Lafeber, M.; Sablerolles, R.S.G.; Roders, I.V.; Hoef, A. van de; Grafhorst, K. van; ... ; Kuy, P.H.M. van der 2024
Background Electronic informed consent (eConsent) usage has expanded in recent years in Europe, especially during the pandemic. Slow recruitment rate and limitations in participant outreach are the... Show moreBackground Electronic informed consent (eConsent) usage has expanded in recent years in Europe, especially during the pandemic. Slow recruitment rate and limitations in participant outreach are the challenges often faced in clinical research. Given the benefts of eConsent and group counselling reported in the literature, group eConsent was implemented in recruitment for the SWITCH-ON study. We aim to explore the experience of participants who attended group eConsent for the SWITCH-ON study and evaluate its potential for future use. Methods SWITCH-ON study aims to analyse the immunogenicity of a healthy population following bivalent COVID19 booster vaccination. Four hundred thirty-four healthcare workers aged 18–65 were successfully recruited and sent a questionnaire about their experience with group eConsent. Out of 399 completed questionnaires (response rate 92%), 39 participants did not join group eConsent. The remaining 360 responses were included in the fnal analysis. Quantitative and qualitative data were reported using descriptive statistical analysis and thematic analysis respectively. Results Participants found that group eConsent was an efcient method that it allowed them to hear each other’s questions and concerns and created a sense of togetherness. However, limited privacy, barriers to asking questions in a group, and peer pressure can limit the use of group eConsent. One hundred sixty-fve (46%) participants thought that group eConsent was suitable to recruit participants with diseases or conditions, while 87 (24%) reported limitations with this method. The remaining participants suggested that applicability of group eConsent depended on the diseases or conditions of the study population, and one-to-one conversation should always be available. Participants who had experienced both one-to-one and group eConsent shared diferent preferred consent formats for future studies. Conclusion Group eConsent was positively evaluated by the participants of a low-risk vaccination study. Participants advised using webinars to provide general information about the study, followed by an individual session for each participant, would retain the benefts of group eConsent and minimise the limitations it posed. This proposed setting addresses privacy questions and makes group eConsent easier to implement. Show less
In België is er sinds 2022 veel aandacht voor het ‘no conflict of interest’-principe. Dit principe is neergelegd in artikel 9 bis van de mer-richtlijn en houdt in essentie in dat lidstaten ervoor... Show moreIn België is er sinds 2022 veel aandacht voor het ‘no conflict of interest’-principe. Dit principe is neergelegd in artikel 9 bis van de mer-richtlijn en houdt in essentie in dat lidstaten ervoor moeten zorgen dat de bevoegde instanties hun uit de richtlijn voortvloeiende taken op objectieve wijze vervullen. Als de bevoegde instantie tevens de opdrachtgever is, moet er een passende scheiding worden aangebracht tussen conflicterende functies. De Raad voor Vergunningsbetwistingen (RvVb) oordeelde in het Wasserij-arrest dat dit artikel niet goed in de Vlaamse regelgeving is geïmplementeerd. Op 26 maart 2024 heeft de Belgische Raad van State een prejudiciële vraag gesteld aan het Hof van Justitie over de uitleg die moet worden gegeven aan artikel 9 bis van de richtlijn.Deze ontwikkeling in Vlaanderen is de aanleiding om te kijken hoe Nederland artikel 9 bis heeft geïmplementeerd: zou het Omgevingsbesluit wel de toets van de RvVb doorstaan? Show less
Objectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19... Show moreObjectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19 naive adults aged 18e30 years were recruited from a previous study on primary vaccination regimens that compared 20 mg ID vaccinations with 100 mg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 mg) or the standard-of-care intramuscular (IM) booster dose (50 mg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18e40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. Results: In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150e11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003e6322) BAU/mL; 6629 (4913e8946) BAU/mL; and 5264 (4032e6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Discussion: Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. Show less
Balsby, I.M.; Nielsen, S.M.; Christensen, R.; Henriksen, M.; Dahl, L.U.M.; Berg, J.I.; ... ; Dossing, A. 2024
Objective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically... Show moreObjective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors’ effect was explored in meta-regression and stratified models with pain as the dependent variable. Results: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of −0.51 (95% confidence interval −0.61 to −0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. Conclusion: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO registration ID: CRD42022298984 Show less
Stoelinga, A.E.C.; Biewenga, M.; Drenth, J.P.H.; Verhelst, X.; Meer, A.J.P. van der; Boer, Y.S. de; ... ; Dutch Autoimmune Hepatitis Study 2024
Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA).... Show moreBackground & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Show less
Meer, M.T. van der; Liscio, E.; Jonker, C.M.; Plaat A.; Vossen, P.T.J.M.; Murukannaiah, P.K. 2024
