New Models for Europe’s Future Scoping of Tasks and Approaches. Bertelsmann Stiftung Vision Europe Paper 2 May 2020.

"Europe as we know it is too weak, too slow, too inefficient." Emmanuel Macron's succinct verdict of 2017 is still valid at the beginning of the new Twenties – and it is particularly relevant in the context of the slow joint EU response to the current corona crisis. The corona crisis exemplifies a general lack of capacity to act of the European Union – both internally and externally. In terms of foreign policy, the European Union finds itself in a world in which it must be stronger and more sovereign if it wants to maintain a place in the global order that reflects its economic and cultural self-understanding as well as its ethical stand- ards. Moreover, Europe is also in a weaker position internally. The formula of the "ever closer union" has always been more idealistic than the heterogeneous European reality. However, where in the past there was primarily resistance to further integration, today we observe real dissociation moves away from European unity. Europe needs to change in order to persist in a changing world. Europe must become stronger internally in order to be strong externally. The premise of this paper and the underlying project "A strong Europe in a globalised world" is that this calls for a broad and honest discussion on future models for Europe. The current global public health crisis is one of several policy areas where the EU needs to become more effective. In the face of a crisis, however, the EU's other challenges should not be neglected, but should be approached with greater energy: Even though much attention is being paid to acute crisis manage- ment, the other problems have not diminished. On the contrary, a new and major problem has emerged. All future tasks for Europe - Corona in advance - must now be tackled without delay. The scoping paper is intended as a first step on this path. It illustrates the internal and external challenges, problems and crises that the common Europe must face. The European Union in its present form is ill equipped to take on this task book. From an analysis of the past integration process, the common Europe emerges as a federal idea without a federal plan. Since the ideal has always been more popular than the practical ways to achieve it, actual European integration often proceeds very pragmatically and out of the situation, without following a "grand plan”. This situa- tional integration model has reached its limits. A new model for Europe's future must be able to strengthen the Union both internally and externally and deal more constructively with the existing dispar- ities between Member States. We formulate a number of test questions so as to gear the discussion of future models from the outset to the practical requirements of the coming Europe and outline a solution space. On this basis, we offer then a brief overview of the most important models currently under debate. The scoping paper paves the way for upcoming discussion. It does not claim to present already answers or a completely new model. This will be the task of the ongoing process. However, the focus of the latter cannot be limited to structural issues. At the same time, the policies of the European Union need to be re-examined. The joint consideration of "European public goods" and of future models corresponds to the duality of function and form. In the solution space for European future models, form and function must always be viewed together. The paper concludes with a plea to consider not only "full" future models. It will be at least as important to reflect on individual and partial proposals (e.g. Eurozone budget, EU army, European climate bank). The debate on the future of Europe will be stronger and closer to the reality of reform if it takes a prag- matic approach whenever opportunities arise and the need is greatest. Whether giant leaps or small steps, all that matters is that it goes ahead. What matters is that more and more people come together and move forward for a Europe renewed in its traditional strengths and for its new challenges. This is the path taken by the project "A strong Europe in a globalised world.

European Public Goods: Their Contribution to a Strong Europe. Bertelsmann Stiftung Vision Europe Paper 3 September 2020.

Over the last decade, the European Union has been hit by multiple crises of various kinds. Although the corona-virus pandemic, with its health, social and economic consequences, currently dominates policy perception and action in Europe, it is only the latest in a series of challenges. The EU's limited ability to respond effectively to such challenges has highlighted the need for reform. The project "A strong Europe in a globalized world" propos-es to advance the reform process by means of the concept of European public goods. In the present paper, we provide a definition of this concept and illustrate its potential in the debate on future models for a stronger and more sovereign Europe. The concept of European public goods draws on the welfare-economic concept of public goods (or common goods). In contrast to private goods, public goods justify the provision of services by the state when at least one of the following forms of market failures occurs: no rivalry between buyers, no exclusion of individual consumers, natural monopoly. Within a federal system, public goods can be provided by different levels of government. The theory of fiscal fed-eralism offers an economic approach for the allocation of tasks to different government levels of a federal state. Applied to the EU - which is not yet a federal state, but has gone far beyond the confederation of states -, it en-tails that a public good should be provided by the central level if the following criteria are met: Europe-wide benefits, Europe-wide homogeneous preferences among the inhabitants of the Community and most cost-effective realization at the European level due to economies of scale. In this case, we speak of European public goods. However, the above three criteria could point in opposite directions and, thus, provide no clear-cut argument for or against the Europeanization of a public task. A weighing up decision is then necessary. This could be support-ed, for example, by a cost-benefit analysis, which derives the European added value of a public good by first determining for each criterion the difference between the benefits of the European and national provision, and then aggregating the resulting three "partial net benefits" into an "overall net benefit". Such a procedure meets not only the inherently important requirement of justifying shifts of competence as well as possible, but also the de-mand for political transparency. The concept of European public goods described here presupposes that, in order to increase the Community's capability to act, the right task priorities must first be set for the respective time and problem context. Today more than ever, it is important that each level of government in Europe takes on the public tasks for which it is best suited. In recent years, the Union's current field of action has been increasingly assessed in the light of the theory of fiscal federalism. An overview of the findings suggests that the EU’s financially relevant action priorities focus too much on regional or even local public goods and too little on European public goods. A successful implementation of the concept also requires that consideration be given to how to get there. From today's perspective, three aspects in particular are important for the further analysis: (i) the governance issues associated with the catchword "connectivity" arising from the provision of European public goods within a multi-level system; (ii) the creation of new financial leeway for European public goods already within the next multi-annual financial framework 2021-2027; (iii) breaking the alleged taboo of treaty changes

Associations between comorbidities, their treatment and survival in patients with interstitial lung diseases – a claims data analysis

Background: Interstitial lung diseases (ILDs) are associated with a high burden of disease. However, data on the prognostic impact of comorbidities and comorbidity-related pharmaceutical treatments in patients with various ILDs remain sparse. Methods: Using longitudinal claims data from a German Statutory Health Insurance Fund, we assessed comorbidity in ILD subtypes and associated drug treatments. Baseline comorbidity was assessed via the Elixhauser Comorbidity Index that was amended by ILD-relevant conditions. Drug treatment was assessed on the substance level using the ATC-codes of drugs prescribed at the time of ILD diagnosis. Subsequently, the comorbid conditions (main analysis) and pharmaceutical substances (secondary analysis) with a meaningful association to survival were identified for the complete ILD cohort and within the subtype strata. For this, we applied multivariate Cox models using a LASSO selection process and visualized the findings within comorbidomes. Results: In the 36,821 patients with ILDs, chronic obstructive pulmonary disease (COPD), arterial hypertension, and ischaemic heart disease (IHD) were the most prevalent comorbidities. The majority of patients with cardiovascular diseases received pharmaceutical treatment, while, in other relevant comorbidities, treatment quotas were low (COPD 46%, gastro-oesophageal reflux disease 65%). Comorbidities had a clinically meaningful detrimental effect on survival that tended to be more pronounced in the case of untreated conditions (e.g. hazard ratios for treated IHD 0.97 vs. 1.33 for untreated IHD). Moreover, comorbidity impact varied substantially between distinct subtypes. Conclusions: Our analyses suggest that comorbid conditions and their treatment profile significantly affect mortality in various ILDs. Therefore, comprehensive comorbidity assessment and management remains important in any ILD

nvestigating the Utility of Interviewer Observations on the Survey Response Process

TBD

Chapter 8: Examining the Utility of Interviewer Observations on the Survey Response Process. Appendix 8

Appendix 8A Additional Evaluation of Derived NSFG Classes Figure A8A.1 Figure A8A.2 Table A8A.1 Table A8A.2 Table A8A.3 Appendix 8B Additional Details on ESS Item

The therapy of idiopathic pulmonary fibrosis: what is next?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I–III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease

A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease

Nintedanib; Drug Interactions; Systemic SclerosisNintedanib; Interacciones medicamentosas; Esclerosis sistémicaNintedanib; Interaccions farmacològiques; Esclerosi sistèmicaBackground and Objectives Nintedanib is a tyrosine kinase inhibitor approved for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD), idiopathic pulmonary fibrosis, and other chronic fibrosing ILDs with a progressive phenotype. As nintedanib may cause foetal harm, patients taking nintedanib should avoid pregnancy. The objective of this study was to investigate the effect of nintedanib co-administration on the pharmacokinetics of Microgynon (ethinylestradiol and levonorgestrel) in female patients with SSc-ILD. Methods This was an open-label, two-period, fixed-sequence, drug–drug interaction study. Female patients with SSc and ≥ 10% extent of fibrotic ILD on a high-resolution computed tomography scan were eligible to participate. In Period 1, patients received one Microgynon tablet (ethinylestradiol 30 μg and levonorgestrel 150 μg) ≥ 3 days before the first administration of nintedanib in Period 2. In Period 2, patients received one Microgynon tablet following intake of nintedanib 150 mg twice daily for ≥ 10 consecutive days. The primary pharmacokinetic endpoints were the areas under the plasma concentration–time curve of ethinylestradiol and levonorgestrel over the time interval from 0 to the last quantifiable data point (AUC0–tz) and the maximum measured concentrations of ethinylestradiol and levonorgestrel in plasma (Cmax). The secondary pharmacokinetic endpoint was the area under the plasma concentration–time curve of ethinylestradiol and levonorgestrel over the time interval from 0 extrapolated to infinity (AUC0–∞). The relative exposures of ethinylestradiol and levonorgestrel when administered alone and in combination with nintedanib were assessed using an ANOVA model. Results Seventeen patients were treated. Pharmacokinetic data from 15 patients were analysed. Plasma concentration–time profiles of ethinylestradiol and levonorgestrel were similar following administration of Microgynon before and after administration of nintedanib for ≥ 10 consecutive days. Adjusted geometric mean (gMean) ratios [90% confidence intervals (CIs)] for AUC0‒tz (101.4% [92.8, 110.7]) and AUC0‒∞ (101.2% [94.0, 109.1]) indicated that there was no difference in total ethinylestradiol exposure when Microgynon was administered before or after administration of nintedanib. The adjusted gMean ratio for Cmax of ethinylestradiol (116.7% [90% CI 107.6, 126.5]) indicated an increase in peak exposure in the presence of nintedanib. Adjusted gMean ratios [90% CIs] for AUC0-tz (96.4% [91.5, 101.6]) and Cmax (100.9% [89.9, 113.2]) indicated that there was no difference in total or peak levonorgestrel exposure when Microgynon was administered before or after administration of nintedanib. The adjusted gMean ratio for AUC0‒∞ of levonorgestrel indicated a decrease in total exposure in the presence of nintedanib (88.1% [90% CI 80.0, 97.0]). Conclusion Pharmacokinetic data indicate that there is no relevant effect of nintedanib on plasma exposure to ethinylestradiol and levonorgestrel in female patients with SSc-ILD

Healthcare utilisation and costs in the diagnosis and treatment of progressive-fibrosing interstitial lung diseases

There are over 200 interstitial lung diseases (ILDs). In addition to patients with idiopathic pulmonary fibrosis (IPF), a percentage of patients with other ILDs also develop progressive fibrosis of the lung during their disease course. Patients with progressive-fibrosing ILDs may show limited response to immunomodulatory therapy, worsening symptoms and lung function and, ultimately, early mortality. There are few data for ILDs that may present a progressive fibrosing phenotype specifically, but we believe the burden and healthcare costs associated with these conditions may be comparable to those reported in IPF. This review discusses the burden of ILDs that may present a progressive fibrosing phenotype and the factors impacting healthcare utilisation

Best supportive care for idiopathic pulmonary fibrosis: Current gaps and future directions

Best supportive care (BSC) is generally defined as all the interventions and the multiprofessional approach aimed to improve and optimise quality of life (QoL) in patients affected by progressive diseases. In this sense, it excludes and might be complementary to other interventions directly targeting the disease. BSC improves survival in patients with different types of cancer. Patients with idiopathic pulmonary fibrosis (IPF) experience a vast range of symptoms during the natural history of the disease and might have a beneficial effect of BSC interventions. This review highlights the current evidence on interventions targeting QoL and gaps for the clinical assessment of BSC in the treatment of IPF patients. Very few interventions to improve QoL or improve symptom control are currently supported by well-designed studies. Sound methodology is paramount in evaluating BSC in IPF, as well as the use of validated tools to measure QoL and symptom control in this specific group of patients