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Aim: To study the association between femoral neck (FN) bone mineral density (BMD) T‐score and fracture risk in individuals with and without type 2 diabetes (T2D). Materials and Methods: We performed a single‐centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual‐energy X‐ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T‐score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10‐year absolute fracture risk. Results: In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T‐score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24–2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01–2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64–1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73–2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10‐year fracture risk. Conclusions: The FN BMD T‐score was significantly associated with hip, non‐spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T‐score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T‐score to predict fracture risk. [ABSTRACT FROM AUTHOR]

Summary: This nationwide multidisciplinary survey found dissatisfaction among physicians with current osteoporotic vertebral compression fracture care, revealing significant disparities in diagnosis, treatment, and follow-up practices. Issues include poor communication and differing guidelines. Improving interdisciplinary collaboration and standardized care strategies is essential for better patient outcomes. Purpose: This survey aims to assess current preferred care practices for symptomatic osteoporotic vertebral compression fractures (OVCF) in the Netherlands, focusing on guideline adherence, identifying knowledge gaps, and clarifying consensus and collaboration across medical disciplines in OVCF treatment. Methods: This cross-sectional study was conducted via Qualtrics (Provo, UT) using a self-administered online survey distributed to 238 general practitioners and physicians in orthopedics, traumatology, internal medicine, rheumatology, and geriatrics working at 51 hospitals in the Netherlands. The survey, conducted in Dutch, included 36 multiple-choice and two open questions and was accessible via an anonymous email link or QR code. General practitioners received additional questions specific to their role. Data was anonymized, stored securely, and analyzed using descriptive statistics in Microsoft Excel and SPSS (Version 24). Open-ended responses were coded and categorized. The survey was conducted prior to the publication of the updated Federation of Medical Specialists guidelines in 2024. Results: Physicians across various disciplines uniformly expressed dissatisfaction with current OVCF care. The survey highlighted significant disparities in diagnosis, treatment, and follow-up practices. A lack of communication between primary and secondary care providers and differing guidelines further complicate OVCF management. These issues point to considerable variation in clinical practice and gaps in interdisciplinary collaboration. Conclusion: Addressing the identified issues requires fostering interdisciplinary collaboration and creating cohesive care strategies. Ensuring access to diagnostic resources in both primary and secondary care and establishing coordinated care models promises more structured and standardized treatment. These steps are crucial for enhancing patient outcomes in OVCF management. [ABSTRACT FROM AUTHOR]

Background: Long‐term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross‐sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). Methods: A dual‐energy X‐ray absorptiometry of lumbar spine (L1–L4) and hip was performed in 24 children, residing in a long‐stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25‐hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. Results: Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z‐score > − 2.0). Of the 16 children with a low BMD (Z‐score ≤ − 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin‐corrected calcium (2.28–2.50 mmol/L) and (supplemented) vitamin D (16–137 nmol/L) were within the normal range. Conclusions: This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines. [ABSTRACT FROM AUTHOR]

Background: The use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS)., Methods: This three-year prospective cohort study included FLS patients aged ≥ 50 years with a recent fracture (median age 62 [IQR 56-69] years, 68.7 % females) and without anti-osteoporosis treatment indication. HR-pQCT scans (distal radius and tibia) were obtained at baseline (T0) and three-year follow-up (T3). Volumetric bone mineral density and bone area, microarchitecture, and strength (micro-finite element analysis) were determined. The association between three-year continuous PPI use and the percentage change in HR-pQCT parameters between T0 and T3 was assessed using sex-stratified multivariate linear regression analyses. Covariates included age, BMI, vitamin-D deficiency (< 50 nmol/l), glucocorticoid use, and cardiovascular co-morbidity (males and females) fracture type (major/hip vs. all others, only males) and probable sarcopenia (only females)., Results: In total, 282 participants had available medication data throughout follow-up, of whom 20.6 % were continuous PPI users. In both males and females with complete HR-pQCT follow-up data (males: N = 69 radius, N = 84 tibia; females: N = 147 radius, N = 168 tibia), PPI use was not associated with the percentage change of any of the bone microarchitecture or strength parameters between T0 and T3 at the radius and tibia as compared to non-use., Conclusion: Compared to non-use, PPI use was not associated with the change of bone microarchitecture and strength in FLS patients at three years of follow-up. These results do not support that an altered bone microarchitecture or strength may contribute to the increased fracture risk associated with PPI use, as reported in observational studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MS, MB, WV, JD, LV, RV and CW declare that they have no conflict of interest. JB reports grands for lectures and the position in the advisory board from UCB and Amgen outside the submitted work, and Payments to the institution form Novo Nordisk Fonden Denmark. HW reports a speakers fee for lectures from UCB, outside the submitted work. The Weijerhorst Foundation had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4 + T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation., Competing Interests: Declaration of interests K.L., P.M., and B.O. are co-founders, board directors, and shareholders of ImmuneWatch. None of the work presented here was influenced in any way by this. ImmuneWatch had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine the hazard ratios (HR) for various fracture sites and identify associated risk factors in a cohort of relatively healthy adult people with newly diagnosed type 1 diabetes (T1D)., Methods: The study utilized data from the UK Clinical Practice Research Datalink GOLD (1987-2017). Participants included people aged 20 and above with a T1D diagnosis code (n = 3281) and a new prescription for insulin. Controls without diabetes were matched based on sex, year of birth, and practice. Cox regression analysis was conducted to estimate HRs for any fracture, major osteoporotic fractures (MOFs), and peripheral fractures (lower-arm and lower-leg) in people with T1D compared to controls. Risk factors for T1D were examined and included sex, age, diabetic complications, medication usage, Charlson comorbidity index (CCI), hypoglycemia, previous fractures, falls, and alcohol consumption. Furthermore, T1D was stratified by duration of disease and presence of microvascular complications., Results: The proportion of any fracture was higher in T1D (10.8 %) than controls (7.3). Fully adjusted HRs for any fracture (HR: 1.43, CI95%: 1.17-1.74), MOFs (HR: 1.46, CI95%: 1.04-2.05), and lower-leg fractures (HR: 1.37, CI95%: 1.01-1.85) were statistically significantly increased in people with T1D compared to controls. The primary risk factor across all fracture sites in T1D was a previous fracture. Additional risk factors at different sites included previous falls (HR: 1.64, CI95%: 1.17-2.31), antidepressant use (HR: 1.34, CI95%: 1.02-1.76), and anxiolytic use (HR: 1.54, CI95%: 1.08-2.29) for any fracture; being female (HR: 1.65, CI95%: 1.14-2.38) for MOFs; the presence of retinopathy (HR: 1.47, CI95%: 1.02-2.11) and previous falls (HR: 2.04, CI95%: 1.16-3.59) for lower-arm and lower-leg fractures, respectively. Lipid-lowering medication use decreased the risk of MOFs (HR: 0.66, CI95%: 0.44-0.99). Stratification of T1D by disease duration showed that the relative risk of any fracture in T1D did not increase with longer diabetes duration (0-4 years: HR: 1.52, CI95%: 1.23-1.87; 5-9 years: HR: 1.30, CI95%: 0.99-1.71; <10 years: HR: 1.07, CI95%: 0.74-1.55). Similar patterns were observed for other fracture sites. Moreover, the occurrence of microvascular complications in T1D was linked to a heightened risk of fractures in comparison to controls. However, when considering the T1D cohort independently, the association was not statistically significant., Conclusion: In a cohort of relatively healthy and newly diagnosed people with T1D HRs for any fracture, MOFs, and lower-leg fractures compared to controls were increased. A previous fracture was the most consistent risk factor for a subsequent fracture, whereas retinopathy was the only diabetes related one. We postulate a potential initial fracture risk, succeeded by a subsequent risk reduction, which might potentially increase in later years due to the accumulation of complications and other factors., Competing Interests: Declaration of competing interest Peter Vestergaard is head of research in the Steno Diabetes Center North Denmark sponsored by the Novo Nordisk Foundation. Joop van den Bergh: unrestricted research grant and lecture fee from Amgen and UCB, is consultant for PoroUS. Nicklas H. Rasmussen holds shares in Novo Nordisk, has lecture fees from Boehringer Ingelheim and travel expenses from UCB. The other authors Johanna Driessen, Patrick Souverein and Annika Kvist declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Over the past decade, frequent use of large quantities of nitrous oxide (N2O) has become more common in the Netherlands. Although N2O poses several negative health consequences for a subgroup of problematic N2O users, there is a lack of knowledge on what characterizes these intensive users. This study therefore aims to provide the demographic and substance use characteristics and experiences during treatment of treatment seeking problematic N2O users and to compare this with a matched group of treatment-seeking problematic cocaine users., Methods: A retrospective chart review was performed of patients who were referred for treatment of problematic N2O use at a large Dutch addiction care facility from January 2020 to September 2022, extracting demographics, pattern of use and follow-up data. Additionally, a subgroup of N2O users was propensity-score matched (1:1) with a subgroup of treatment seeking problematic cocaine users, both groups excluding users with substance use disorders or frequent use of substances other than N2O and cocaine, respectively., Results: 128 patients with a N2O use disorder were included in the total sample and a subgroup of 77 N2O-only users was propensity-score matched on age and sex to 77 cocaine-only users. N2O users were typically young (mean age 26.2 years), male (66.4%), unmarried (82.9%), with a low education level (59.0%) and born in the Netherlands (88.2%), with parents born in Morocco (45.3%). N2O was used intermittently (median 10 days/month, IQR 4.0-17.5 days) and often in very large quantities (median 5 kg [ca. 750 balloons] per average using day, IQR 2-10 kg). Compared to the patients with a cocaine use disorder, matched N2O users were lower educated, more often from Moroccan descent, and less likely to be alcohol or polysubstance users. Despite receiving similar treatments, N2O users were twice as likely to discontinue treatment before completion compared to cocaine users (63 vs. 35%, p = 0.004)., Conclusion: Treatment-seeking problematic N2O users are demographically different from treatment-seeking problematic cocaine users and are much more likely to dropout from psychological treatment. Further research is needed into the needs and other factors of problematic N2O users that relate to poor treatment adherence in problematic N2O users., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Climate change mitigation will trigger major changes in human activity, energy systems, and material use, potentially shifting pressure from climate change to other environmental problems. We provide a comprehensive overview of such "environmental problem shifting" (EPS). While there is considerable research on this issue, studies are scattered across research fields and use a wide range of terms with blurred conceptual boundaries, such as trade-off, side effect , and spillover . We identify 506 relevant studies on EPS of which 311 are empirical, 47 are conceptual-theoretical, and 148 are synthetic studies or reviews of a particular mitigation option. A systematic mapping of the empirical studies reveals 128 distinct shifts from 22 categories of mitigation options to 10 environmental impacts. A comparison with the recent IPCC report indicates that EPS literature does not cover all mitigation options. Moreover, some studies systematically overestimate EPS by not accounting for the environmental benefits of reduced climate change. We propose to conceptually clarify the different ways of estimating EPS by distinguishing between gross, net, and relative shifting. Finally, the ubiquity of EPS calls for policy design which ensures climate change mitigation that minimizes unsustainability across multiple environmental dimensions. To achieve this, policymakers can regulate mitigation options-for example, in their choice of technology or location-and implement complementary environmental policies., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of the randomized controlled CAIRO5 trial (NCT02162563) were included. All CRLM were semi-automatically segmented in pre-treatment CT scans and radiomics features were calculated from these segmentations. Additionally, data from the Netherlands Cancer Institute (NKI) were used for external validation. A total of 255 patients from the CAIRO5 trial were included. Random Forest, Gradient Boosting, Gradient Boosting + LightGBM, and Ensemble machine-learning classifiers showed AUC scores of 0.77 (95%CI 0.62-0.92), 0.77 (95%CI 0.64-0.90), 0.72 (95%CI 0.57-0.87), and 0.86 (95%CI 0.76-0.95) in the internal test set. Validation of the models on the external dataset with 129 patients resulted in AUC scores of 0.47-0.56. Machine-learning models incorporating CT imaging features could identify the genetic mutation status in patients with CRLM with a good accuracy in the internal test set. However, in the external validation set, the models performed poorly. External validation of machine-learning models is crucial for the assessment of clinical applicability and should be mandatory in all future studies in the field of radiomics.

While many climate activist groups enthusiastically advocate for the removal of fossil-fuel subsidies, we argue that this overstates both the climate effectiveness and political feasibility of such a strategy. Through synthesizing information from various global studies, we show that subsidies contribute to a relatively small portion of climate change and local externality problems, likely accounting for around 1%. We further argue that reform of fossil-fuel subsidies is hampered by various political and social factors, more so than the diffusion of carbon pricing. Based on these results, we argue that the far greater problem of unpriced externalities warrants a redirection or expansion of the enthusiasm for subsidy reform toward carbon pricing. This makes sense also as subsidy reform and carbon pricing essentially represent two sides of the same coin since both contribute to climate mitigation by raising fossil-fuel prices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Romosozumab is a monoclonal antibody that binds to sclerostin (an inhibitor of the Wingless-related integration site (Wnt) signaling pathway). It is a new osteoanabolic drug that simultaneously increases bone formation and decreases bone resorption. It has recently been approved by the US and EU authorities in postmenopausal women with at high risk of fractures., Areas Covered: The literature on romosozumab in preclinical and in phase II and III clinical studies has been reviewed about the effect on bone, bone markers, and fracture reduction and its safety., Expert Opinion: Compared to antiresorptive agents, its unique mechanism of action results in a quicker and greater increase in bone mineral density, it repairs and restores trabecular and cortical bone microarchitecture, and reduces fracture risk more rapidly and more effectively than alendronate, with persisting effects for at least two years after transition to antiresorptive agents. This finding has introduced the concept that, in patients at very high risk of fractures, the optimal sequence of treatment is to start with an osteoanabolic agent, followed by a potent AR drug. Recent national and international guidelines recommend the use of romosozumab as an initial treatment in patients at very high fracture risk without a history of stroke or myocardial infarction.

New evidence points toward that impaired postural control judged by center of pressure measures during quiet stance is a predictor of falls in people with type 1 and type 2 diabetes-even in occurrence of well-known risk factors for falls., Introduction/aim: People with type 1 diabetes (T1D) and type 2 diabetes (T2D) are at risk of falling, but the association with impaired postural control is unclear. Therefore, the aim was to investigate postural control by measuring the center of pressure (CoP) during quiet standing and to estimate the prevalence ratio (PR) of falls and the fear of falling among people with diabetes compared to controls., Methods: In a cross-sectional study, participants with T1D (n = 111) and T2D (n = 106) and controls without diabetes (n = 328) were included. Study procedures consisted of handgrip strength (HGS), vibration perception threshold (VPT), orthostatism, visual acuity, and postural control during quiet stance measured by CoP Area (degree of body sway) and CoP Velocity (speed of the body sway) with "eyes open," "eyes closed" in combination with executive function tasks. A history of previous falls and fear of falling was collected by a questionnaire. CoP Area and CoP Velocity measurements were analyzed by using a multiple linear regression model. The PR of falls and the fear of falling were estimated by a Poisson regression model. Age, sex, BMI, previous falls, alcohol use, drug, HGS, VPT, orthostatism, episodes of hypoglycemia, and visual acuity were covariates in multiple adjusted analyses., Results: Significantly larger mean CoP Area measures were observed for participants with T1D (p = 0.022) and T2D (0.002), whereas mean CoP Velocity measures were only increased in participants with T2D (p = 0.027) vs. controls. Additionally, T1D and T2D participants had higher PRs for falls (p = 0.044, p = 0.014) and fear of falling (p = 0.006, p < 0.001) in the crude analyses, but the PRs reduced significantly when adjusted for mean CoP Area and mean CoP Velocity , respectively. Furthermore, multiple adjusted PRs were significantly higher than crude the analyses.    CONCLUSION: Impaired postural control during quiet stance was seen in T1D and T2D compared with controls even in the occurrence of well-known risk factors. and correlated well with a higher prevalence of falls., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: The aim of this longitudinal study was to assess trabecular bone scores (TBS) in institutionalized adults with refractory epilepsy and intellectual disability and to study the association of TBS and incident fractures during seven years of follow-up., Methods: In 2009 and 2016, all institutionalized adult patients of a long-stay care facility in the Netherlands (n=261) were invited to undergo a dual-energy X-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and assessment of TBS. Vertebrae T4-L4 were analyzed using quantitative morphometry. New and worsening vertebral fractures (VFs) were considered as incident VFs. Data regarding clinical fractures were extracted from the medical files. Patients were treated with anti-osteoporosis medication according to the Dutch guideline., Results: Baseline and follow-up DXA, VFA and TBS could be obtained in 136 patients (83 male) aged between 18 and 79 years old (44.7±15.5). At baseline, 36 patients (26.5%) were diagnosed with osteoporosis, 68 (50.0%) with osteopenia and 32 patients (23.5%) had a normal bone mineral density (BMD). As for TBS, 26 patients (19.1%) had a partially degraded microarchitecture and 26 patients (19.1%) a degraded microarchitecture. During seven years of follow-up, 80 patients (59%) sustained at least one fracture, of which 28 patients (35%) had one or more major osteoporotic fractures. Thirty-four patients (25.0%) had at least one new or worsening morphometric VF. Compared to baseline, TBS significantly decreased over seven years of follow-up in non-treated patients (-0.039±0.064, p<.001). In patients who were treated with bisphosphonates for more than one year during follow-up, TBS did not change significantly (p=.093). In multivariate analyses, no significant associations were found between TBS at baseline and incident fractures during follow-up., Conclusion: In this study, we found a high incidence of fractures and TBS decreased significantly over seven years of follow-up in non-treated institutionalized adult patients with refractory epilepsy and intellectual disability, but TBS was not associated with incident fractures., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Climate change has revived the debate on growth-versus-environment. In line with this, recently it has been proposed to shift the target focus of IPCC scenarios from emissions to post-growth. We argue here that this confounds ends and means, since while reduction of growth may be an outcome of good climate policies, it should not be a goal in itself. In fact, a post- or degrowth goal would mean an ineffective and costly way to reduce emissions. Instead, we suggest that the debate about pursuing economic growth versus achieving climate goals will become more transparent and policy-relevant through refocusing scenarios from targets to policy., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Transformation toward a sustainable future requires an earth stewardship approach to shift society from its current goal of increasing material wealth to a vision of sustaining built, natural, human, and social capital-equitably distributed across society, within and among nations. Widespread concern about earth's current trajectory and support for actions that would foster more sustainable pathways suggests potential social tipping points in public demand for an earth stewardship vision. Here, we draw on empirical studies and theory to show that movement toward a stewardship vision can be facilitated by changes in either policy incentives or social norms. Our novel contribution is to point out that both norms and incentives must change and can do so interactively. This can be facilitated through leverage points and complementarities across policy areas, based on values, system design, and agency. Potential catalysts include novel democratic institutions and engagement of non-governmental actors, such as businesses, civic leaders, and social movements as agents for redistribution of power. Because no single intervention will transform the world, a key challenge is to align actions to be synergistic, persistent, and scalable., (© 2022. The Author(s).)

In subjects older than 50 years, the presence of clinical risk factors (CRFs) for fractures or a recent fracture is the cornerstone for case finding. In patients who are clinically at high short- and long-term risk of fractures (those with a recent clinical fracture or with multiple CRFs), further assessment with bone mineral density (BMD) measurement using dual-energy absorptiometry (DXA), imaging of the spine, fall risk evaluation and laboratory examination contributes to treatment decisions according to the height and modifiability of fracture risk. Treatment is available with anti-resorptive and anabolic drugs, and from the start of treatment a lifelong strategy is needed to decide about continuous, intermittent, and sequential therapy. Implementation of guidelines requires further initiatives for improving case finding, public awareness about osteoporosis and national policies on reimbursement of assessment and therapy., Competing Interests: Declaration of Competing interest Piet Geusens. Clinical studies, advisory boards, speaker fees from Abbott, Amgen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Fresenius, Mylan, Sandoz, Merck. Natasha M. Appelman-Dijkstra. Clinical studies/speaker fees from Amgen, UCB, Kyowa Kirin, M. Carola Zillikens. Hanna Willems. Clinical studies/advisory boards/speaker fees from Amgen, UCB. Willem F. Lems. Advisory boards/speaker fees Amgen, UCB, Pfizer, Galapagos. Joop van den Bergh. Advisory boards/speaker fees from Amgen, UCB., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)