Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

Funding Information: Marius M. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, MSD, and Pfizer. Nicola Benjamin has received fees for lectures and/or consultations from Actelion. Ekkehard Grünig has received fees for lectures and/or consultations from Actelion, Bayer, GSK, MSD, United Therapeutics, and Pfizer. Karen M. Olsson has received fees for lectures and/or consultations from Actelion, Bayer, United Therapeutics, GSK, and Pfizer. C. Dario Vizza has received fees from Actelion, Bayer, GSK, MSD, Pfizer, and United Therapeutics Europe. Anton Vonk-Noordegraaf has received fees for lectures and/or consultation from Actelion, Bayer, GSK, and MSD. Oliver Distler has/had a consultancy relationship with and/or has received research funding from 4-D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemoAb, EpiPharm, Ergonex, espeRare foundation, GSK, Genentech/Roche, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm, and Sinoxa in the area of potential treatments of scleroderma and its complications including pulmonary arterial hypertension. In addition, Prof Distler has a patent for mir-29 for the treatment of systemic sclerosis licensed. Christian Opitz has received fees from Actelion, Bayer, GSK, Pfizer, and Novartis. J. Simon R. Gibbs has received fees for lectures and/or consultations from Actelion, Bayer, Bellerophon, GSK, MSD, and Pfizer. Marion Delcroix has received fees from Actelion, Bayer, GSK, and MSD. H. Ardeschir Ghofrani has received fees from Actelion, Bayer, Gilead, GSK, MSD, Pfizer, and United Therapeutics. Doerte Huscher has received fees for lectures and consultations from Actelion. David Pittrow has received fees for consultations from Actelion, Biogen, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi. Stephan Rosenkranz has received fees for lectures and/or consultations from Actelion, Bayer, GSK, Pfizer, Novartis, Gilead, MSD, and United Therapeutics. Martin Claussen reports honoraria for lectures from Boehringer Ingelheim Pharma GmbH and Roche Pharma and for serving on advisory boards from Boehringer Ingelheim, outside the submitted work. Heinrike Wilkens reports personal fees from Boehringer and Roche during the conduct of the study and personal fees from Bayer, Biotest, Actelion, GSK, and Pfizer outside the submitted work. Juergen Behr received grants from Boehringer Ingelheim and personal fees for consultation or lectures from Actelion, Bayer, Boehringer Ingelheim, and Roche. Hubert Wirtz reports personal fees from Boehringer Ingelheim and Roche outside the submitted work. Hening Gall reports personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics outside the submitted work. Elena Pfeuffer-Jovic reports personal fees from Actelion, Boehringer Ingelheim, Novartis, and OMT outside the submitted work. Laura Scelsi reports personal fees from Actelion, Bayer, and MSD outside the submitted work. Siliva Ulrich reports grants from Swiss National Science Foundation, Zurich Lung, Swiss Lung, and Orpha Swiss, and grants and personal fees from Actelion SA/Johnson & Johnson Switzerland and MSD Switzerland outside the submitted work. The remaining authors have no conflicts of interest to disclose. Funding Information: This work was supported by the German Centre of Lung Research (DZL). COMPERA is funded by unrestricted grants from Acceleron , Actelion Pharmaceuticals , Bayer , OMT , and GSK . These companies were not involved in data analysis or the writing of this manuscript. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.publishersversionPeer reviewe

Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients’ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan–Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy

Von der Feiermanie zum Verpflichtungsritual. Zur totalitären Dynamik bei der Gestaltung von Feiern für Vierzehnjährige

Einer „kritischen" Aufarbeitung der deutschen Geschichte liegt es nahe, die außerkirchlichen Feiern, die Wiederbelebung von „Bräuchen" oder die Organisation von Ritualen nur als Herrschaftsmittel zu betrachten. Dann erscheinen die Akteure als Marionetten in einem obrigkeitlich verordneten Spiel. Diese Sichtweise mag vielen „Kundgebungen" angemessen sein, verfehlt aber bei den „Lebenswendefeiern", wie man abstrakt formulierte, den Gegenstand sowie das Selbstverständnis der Akteure in einem unzulässigen Maß. In Situationen des Abschieds vom Gewohnten, des krisenhaften Aufbrechens neuer Erfahrungswelten sind Orientierungen, Wegweisungen gefragt. Deshalb ist es angemessen, den nach der Machtübernahme erhobenen Anspruch der Nazis auf Wiederbelebung alter Bräuche in neuem Geist auf das Angebot einer an die menschliche Entwicklung angepassten Sinnorientierung hin zu überprüfen. […] Warum man freilich überhaupt annahm, dass von einer staatlichen Institution [wie dem Nationalsozialistischen-Lehrerbund (NSLB)] eine solche Sinnorientierung erwartet wurde, möchte der Autor durch die folgende ideologiegeschichtliche Skizze verständlich machen. (DIPF/Orig./ah

Peter Dudek: "Der Rückblick auf die Vergangenheit wird sich nicht vermeiden lassen". Zur pädagogischen Verarbeitung des Nationalsozialismus in Deutschland (1945 -1990). Opladen: Westdeutscher Verlag 1995. [...] [Sammelrezension]

Sammelrezension von: 1. Peter Dudek: "Der Rückblick auf die Vergangenheit wird sich nicht vermeiden lassen". Zur pädagogischen Verarbeitung des Nationalsozialismus in Deutschland (1945 -1990). Opladen: Westdeutscher Verlag 1995, 346 S. 2. Peter Dudek/Thilo Rauch/Marcel Weeren: Pädagogik und Nationalsozialismus. Bibliographie pädagogischer Hochschulschriften und Abhandlungen in der BRD und DDR 1945-1990. Wiesbaden: Deutscher Universitätsverlag 1995, 263 S

The German youth movement and the aim of self-education in the context of educational policy in the era of Wilhelm II

Während in den bisherigen Auseinandersetzungen mit der Wandervogelbewegung deren Selbstzeugnisse und damit die Bedürfnislage und das Wollen ihrer Anhänger im Mittelpunkt standen, wird in diesem Beitrag nach den durch die Autonomiebestrebungen bewirkten Veränderungen der Machtverhältnisse und Funktionszuweisungen auf dem Erziehungssektor gefragt. Die zentrale These des Verfassers ist, daß die Wandervogelbewegung ein Feld für die Selbsterziehung im Jugendalter in Reaktion auf die Vereinnahmungstendenzen der wilhelminischen Erziehungspolitik eröffnete, wobei sie von einem Bildungsbürgertum gestützt wurde, das am Ideal einer autonomen Persönlichkeitsentwicklung orientiert war. Insbesondere werden Überlegungen diskutiert, die das erziehungspolitische Interesse an der Tolerierung der Jugendbewegung begründen und auf die Beschränkungen hinweisen, denen die Innovationsimpulse der Jugendbewegung für das Erziehungswesen dadurch unterworfen waren. (DIPF/Orig.

Bahrdt, Carl Friedrich: Geschichte und Tagebuch meines Gefängnisses nebst Geheimen Urkunden und Aufschlüssen über Deutsche Union. [Rezension]

Rezension von: Bahrdt, Carl Friedrich: Geschichte und Tagebuch meines Gefängnisses nebst Geheimen Urkunden und Aufschlüssen über Deutsche Union

Political and social functions of institutions for teacher training in 1941-1945

Die Einführung der LBA wird von der Schulgeschichtsschreibung vielfach als der Versuch der NS-Diktatur gedeutet, die Lehrerbildung auf ein 40 oder gar 150 Jahre zurückliegendes Niveau zu drücken. Der Verfasser hält diese Deutung für wenig stichhaltig. Er prüft, ob die Ausbildung von Lehrernachwuchs überhaupt die vorrangige Zweckbestimmung der LBA war. Zweifel daran scheinen ihm angebracht, weil dem akuten Lehrermangel auf anderem Wege - Ausbildung von Schulhelfern - begegnet wurde. Demgegenüber kann er zeigen, daß die LBA in dem größeren Zusammenhang einer Funktionsänderung vieler Bildungseinrichtungen während des Krieges standen. Zwischen dieser Einsicht und dem Aufgabenverständnis der Lehrer, HJ-Führer und Schüler der LBA stellt der Verfasser eine Beziehung her, in deren Mittelpunkt die „Selbstführung“ der Jugend als Mittel der politischen Beeinflussung steht. (DIPF/Orig.