The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index

Background Validity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised. Methods Three investigators assigned an activity score on a 0–10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate–multivariate linear regression analyses were used to define variables predicting the ‘gold standard’, their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0–10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS). Results A weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) \u3e18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein \u3e1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted \u3c70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease. Changes in the index paralleled those of MSS (p=0.0001). Conclusions A preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies

Estimating fine age structure and time trends in human contact patterns from coarse contact data: the Bayesian rate consistency model

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many contact surveys have been conducted to measure changes in human interactions in the face of the pandemic and non-pharmaceutical interventions. These surveys were typically conducted longitudinally, using protocols that differ from those used in the pre-pandemic era. We present a model-based statistical approach that can reconstruct contact patterns at 1-year resolution even when the age of the contacts is reported coarsely by 5 or 10-year age bands. This innovation is rooted in population-level consistency constraints in how contacts between groups must add up, which prompts us to call the approach presented here the Bayesian rate consistency model. The model incorporates computationally efficient Hilbert Space Gaussian process priors to infer the dynamics in age- and gender-structured social contacts and is designed to adjust for reporting fatigue in longitudinal surveys. We demonstrate on simulations the ability to reconstruct contact patterns by gender and 1-year age interval from coarse data with adequate accuracy and within a fully Bayesian framework to quantify uncertainty. We investigate the patterns of social contact data collected in Germany from April to June 2020 across five longitudinal survey waves. We reconstruct the fine age structure in social contacts during the early stages of the pandemic and demonstrate that social contacts rebounded in a structured, non-homogeneous manner. We also show that by July 2020, social contact intensities remained well below pre-pandemic values despite a considerable easing of non-pharmaceutical interventions. This model-based inference approach is open access, computationally tractable enabling full Bayesian uncertainty quantification, and readily applicable to contemporary survey data as long as the exact age of survey participants is reported.Comment: 39 pages, 16 figure

Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis

Background. Invasive aspergillosis (IA) remains a leading cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To date, no reliable immunological biomarkers for management and outcome of IA exist. Here, we investigated reconstitution of antifungal immunity in patients during the first 12 months after HSCT and correlated it with IA. Methods. Fifty-one patients were included, 9 with probable/proven IA. We determined quantitative and qualitative reconstitution of polymorphonuclear (PMN), CD4, CD8, and natural killer (NK) cells against Aspergillus fumigatus over 5 time points and compared the values to healthy donors. Results. Absolute CD4 and CD8 cell counts, antigen-specific T-cell responses, and killing capacity of PMN against A. fumigatus were significantly decreased in all patients over 12 months. In patients with probable/proven IA, reactive oxygen species (ROS) production tended to be lower compared to patients without IA, and absolute NK-cell counts remained below 200 cells/µL. Patients with well-controlled IA showed significantly higher ROS production and NK-cell counts compared to patients with poor outcome. Conclusions. This study highlights the importance of functional PMN, T-cell, and NK-cell immunity for the outcome of IA. Larger multicenter studies should address the potential use of NK-cell counts for the management of antifungal therap

Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Data on the role of tobacco exposure in systemic sclerosis (SSc) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations in the EUSTAR database

Social contact patterns during the COVID-19 pandemic in 21 European countries - evidence from a two-year study

BACKGROUND: Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses. METHODS: The analysis was based on repeated cross-sectional contact survey data collected in a standardized international study from 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts. RESULTS: The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to < 5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied. CONCLUSIONS: Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses

Effect of risk status for severe COVID-19 on individual contact behaviour during the SARS-CoV-2 pandemic in 2020/2021-an analysis based on the German COVIMOD study.

BACKGROUND: One of the primary aims of contact restriction measures during the SARS-CoV-2 pandemic has been to protect people at increased risk of severe disease from the virus. Knowledge about the uptake of contact restriction measures in this group is critical for public health decision-making. We analysed data from the German contact survey COVIMOD to assess differences in contact patterns based on risk status, and compared this to pre-pandemic data to establish whether there was a differential response to contact reduction measures. METHODS: We quantified differences in contact patterns according to risk status by fitting a generalised linear model accounting for within-participant clustering to contact data from 31 COVIMOD survey waves (April 2020-December 2021), and estimated the population-averaged ratio of mean contacts of persons with high risk for a severe COVID-19 outcome due to age or underlying health conditions, to those without. We then compared the results to pre-pandemic data from the contact surveys HaBIDS and POLYMOD. RESULTS: Averaged across all analysed waves, COVIMOD participants reported a mean of 3.21 (95% confidence interval (95%CI) 3.14,3.28) daily contacts (truncated at 100), compared to 18.10 (95%CI 17.12,19.06) in POLYMOD and 28.27 (95%CI 26.49,30.15) in HaBIDS. After adjusting for confounders, COVIMOD participants aged 65 or above had 0.83 times (95%CI 0.79,0.87) the number of contacts as younger age groups. In POLYMOD, this ratio was 0.36 (95%CI 0.30,0.43). There was no clear difference in contact patterns due to increased risk from underlying health conditions in either HaBIDS or COVIMOD. We also found that persons in COVIMOD at high risk due to old age increased their non-household contacts less than those not at such risk after strict restriction measures were lifted. CONCLUSIONS: Over the course of the SARS-CoV-2 pandemic, there was a general reduction in contact numbers in the German population and also a differential response to contact restriction measures based on risk status for severe COVID-19. This differential response needs to be taken into account for parametrisations of mathematical models in a pandemic setting

Social contact patterns during the COVID-19 pandemic in 21 European countries - evidence from a two-year study

CoMix Europe Working Group: Daniela Paolotti, Michele Tizzani, Ciro Cattuto, Andrea Schmidt, Gerald Gredinger, Sophie Stumpfl, Joaquin Baruch, Tanya Melillo, Henrieta Hudeckova, Jana Zibolenova, Zuzana Chladna, Magdalena Rosinska, Marta Niedzwiedzka-Stadnik, Krista Fischer, Sigrid Vorobjov, Hanna Sõnajalg, Christian Althaus, Nicola Low, Martina Reichmuth, Kari Auranen, Markku Nurhonen, Goranka Petrović, Zvjezdana Lovric Makaric, Sónia Namorado, Constantino Caetano, Ana João Santos, Gergely Röst, Beatrix Oroszi, Márton Karsai, Mario Fafangel, Petra Klepac, Natalija Kranjec, Cristina Vilaplana, Jordi Casabona.Sónia Namorado, Constantino Caetano, and Ana João Santos (Department of Epidemiology, National Institute of Health Dr Ricardo Jorge, Portugal).Background: Most countries have enacted some restrictions to reduce social contacts to slow down disease transmission during the COVID-19 pandemic. For nearly two years, individuals likely also adopted new behaviours to avoid pathogen exposure based on personal circumstances. We aimed to understand the way in which different factors affect social contacts - a critical step to improving future pandemic responses. Methods: The analysis was based on repeated cross-sectional contact survey data collected in a standardized international study from 21 European countries between March 2020 and March 2022. We calculated the mean daily contacts reported using a clustered bootstrap by country and by settings (at home, at work, or in other settings). Where data were available, contact rates during the study period were compared with rates recorded prior to the pandemic. We fitted censored individual-level generalized additive mixed models to examine the effects of various factors on the number of social contacts. Results: The survey recorded 463,336 observations from 96,456 participants. In all countries where comparison data were available, contact rates over the previous two years were substantially lower than those seen prior to the pandemic (approximately from over 10 to < 5), predominantly due to fewer contacts outside the home. Government restrictions imposed immediate effect on contacts, and these effects lingered after the restrictions were lifted. Across countries, the relationships between national policy, individual perceptions, or personal circumstances determining contacts varied. Conclusions: Our study, coordinated at the regional level, provides important insights into the understanding of the factors associated with social contacts to support future infectious disease outbreak responses.The following funding sources are acknowledged as providing funding for the named authors. HPRU in Modelling & Health Economics (NIHR200908: KLMW); European Union Horizon 2020 research and innovation programme (EpiPose 101003688: AG, WJE); European Research Council under the European Union Horizon 2020 research and innovation programme (TransMID 682540: CF, PB, NH) This research was partly funded by the Global Challenges Research Fund (GCRF) project RECAP managed through RCUK and ESRC (ES/P010873/1: CIJ) NIHR (PR_OD_1017_20002: WJE) UK MRC (MC_PC_19065—Covid 19: Under standing the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: WJE). In Belgium, CoMix data collection in Belgium was made possible with fnancial support of Janssen Pharmaceuticals and the national public health institute of Belgium, Sciensano. In Germany, the COVIMOD project is funded by intramural funds of the Institute of Epidemiology and Social Medicine, University of Münster, and of the Institute of Medical Epidemiology, Biometry and Informatics, Martin Luther University Halle-Wittenberg, as well as by funds provided by the Robert Koch Institute, Berlin, the Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V. via the HZEpiAdHoc "The Helmholtz Epidemiologic Response against the COVID-19 Pandemic" project, the Saxonian COVID-19 Research Consortium SaxoCOV (co-fnanced with tax funds on the basis of the budget passed by the Saxon state parliament), the Federal Ministry of Education and Research (BMBF) as part of the Network University Medicine (NUM) via the egePan Unimed project (funding code: 01KX2021) and the Deutsche Forschungsge meinschaft (DFG, German Research Foundation, project number 458526380)info:eu-repo/semantics/publishedVersio

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges