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Background: An infection with SARS-CoV-2 can lead to a variety of symptoms and complications, which can impair athletic activity. Objective: We aimed to assess the clinical symptom patterns, diagnostic findings, and the extent of impairment in sport practice in a large cohort of athletes infected with SARS-CoV-2, both initially after infection and at follow-up. Additionally, we investigated whether baseline factors that may contribute to reduced exercise tolerance at follow-up can be identified. Methods: In this prospective, observational, multicenter study, we recruited German COVID elite-athletes (cEAs, n = 444) and COVID non-elite athletes (cNEAs, n = 481) who tested positive for SARS-CoV-2 by PCR (polymerase chain reaction test). Athletes from the federal squad with no evidence of SARS-CoV-2 infection served as healthy controls (EAcon, n = 501). Questionnaires were used to assess load and duration of infectious symptoms, other complaints, exercise tolerance, and duration of training interruption at baseline and at follow-up 6 months after baseline. Diagnostic tests conducted at baseline included resting and exercise electrocardiogram (ECG), echocardiography, spirometry, and blood analyses. Results: Most acute and infection-related symptoms and other complaints were more prevalent in cNEA than in cEAs. Compared to cEAs, EAcon had a low symptom load. In cNEAs, female athletes had a higher prevalence of complaints such as palpitations, dizziness, chest pain, myalgia, sleeping disturbances, mood swings, and concentration problems compared to male athletes (p < 0.05). Until follow-up, leading symptoms were drop in performance, concentration problems, and dyspnea on exertion. Female athletes had significantly higher prevalence for symptoms until follow-up compared to male. Pathological findings in ECG, echocardiography, and spirometry, attributed to SARS-CoV-2 infection, were rare in infected athletes. Most athletes reported a training interruption between 2 and 4 weeks (cNEAs: 52.9%, cEAs: 52.4%), while more cNEAs (27.1%) compared to cEAs (5.1%) had a training interruption lasting more than 4 weeks (p < 0.001). At follow-up, 13.8% of cNEAs and 9.9% of cEAs (p = 0.24) reported their current exercise tolerance to be under 70% compared to pre-infection state. A persistent loss of exercise tolerance at follow-up was associated with persistent complaints at baseline, female sex, a longer break in training, and age > 38 years. Periodical dichotomization of the data set showed a higher prevalence of infectious symptoms such as cough, sore throat, and coryza in the second phase of the pandemic, while a number of neuropsychiatric symptoms as well as dyspnea on exertion were less frequent in this period. Conclusions: Compared to recreational athletes, elite athletes seem to be at lower risk of being or remaining symptomatic after SARS-CoV-2 infection. It remains to be determined whether persistent complaints after SARS-CoV-2 infection without evidence of accompanying organ damage may have a negative impact on further health and career in athletes. Identifying risk factors for an extended recovery period such as female sex and ongoing neuropsychological symptoms could help to identify athletes, who may require a more cautious approach to rebuilding their training regimen. Trial Registration Number: DRKS00023717; 06.15.2021—retrospectively registered. [ABSTRACT FROM AUTHOR]

Auscultation torsos are widely used to teach position-dependent heart sounds and murmurs. To provide a more realistic teaching experience, both whole body auscultation mannequins and torsos have been used in clinical examination skills training at the Medical Faculty of the University of Muenster since the winter term of 2008-2009. This training has since been extended by simulated patients, which are normal, healthy subjects who have undergone attachment of the electronic components of the auscultation mannequins to their chests to mimic pathophysiological conditions ("hybrid models"). The acceptance of this new learning method was examined in the present pilot study. In total, 143 students in their second preclinical year who were participating in auscultation training were randomized into an intervention group (hybrid models) and a control group (auscultation mannequins). One hundred forty-two (99.3%) of these students completed a self-assessment Likert-scale questionnaire regarding different teaching approaches (where 1 = "very poor" to 100 = "very good"). The questionnaire focused on the "value of learning" of different teaching approaches. Direct comparison showed that students evaluated the hybrid models to be significantly more effective than the auscultation mannequins (median: 83 vs. 64, P < 0.001). The cardiac auscultation training was generally assessed positively (median: 88). Additionally, verbal feedback was obtained from simulated patients and tutors (trained students who had successfully passed the course a few semesters earlier). Personal feedback showed high satisfaction from student tutors and simulated patients. Hybrid simulators for teaching cardiac auscultation elucidated positive responses from students, tutors, and simulated patients.

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Background/Objective: Child maltreatment is associated with increased risk of psychological consequences, contributes to morbidity and has long lasting effects on mental health and quality of life. Child maltreatment has not been assessed in patients with pulmonary arterial hypertension (PAH). We examined the prevalence of child maltreatment and determined their impact on disease severity in patients with PAH. Methods: A cross-sectional observational multicenter study at two PH centers in Germany was conducted. Patients with a confirmed diagnosis of PAH were given a self-administered questionnaire. Child maltreatment using the Childhood Trauma Questionnaire (CTQ), quality of life (QoL), anxiety, depression, and lifestyle factors were assessed and enhanced by clinical parameters 6-min walk distance (6MWD), WHO functional class (WHO FC), and serum levels of N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). Prevalence rates of child maltreatment were compared to the general population and impact of child maltreatment on disease severity was calculated by logistic regression analysis. Results: Two-hundred and seventeen patients, 71% female and a median age of 56 years were enrolled in this study. Patients with PAH had higher rates of emotional abuse and lower rates of physical neglect compared to the German population while rates of emotional neglect, physical abuse, and sexual abuse did not differ between patients and German population. Patients with any form of child maltreatment were more likely to be active smokers, had a worse QoL and more anxiety or depression. Moderate associations between child maltreatment, mental health, QoL, lifestyle factors and clinical parameters could be observed. Logistic regression analysis showed a significant impact of CTQ-total score on disease severity with an OR of 1.022 (95%-CI: 1.001–1.042, p = 0.035). Conclusion: We found a higher rate of child maltreatment in patients with PAH in comparison to the German population. Correlations suggest moderate associations between CTQ-scores and mental health as well as QoL. Child maltreatment had significant impact on disease severity. However, effects were moderate. We conclude that child maltreatment has effects on mental health and quality of life in patients with PAH and may have limited effect on disease severity. [ABSTRACT FROM AUTHOR]

Introduction: Data on burden of pulmonary arterial hypertension (PAH) are mostly limited to physical and clinical endpoints as well as quality of life. Research on employment, work productivity, and educational background is scarce. The aim of this study was to assess the impact of PAH on employment status and work productivity in Germany. Materials and Methods: In a multicenter cross-sectional survey, patients with PAH were surveyed in two large pulmonary hypertension referral centers in Germany. The survey contained questions on education, employment, work productivity and impairment (WPAI, also at the time of diagnosis), quality of life, and socioeconomic status. Additional data was assessed using clinical research database for 6-min walk distance (6MWD), WHO functional class, and N-terminal fragment of pro-brain natriuretic peptide. All patients provided written informed consent, and the institutional review board approved this study. Results: In total, 212 patients were surveyed (72% female; median, 57 years) approximately 6 years after initial PAH diagnosis. A total of 76% had an idiopathic PAH followed by hereditary and associated PAH (10% each). Employment at the time of diagnosis was 48% (34% full-time, 14% part-time), with productivity measured by a WPAI score of 6 points and decreased to 29% (21% full-time, 8% part-time) at the time of the survey (with a WPAI score of 2 points, p < 0.001). Logistic regression showed education and 6MWD as predictors for employment. Patients in moderate or high educational category had a 3.6- or 5.6-fold chance, respectively, of being employed (p = 0.025 and p = 0.019), and per 50-m increase of 6MWD, the odds of being employed were 1.2, p = 0.042. Conclusion: Patients with PAH had a reduced employment rate, which was influenced by education and 6MWD. There was a considerable loss of employment over the course of the disease. Employment should be one possible treatment goal in patients with PAH to provide social participation to this patient group. [ABSTRACT FROM AUTHOR]

Background: We analyzed the effects of the SARS‐CoV‐2 pandemic on neurologic emergencies, depending on the patients' triage score in a setting with relatively few COVID‐19 cases and without lack of resources. Methods: Consecutive patients of a tertiary care center with a dedicated neurologic emergency room (nER) were analyzed. The time period of the first lockdown in Germany (calendar weeks 12–17, 2020) was retrospectively compared to the corresponding period in 2019 regarding the number of patients presenting to the nER, the number of patients with specific triage scores (Heidelberg Neurological Triage Score), the number of patients with stroke, and the quality of stroke care. Results: A total of 4330 patients were included. Fewer patients presented themselves in 2020 compared to 2019 (median [interquartile range] per week: 134 [118–143] vs. 187 [182–192]; p = 0.015). The median numbers of patients per week with triage 1 (emergent) and 4 (non‐urgent) were comparable (51 [43–58] vs. 59 [54–62]; p = 0.132, and 10 [4–16] vs. 16 [7–18]; p = 0.310, respectively).The median number of patients per week declined in categories 2 and 3 in 2020 (41 [37–45] vs. 57 [52–61]; p = 0.004, and 28 [23–35] vs. 61 [52–63]; p = 0.002, respectively. No change was observed in the absolute number of strokes (138 in 2019 and 141 in 2020). Quality metrics of stroke revascularization therapies (symptom‐to‐door time, door‐to‐needle time or relative number of therapies) and stroke severity remained constant. Conclusion: During the lockdown period in 2020, the number of patients with emergent symptoms remained constant, while fewer patients with urgent symptoms presented to the nER. This may imply behavioral changes in care‐seeking behavior. [ABSTRACT FROM AUTHOR]

Objective: Investigation of the treatment of femur fractures and the type of femur fracture‐associated complications regarding timing of surgery and length of hospital stay. Methods: In this retrospective cohort study, a total of 358 hip fractures were evaluated retrospectively from 1 January 2008 until 31 December 2010 at a level I trauma center in Germany. Inclusion criteria was age >18 years and a proximal femur fracture. Both sexes were evaluated. Mean age was 75.5 years, most patients were female (63.7%). Intervention was the operative treatment of proximal femur fracture. Outcome parameters were time until surgery, complications, reoperations, mortality, and length of hospital stay. Results: Among the proximal femur fractures (n = 358), 46.6% were pertrochanteric, 11.2% subtrochanteric, and 42.2% femoral neck fractures. Operation upon hip fractures was managed regularly within 24 hours of injury (73%; mean for femoral neck: 28.3 hrs.; mean for pertrochanteric fractures: 21.4 hrs.; mean for subtrochanteric fractures: 19.5 hrs.). Delayed treatment, as well as implantation of hip total endoprosthesis (TEP), increased the overall length of hospital stay (15.4 vs 17.6 days; 18.1 vs 15.8 days). Accordingly, surgical procedures performed within 24 hours of injury resulted in a shorter hospital residence. Longest delay of operation was measured for hip fractures (28.3 hrs.). In 351 patients, secondary injuries were detected in 94 individuals (26%), with fractures being the most common secondary injury (n = 40). We recorded postoperative complications of nonsurgical and surgical origin, and 33.6% of our patient cohort displayed complications. Complications were distributed among 118 patients. There was no significant difference in complications regarding the time of operation, with most nonsurgical and surgical complications appearing within 24 hours after operation (n = 110 vs n = 31). Nonsurgical complications, such as anemia (n = 49) and electrolyte imbalances (n = 30), were observed more frequently than surgical complications (n = 107 vs n = 34); however, these complications were reduced by delay in surgery (82.0% in 6–24 hrs. vs 74.2% in ≥24 hrs.). Anticoagulant therapy and age did not affect postoperative complications. The hospital mortality of patients was 6.2%. Follow‐up was restrained to ambulatory visits in the clinic. Conclusions: Surgical management of hip fractures performed within 24 hours of injury minimizes hospital stay. We did not detect significant differences in the spectrum or number of complications regarding delay of surgery. Surgical complications mainly occur with rapid primary care, and medical complications can be reduced by more intensive preparation of patient and operation procedures. [ABSTRACT FROM AUTHOR]

• High validity of findings through physical experience of automated vehicles. • Application of automated vehicles in a realistic traffic environment. • Full transparency with pre-registration and definitions, measures, and dataset. • Analysis of attitudes and emotions towards self-driving cars. • Acceptance, perceived safety, and age predict intention to use automated vehicles. Automated vehicles (AVs) have left the laboratories and can be experienced in several projects, e.g. at the premises of a clinic in Germany. With this transition, research on AV attitudes no longer needs to rely on questionnaires with hypothetical scenarios and simulations. Previous research – limited by the unavailability of AVs – has provided ambivalent results regarding age and gender differences in attitudes towards AVs. We present research results about the role of age and gender in connection with attitudes such as acceptance, perceived safety, and trust, as well as intention to use. We additionally demonstrate relationships between those constructs and emotions such as amusement, fear, and surprise. Data were collected from participants (n = 125) after having experienced an AV ride with level 4 automation on two campuses of a clinic in Berlin, Germany. Results reveal strong correlations between all attitudes (0.55 ≤ r ≤ 0.71; p < 0.01) and show acceptance and perceived safety to be solid predictors of intention to use AVs. We also found age to be a significant predictor for usage intention even when other attitudes are considered (β = −0.22; p < 0.01). MANOVA results point to gender differences in all constructs, but with limited confidence (5.40 ≤ F ≤ 18.34; p ≤ 0.02). However, we reject our hypothesis that young men are highly accepting, trusting, and intending to use AVs compared to other combinations of age and gender. We recommend using a mix of attitude, emotion, and behavioural (intention) measures in future research on AVs together with more transparency regarding construct definitions and study materials. [ABSTRACT FROM AUTHOR]

Objective: Several independent prognostic factors, such as age of onset, type of onset, body mass index (BMI), and progression rate have been identified for amyotrophic lateral sclerosis (ALS) in Caucasians. The aim of this study was to identify such factors in Chinese patients and to compare their impact with German patients. Methods: Comparison of prognostic factors was based on two hospital-based registries. The registry of the German Network for Motor Neuron Diseases contains 3100 patients with ALS. The Chinese registry comprises 2101 patients who were collected between 2003 and 2015 in the metropolitan area of Beijing. Results: Disease progression was slower in China [median loss of 0.50 points (IQR 0.26–0.87 points) versus 0.55 points (IQR 0.28–1.00 points) of ALS functional rating scale revised (ALS-FRS-R) score per month; p < 0.0001]. Survival of patients with ALS was similar in Germany and China (p > 0.05). We found that younger age of onset (p < 0.0001), spinal onset (p < 0.0001), high BMI (p < 0.0001) and low progression rate (p < 0.0001) were positive prognostic factors in China as well as in Germany. Interpretation: Prognostic factors, which are known to modify the course of disease in Caucasians, apply to Chinese patients as well. The results indicate that despite the apparent differences regarding genotype and clinical phenotype, findings from interventional studies in Caucasians aiming at disease-modifying prognostic factors (such as body weight) may be transferred to Chinese patients. [ABSTRACT FROM AUTHOR]

After years of hypothetical surveys and simulator studies, automated vehicles (AVs) are now being tested in realistic traffic environments adding validity to knowledge about their acceptance. We present data from a pilot test with participants (n = 125) after experiencing a ride in an electric AV on a large clinic area in Berlin, Germany. As a first contribution, we bridge the gap between missing definitions of key constructs, confusion about their operationalisations, and a rigorous test of their statistical properties and data structure by examining scales on acceptance, trust, perceived safety, intention to use, and—for the first time applied to AVs—the emotions amusement, fear, surprise, and boredom. Tests of reliability and normality were satisfying for almost all constructs (Cronbach’s alphas ≥ .69; six of eight scales normally distributed). The vehicles were accepted (M = 1.22; SD = 0.70; range -2 to 2), trusted (M = 3.29; SD = 0.81; range 1 to 5), and perceived as safe (M = 3.29; SD = 1.03; range 1 to 5). However, factor analyses did not reflect the hypothesised data structure, and validity concerns question the suitability of some constructs for attitude assessment of electric AVs. Our open item for comments added valuable insights in qualitative aspects of user attitudes towards electric AVs regarding driving style, technical features, and (unsettling) audio-visual feedback. We thus argue for broader conceptualisations of key constructs based on interdisciplinary exchange and multi-methodical study designs. [ABSTRACT FROM AUTHOR]

Purpose: There is a growing evidence for over-, under-, or misuse of health care in patients with inflammatory bowel disease. Most studies looked at treatment variability or used quality measures, which mostly capture supportive interventions rather than treatment of IBD in itself. We aimed to evaluate if current recommendations in clinical practice guidelines regarding the medical treatment of patients with inflammatory bowel diseases are being followed in Germany. Methods: A questionnaire was sent to 1901 patients insured with two large German statutory sickness funds and an ICD 10 diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). The questionnaire asked about drug treatment, indications for drug treatment, provision of surveillance endoscopies in ulcerative colitis patients, and smoking status in Crohn's disease patients. Results: Out of 460 evaluable patients, 62.4% of UC patients and 53.9% of CD patients were treated with mesalamine according to guidelines, 91.3% of all patients were treated with glucocorticoids according to guideline recommendations, while only 75.6% received recommended immunosuppressive treatment. Of UC patients, 94.5% had surveillance colonoscopies at the recommended interval and 58.8% of CD patients were non-smokers. No predictor for overall treatment according to guidelines could be found while being of age older than 60 or being treated outside of a dedicated IBD clinic was associated with less immunosuppressive treatment. Conclusions: A large proportion of patients with IBD do not receive drug treatment in accordance with clinical practice guidelines. Quality improvement measures are much needed. [ABSTRACT FROM AUTHOR]

The authors test Naert and Weverbergh's empirical finding that attraction-type specifications are characterized by a predictive power greater than that of their nonrobust counterparts. The empirical results, obtained by use of data on the German cigarette market, do not support the conclusions of Naert and Weverbergh. [ABSTRACT FROM AUTHOR]

Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren's syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis.Objectives: To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS.Methods: An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects.Measurements and Main Results: A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS-associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated.Conclusions: Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region. [ABSTRACT FROM AUTHOR]

The form factors of protons and neutrons provide a natural and direct insight into their internal structure. They were a main research goal in the nuclear physics program of the Universitat Mainz, which led to some of the most precise measurements to date. This article gives an overview, starting from the very first experiments at the now obsolete linear accelerator and ending at the exhaustive experiments currently underway at the MAMI facilities. PACS Nos.: 14.20.Dh, –13.40.Gp, –25.30.Bf [ABSTRACT FROM AUTHOR]

The article summarizes presentations at a symposium on bibliographical resources for Eastern and Central European studies, held at the Herder-Institut in Marburg, Germany. Online resources were presented from Germany (primarily), Austria, Sweden, the United Kingdom, and the United States. [ABSTRACT FROM AUTHOR]

This article considers issues concerning cases where the use of placebo is lawful or is not lawful under aspects of German criminal law. It will differentiate between cases of individual therapy and cases of supervised experiments within the scope of medical tests. Thereby, it reveals that a medication of placebo with regard to an individual patient seems to be lawful if there is no alternative possibility of a better treatment using a chemically effective medicine and if the limits of presumed consent are complied with. On the other hand, in the context of the supervised experiment, the assignment of a patient to a group treated with placebo is only lawful if the patient has been fully informed about the possibilities of a treatment and if the patient has given consent to it. [ABSTRACT FROM AUTHOR]

Focuses on the financing of railways in German States as of year 1840 and 1860. Management on the planning, construction and operation; Contribution of privately-owned railway companies on profitability of the industry; Acquisition of revenues for economic growth.

210 expert reports on suicides of German soldiers in the years 1940-1943 were examined. The original intention of the reports was to ascertain a responsibility of the „Wehrmacht“ for the suicides, which the expert confirmed in 22,9% of the cases. The mean age of the soldiers was 33 years, 71% were married, only 6% had a high school education. 75% belonged to other ranks. Only 1,4% belonged to military service less than one month, 23% committed suicide within one day after the beginning of the crisis. 88% chose shooting, hanging and drowning as suicide methods. The expert considered 67,6% of all soldiers as mentally disturbed; just personality disorders occurred in 30,5%. In 51,4% of all cases, the motive for committing suicide was in relationship to the military service, e. g. fear of punishment or suffering from homesickness. 19,2% had reasons relating to merely personal problems, like marital crises. The motive of a third group (29,4%) had to do with illness, either lacking of ability to stand a real illness or a not yet diagnosed, but imagined illness, or the soldiers committed suicide due to a mental illness like schizophrenia or depression. All in all, analysing the suicide motives there can be found a various number of problems of daily living. However, the majority of them might have not occurred if there would have been peace. Yet, from several studies we know that during war the suicide rate is lower than in peace; several reasons for this are discussed in the article. [ABSTRACT FROM AUTHOR]

Signs of maturity such as weight, length and head circumference are still a measure used to investigate cases of suspected neonaticides as they help to differentiate between newborns born dead or alive. However, limit values for these signs have not changed for a long time. Our study considers whether limit values should have changed and which validity the current ones have. We investigated the cases of 3162 newborns, dividing them into a mature and an immature collective on the basis of the gestational week. Application of these signs of maturity (2500g, 48cm, 34cm) had a high predictive value concerning maturity (>99%), and even applying only one sign of maturity gave a predictive value over 97%. Clinically the mature collective showed a slightly lower rate of ventilation (2% compared to 2.4% for the non-mature collective). Coherences between maternal age/weight and postnatal ventilation could be shown. Coherences with reanimation could not be investigated since the case number was too low. Our results show that, for valid forensic investigation, these numeric signs of maturity have to be supplemented by further investigations and other influencing factors have to be considered. Therefore, clinical instruments such as the Petrussa-Index, clavicule length measuring and foot length measuring must be considered. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Hypertrophic scars and keloid formation are common problems which are not only the result of surgical procedures. Many treatment protocols exist without standardization. The aim of our study was to compare various treatment protocols using a 2940nm Er:YAG laser with and without additional silicone gel application. Patients and methods: Twenty-one patients suffering from keloids or hypertrophic scars were treated in four groups with the Burane XL Er:YAG laser (Quantel Derma GmbH; Erlangen, Germany) either in thermal or combined thermoablative mode with or without additional silicone gel application under non-blinded conditions. The appearance of the scars (redness, hardness and elevation) before therapy, and 12 months after therapy was evaluated by therapists based on a scaling system from 0 to 3 (0=minimum, 3=maximum). Results: The patient group was made up of 21 people, 16 females and five males, ranging in age from 16 to 79 years. All patients had a mean reduction of redness, hardness and scar elevation by 51.3% (p =0.0012), 48.9% (p =0.0015) and 50.0% (p =0.0015), respectively. There was no significant difference between groups with or without additional silicone gel application (p >0.05). Conclusion: Our pilot study proved the effectiveness of Er:YAG laser treatments (thermal and combined thermoablative mode) for the reduction of hypertrophic scars and keloids. However, the additional application of silicone gel was not as effective as postulated. Larger randomized double-blinded studies are needed to further evaluate treatment protocols for hypertrophic scars and keloids. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a disease that still has to be primarily treated symptomatically or palliatively. It is therefore all the more important, in addition to initiating treatment, such as percutaneous endoscopic gastrostomy (PEG), noninvasive ventilation therapy (NIVT) and invasive ventilation therapy via tracheotomy (IVT), to discuss the possible termination of these measures early on., Question: What is the importance of advance directives for those affected and where are possible deficits in therapy planning for the end of life?, Material and Method: Between March 2017 and January 2019 patients with a clinically confirmed diagnosis of ALS at six treatment centers were asked to fill out a questionnaire. A total of 328 people returned the completed forms., Results: Of the participants 72% had already made an advance directive (AD), 25% planned to fill one out and only 3% refused to do so. In composing the AD most patients (90%) had support, although 56% lacked medical counselling and only 18% had drawn up the will together with the doctor and relatives, with the majority of the rest also wanting support from a doctor. A total of 37% of all patients wanted a contact person to talk about their illness but only 40% of them had such a contact person. Of the patients 22% stated that they had considered suicide and of these only 55% stated that they had no contact person for the psychological stress caused by the illness but 31% wished to have such a person., Discussion and Conclusion: A coordinated care of ALS patients, which also takes the psychosocial aspects into account is urgently needed., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: C. Eickhoff, B. Schöne-Seifert, D. Kettemann, E. Bormann, T. Grehl, M. Boentert, J.C. Koch, C. Schmitt, B. Schrank, C. Schröter und T. Meyer geben an, dass kein Interessenkonflikt besteht. Für die Erhebung lagen positive Ethikvoten des Universitätsklinikums Münster sowie der Landesärztekammern Hessen und Westfalen-Lippe vor (2016-618-f-S)., (© 2024. The Author(s).)

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals., (© 2024. The Author(s).)

Kidney disease represents an increasing global health problem. Its mitigation requires effective communication between all stakeholders involved in assessment, diagnosis and therapy and individuals affected by kidney disease. However, as of today the nomenclature for kidney function and kidney disease is far from uniform. In 2019, the international non-profit organization Kidney Disease: Improving Global Outcomes (KDIGO) has implemented a consensus process to develop a glossary in English language to standardize the nomenclature for kidney function, kidney structure and kidney disease. Guiding principles for this process were (1) precision, (2) patient-centeredness and (3) consistency with KDIGO guidelines. The current position paper includes a translation of this nomenclature into German that was developed on behalf of the national societies for nephrology in Germany, Austria and Switzerland., Competing Interests: Alle Autoren geben keine Interessenskonflikte an in Hinblick auf den Artikel., (Georg Thieme Verlag KG Thieme. All rights reserved.)

Background: The annual incidence of new cancer cases has been increasing worldwide for many years, and is likely to continue to rise. In Germany, the number of new cancer cases is expected to increase by 20% until 2030. Half of all cancer patients experience significant emotional and psychosocial distress along the continuum of their disease, treatment, and aftercare, and also as long-term survivors. Consequently, in many countries, psycho-oncological programs have been developed to address this added burden at both the individual and population level. These programs promote the active engagement of patients in their cancer therapy, aftercare and survivorship planning and aim to improve the patients' quality of life. In Germany, the "new form of care isPO" ("nFC-isPO"; integrated, cross-sectoral psycho-oncology/integrierte, sektorenübergreifende Psycho-Onkologie) is currently being developed, implemented and evaluated. This approach strives to accomplish the goals devised in the National Cancer Plan by providing psycho-oncological care to all cancer patients according to their individual healthcare needs. The term "new form of care" is defined by the Innovation Fund (IF) of Germany's Federal Joint Committee as "a structured and legally binding cooperation between different professional groups and/or institutions in medical and non-medical care". The nFC-isPO is part of the isPO project funded by the IF. It is implemented in four local cancer centres and is currently undergoing a continuous quality improvement process. As part of the isPO project the nFC-isPO is being evaluated by an independent institution: the Institute for Medical Sociology, Health Services Research, and Rehabilitation Science (IMVR), University of Cologne, Germany. The four-year isPO project was selected by the IF to be eligible for funding because it meets the requirements of the federal government's National Cancer Plan (NCP), in particular, the "further development of the oncological care structures and quality assurance" in the psycho-oncological domain. An independent evaluation is required by the IF to verify if the new form of care leads to an improvement in cross-sectoral care and to explore its potential for permanent integration into the German health care system., Methods: The nFC-isPO consists of six components: a concept of care (C1), care pathways (C2), a psycho-oncological care network (C3), a care process organization plan (C4), an IT-supported documentation and assistance system (C5) and a quality management system (C6). The two components concept of care (C1) and care pathways (C2) represent the isPO clinical care program, according to which the individual cancer patients are offered psycho-oncological services within a period of 12 months after program enrolment following the diagnosis of cancer. The remaining components (C3-C6) represent the formal-administrative aspects of the nFC-isPO that are intended to meet the legally binding requirements of patient care in the German health care system. With the aim of systematic development of the nFC-isPO while at the same time enabling the external evaluators to examine its quality, effectiveness and efficiency under conditions of routine care, the project partners took into consideration approaches from translational psycho-oncology, practice-based health care research and program theory. In order to develop a structured, population-based isPO care program, reference was made to a specific program theory, to the stepped-care approach, and also to evidence-based guideline recommendations., Results: The basic version, nFC-isPO, was created over the first year after the start of the isPO project in October 2017, and has since been subject to a continuous quality improvement process. In 2019, the nFC-isPO was implemented at four local psycho-oncological care networks in the federal state North Rhine-Westphalia, in Germany. The legal basis of the implementation is a contract for "special care" with the German statutory health insurance funds according to state law (§ 140a SCB V; Social Code Book V for the statutory health insurance funds). Besides the accompanying external evaluation by the IMVR, the nFC-isPO is subjected to quarterly internal and cross-network quality assurance and improvement measures (internal evaluation) in order to ensure continuous quality improvement process. These quality management measures are developed and tested in the isPO project and are to be retained in order to ensure the sustainability of the quality of nFC-isPO for later dissemination into the German health care system., Discussion: Demands on quality, effectiveness and cost-effectiveness of in the German health care system are increasing, whereas financial resources are declining, especially for psychosocial services. At the same time, knowledge about evidence-based screening, assessment and intervention in cancer patients and about the provision of psychosocial oncological services is growing continuously. Due to the legal framework of the statutory health insurance in Germany, it has taken years to put sound psycho-oncological findings from research into practice. Ensuring the adequate and sustainable financing of a needs-oriented, psycho-oncological care approach for all newly diagnosed cancer patients, as required by the NCP, may still require many additional years. The aim of the isPO project is to develop a new form of psycho-oncological care for the individual and the population suffering from cancer, and to provide those responsible for German health policy with a sound basis for decision-making on the timely dissemination of psycho-oncological services in the German health care system., Trial Registration: The study was pre-registered at the German Clinical Trials Register (https://www.drks.de/DRKS00015326) under the following trial registration number: DRKS00015326 ; Date of registration: October 30, 2018., (© 2022. The Author(s).)

Refractory celiac disease (RCD) refers to a rare subgroup of patients with celiac disease who show clinical signs of malabsorption despite a gluten-free diet. RCD is divided into an autoimmune phenotype (RCD type I) and pre-lymphoma (RCD type II). To reflect the clinical reality in managing this disease in Germany, a national register was established based on a questionnaire developed specifically for this purpose. Between 2014 and 2020, a total of 53 patients were registered. The diagnosis of RCD was confirmed in 46 cases (87%). This included 27 patients (59%) with RCD type I and 19 patients (41%) with RCD type II. A wide range of diagnostic and therapeutic measures was used. Therapeutically, budesonide was used in 59% of the RCD patients regardless of the subtype. Nutritional therapy was used in only 5 patients (11%). Overall mortality was 26% (12 patients) with a clear dominance in patients with RCD type II (9 patients, 47%). In summary, RCD needs to become a focus of national guidelines to increase awareness, establish standards, and thus enable the treating physician to make the correct diagnosis in a timely manner. Moreover, we concluded that when treating such patients, contacting a specialized center is recommended to ensure sufficient management., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting., Methods: A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated., Results: 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures., Conclusion: Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

Even early at the beginning of the coronavirus disease 2019 (COVID‑19) pandemic, stroke was described as a manifestation or complication of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current meta-analyses reported a stroke rate of approximately 1.5%. Stroke in COVID‑19 positive patients occurs more frequently in severe courses of the infection and in older patients with cardiovascular comorbidities; however, young patients without cardiovascular risk factors are also not uncommonly affected. The mechanisms of stroke are predominantly embolic. The thrombi frequently occlude large intracranial vessels and in more than 20% affect multiple vascular territories, whereas infarctions due to small vessel disease are uncommon. The exact source of the embolism remains cryptogenic in more than 40% of patients. The mortality caused by the co-occurrence of a SARS-CoV‑2 infection and a stroke exceeds 15-30%. While acute stroke treatment was severely affected in some European regions, the rates of recanalization treatment in Germany largely remained stable during the first pandemic wave; however, 20-30% fewer patients with minor stroke and transient ischemic attacks (TIA) presented to hospitals during the first wave in spring 2020. The present narrative review summarizes the current evidence regarding the epidemiology and pathogenesis of stroke associated with COVID‑19 and describes the effect of the pandemic so far on the provision of acute stroke treatment.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide. Given scarce resources, nonlaboratory diagnostics are crucial. In this cross-sectional study, two-thirds of European patients with confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of these symptoms in early diagnostics., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The responsibility for helping patients understand potential health benefits and risks, especially regarding screening tests, falls largely to general practitioners (GPs). The Berlin Numeracy Test (BNT) specifically measures risk literacy (i.e., the ability to understand different aspects of statistical numeracy associated with accurate interpretation of information about risks). This study explored the association between risk literacy levels and clinical experience in GPs vs. medical students. Additionally, the effect of GP risk literacy on evaluation of the predictive value of screening tests was examined., Methods: The participants were 84 GPs and 92 third-year medical students who completed the BNT (total score range 0-4 points). The GPs received an additional case scenario on mammography screening as a simple measure of performance in applying numeracy skills., Results: Despite having an average of 25.9 years of clinical experience, GPs scored no better than medical students on risk literacy (GPs: 2.33 points, 95% confidence interval [CI] 2.08-2.59; students: 2.34, 95% CI 2.07-2.61; P = .983). Of all GPs, 71.6% (n = 58) greatly overestimated the real predictive value., Conclusions: In this study, we found no difference in risk literacy between current students and current GPs. GPs lack risk literacy and consequently do not fully understand numeric estimates of probability in routine screening procedures.

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO 2 peak), maximal oxygen consumption normalized for body weight (VO 2 peak/kg), and oxygen consumption at the anaerobic threshold (VO 2 @AT). In women, 1 mL/min higher VO 2 peak, VO 2 peak/kg, and VO 2 @AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF.

Recent reports of local extinctions of arthropod species 1 , and of massive declines in arthropod biomass 2 , point to land-use intensification as a major driver of decreasing biodiversity. However, to our knowledge, there are no multisite time series of arthropod occurrences across gradients of land-use intensity with which to confirm causal relationships. Moreover, it remains unclear which land-use types and arthropod groups are affected, and whether the observed declines in biomass and diversity are linked to one another. Here we analyse data from more than 1 million individual arthropods (about 2,700 species), from standardized inventories taken between 2008 and 2017 at 150 grassland and 140 forest sites in 3 regions of Germany. Overall gamma diversity in grasslands and forests decreased over time, indicating loss of species across sites and regions. In annually sampled grasslands, biomass, abundance and number of species declined by 67%, 78% and 34%, respectively. The decline was consistent across trophic levels and mainly affected rare species; its magnitude was independent of local land-use intensity. However, sites embedded in landscapes with a higher cover of agricultural land showed a stronger temporal decline. In 30 forest sites with annual inventories, biomass and species number-but not abundance-decreased by 41% and 36%, respectively. This was supported by analyses of all forest sites sampled in three-year intervals. The decline affected rare and abundant species, and trends differed across trophic levels. Our results show that there are widespread declines in arthropod biomass, abundance and the number of species across trophic levels. Arthropod declines in forests demonstrate that loss is not restricted to open habitats. Our results suggest that major drivers of arthropod decline act at larger spatial scales, and are (at least for grasslands) associated with agriculture at the landscape level. This implies that policies need to address the landscape scale to mitigate the negative effects of land-use practices.

Purpose: Many recommendations from clinical practice guidelines are not implemented. We aimed to develop and evaluate a multifaceted strategy for the implementation of guidelines for Crohn's disease (CD) and ulcerative colitis (UC)., Methods: In the intervention region (Berlin, Germany), a continuing medical education course was held, brief guidelines for practice were distributed to all family physicians and gastroenterologists, and patient guidelines were distributed to all surveyed patients. Educational outreach visits with local opinion leaders were also conducted. No specific interventions were performed in the control region (Hamburg, Germany). Prior to the intervention and 1 year later, 1900 members of three statutory sickness funds were asked about their treatment according to guidelines with (1) long-term aminosalicylates and (2) immunosuppressants, (3) whether they took long-term glucocorticoids for maintenance of remission, (4) if they smoked, in CD patients, and (5) about the surveillance colonoscopies, in UC patients., Results: Response rate after implementation was 20.1%. Responders differed between intervention and control region by age and by distribution between patients with UC or CD. After 1 year, more patients were treated according to clinical practice guidelines in the control region than in the intervention region. More patients in the intervention region took immunosuppressants after 1 year, and fewer had a surveillance colonoscopy. However, no before-after comparison was statistically significant., Conclusions: This implementation strategy of UC and CD guidelines did not result in a statistically significant effect. Future implementation of guidelines for inflammatory bowel disease might need thorough evaluation of barriers and the support of theory-based concepts.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.

The number of patients suffering from a sexually transmitted disease (STD) in Germany is rising steadily. Mostly MSM (men who have sex with men) are affected. We report the case of an HIV-positive patient with syphilis, in whom the implantation of permanent fillers into the buttocks and thighs, for cosmetic purposes, prevented standard therapy of syphilis by intramuscular penicillin administration. According to current guidelines intravenous ceftriaxone (2 g once daily) was administered instead.

Background: Prenatal and early postnatal exposures to environmental factors are considered responsible for the increasing prevalence of allergic diseases. Although there is some evidence for allergy-promoting effects in children because of exposure to plasticizers, such as phthalates, findings of previous studies are inconsistent and lack mechanistic information., Objective: We investigated the effect of maternal phthalate exposure on asthma development in subsequent generations and their underlying mechanisms, including epigenetic alterations., Methods: Phthalate metabolites were measured within the prospective mother-child cohort Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk (LINA) and correlated with asthma development in the children. A murine transgenerational asthma model was used to identify involved pathways., Results: In LINA maternal urinary concentrations of mono-n-butyl phthalate, a metabolite of butyl benzyl phthalate (BBP), were associated with an increased asthma risk in the children. Using a murine transgenerational asthma model, we demonstrate a direct effect of BBP on asthma severity in the offspring with a persistently increased airway inflammation up to the F2 generation. This disease-promoting effect was mediated by BBP-induced global DNA hypermethylation in CD4 + T cells of the offspring because treatment with a DNA-demethylating agent alleviated exacerbation of allergic airway inflammation. Thirteen transcriptionally downregulated genes linked to promoter or enhancer hypermethylation were identified. Among these, the GATA-3 repressor zinc finger protein 1 (Zfpm1) emerged as a potential mediator of the enhanced susceptibility for T H 2-driven allergic asthma., Conclusion: These data provide strong evidence that maternal BBP exposure increases the risk for allergic airway inflammation in the offspring by modulating the expression of genes involved in T H 2 differentiation through epigenetic alterations., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms (SNPs) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNPs in 219 case subjects and 262 controls from Finland. Association was particularly pronounced at 4 loci, all with genomewide significance (P < 5 × 10(-8) ): rs2187668 (PGWAS  = 1.4 × 10(-12) ), rs9267531 (PGWAS  = 4.7 × 10(-10) ), rs4410767 (PGWAS  = 1.0 × 10(-9) ) and rs3094084 (PGWAS  = 1.1 × 10(-9) ). All mentioned SNPs are located within the major histocompatibility complex (MHC) region of chromosome 6 and near genes of known immune functions or associations with other autoimmune diseases such as HLA-DQ alpha chain 1 (HLA-DQA1), MICA, MICB, MSH5, TRIM39 and RPP21. For example, TRIM39/RPP21 read through transcript is a known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genomewide analysis of disease association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLA-DQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39 and RPP21)., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Atypical fibroxanthoma is a rare mesenchymal tumor of the head and neck region., Methods: We analyzed the files of 3 large dermatology hospitals from the years 2001 to 2013 in southeast Germany., Results: We identified 53 patients (56 tumors) with a male predominance. The mean age was 78.0 years ± 8.3 years. Mohs surgery was performed in all cases resulting in complete remission in 45 patients. Five patients had a relapse within 2 years, and 4 developed metastases. None of the tumors with a safety margin of ≥2 cm relapsed. The majority of cases were found in the Dresden region., Conclusion: Atypical fibroxanthoma demonstrates an uneven geographic distribution in southeast Germany that demands further investigations. Mohs surgery with ≥2 cm safety margins is the treatment of choice. A regular follow-up is recommended., (© 2014 Wiley Periodicals, Inc.)

Background: The individual risk of recurrence in hormone receptor-positive primary breast cancer patients determines whether adjuvant endocrine therapy should be combined with chemotherapy. Clinicopathological parameters and molecular tests such as EndoPredict(®) (EPclin) can support decision making in patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative cancer., Objective: Using a life-long Markov state transition model, we determined the health economic impact and incremental cost effectiveness of EPclin-based risk stratification in combination with clinical guidelines [German-S3, National Comprehensive Cancer Center Network (NCCN), and St. Gallen] to decide on chemotherapy use., Methods: Information on overall and metastasis-free survival came from Austrian Breast & Colorectal Cancer Study Group clinical trials 6/8 (n = 1,619) and published literature. Effectiveness was assessed as quality-adjusted life-years (QALYs). Costs (2010) were assessed from a German third-party payer perspective., Results: Lifetime costs per patient ranged from 28,268 (St.Gallen and EPclin) to 33,756 (NCCN). Due to an imperfect prognostic value and differences in chemotherapy use, strategies achieved between 13.165 QALYs (NCCN) and 13.173 QALYs (EPclin alone) per patient. Using German-S3 as reference, three strategies showed dominant results (St. Gallen and EPclin, German-S3 and EPclin, EPclin alone). Compared to German-S3, the addition of EPclin saved 3,388 and gained 0.002 QALYs per patient. Combining guidelines with EPclin remained preferable in sensitivity analysis., Conclusion: Our study suggests that molecular markers can be sensibly combined with clinical guidelines to determine the risk profile of adjuvant breast cancer patients. Compared with the current German best practice (German-S3), combinations of EPclin with the St. Gallen, German-S3 or NCCN guideline and EPclin alone were dominant from the perspective of the German healthcare system.

Aim: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT)., Methods: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy., Results: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can determine the need for an immunosuppressive drug therapy or if a "watch and wait" approach is reasonable already early in the treatment course of UC., Conclusion: Using six simple clinical parameters, we can estimate the patients individual risk of developing a progressive disease course.

Background: As a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University., Methods: 240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method., Results: There was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students' self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students' DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies., Conclusions: Training ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.

Out of 302 AIDS-related lymphoma (ARL) patients enrolled in the German ARL cohort study, 18 patients had plasmablastic lymphoma (PBL). Twelve out of 18 patients (67%) have died with a median survival of 4 months (range 0-11 months). In univariate analysis, an intermediate or high international prognostic index score was associated with a significantly lower overall survival and progression-free survival. The predominant cause of death was progressive lymphoma (67%). Our data indicate that the outcome of AIDS-related PBL is still very poor.

Background: Chronic wounds are both time consuming as well as costly. A new therapeutic option for those wounds might be amelogenin, which supplies a temporary matrix to the fibroblasts and keratinocytes., Objective: To prove the hypotheses for a divergent therapeutic outcome, we treated granulated vs. sclerotic chronic venous leg ulcers with amelogenin (Xelma®) 1×/week for 5-8 weeks., Methods: The analysis of the treatment was performed by applying a recently published mathematical model. This model can predict and evaluate different wound treatment methods by treating only few patients which is even more practicable for diseases with different influencing factors within patients groups because it is easier to collect only a small homogenous number of patients than multiple., Results: We treated 12 granulated vs. 16 sclerotic ulcerations. 5 (42%) of the granulated ulcerations with a mean initial wound area of 18.3cm(2) showed optimal wound healing (>90% epithelization). The average area of new epithelia was 11.9cm(2). Nine (56%) of the sclerotic ulcerations showed optimal wound healing with an initial wound area of 7.5cm(2) and a total average area of 4.1cm(2) with new epithelia. For comparison of those groups, we extrapolate to a hypothetic mean sclerotic wound area of 18.3cm(2) analogue to the granulated ulcerations. This calculates to a mean neoepithel of only 6cm(2) for sclerotic ulcerations. Further on, we calculated about 2% of the wound area that proliferated in contrast to about 3% in granulated wounds., Conclusions: Although sclerotic ulcerations show higher growth rates, Xelma® seems to be more effective in granulated ulcerations. For larger sclerotic ulcerations the mean maximal covered wound area with neoepithelia is reduced to about 33% in contrast to 65% in granulated ulcerations., (Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)