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European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5 th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

This analysis presents data from a new perspective offering key insights into the spread patterns of norovirus and influenza epidemic events. We utilize optic flow analysis to gain an informed overview of a wealth of statistical epidemiological data and identify trends in movement of influenza waves throughout Germany on the NUTS 3 level (413 locations) which maps municipalities on European level. We show that Influenza and norovirus seasonal outbreak events have a highly distinct pattern. We investigate the quantitative statistical properties of the epidemic patterns and find a shifted distribution in the time between influenza and norovirus seasonal peaks of reported infections over one decade. These findings align with key biological features of both pathogens as shown in the course of this analysis.

Objectives: Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated., Methods: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats., Results: In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France., Conclusions: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Episodic breathlessness is one form of refractory breathlessness. Better understanding of the symptom is necessary for effective management., Aim: The aim was to describe the characteristics of episodic breathlessness in patients with advanced chronic obstructive pulmonary disease or lung cancer., Design: This is a longitudinal cohort study. Outcomes were assessed monthly by up to 13 telephone interviews: peak severity (modified Borg scale: 0-10), duration, frequency, and timing of breathlessness episodes. Data from each episode were pooled and analyzed using descriptive statistics. Associations between outcomes were explored by correlation coefficients., Setting/participants: Patients with chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease classification stage III or IV) or primary lung cancer (any stage) were recruited in two inpatient units (internal medicine) and two outpatient clinics in Oldenburg, Germany., Results: A total of 82 patients (50 chronic obstructive pulmonary disease, 32 lung cancer), mean age (standard deviation) 67 years (8 years) and 36% female, were included reporting on 592 breathlessness episodes (chronic obstructive pulmonary disease: 403, lung cancer: 189). Peak severity was perceived significantly higher in chronic obstructive pulmonary disease patients than in lung cancer patients (mean (standard deviation) Borg scale: 6.2 (2.1) vs 4.2 (1.9); p < 0.001). Episodes described by chronic obstructive pulmonary disease patients were longer than those described by lung cancer patients (median (range): 7 min (0-600) vs 5 min (0.3-120), p = 0.002)). Frequency was similar and most often daily in both groups. Severity and frequency of episodes were correlated in lung cancer patients (r = 0.324, p = 0.009)., Conclusion: Most breathlessness episodes are short (minutes) and severe with significant differences between chronic obstructive pulmonary disease and lung cancer patients. Effective management strategies are warranted to improve symptom relief and coping., (© The Author(s) 2015.)

Background: Postoperative wound infection is a preventable risk. One potential postoperative complication is blistering, which leads to increased pain, delayed healing, and higher care costs. The incidence of wound blisters has been reported to be between 6 and 24%. The aim of this study is to assess whether the risks of postoperative blistering and wound infections within the first 6 days postsurgery will be reduced using a special dressing compared to a standard one., Methods/design: This is a randomized clinical trial in a University hospital. Patients presenting for knee or hip arthroplasty or spine procedures will be assessed against study inclusion and exclusion criteria. After giving written informed consent, patients will be randomized to participate in the 7-day study during hospitalization. One hundred patients will be randomized per group. The primary outcome measure is blistering incidence from day 0 to day 6 postsurgery. Photo documentation will be evaluated in a blinded manner by the Clinical Evaluation Committee (CEC)., Discussion: A new dressing will be compared to the standard wound dressing regarding the risk of postoperative blistering, wound infection, and patient comfort. This study will assess the potential advantages of a modern wound dressing., Trial Registration: ClinicalTrials.gov identifier NCT01988818 (Entered 13 November 2011).

Background: Health services research aims to generate knowledge about care processes of people with illnesses who access health-care services. In addition, the consequences of those processes in the care routine concerning the involved persons and the health system are analyzed. CONCEPT OF THE THEORETICAL WORK: In the first part of the manuscript, an overview concerning the current definitions and subsumptions of the concept of health services research is given. The second part of the manuscript focuses on demonstrating how evidence-based health services research can be used to enable optimization of the care system. The concept is called the "circle of care optimization". In the first step the current care situation concerning its deficits and their reasons is analyzed. In the second step a relevant care goal is defined. In the third step an improvement of an existing care process is developed to achieve the defined care goal. In the fourth step, a comparative empirical study with a high-quality study design is carried out, to assess whether the improved care process is superior to the current care as usual. A health economic evaluation will be performed if applicable. If the results show no or only small advantages, the "circle" starts again with step 3. However, if the results show a significant effect in favour of the new care process and are relevant for the delivery of care and efficient in the context of health economics, a fifth step will be performed which involves developing and testing strategies for implementation. Where relevant, the consequences of implementation are investigated in a sixth step. A "best-practice" practical example is demonstrated to illustrate the "circle of care optimization"., Conclusions: conclusions are derived by illustrating future challenges for health services research., (© Georg Thieme Verlag KG Stuttgart · New York.)

Patients receiving treatment for acute myelogenous leukemia (AML) and recipients of allogeneic stem cell transplantation (aSCT) are at high risk of contracting Clostridium difficile infection (CDI), the most frequently observed nosocomial diarrhea and enterocolitis. Data were retrieved from the prospective Cologne Cohort of Neutropenic Patients. Patients hospitalized for aSCT as well as patients receiving treatment for AML were included in the analysis. Risk factor analysis for the occurrence of CDI was performed by backward-stepwise logistic regression (P < .1). During the period from January 2007 to August 2010, 310 hospitalizations of 152 patients with AML and 229 hospitalizations of 223 patients undergoing aSCT were eligible for analysis. Incidence rates for CDI per 10,000 patient days were 17.9 for AML patients and 27.4 for aSCT recipients. Among AML and aSCT patients, median time from initiation of chemotherapy to CDI was 10 days (range, -8 to 101 days) and 17 days (range, 6 to 79), respectively. Logistic regression identified carbapenem exposure to be associated with development of CDI in AML patients (odds ratio [OR], 2.2) and aSCT recipients (OR, 1.4). In both groups, previous exposure to carbapenems was significantly associated with development of CDI. A follow-up study, assessing the effect of an antibiotic stewardship intervention to decrease the administration of carbapenems in hematological high-risk patients, is warranted., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

Patients who are treated with a mastoidectomy usually suffer from an inflammation of the petrosal bone. The intervention is a time consuming landmark based surgery and usually performed with a powered drill. Delicate risk structures must be respected. Navigated Control (NC) describes the control for a power driven instrument which is controlled by a surgeon and additionally controlled according to the position of the instrument relatively to a deliberated position known from a preoperatively segmented work space which excludes risk structures. The force of a drill can be regulated by the principle of NC. Following results were received: 1. Risk structure segmentation is feasible 2. The drill and a phantom can be registered. 3. With NC the resection is faster, more accurate and with no risk structures damage. 4. The phantom is suitable.

Accuracy represents the outstanding criterion for navigation systems. Surgeons have noticed a great discrepancy between the values from the literature and system specifications on one hand, and intraoperative accuracy on the other. A unitary understanding for the term accuracy does not exist in clinical practice. Furthermore, an incorrect equality for the terms precision and accuracy can be found in the literature. On top of this, clinical accuracy differs from mechanical (technical) accuracy. From a clinical point of view, we had to deal with remarkably many different terms all describing accuracy. This study has the goals of: 1. Defining "accuracy" and related terms, 2. Differentiating between "precision" and "accuracy", 3. Deriving the term "surgical accuracy", 4. Recommending use of the the term "surgical accuracy" for a navigation system. To a great extent, definitions were applied from the International Standardisation Organisation-ISO and the norm from the Deutsches Institut für Normung e.V.-DIN (the German Institute for Standardization). For defining surgical accuracy, the terms reference value, expectation, accuracy and precision are of major interest. Surgical accuracy should indicate the maximum values for the deviation between test results and the reference value (true value) A(max), and additionally indicate precision P(surg). As a basis for measurements, a standardized technical model was used. Coordinates of the model were acquired by CT. To determine statistically and reality relevant results for head surgery, 50 measurements with an accuracy of 50, 75, 100 and 150 mm from the centre of the registration geometry are adequate. In the future, we recommend labeling the system's overall performance with the following specifications: maximum accuracy deviation A(max), precision P and information on the measurement method. This could be displayed on a seal of quality.

Navigated Control (NC) describes an additional control for a tracked power driven instrument within a preoperatively segmented work space. In head surgery the authors first implemented NC in functional endoscopic sinus surgery (FESS). Recently the feasibility of NC for surgery on the petrosal bone is evaluated. NC in FESS and in petrosal bone surgery may reduce the risk of comorbidity and the time effort compared to the conventional surgical interventions.

Background and Objective: Little representative data of the epidemiology of attempted suicide exists in Germany. In this study the frequency of parasuicidal drug intoxication, the distribution of age and gender, as well as the kind and origin of used drugs were evaluated. Furthermore the knowledge about used drugs and possible adverse effects of a previously given medication were analysed., Patients and Methods: Over a period of 2 years (January 1998-December 1999) 155 patients (41 males, 114 females, average age 40.5 years) with drug intoxication by attempted suicide were recruited at the University Hospital of Dresden, Germany, for further retrospective analysis., Results: 74 % of these patients were women. Sedatives and hypnotics were most frequently used for parasuicide (44 %), followed by analgesics (18 %) and antidepressants (12 %). Benzodiazepines and benzodiazepine-agonists were the most commonly used drugs (32 %). Moreover, 80 % of all drugs used had been prescribed by physicians. Approximately half of the patients were well-informed about drugs taken. In 43 (47 %) of 92 patients with long-term medication an adverse effect was considered as a possible cause of the attempted suicide., Conclusion: Our data underline the importance of attempted suicide in view of the frequency of their use, the need of hospitalization, the required intensive care and possible relapses. Because the majority of drugs used were prescribed by physicians, before giving any medication to their possible suicidal use should be considered.

Background and Objective: Even in young adult age, psychological disorders are highly prevalent. Family doctors and gynaecologists are the physicians most often consulted by young women. Hence, they have a special responsibility to diagnose psychiatric disorders and--if necessary--to refer to a specialist., Patients and Methods: In a prospective epidemiological study, 342 young women (between 18 and 25 years of age) were questioned two times with a structured interview (F-DIPS) designed for mental disorders. In the time period (1997 and 1998), we also investigated, by analysing personal health insurance data, primary-care physicians' diagnoses and payments for services rendered. The diagnoses were compared., Results: There was only a small accordance between F-DIPS and claimcards. Ambulant treating doctors diagnosed somatoform disorders in 28 % of the young women (F-DIPS: 3, 8 %). The F- DIPS found mostly phobic disorders (29 %) (claimcards: 6,1 %). A disorder-specific therapy was only rarely initiated. The treatment (psychotherapy and/or drug therapy) of women with psychiatric disorders appeared to be insufficient., Conclusion: The study indicates that primary-care physicians should be urgently trained in psychiatric diagnostics und therapy.

Since 1980, BMBF, in co-operation with the appointed project representative BEO (Biology, Energy, Environment), supports research projects with the central goal of the reduction of animal testing. Beginning with the announcement about promoting "Projects in Replacement Methods to Animal Testing" in 1984, a separate incentive topic of research was fostered within the framework of the biotechnological program of the German Federal Government. It is being updated continuously by current reports. The BMBF incentive topic represents the largest and longest running support activity in the field world-wide. During a time-span of 20 years, about 14 million German Marks (approx. 7 millions per annum) were provided, supporting about 230 projects. To date, all applications judged favourably in regard to contributing to potential and substantial savings could also be funded. The incentive topic is being realised in accordance with the 3R principle, following Russel and Burch. Primary attention is given to tests with high levels of stress or involving large numbers of animals. At present, special attention is given to the development and validation of alternatives to animal testing which are required by law. Emphasis is also put on joint projects by testing and regulation authorities together with industrial users in order to broaden the application of these methods and to aid in accelerating the amendment of respective legal regulations. The BMBF continues to adhere to the objectives of the emphasised support and will furnish funding at the present level in the future. Also, together with representatives of testing- and regulating authorities, of industry, science, respective federal authorities and animal protection, the BMBF has developed a new concept to expand funded activities in the future to include animal testing in basic research in a target-fashioned structure. This will be published shortly through a new public announcement. As a complement to the present application procedure ("bottom-up-principle"), new research approaches are being prepared within a limited scope regarding particularly relevant topics (i.e. transgenic animal models) as a "top-down-principle" by means of workshops and accompanying studies. Additionally, reports are appearing concerning the results of selected projects supported by the emphasised support of the BMBF for "Biologica", particularly regarding the realisation of results in the practical reduction of animal testing. The BMBF is supporting a total of 27 projects with respect to "Biologica". Central to the majority of these projects (21) is the test of vaccines, and there in particular, the potency test of particular vaccines. Using four examples, it is being demonstrated that the practical translation of the results of projects always requires the co-operation of the respective partners, and that the complete application of suitable replacement methods usually becomes possible only after the conclusion of a phase of development and testing of several years.