[Evidence-based recommendations for diagnostics and treatment of gouty arthritis in the specialist sector : S2e guidelines of the German Society of Rheumatology in cooperation with the AWMF]. / Evidenzbasierte Empfehlung zur Diagnostik und Therapie der Gichtarthritis im fachärztlichen Sektor : S2e-Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh) in Kooperation mit der AWMF.

Due to the increasing prevalence of gout, particularly in old age, the disease is becoming of increasing importance in Germany. Gout is one of the most common forms of recurrent inflammatory arthritis and is induced by the deposition of monosodium urate crystals in synovial fluid and other tissues. The principal goals of therapy in chronic gout are the symptomatic treatment of the acute joint inflammation and the causal treatment of the underlying metabolic cause, the hyperuricemia. Only a consistent and permanent reduction of the serum uric acid level ultimately results in an efficient avoidance of further gout attacks and therefore the prevention of structural damage. Due to an often inadequate treatment of gout, the target of healing the disease is often not achieved. A correct and timely diagnosis and adequate assessment of comorbidities associated with gout are, however, of substantial importance for patient and physician to achieve remission of the disease. In order to create a solid basis for a timely and effective treatment of affected patients, in 2016 the German Society of Rheumatology (DGRh) initiated the development of S2e guidelines on gouty arthritis for specialists. This article summarizes these S2e guidelines on the management of gouty arthritis in the specialist sector.

[Outcome Quality in Medical Rehabilitation: Relationship Between "Patient-Reported Outcomes" (PROs) and Social Security Contributions]. / Ergebnisqualität medizinischer Rehabilitation: Zum Zusammenhang zwischen "Patient Reported Outcomes" (PROs) und geleisteten Sozialversicherungsbeiträgen.

Aim of the Study The outcome quality of medical rehabilitation is evaluated often by "Patient Reported Outcomes" (PROs). It is examined to what extent these PROs are corresponding with "hard" or "objective" outcomes such as payments of contributions to social insurance. Methods The "rehabilitation QM outcome study" includes self-reports of patients as well as data from the Rehabilitation Statistics Database (RSD) of the German pension insurance Baden-Wurttemberg. The sample for the question posed includes N=2 947 insured who were treated in 2011 in 21 clinics of the "health quality network" and who were either employed or unemployed at the time of the rehabilitation application (e. g. the workforce or labour force group, response rate: 55%). The sample turned out widely representative for the population of the insured persons. Results PROs and payment of contributions to pension insurance clearly correspond. In the year after the rehabilitation improved vs. not improved rehabilitees differed clearly with regard to their payments of contributions. Conclusions The results support the validity of PROs. For a comprehensive depiction of the outcome quality of rehabilitation PROs and payments of contributions should be considered supplementary.

[Hyperuricemia. When and how to treat?]. / Hyperurikämie. Wann und wie behandeln?

The prevalence of (asymptomatic) hyperuricemia and gout has substantially increased in recent decades. This development is due to fundamental lifestyle changes, dramatically rising prevalence of obesity and metabolic syndrome, as well as the increasing age of patients. Therefore, medical treatment of hyperuricemia has regained interest in recent years, in particular since after decades of therapeutic stagnation, new treatments of hyperuricemia have been approved or are currently being investigated in clinical trials. European and American guidelines/recommendations for treatment of hyperuricemia and gout have been updated and revised. Furthermore, the role of asymptomatic hyperuricemia as an (independent) cardiovascular risk factor is again under debate. This article provides assistance in integrating our present knowledge in a therapeutic context and summarizes currently recommended treatment strategies.

[Financial incentives on weight loss after rehabilitation]. / Finanzielle Anreize zur Gewichtsreduktion nach stationärer Rehabilitation.

INTRODUCTION: Increasing rates of obesity and associated diseases and their consequences make the implementation of preventive and counteracting measures necessary. The aim of this study was the examination of the long-term effects of financial incentives on weight loss in obese patients and the identification of influencing factors. METHODS: 700 obese patients were randomly assigned to one of three study conditions: For reaching a pre-defined target weight within 4 months they were rewarded with Euro 150, Euro 300 or not at all. The effect of the incentives on weight loss in different subgroups was compared. After 18 months, other possible influences on weight loss were analyzed by comparing responders and non-responders. RESULTS: Financial rewards led to significant weight loss in all subgroups, whereupon the height of the incentive only mattered in some. After 22 months, for several subgroups, the incentive's effect was still visible. Furthermore, responders showed more healthy behaviour, were better informed and reported more social support. CONCLUSION: Especially for patient groups who do not lose weight in orthodox treatments alone, financial incentives can be an effective supplement. In addition it became clear that this kind of reward programme can be implemented area-wide.

[Metabolic bone disease osteomalacia]. / Metabolische Knochenkrankheit Osteomalazie.

Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

[Is vocational reintegration of young cancer patients possible?]. / Lassen sich junge Tumorpatienten beruflich reintegrieren?

BACKGROUND: Besides an improvement in quality of life, one of the major targets of rehabilitation programmes is to preserve the ability to work and to integrate the patient into working life again. Cancer in particular is often associated with a loss of employment and joblessness, frequently caused by incomplete rehabilitation. METHODS: The programme is aimed at young cancer patients aged between 18 and 40 years. In addition to medical rehabilitation, they undergo a specially developed programme which they complete in groups of no more than 5 persons. At baseline and at the end of the 3 weeks rehabilitation, tests on physical and mental capacity are conducted. During rehabilitation, different training programmes concerning mobility at work, fine motor skills and cognitive abilities are held, complemented by an intensive psycho-social training programme. Additionally, patients receive individual social counselling. RESULTS: So far, 34 patients with an average age of 31.8 years have participated in the programme, 65% of them suffering from malignant haematological diseases. The combination of a medical and a vocational rehabilitation programme was judged extremely positively by the participants, which remained the case 6 months after completion of the programme. The rehabilitation programme significantly reduced work incapacity periods: at baseline, only 6% of the participants had not experienced such periods, but after 3 and 6 months, this rate had increased to 61% and 62% respectively. This was accompanied by an increased health-related quality of life and reduced fatigue. CONCLUSION: With our pilot project we were able to show that such a programme is feasible, can be well integrated into clinical routine and is successful.

Prevalence of osteoporosis among cancer patients in Germany: prospective data from an oncological rehabilitation clinic.

UNLABELLED: In this prospective study, we measured bone mineral density (BMD) in 1,041 cancer patients undergoing an oncological rehabilitation program in an inpatient rehabilitation clinic. There was an osteoporosis prevalence of approximately 16%, independent of sex, which is considerably higher than in the community-dwelling population. INTRODUCTION: There is evidence that cancer patients are at risk of an increased BMD-loss following the disease and its therapy. Nevertheless, there is only little data available about the prevalence of osteoporosis in German cancer patients. Therefore, we measured BMD in 1,041 oncological inpatients undergoing rehabilitation. METHODS: From February 2006 to September 2009, BMD was measured in oncological patients with dual-energy x-ray absorptiometry (DXA; femur and spine). Statistical analysis for prevalence of osteoporosis was done in descriptive manner calculating means, standard deviation, frequencies, and 95% confidence intervals. To compare the prevalence of osteoporosis in different subgroups, χ (2) tests were done with p < 0.05. To create a risk profile, odds ratios were calculated using uni- and multivariate logistic regression. RESULTS: In 1,041 patients with a mean age of 57.1 years (11.0 years), DXA-measures were performed. Of them, 22% were male and 78% were female. The osteoporosis prevalence was about 16% (13.8, 18.2), independent of sex (p = 0.9722) or cancer type (p = 0.7174). As risk factors influencing the development of osteoporosis, age, weight, menopausal state, and hormone replacement therapy were identified in women and weight only in men. CONCLUSIONS: Compared to the general population, the rate of osteoporosis is distinctly elevated in German cancer patients independent of sex or cancer type. Hence, a general recommendation for a DXA screening in these patients appears to be justified.

[Hemato-oncological diseases. Associated rheumatic symptoms]. / Hämatologisch-onkologische Erkrankungen. Assoziierte rheumatische Symptome.

Paraneoplastic syndromes are observed in up to 8% of tumor patients. These disorders arise from tumor secretion of hormones, peptides, growth factors or cytokines or from immune cross-reactivity between malignant and normal tissues. Among many others paraneoplastic syndromes may also affect the rheumatologic system resulting in various musculoskeletal symptoms and/or syndromes. On the other hand, mainly hematological or lymphoproliferative diseases may also cause rheumatic symptoms by cell invasion or when affecting cellular elements of blood or the coagulation system. The aim of this article is to provide an overview of the various associations between rheumatic symptoms and hemato-oncological diseases which might be of importance in clinical practice.

[Vocational interventions integrated in inpatient rehabilitation]. / Medizinisch-berufliche Interventionen in der stationären orthopädischen Rehabilitation. Explorative Evaluation eines Pilot-projektes aus Patientensicht.

Orientation on work place associated problems is a typical assignment of medical rehabilitation in Germany. The implementation of special vocational programmes, however, may be associated with several challenges concerning staff and space required, which could be difficult to overcome.

E-cadherin is functionally involved in the maturation of the erythroid lineage.

Differentiation and proliferation of hematopoietic progenitors take place in the bone marrow and is a tightly controlled process. Cell adhesion molecules of the integrin and immunoglobulin families have been shown to be involved in these processes, but almost nothing was known about the involvement of the cadherin family in the hematopoietic system. A PCR screening of RNA of human bone marrow mononuclear cells with specific primers for classical cadherins revealed that E-cadherin, which is mainly expressed by cells of epithelial origin, is also expressed by bone marrow cells. Western blot analysis and immunofluorescence staining of bone marrow sections confirmed this unexpected finding. A more detailed analysis using immunoaffinity columns and dual color flow cytometry showed that the expression of E-cadherin is restricted to defined maturation stages of the erythropoietic lineage. Erythroblasts and normoblasts express E-cadherin, mature erythrocytes do not. A functional role of E-cadherin in the differentiation process of the erythroid lineage was indicated by antibody-inhibition studies. The addition of anti-E-cadherin antibody to bone marrow mononuclear cultures containing exogeneous erythropoietin drastically diminished the formation of erythropoietic cells. These data suggest a non-anticipated expression and function of E-cadherin in one defined hematopoietic cell lineage.

Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group.

PURPOSE: To compare mantle-cell lymphomas (MCLs) and follicle-center lymphomas (FCLs) for their features of clinical presentation, response to chemotherapy, and prognosis on the basis of a prospective randomized clinical trial. PATIENTS AND METHODS: Patients with MCL and FCL who entered onto the prospective randomized comparison of cyclophosphamide, vincristine, and prednisone (COP) versus prednimustine and mitoxantrone (PmM) followed by a second randomization for interferon (IFN) maintenance versus observation only. RESULTS: One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL. With FCL, both sexes were equally affected (men, 47%); patients with MCL were predominantly men (78%; P < .0004) and had a higher median age (64 v 53 years; P < .0001). Patients with MCL also had more widespread disease, reflected by the proportion of patients with two or greater extranodal manifestations (43% v 21%; P < .005) and nine or greater involved nodal areas (64% v 45%; nonsignificant [NS]). Response to chemotherapy was significantly lower in patients with MCL (complete remission [CR] + partial remission [PR], 69% v 88%; P < .05) and occurred at a slower pace. Patients with MCL also had a shorter event-free interval (median, 8 v 24 months; P < .0001) and overall survival (median, 28 v 77 months; P < .0001). In both subtypes, however, patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60% for MCL and greater than 75% for FCL. CONCLUSION: MCL and FCL differ substantially in their features of presentation, response to chemotherapy, and long-term prognosis. The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies.

AML: immunophenotypic heterogeneity and prognostic significance of c-kit expression.

Antigenic profiles in AML that have generally accepted prognostic significance, and allow treatment stratification, have not yet been defined. In a previous report of Ashman et al., the proto-oncogene c-kit defined by binding of the moab YB5.B8 was expressed on about one third of AML cases, mainly of the undifferentiated FAB-subtypes and associated with poor prognosis and overall survival. In this study, the moab 17F11 also directed against the c-kit structure stained 41/47 AML and 6/8 CML blast specimens, whereas all investigated 40 ALL samples were c-kit negative. c-kit was not restricted to any particular, undifferentiated FAB-subtype, but found in 9/9 AML-M0/M1, 18/19 AML-M2, 0/1 AML-M3, 11/13 AML-M4 and 3/5 AML-M5 subtypes. Immunophenotypical analysis showed no restriction of c-kit expression to immature, CD34+ precursors, but c-kit was also expressed on CD4+ CD34- precursor cells differentiating towards the monocyte lineage. In addition, multi-color labelings revealed an extraordinary heterogeneity of concomitant antigen expression on c-kit+ cells 10/36 c-kit+ CD34+ samples expressing CD56 and 16/36 c-kit+ CD34+ samples being CD7 positive; two c-kit+ CD34+ specimens carried the B-cell antigen CD19. In correlation to clinical outcome c-kit expression as single parameter was not predictive for poor response to therapy and short survival as previously suggested.

Differential expression of adhesion molecules in acute leukemia.

Interactions between hematopoietic cells and the stromal microenvironment are mediated by membrane-bound adhesion molecules. As the expression patterns of these molecules may alter the adhesive qualities of leukemic blasts, leukemic samples were investigated for the expression of beta 1-, beta 2-, beta 3-integrins, CD44, the three selectins and several members of the immunoglobulin family. CD44 (167/169), LFA-3 (158/169), the beta 1-integrins VLA-4 (120/123) and VLA-5 (45/51) and the beta 2-integrin LFA-1 (149/157) were found on > 70% of blasts in most cases of leukemias. Other molecules were restricted to specific differentiation stages and lineage. The beta 2-integrins Mac-1 (CD11b/CD18) and gp 150,95 (CD11c/CD18) were preferentially expressed on M4 and M5 subtypes, and NCAM (CD56) was only found on a subset of acute myeloid leukemias (17/113). Unexpectedly, the beta 1-integrins VLA-1 (1/51), VLA-2 (18/123), VLA-3 (5/43), VLA-6 (15/29) and the E-selectin (2/47) were expressed on > 70% blasts on a subset of leukemias of varied phenotype. These molecules were absent on normal CD34+ bone marrow precursors. The simultaneous analysis generally revealed a higher percentage of positive blasts in the blood than in bone marrow. Our observations therefore suggest that in leukemia these antigens are displayed on a non-adherent population that is defective and is unable to convert to an adherent, functionally active conformational state.

Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. German Low-Grade Lymphoma Study Group.

The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) in patients with advanced low-grade non-Hodgkin's lymphomas in way of a prospective randomized multicenter trial. Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic (CB-CC (Kiel-classification)) or follicle center lymphoma (FCL (REAL classification)) and centrocytic (CC) or mantle-cell-lymphoma (MCL) were randomized for therapy with either PmM or COP and are fully evaluable for response and toxicity. PmM consisted of prednimustine 100 mg/m2/day on days 1-5 and mitoxantrone 8 mg/m2 /day days 1 and 2, while COP comprised cyclophosphamide 400 mg/m2/day on days 1-5, vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1-5. Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second randomization for interferon alpha maintenance vs observation only. Overall response rates were comparable with 83% complete and partial remissions after COP and 84% remissions after PmM. PmM revealed a significantly higher rate of complete remissions (36 vs 18%, P < 0.006), the majority being achieved after four courses. The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM resulted in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months, respectively (P=0.04). Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL (16 vs 30%, P=0.12, NS) while overall response rates were in a similar range (81 vs 85%). In both subtypes, PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP. Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP (43 vs 31 %, P < 0.0001). This difference was clinically irrelevant, however, since serious infectious complications were encountered in less than 3% of cycles after both regimens. COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia (31 vs 2%) as well as of peripheral neurotoxicity (23 vs 2%). These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin's lymphoma. PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects. A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha.

Granulocyte colony-stimulating factor treatment of leucopenia during fractionated radiotherapy.

11 patients suffering from an isolated leucopenia during fractionated radiotherapy were treated with granulocyte colony stimulating factor (G-CSF). 4 of the patients received radiotherapy alone, and 7 patients received concomitant chemotherapy. G-CSF treatment was initiated at the occurrence of leucopenia and maintained for the duration of radiotherapy. The applied daily dose was 5 micrograms/kg subcutaneously. 10 of the 11 treated patients reacted with an increased leucocyte count, from an average of 1342 leucocytes per microliter (+/- 502/microliters) to 24,568 leucocytes per microliter (+/- 950/microliters). Neutrophil counts increased on average from 64.9% (+/- 13.9%) to 91.1% (+/- 2.3%) (n = 7). In 1 patient thrombocytopenia occurred during the continued radiotherapy. 1 other patient reacted with an unexplained fall of leucocytes after two doses of G-CSF and one fraction of mediastinal irradiation. Side-effects observed during G-CSF treatment consisted of mild bone pain (1/11) and transient increases of serum alkaline phosphatase levels (4/11). Our observations indicate that G-CSF treatment is well tolerated during continuous fractionated radiotherapy. Therefore, we conclude that G-CSF can be used clinically to alleviate neutropenia caused by radiotherapy or by combined radio-chemotherapy.

Treatment of steroid-resistant graft-versus-host disease after allogeneic bone marrow transplantation with anti-CD3/TCR monoclonal antibodies.

Acute graft-versus host disease (GVHD), one of the major complications of allogeneic bone marrow transplantation (BMT), occurs in 30-50% of all patients transplanted from HLA-identical sibling donors and in 50-80% of all patients transplanted from an unrelated or HLA-mismatched family donor, despite GVHD prophylaxis with methotrexate and cyclosporin. We report our experience with OKT3/BMA031 treatment in 14 patients with severe steroid-resistant GVHD following allogeneic BMT. Three of 5 patients treated in the early post-transplant period with OKT3 remitted and 2 of 3 became long-term survivors. Two patients treated for extensive chronic GVHD showed only minor responses. Five of 7 patients treated with BMA031 showed a partial remission; no complete remission was seen after treatment with this antibody. Shortly after the introduction of OKT3 or BMA031 therapy a rapid decline of the lymphocyte count, especially the CD3+ subset, was observed coinciding with a relative increase of CD56+ lymphocytes and of gamma/delta TCR+ T cells. Increasing numbers of CD3+ lymphocytes preceded recurrence of acute GVHD in three patients. In contrast, persisting CD3-lymphocytopenia was associated with complete clearance of acute GVHD. The incidence of infectious complications following OKT3 or BMA031 therapy was high (42%). Thus, to improve treatment results of severe acute GVHD, prophylactic or pre-emptive strategies are required to reduce the rate of fatal viral and fungal infections.

The possible role of G-CSF in the pathogenesis of Sweet's syndrome.

Sweet's syndrome (SS) is characterized by the clinical features of fever, leucocytosis, neutrophilia and the sudden onset of asymmetric, often very painful skin lesions and dense dermal infiltrates of mature neutrophils without signs of vasculitis. Apart from idiopathic cases the disease is frequently associated with hematological malignancies, but it may also be observed in patients with solid tumors, mainly tumors of the genito-urinary tract. In the past, numerous theories have been proposed to explain the pathogenesis of this rare disease. SS has been interpreted as a direct response to mechanical and chemical irritants, an infectious disease or a disorder of neutrophilic chemotaxis and/or phagocytosis, but most often it has been described as a hypersensitivity reaction. Each of these theories can account for particular symptoms, but none of them reconciles the dominating clinical and laboratory features of the disease. Furthermore recently published casuistic observations suggest the involvement of certain cytokines in particular G-CSF and Il-6 in the pathogenesis of the disease, which might explain many of the observed clinical and laboratory findings. The following article summarizes these data and gives a review of the current literature.

[Rapidly progressing renal insufficiency as the primary manifestation of systemic sarcoidosis]. / Rasch progrediente Niereninsuffizienz als Primärmanifestation einer systemischen Sarkoidose.

CASE REPORT: We report the history of a 67-year-old patient who was admitted to hospital because of rapidly progressive renal insufficiency. The renal biopsy revealed granulomatous interstitial nephritis. The diagnosis of systemic sarcoidosis was confirmed by typical findings of bronchoalveolar lavage and of transbronchial, liver and bone marrow biopsy. Indications for sarcoidosis-related nephrocalcinosis/nephrolithiasis or glomerulonephritis were absent. Simultaneously a monoclonal gammopathy of unknown significance (MGUS) was diagnosed. While the patient having been uremic at the time of diagnosis, the administration of prednisolone effectively improved renal function. CONCLUSIONS: As a rare manifestation of sarcoidosis granulomatous interstitial nephritis can cause rapidly progressive renal insufficiency, which can effectively be treated by steroids, if distinct interstitial fibrosis is absent.

[Innovative individualized rehabilitation concepts in oncology]. / Innovative individualisierte Rehabilitationskonzepte in der Onkologie.

Die onkologische Rehabilitation zielt auf die Verbesserung der körperlichen, psychischen und sozialen Fähigkeiten und Unterstützung bei der Bewältigung der Krankheit ("Coping") ab. Ein wichtiges Ziel ist dabei neben der psycho-onkologischen Therapie die Steigerung der körperlichen Aktivität zur Prävention und Therapie chronischer Krankheiten, insbesondere auch der mit steigender Überlebensrate an Bedeutung zunehmenden Folge- und Begleiterkrankungen. Immer mehr Beobachtungsstudien weisen außerdem darauf, dass körperliche Aktivität auch die Prognose der Krebserkrankung günstig beeinflussen kann. Die beste Evidenz besteht dabei bislang für das (Hormonrezeptor-positive) postmenopausale Mamma-Karzinom. Eine nachhaltige Lebensstilmodifikation ist bislang oft nur schwer erreichbar. Langfristig angelegte, interdisziplinäre Rehabilitationskonzepte, deren Ziel eine intensive und nachhaltige Steigerung der körperlichen Aktivität ist, scheinen bei Brustkrebspatientinnen ein erfolgversprechender Ansatz zu sein und werden durch das hier vorgestellte Studienkonzept exemplarisch erläutert.