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Eating Behaviour in the General Population: An Analysis of the Factor Structure of the German Version of the Three-Factor-Eating-Questionnaire (TFEQ) and Its Association with the Body Mass Index.
LIFE Adult

Abstract (Expand)

The Three-Factor-Eating-Questionnaire (TFEQ) is an established instrument to assess eating behaviour. Analysis of the TFEQ-factor structure was based on selected, convenient and clinical samples so … far. Aims of this study were (I) to analyse the factor structure of the German version of the TFEQ and (II)--based on the refined factor structure--to examine the association between eating behaviour and the body mass index (BMI) in a general population sample of 3,144 middle-aged and older participants (40-79 years) of the ongoing population based cohort study of the Leipzig Research Center for Civilization Diseases (LIFE Health Study). The factor structure was examined in a split-half analysis with both explorative and confirmatory factor analysis. Associations between TFEQ-scores and BMI values were tested with multiple regression analyses controlled for age, gender, and education. We found a three factor solution for the TFEQ with an 'uncontrolled eating', a 'cognitive restraint' and an 'emotional eating' domain including 29 of the original 51 TFEQ-items. Scores of the 'uncontrolled eating domain' showed the strongest correlation with BMI values (partial r = 0.26). Subjects with scores above the median in both 'uncontrolled eating' and 'emotional eating' showed the highest BMI values (mean = 29.41 kg/m(2)), subjects with scores below the median in all three domains showed the lowest BMI values (mean = 25.68 kg/m(2); F = 72.074, p<0.001). Our findings suggest that the TFEQ is suitable to identify subjects with specific patterns of eating behaviour that are associated with higher BMI values. Such information may help health care professionals to develop and implement more tailored interventions for overweight and obese individuals.

Authors: A. Loffler, T. Luck, F. S. Then, C. Sikorski, P. Kovacs, Y. Bottcher, J. Breitfeld, A. Tonjes, A. Horstmann, M. Loffler, C. Engel, J. Thiery, A. Villringer, M. Stumvoll, S. G. Riedel-Heller

Date Published: 1st Aug 2015

Publication Type: Not specified

Economic modeling of risk-adapted screen-and-treat strategies in women at high risk for breast or ovarian cancer
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The ’German Consortium for Hereditary Breast and Ovarian Cancer’ (GC-HBOC) offers women with a family history of breast and ovarian cancer genetic counseling. The aim of this modeling study …y was to evaluate the cost-effectiveness of genetic testing for BRCA 1/2 in women with a high familial risk followed by different preventive interventions (intensified surveillance, risk-reducing bilateral mastectomy, risk-reducing bilateral salpingo-oophorectomy, or both mastectomy and salpingo-oophorectomy) compared to no genetic test. METHODS A Markov model with a lifelong time horizon was developed for a cohort of 35-year-old women with a BRCA 1/2 mutation probability of ≥ 10%. The perspective of the German statutory health insurance (SHI) was adopted. The model included the health states ’well’ (women with increased risk), ’breast cancer without metastases’, ’breast cancer with metastases’, ’ovarian cancer’, ’death’, and two post (non-metastatic) breast or ovarian cancer states. Outcomes were costs, quality of life years gained (QALYs) and life years gained (LYG). Important data used for the model were obtained from 4380 women enrolled in the GC-HBOC. RESULTS Compared with the no test strategy, genetic testing with subsequent surgical and non-surgical treatment options provided to women with deleterious BRCA 1 or 2 mutations resulted in additional costs of \text€7256 and additional QALYs of 0,43 (incremental cost-effectiveness ratio of \text€17,027 per QALY; cost per LYG: \text€22,318). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSION The provision of genetic testing to high-risk women with a BRCA1 and two mutation probability of ≥ 10% based on the individual family cancer history appears to be a cost-effective option for the SHI.

Authors: Dirk Müller, Marion Danner, Rita Schmutzler, Christoph Engel, Kirsten Wassermann, Björn Stollenwerk, Stephanie Stock, Kerstin Rhiem

Date Published: 1st Jul 2019

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Editorial: networking clinical research
Management of health information systems

Abstract

Not specified

Authors: M. Loeffler, Alfred Winter

Date Published: 2007

Publication Type: Journal article

Education as protector against dementia, but what exactly do we mean by education?
LIFE Adult

Abstract (Expand)

OBJECTIVES: even though a great number of research studies have shown that high education has protective effects against dementia, some studies did not observe such a significant effect. In that respect, … the aim of our study was to investigate and compare various operationalisation approaches of education and how they impact dementia risk within one sample. METHODS: data were derived from the Leipzig longitudinal study of the aged (LEILA75+). Individuals aged 75 and older underwent six cognitive assessments at an interval of 1.5 years and a final follow-up 15 years after the baseline assessment. We operationalised education according to different approaches used in previous studies and analysed the impact on dementia incidence via multivariate cox regression modelling. RESULTS: the results showed that whether education is identified as significant protector against dementia strongly depends on the operationalisation of education. Whereas the pure number of years of education showed statistically significant protective effects on dementia risk, other more complex categorical classification approaches did not. Moreover, completing >10 years of education or a tertiary level seems to be an important threshold to significantly reduce dementia risk. CONCLUSION: findings suggest a protective effect of more years of education on a lower dementia risk with a particular critical threshold of completing >10 years of education. Further, the findings highlight that, when examining risks and protective factors of dementia, a careful consideration of the underlying definitions and operationalisation approaches is required.

Authors: F. S. Then, T. Luck, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 9th Apr 2016

Publication Type: Journal article

Human Diseases: dementia

Effectiveness of cytopenia prophylaxis for different filgrastim and pegfilgrastim schedules in a chemotherapy mouse model
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVES Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to treat neutropenia during cytotoxic chemotherapy. The optimal scheduling of rhG-CSF is unknown and can …n hardly be tested in clinical studies due to numerous therapy parameters affecting outcome (chemotherapeutic regimen, rhG-CSF schedules, individual covariables). Motivated by biomathematical model simulations, we aim to investigate different rhG-CSF schedules in a preclinical chemotherapy mouse model. METHODS The time course of hematotoxicity was studied in CD-1 mice after cyclophosphamide (CP) administration. Filgrastim was applied concomitantly in a 2 x 3-factorial design of two dosing options (2 x 20 mug and 4 x 10 mug) and three timing options (directly, one, and two days after CP). Alternatively, a single dose of 40 mug pegfilgrastim was applied at the three timing options. The resulting cytopenia was compared among the schedules. RESULTS Dosing and timing had a significant influence on the effectiveness of filgrastim schedules whereas for pegfilgrastim the timing effect was irrelevant. The best filgrastim and pegfilgrastim schedules exhibited equivalent toxicity. Monocytes dynamics performed analogously to granulocytes. All schedules showed roughly the same lymphotoxicity. CONCLUSION We conclude that effectiveness of filgrastim application depends heavily on its scheduling during chemotherapy. There is an optimum of timing. Dose splitting is better than concentrated applications. Effectiveness of pegfilgrastim is less dependent on timing. OBJECTIVES Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used to treat neutropenia during cytotoxic chemotherapy. The optimal scheduling of rhG-CSF is unknown and can hardly be tested in clinical studies due to numerous therapy parameters affecting outcome (chemotherapeutic regimen, rhG-CSF schedules, individual covariables). Motivated by biomathematical model simulations, we aim to investigate different rhG-CSF schedules in a preclinical chemotherapy mouse model. METHODS The time course of hematotoxicity was studied in CD-1 mice after cyclophosphamide (CP) administration. Filgrastim was applied concomitantly in a 2 x 3-factorial design of two dosing options (2 x 20 mug and 4 x 10 mug) and three timing options (directly, one, and two days after CP). Alternatively, a single dose of 40 mug pegfilgrastim was applied at the three timing options. The resulting cytopenia was compared among the schedules. RESULTS Dosing and timing had a significant influence on the effectiveness of filgrastim schedules whereas for pegfilgrastim the timing effect was irrelevant. The best filgrastim and pegfilgrastim schedules exhibited equivalent toxicity. Monocytes dynamics performed analogously to granulocytes. All schedules showed roughly the same lymphotoxicity. CONCLUSION We conclude that effectiveness of filgrastim application depends heavily on its scheduling during chemotherapy. There is an optimum of timing. Dose splitting is better than concentrated applications. Effectiveness of pegfilgrastim is less dependent on timing.

Authors: Markus Scholz, Manuela Ackermann, Frank Emmrich, Markus Loeffler, Manja Kamprad

Date Published: 2009

Publication Type: Journal article

Effectiveness of different central venous catheter fixation suture techniques: An in vitro crossover study
Genetical Statistics and Systems Biology

Abstract (Expand)

PURPOSE Proper fixation of central venous catheters (CVCs) is an integral part of safety to avoid dislodgement and malfunction. However, the effectiveness of different CVC securement sutures is unknown. …. METHODS Analysis of maximum dislodgement forces for CVCs from three different manufacturers using four different suture techniques in an in vitro tensile loading experiment: 1. \textquotedblclamp only\textquotedbl, 2. \textquotedblclamp and compression suture\textquotedbl, 3. \textquotedblfinger trap\textquotedbl and 4. \textquotedblcomplete\textquotedbl, i.e., \textquotedblclamp + compression suture + finger trap\textquotedbl. Twenty-five tests were performed for each of the three CVC models and four securement suture techniques (n = 300 test runs). RESULTS The primary cause of catheter dislodgement was sliding through the clamp in techniques 1 and 2. In contrast, rupture of the suture was the predominant cause for dislodgement in techniques 2 and 3. Median (IQR 25-75%) dislodgement forces were 26.0 (16.6) N in technique 1, 26.5 (18.8) N in technique 2, 76.7 (18.7) N in technique 3, and 84.8 (11.8) N in technique 4. Post-hoc analysis demonstrated significant differences (P < .001) between all pairwise combinations of techniques except technique 1 vs. 2 (P = .98). CONCLUSIONS \textquotedblFinger trap\textquotedbl fixation at the segmentation site considerably increases forces required for dislodgement compared to clamp-based approaches.

Authors: Manuel Florian Struck, Lars Friedrich, Stefan Schleifenbaum, Holger Kirsten, Wolfram Schummer, Bernd E. Winkler

Date Published: 12th Sep 2019

Publication Type: Journal article

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial
SepNet - German Competence Network Sepsis

Abstract (Expand)

PURPOSE Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether …r survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. METHODS The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. RESULTS The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. CONCLUSIONS Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

Authors: Frank Bloos, Hendrik Rüddel, Daniel Thomas-Rüddel, Daniel Schwarzkopf, Christine Pausch, Stephan Harbarth, Torsten Schreiber, Matthias Gründling, John Marshall, Philipp Simon, Mitchell M. Levy, Manfred Weiss, Andreas Weyland, Herwig Gerlach, Tobias Schürholz, Christoph Engel, Claudia Matthäus-Krämer, Christian Scheer, Friedhelm Bach, Reimer Riessen, Bernhard Poidinger, Karin Dey, Norbert Weiler, Andreas Meier-Hellmann, Helene H. Häberle, Gabriele Wöbker, Udo X. Kaisers, Konrad Reinhart

Date Published: 1st Nov 2017

Publication Type: Journal article

Human Diseases: disease by infectious agent

Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial.
SepNet - German Competence Network Sepsis

Abstract (Expand)

CONTEXT: Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different … mechanisms remains controversial. OBJECTIVE: To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. DESIGN, SETTING, AND PATIENTS: A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. INTERVENTIONS: Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. MAIN OUTCOME MEASURE: Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. RESULTS: Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43). CONCLUSION: Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00534287.

Authors: F. M. Brunkhorst, M. Oppert, G. Marx, F. Bloos, K. Ludewig, C. Putensen, A. Nierhaus, U. Jaschinski, A. Meier-Hellmann, A. Weyland, M. Grundling, O. Moerer, R. Riessen, A. Seibel, M. Ragaller, M. W. Buchler, S. John, F. Bach, C. Spies, L. Reill, H. Fritz, M. Kiehntopf, E. Kuhnt, H. Bogatsch, C. Engel, M. Loeffler, M. H. Kollef, K. Reinhart, T. Welte

Date Published: 13th Jun 2012

Publication Type: Not specified

Human Diseases: bacterial infectious disease

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.
SepNet - German Competence Network Sepsis

Abstract (Expand)

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock … remains controversial. Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT00670254.

Authors: D. Keh, E. Trips, G. Marx, S. P. Wirtz, E. Abduljawwad, S. Bercker, H. Bogatsch, J. Briegel, C. Engel, H. Gerlach, A. Goldmann, S. O. Kuhn, L. Huter, A. Meier-Hellmann, A. Nierhaus, S. Kluge, J. Lehmke, M. Loeffler, M. Oppert, K. Resener, D. Schadler, T. Schuerholz, P. Simon, N. Weiler, A. Weyland, K. Reinhart, F. M. Brunkhorst

Date Published: 1st Nov 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

Effect of interleukin-10 gene polymorphisms on clinical outcome of patients with aggressive non-Hodgkin's lymphoma: an exploratory study.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: Current chemotherapy can achieve high response rates in aggressive non-Hodgkin's lymphoma (NHL), but the factors that influence regression and survival remain unknown. The present exploratory … study tested the hypothesis whether interleukin-10 (IL-10) polymorphisms predict clinical outcome, leukocytopenia, or infectivity during therapy. IL-10 was chosen because immune alterations are a major risk factor for NHL, and IL-10 is a cytokine involved in inflammatory processes associated with clinical outcome. EXPERIMENTAL DESIGN: Five hundred patients with aggressive NHL treated with CHOP/CHOEP were analyzed for IL-10 gene polymorphisms, including distal loci -7400InDel, -6752AT (rs6676671), and -6208CG (rs10494879) in comparison with proximal loci -3538AT (rs1800890), -1087AG (rs1800896), and -597AC (rs1800872) according to the incidence and outcome of the lymphoma. RESULTS: No differences in allele frequencies or haplotypes were found comparing a cohort of patients with aggressive NHL/diffuse large B-cell lymphoma with a healthy control group. Patients with aggressive NHL characterized by IL-10(-7400DelDel) had shorter overall survival periods compared with the other genotypes (P = 0.004). The 3-year rate is 43.4% for IL-10(-7400DelDel) and 73.4% for IL-10(-7400InIn) and IL-10(-7400InDel) together. A significant increased risk for event-free survival is found for carriers of the genotype IL-10(-6752TT-6208CC-3538AA) (P = 0.047). Multivariate analysis of IL-10(-7400) gene variation in relation to overall survival adjusted to international prognostic index revealed a relative risk of 1.9 for carriers of IL-10(-7400DelDel) (P = 0.037). No associations were found analyzing diffuse large B-cell lymphoma patients separately. CONCLUSION: Our results indicate that IL-10 gene variations could be associated to the clinical course of aggressive NHL, which points out the importance of host factors and respective genetic elements for treatment response.

Authors: D. Kube, T. D. Hua, F. von Bonin, N. Schoof, S. Zeynalova, M. Kloss, D. Gocht, B. Potthoff, M. Tzvetkov, J. Brockmoller, M. Loffler, M. Pfreundschuh, L. Trumper

Date Published: 15th Jun 2008

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial.
SepNet - German Competence Network Sepsis

Abstract (Expand)

IMPORTANCE: High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten … the diagnosis of sepsis, but effect on outcome is unclear. OBJECTIVE: To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. DESIGN, SETTING, AND PARTICIPANTS: The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 x 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. INTERVENTIONS: Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 microg, followed by a continuous intravenous infusion of sodium selenite, 1000 microg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. MAIN OUTCOMES AND MEASURES: The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. RESULTS: Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure. CONCLUSIONS AND RELEVANCE: Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00832039.

Authors: F. Bloos, E. Trips, A. Nierhaus, J. Briegel, D. K. Heyland, U. Jaschinski, O. Moerer, A. Weyland, G. Marx, M. Grundling, S. Kluge, I. Kaufmann, K. Ott, M. Quintel, F. Jelschen, P. Meybohm, S. Rademacher, A. Meier-Hellmann, S. Utzolino, U. X. Kaisers, C. Putensen, G. Elke, M. Ragaller, H. Gerlach, K. Ludewig, M. Kiehntopf, H. Bogatsch, C. Engel, F. M. Brunkhorst, M. Loeffler, K. Reinhart

Date Published: 1st Sep 2016

Publication Type: Journal article

Human Diseases: disease by infectious agent

Effect size estimates from umbrella designs: Handling patients with a positive test result for multiple biomarkers using random or pragmatic subtrial allocation
SMITH - Smart Medical Information Technology for Healthcare

Abstract

Not specified

Authors: Miriam Kesselmeier, Norbert Benda, André Scherag

Date Published: 14th Aug 2020

Publication Type: Journal article

Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND Women with highly penetrant BRCA mutations have a 55-60 % lifetime risk for breast cancer and a 16-59 % lifetime risk of developing ovarian cancer. However, penetrance differs interindividually, …, indicating that environmental and behavioral factors may modify this risk. It is well documented that the risk for sporadic breast cancer disease can be modified by changing lifestyle factors that primarily include physical activity, dietary habits, and body weight. It can thus be hypothesized that the modification of these lifestyle factors may also influence the incidence and progression of cancer in BRCA mutation carriers. METHODS/DESIGN This multicenter, interdisciplinary, prospective, two-armed, randomized (1:1) controlled trial aims to enroll a minimum of 600 BRCA1 and BRCA2 mutation carriers to partake in either a lifestyle intervention or usual care. The study primarily aims to demonstrate an improvement of nutritional behavior (adherence to the Mediterranean diet), body mass index, and physical fitness. Furthermore, the effects on quality of life, stress coping capacity, breast cancer incidence, and mortality will be investigated. The intervention group (IG) will receive a structured lifestyle intervention over 12 months, whereas the control group (CG) will only receive information regarding a healthy lifestyle. During the first 3 months, women in the IG will receive structured, individualized, and mainly supervised endurance training with a minimum of 18 MET-h physical activity per week and nutrition education based on the Mediterranean diet. Over the following 9 months, IG monthly group training sessions and regular telephone contacts will motivate study participants. The CG will receive one general training session about healthy nutrition in accordance with the recommendations of the German Society of Nutrition (standard of care in Germany) and the benefits of regular physical activity on health status. At randomization and subsequent time points (3 and 12 months), cardiopulmonary fitness will be assessed by spiroergometry, and nutritional and psychological status will be assessed by validated questionnaires, interviews, and clinical examinations. DISCUSSION As data on the role of lifestyle intervention in women with a hereditary risk for breast and ovarian cancer are currently lacking, this study will be of major importance from a scientific, as well as a practical advice viewpoint. It will investigate the optimal strategy to improve physical fitness, nutritional status, and psychological factors such as quality of life, perceived stress, optimism, as well as incidence and outcome of cancer in this selected group of women at high risk. If the study indicates a positive long-term outcome, a structured lifestyle intervention program could be added to health care prevention strategies for BRCA1 and BRCA2 mutation carriers. TRIAL REGISTRATION ClinicalTrials.gov: NCT02516540 . Registered on 22 July 2015.

Authors: Marion Kiechle, Christoph Engel, Anika Berling, Katrin Hebestreit, Stephan C. Bischoff, Ricarda Dukatz, Michael Siniatchkin, Katharina Pfeifer, Sabine Grill, Maryam Yahiaoui-Doktor, Ellen Kirsch, Uwe Niederberger, Ute Enders, Markus Löffler, Alfons Meindl, Kerstin Rhiem, Rita Schmutzler, Nicole Erickson, Martin Halle

Date Published: 1st Dec 2016

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Effects of psychological eating behaviour domains on the association between socio-economic status and BMI.
LIFE Adult

Abstract (Expand)

OBJECTIVE: The current study investigates potential pathways from socio-economic status (SES) to BMI in the adult population, considering psychological domains of eating behaviour (restrained eating, … uncontrolled eating, emotional eating) as potential mediators stratified for sex. DESIGN: Data were derived from the population-based cross-sectional LIFE-Adult-Study. Parallel-mediation models were conducted to obtain the total, direct and indirect effects of psychological eating behaviour domains on the association between SES and BMI for men and for women. SETTING: Leipzig, Germany. SUBJECTS: We studied 5935 participants aged 18 to 79 years. RESULTS: Uncontrolled eating mediated the association between SES and BMI in men only and restrained eating in both men and women. Emotional eating did not act as mediator in this relationship. The total effect of eating behaviour domains on the association between SES and BMI was estimated as beta=-0.03 (se 0.02; 95 % CI -0.062, -0.003) in men and beta=-0.18 (se 0.02; 95 % CI -0.217, -0.138) in women. CONCLUSIONS: Our findings do not indicate a strong overall mediation effect of the eating behaviour domains restrained eating, uncontrolled eating and emotional eating on the association between SES and BMI. Further research on other pathways of this association is strongly recommended. Importantly, our findings indicate that, independent from one's social position, focusing on psychological aspects in weight reduction might be a promising approach.

Authors: A. Loffler, T. Luck, F. S. Then, C. Luck-Sikorski, A. Pabst, P. Kovacs, Y. Bottcher, J. Breitfeld, A. Tonjes, A. Horstmann, M. Loffler, C. Engel, J. Thiery, A. Villringer, M. Stumvoll, S. G. Riedel-Heller

Date Published: 25th Jul 2017

Publication Type: Journal article

Ein 3LGM^2-Modell des Informationssystems des Universitätsklinikums Leipzig und seine Anwendung im Informationsmanagement
Management of health information systems

Abstract

Not specified

Authors: T. Wendt, B. Brigl, A. Häber, Alfred Winter

Date Published: 2004

Publication Type: InCollection

Ein 3LGM^2 Modell des Krankenhausinformationssystems des Universitätsklinikums Leipzig und seine Verwertbarkeit für das Informationsmanagement
Management of health information systems

Abstract

Not specified

Authors: B. Brigl, A. Häber, T. Wendt, Alfred Winter

Date Published: 2004

Publication Type: InCollection

Ein Entscheidungsunterstützungssystem für das Informationsmanagement
Management of health information systems

Abstract (Expand)

Einleitung: Die Menge an Daten, die bei der Ausführung strategischer, taktischer und operativer Aufgaben im Informationsmanagement im Krankenhaus entstehen, wächst kontinuierlich. Gleichzeitig befinden … sich diese Daten in unterschiedlichen Datensenken, Formaten und meist ohne semantische Auszeichnung.[zum vollständigen Text gelangen Sie über die oben angegebene URL]

Authors: Christian Kücherer, Franziska Jahn, Konrad Höffner, Birgit Schneider, Barbara Paech, Stefan Smers, Alfred Winter

Date Published: 2017

Publication Type: Misc

Eine objektorientierte Methode zum Datenbankentwurf auf der Basis des modifizierten RM/T-Datenmodells
Management of health information systems

Abstract

Not specified

Author: Alfred Winter

Date Published: 1990

Publication Type: InCollection

Eine Ontologie für die Unterstützung der Lehre und des Informationsmanagements im Gesundheitswesen
Management of health information systems

Abstract

Not specified

Authors: Kais Tahar, Franziska Jahn, Michael Schaaf, Christian Kücherer, Barbara Paech, Alfred Winter

Date Published: 2014

Publication Type: InProceedings

Ein semantisches Netz des Informationsmanagements im Krankenhaus. Lecture Notes in Informatics (LNI)
Management of health information systems

Abstract

Not specified

Authors: Franziska Jahn, M. Schaaf, Barbara Paech, Alfred Winter

Date Published: 2014

Publication Type: InCollection

Ein UML-basiertes Meta-Modell zur Beschreibung von Krankenhausinformationssystemen
Management of health information systems

Abstract

Not specified

Authors: Birgit Brigl, Thomas Wendt, Alfred Winter

Date Published: 2003

Publication Type: Misc

Elektronische Arzneimittelverordnung – Autopilot in der Arzneimitteltherapie? Literatur- und Datenanalyse
Management of health information systems

Abstract

Not specified

Author: Martina Patrizia Neininger Sten Schubert

Date Published: 2015

Publication Type: Journal article

Elevated HbA1c is associated with increased risk of incident dementia in primary care patients.
LIFE Adult

Abstract (Expand)

Type 2 diabetes mellitus (T2DM) is a risk factor of dementia. The effect of T2DM treatment quality on dementia risk, however, is unclear. 1,342 elderly individuals recruited via general practitioner … registries (AgeCoDe cohort) were analyzed. This study analyzed the association between HbA1c level and the incidence of all-cause dementia (ACD) and of Alzheimer's disease dementia (referred to here as AD). HbA1c levels >/=6.5% were associated with 2.8-fold increased risk of incident ACD (p = 0.027) and for AD (p = 0.047). HbA1c levels >/=7% were associated with a five-fold increased risk of incident ACD (p = 0.001) and 4.7-fold increased risk of incident AD (p = 0.004). The T2DM diagnosis per se did not increase the risk of either ACD or AD. Higher levels of HbA1c are associated with increased risk of ACD and AD in an elderly population. T2DM diagnosis was not associated with increased risk if HbA1c levels were below 7%.

Authors: A. Ramirez, S. Wolfsgruber, C. Lange, H. Kaduszkiewicz, S. Weyerer, J. Werle, M. Pentzek, A. Fuchs, S. G. Riedel-Heller, T. Luck, E. Mosch, H. Bickel, B. Wiese, J. Prokein, H. H. Konig, C. Brettschneider, M. M. Breteler, W. Maier, F. Jessen, M. Scherer

Date Published: 20th Dec 2014

Publication Type: Not specified

Human Diseases: diabetes mellitus, dementia, Alzheimer's disease

Elevated serum free light chains do not predict outcome of elderly patients with aggressive CD20(+) B-cell lymphomas.
GLA - German Lymphoma Alliance

Abstract

Not specified

Authors: M. Achenbach, J. T. Bittenbring, M. Ziepert, E. Regitz, G. Ott, A. Rosenwald, M. Pfreundschuh, B. Altmann, G. Held

Date Published: 1st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

Enabling ad-hoc reuse of private data repositories through schema extraction
SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

BACKGROUND: Sharing sensitive data across organizational boundaries is often significantly limited by legal and ethical restrictions. Regulations such as the EU General Data Protection Rules (GDPR) … impose strict requirements concerning the protection of personal and privacy sensitive data. Therefore new approaches, such as the Personal Health Train initiative, are emerging to utilize data right in their original repositories, circumventing the need to transfer data. RESULTS: Circumventing limitations of previous systems, this paper proposes a configurable and automated schema extraction and publishing approach, which enables ad-hoc SPARQL query formulation against RDF triple stores without requiring direct access to the private data. The approach is compatible with existing Semantic Web-based technologies and allows for the subsequent execution of such queries in a safe setting under the data provider’s control. Evaluation with four distinct datasets shows that a configurable amount of concise and task-relevant schema, closely describing the structure of the underlying data, was derived, enabling the schema introspection-assisted authoring of SPARQL queries. CONCLUSIONS: Automatically extracting and publishing data schema can enable the introspection-assisted creation of data selection and integration queries. In conjunction with the presented system architecture, this approach can enable reuse of data from private repositories and in settings where agreeing upon a shared schema and encoding a priori is infeasible. As such, it could provide an important step towards reuse of data from previously inaccessible sources and thus towards the proliferation of data-driven methods in the biomedical domain.

Authors: Lars Christoph Gleim, Md Rezaul Karim, Lukas Zimmermann, Oliver Kohlbacher, Holger Stenzhorn, Stefan Decker, Oya Beyan

Date Published: 1st Jul 2020

Publication Type: Journal article

Enteral nutrition is associated with improved outcome in patients with severe sepsis. A secondary analysis of the VISEP trial.
SepNet - German Competence Network Sepsis

Abstract (Expand)

INTRODUCTION: The optimal nutritional strategy remains controversial, particularly in severely septic patients. Our aim was to analyze the effect of three nutritional strategies--enteral (EN), parenteral … (PN), and combined nutrition (EN+PN)--on the outcome of patients with severe sepsis or septic shock. PATIENTS AND METHODS: This secondary analysis of the prospective, randomized-controlled, multicenter "Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis (VISEP)" trial only included patients with a length of stay in the intensive care unit (ICU) of more than 7 days. Besides patient characteristics, data on nutrition therapy were collected daily for up to 21 days. Morbidity as measured by the mean Sequential Organ Failure Assessment (SOFA) score, incidence of secondary infections, renal replacement therapy, ventilator-free days and severe hypoglycemia, length of ICU stay, and mortality at 90 days were compared between the three nutritional strategies. RESULTS: In all, 353 patients were included in the analysis with the majority (68.5 %) receiving EN+PN, 24.4 % receiving EN, and only 7.1 % receiving PN. Median caloric intake was 918 kcal/day (EN), 1,210 kcal/day (PN), and 1,343 kcal/day (EN+PN; p < 0.001). In the latter group, calories were predominantly administered via the parenteral route within the first week. The rate of death at 90 days was lower with EN than with EN+PN (26.7 % vs. 41.3 %, p = 0.048), as was the rate of secondary infections, renal replacement therapy, and duration of mechanical ventilation. In the adjusted Cox regression analysis, the effect on mortality [hazard ratio (HR)= 1.86, 95 % confidence interval (CI): 1.16-2.98, p = 0.010] and the rate of secondary infections (HR= 1.89, 95 % CI: 1.27-2.81, p = 0.002) remained different between EN and EN+PN. CONCLUSION: In patients with severe sepsis or septic shock and prolonged ICU stay, EN alone was associated with improved clinical outcome compared to EN+PN. This hypothesis-generating result has to be confirmed by a randomized-controlled trial in this specific patient population.

Authors: G. Elke, E. Kuhnt, M. Ragaller, D. Schadler, I. Frerichs, F. M. Brunkhorst, M. Loffler, K. Reinhart, N. Weiler

Date Published: 5th Mar 2013

Publication Type: Not specified

Human Diseases: disease by infectious agent

Entwicklung und Einsatz einer Domänenontologie des Informationsmanagements im Krankenhaus.
Management of health information systems

Abstract

Not specified

Author: Jahn F Schaaf M

Date Published: 2015

Publication Type: InCollection

Entwurf und Implementierung Einer Zentralen Auskunftskomponente Eines Krankenhausinformationssystems
Management of health information systems

Abstract

Not specified

Authors: Alfred Winter, Karin Emser, Reinhold Haux, Friedhelm Raab, Rudolf Repges, Klaus-Peter Schleisiek, Ursula Stoll, Christian Valder

Date Published: 1986

Publication Type: InCollection

Epidemiology of sepsis in Germany: results from a national prospective multicenter study
SepNet - German Competence Network Sepsis

Abstract (Expand)

OBJECTIVE To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. DESIGN Prospective, observational, cross-sectional 1-day …day point-prevalence study. SETTING 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). PATIENTS Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. MEASUREMENTS AND RESULTS Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9-13.8%) for sepsis and 11.0% (95% CI, 9.7-12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (\textless/= 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). CONCLUSIONS The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76-110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Authors: Christoph Engel, Frank M. Brunkhorst, Hans-Georg Bone, Reinhard Brunkhorst, Herwig Gerlach, Stefan Grond, Matthias Gruendling, Guenter Huhle, Ulrich Jaschinski, Stefan John, Konstantin Mayer, Michael Oppert, Derk Olthoff, Michael Quintel, Max Ragaller, Rolf Rossaint, Frank Stuber, Norbert Weiler, Tobias Welte, Holger Bogatsch, Christiane Hartog, Markus Loeffler, Konrad Reinhart

Date Published: 23rd Mar 2007

Publication Type: Journal article

Human Diseases: disease by infectious agent

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors.
GGN - German Glioma Network

Abstract (Expand)

Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-amplified glioblastoma … patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies.Experimental Design:EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR-nonamplified tumors. EGFR single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium.Results: Sixty of 106 EGFR-amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR-amplified tumors, but were not linked to survival.Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. Clin Cancer Res; 23(22); 6846-55. (c)2017 AACR.

Authors: J. Felsberg, B. Hentschel, K. Kaulich, D. Gramatzki, A. Zacher, B. Malzkorn, M. Kamp, M. Sabel, M. Simon, M. Westphal, G. Schackert, J. C. Tonn, T. Pietsch, A. von Deimling, M. Loeffler, G. Reifenberger, M. Weller

Date Published: 15th Nov 2017

Publication Type: Journal article

Human Diseases: brain glioblastoma multiforme

Epigenetic Heterogeneity of B-Cell Lymphoma: Chromatin Modifiers.
MMML-MYC-SYS

Abstract (Expand)

We systematically studied the expression of more than fifty histone and DNA (de)methylating enzymes in lymphoma and healthy controls. As a main result, we found that the expression levels of nearly all … enzymes become markedly disturbed in lymphoma, suggesting deregulation of large parts of the epigenetic machinery. We discuss the effect of DNA promoter methylation and of transcriptional activity in the context of mutated epigenetic modifiers such as EZH2 and MLL2. As another mechanism, we studied the coupling between the energy metabolism and epigenetics via metabolites that act as cofactors of JmjC-type demethylases. Our study results suggest that Burkitt's lymphoma and diffuse large B-cell Lymphoma differ by an imbalance of repressive and poised promoters, which is governed predominantly by the activity of methyltransferases and the underrepresentation of demethylases in this regulation. The data further suggest that coupling of epigenetics with the energy metabolism can also be an important factor in lymphomagenesis in the absence of direct mutations of genes in metabolic pathways. Understanding of epigenetic deregulation in lymphoma and possibly in cancers in general must go beyond simple schemes using only a few modes of regulation.

Authors: L. Hopp, L. Nersisyan, H. Loffler-Wirth, A. Arakelyan, H. Binder

Date Published: 21st Oct 2015

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States.
MMML-MYC-SYS

Abstract (Expand)

Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, … which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12.

Authors: L. Hopp, H. Loffler-Wirth, H. Binder

Date Published: 7th Sep 2015

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

Erfahrungsaustausch zur Verschlüsselung von Diagnosen und Operationen sowie zur ambulanten Diagnosedokumentation
Management of health information systems

Abstract

Not specified

Authors: P. Schmücker, E. Glück, Alfred Winter

Date Published: 4

Publication Type: Misc

Ethische Leitlinien der GI
Management of health information systems

Abstract

Not specified

Authors: Peter Bittner, Rafael Capurro, Wolfgang Coy, Eva Hornecker, Constanze Kurz, Karl-Heinz Rödiger, Britta Schinzel, Ute Twisselmann, Roland Vollmar, Karsten Weber, Alfred Winter, Cornelia Winter

Date Published: 2003

Publication Type: Journal article

Ethische Leitlinien von GMDS, AL-KRZ, BVMI, KH-IT und DVMD
Management of health information systems

Abstract

Not specified

Authors: Alfred Winter, W. Ahrens, B. Bergh, M. Bohrer-Steck, J. Chang-Claude, H. Christ, Thomas M. Deserno, C. Dujat, J. Haerting, C. O. Köhler, U. Kutscha, O. Mosbach-Schulz, J. Müller, A. Mulder-Rathgeber, W. Niederlag, M. Niehsen-Zehrer, K. Pommerening, A. Scharsky, C. Stark, R. Vollmar

Date Published: 2008

Publication Type: Journal article

Evaluating the performance of clinical criteria for predicting mismatch repair gene mutations in Lynch syndrome: a comprehensive analysis of 3,671 families.
GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer

Abstract (Expand)

Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive … and time-consuming, clinical criteria and tumor-tissue analysis are widely used as pre-screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumor-tissue analysis in predicting MMR gene mutations. We analyzed 3,671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mutation. Among all 1,284 families with microsatellite instability-high (MSI-H) colorectal cancer, the overall mutation detection rate was 53.0%. Mutation frequencies and their distribution between the four MMR genes differed significantly between clinical groups (p < 0.001). The highest frequencies were found in families fulfilling the Amsterdam Criteria (46.4%). Families with loss of MSH2 expression had higher mutation detection rates (69.5%) than families with loss of MLH1 expression (43.1%). MMR mutations were found significantly more often in families with at least one MSI-H small-bowel cancer (p < 0.001). No MMR mutations were found among patients under 40-years-old with only colorectal adenoma. Familial clustering of Lynch syndrome-related tumors, early age of onset, and familial occurrence of small-bowel cancer were clinically relevant predictors for Lynch syndrome.

Authors: V. Steinke, S. Holzapfel, M. Loeffler, E. Holinski-Feder, M. Morak, H. K. Schackert, H. Gorgens, C. Pox, B. Royer-Pokora, M. von Knebel-Doeberitz, R. Buttner, P. Propping, C. Engel

Date Published: 1st Jul 2014

Publication Type: Not specified

Human Diseases: colon cancer

Evaluating the performance of the breast cancer genetic risk models BOADICEA, IBIS, BRCAPRO and Claus for predicting BRCA1/2 mutation carrier probabilities: a study based on 7352 families from the German Hereditary Breast and Ovarian Cancer Consortium.
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND: Risk prediction models are widely used in clinical genetic counselling. Despite their frequent use, the genetic risk models BOADICEA, BRCAPRO, IBIS and extended Claus model (eCLAUS), used … to estimate BRCA1/2 mutation carrier probabilities, have never been comparatively evaluated in a large sample from central Europe. Additionally, a novel version of BOADICEA that incorporates tumour pathology information has not yet been validated. PATIENTS AND METHODS: Using data from 7352 German families we estimated BRCA1/2 carrier probabilities under each model and compared their discrimination and calibration. The incremental value of using pathology information in BOADICEA was assessed in a subsample of 4928 pedigrees with available data on breast tumour molecular markers oestrogen receptor, progesterone receptor and human epidermal growth factor 2. RESULTS: BRCAPRO (area under receiver operating characteristic curve (AUC)=0.80 (95% CI 0.78 to 0.81)) and BOADICEA (AUC=0.79 (0.78-0.80)), had significantly higher diagnostic accuracy than IBIS and eCLAUS (p<0.001). The AUC increased when pathology information was used in BOADICEA: AUC=0.81 (95% CI 0.80 to 0.83, p<0.001). At carrier thresholds of 10% and 15%, the net reclassification index was +3.9% and +5.4%, respectively, when pathology was included in the model. Overall, calibration was best for BOADICEA and worst for eCLAUS. With eCLAUS, twice as many mutation carriers were predicted than observed. CONCLUSIONS: Our results support the use of BRCAPRO and BOADICEA for decision making regarding genetic testing for BRCA1/2 mutations. However, model calibration has to be improved for this population. eCLAUS should not be used for estimating mutation carrier probabilities in clinical settings. Whenever possible, breast tumour molecular marker information should be taken into account.

Authors: C. Fischer, K. Kuchenbacker, C. Engel, S. Zachariae, K. Rhiem, A. Meindl, N. Rahner, N. Dikow, H. Plendl, I. Debatin, T. Grimm, D. Gadzicki, R. Flottmann, J. Horvath, E. Schrock, F. Stock, D. Schafer, I. Schwaab, C. Kartsonaki, N. Mavaddat, B. Schlegelberger, A. C. Antoniou, R. Schmutzler

Date Published: 9th Apr 2013

Publication Type: Not specified

Human Diseases: hereditary breast ovarian cancer syndrome

Evaluation eines Mikromanipulators für die Mittelohrchirurgie: Eine präklinische Studie
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Microsurgical preparation is limited by geometric and mechanical constraints. In preparation for clinical use, this study investigates performance, ease of handling and precision of a novel …l manipulator concept for microsurgery. MATERIAL AND METHODS A group of 15 ENT experienced doctors, as well as a group of 17 medical students with low/non surgical experience participated in the study. Each of the subjects carried out 4 trials of simulated surgeries on a phantom with built-in force sensors. The task was to apply a defined force between 1.5 and 2 N using a Fisch micro perforator, 16 cm length, 0.4 mm (Storz) targeting holes with a diameter of 0.5 mm. For comparison, the Fisch micro perforator was moved manually or with the manipulator. RESULTS Assessing the total number of errors proved a significantly lower error number (p\textless0.0001) and an improvement of the accuracy of 76% with the manipulator. The time requirement for the procedure with the micro manipulator is on average 2-3 times higher than with manual control (p\textless0.0001). But it is notable that this time requirement significantly decreases with training (p\textless0.0001). CONCLUSION The study shows a significant reduction in the number of errors by using a new manipulator concept compared to the non-augmented human hand in an experimental setup. We observed a significant learning effect when subjects applied the micro manipulator, resulting in reduction of the time requirement while maintaining a constant number of errors.

Authors: A. Peschka, Th Berger, Th Maier, M. Scholz, T. C. Lüth, G. Strauß

Date Published: 9th Feb 2016

Publication Type: Journal article

Evaluation eines Referenzmodells für ein Krankenhausinformationssystem anhand einer Systemanalyse in den Tiroler Landeskrankenanstalten
Management of health information systems

Abstract

Not specified

Authors: Gudrun Hübner-Bloder, Elske Ammenwerth, B. Brigl, G. Lechleitner, D. Reiter, Alfred Winter

Date Published: 2005

Publication Type: InCollection

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general …l population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. METHODS We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. RESULTS We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. CONCLUSION This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

Authors: A. Osorio, R. L. Milne, G. Pita, P. Peterlongo, T. Heikkinen, J. Simard, G. Chenevix-Trench, A. B. Spurdle, J. Beesley, X. Chen, S. Healey, S. L. Neuhausen, Y. C. Ding, F. J. Couch, X. Wang, N. Lindor, S. Manoukian, M. Barile, A. Viel, L. Tizzoni, C. I. Szabo, L. Foretova, M. Zikan, K. Claes, M. H. Greene, P. Mai, G. Rennert, F. Lejbkowicz, O. Barnett-Griness, I. L. Andrulis, H. Ozcelik, N. Weerasooriya, A-M Gerdes, M. Thomassen, D. G. Cruger, M. A. Caligo, E. Friedman, B. Kaufman, Y. Laitman, S. Cohen, T. Kontorovich, R. Gershoni-Baruch, E. Dagan, H. Jernström, M. S. Askmalm, B. Arver, B. Malmer, S. M. Domchek, K. L. Nathanson, J. Brunet, T. Ramón Y Cajal, D. Yannoukakos, U. Hamann, F. B. L. Hogervorst, S. Verhoef, E. B. Gómez García, J. T. Wijnen, A. van den Ouweland, D. F. Easton, S. Peock, M. Cook, C. T. Oliver, D. Frost, C. Luccarini, D. G. Evans, F. Lalloo, R. Eeles, G. Pichert, J. Cook, S. Hodgson, P. J. Morrison, F. Douglas, A. K. Godwin, O. M. Sinilnikova, L. Barjhoux, D. Stoppa-Lyonnet, V. Moncoutier, S. Giraud, C. Cassini, L. Olivier-Faivre, F. Révillion, J-P Peyrat, D. Muller, J-P Fricker, H. T. Lynch, E. M. John, S. Buys, M. Daly, J. L. Hopper, M. B. Terry, A. Miron, Y. Yassin, D. Goldgar, C. F. Singer, D. Gschwantler-Kaulich, G. Pfeiler, A-C Spiess, Thomas v. O. Hansen, O. T. Johannsson, T. Kirchhoff, K. Offit, K. Kosarin, M. Piedmonte, G. C. Rodriguez, K. Wakeley, J. F. Boggess, J. Basil, P. E. Schwartz, S. V. Blank, A. E. Toland, M. Montagna, C. Casella, E. N. Imyanitov, A. Allavena, R. K. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Ditsch, N. Arnold, D. Niederacher, H. Deissler, B. Fiebig, R. Varon-Mateeva, D. Schaefer, U. G. Froster, T. Caldes, M. de La Hoya, L. McGuffog, A. C. Antoniou, H. Nevanlinna, P. Radice, J. Benítez

Date Published: 1st Dec 2009

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Evaluation of the invasion front pattern of squamous cell cervical carcinoma by measuring classical and discrete compactness.
ProstataCA

Abstract (Expand)

The invasion front pattern of squamous cell carcinoma (SCC) is a conspicuous histological phenomenon, which is assessed without precise criteria. The current study was performed to introduce the classical … (C(C)) and discrete compactness (C(D)) as new morphometric parameters for quantification of this pattern. A retrospective analysis of 76 surgically treated patients with cervical carcinoma was conducted and the pattern of invasion was qualitatively classified as closed, finger-like or diffuse, respectively, by two pathologists. After digitization of the histological slides with a field of view of 10.4 mm x 8.3mm, tumor areas were labeled and C(C) and C(D) were computed based on the drawings (binary images). Additionally, intraindividual variation of compactness was evaluated for 12 selected tumors. The qualitative pattern assessment by the pathologists was moderately reproducible with an interobserver agreement of 72% and a kappa coefficient of 0.44. The values of C(C) and C(D) referring to the invasion front patterns assigned by both pathologists were significantly different between the three classified groups (p< or =0.01 and p< or =0.0001), so that, both theoretically and in practice, compactness regards the same morphological feature. In due consideration of the analysis of the area under the ROC (receiver operating characteristic) curves and the variation coefficient of different tumor regions, C(D) is more suitable for practical use than C(C). Tumors with a microscopic invasion into the parametria and with lymph-vascular space invasion were found to have a lower value of C(D), which indicates a more diffuse pattern of invasion (p=0.028 and p=0.033). We conclude that the discrete compactness C(D) is a new and reproducible parameter for a computer assisted quantification of the invasion front pattern and, thus, defines a further phenotypic feature of SCC of the uterine cervix.

Authors: J. Einenkel, U. D. Braumann, L. C. Horn, N. Pannicke, J. P. Kuska, A. Schutz, B. Hentschel, M. Hockel

Date Published: 25th May 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Evidence for neuroprotective properties of human umbilical cord blood cells after neuronal hypoxia in vitro
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnOne of the most promising options for treatment of stroke using adult stem cells are human umbilical cord blood (HUCB) cells that were already approved for therapeutic … efficacy in vivo. However, complexity of animal models has thus far limited the understanding of beneficial cellular mechanisms. To address the influence of HUCB cells on neuronal tissue after stroke we established and employed a human in vitro model of neuronal hypoxia using fully differentiated vulnerable SH-SY5Y cells. These cells were incubated under an oxygen-reduced atmosphere (O2\textless 1%) for 48 hours. Subsequently, HUCB mononuclear cells (MNC) were added to post-hypoxic neuronal cultures. These cultures were characterized regarding to the development of apoptosis and necrosis over three days. Based on this we investigated the therapeutic influence of HUCB MNC on the progression of apoptotic cell death. The impact of HUCB cells and hypoxia on secretion of neuroprotective and inflammatory cytokines, chemokines and expression of adhesion molecules was proved.\backslashr\backslashnRESULTS\backslashr\backslashnHypoxic cultivation of neurons initially induced a rate of 26% +/- 13% of apoptosis. Hypoxia also caused an enhanced expression of Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Necrosis was only detected in low amounts. Within the next three days rate of apoptosis in untreated hypoxic cultures cumulated to 85% +/- 11% (p \textless or = 0.001). Specific cytokine (VEGF) patterns also suggest anti-apoptotic strategies of neuronal cells. Remarkably, the administration of MNC showed a noticeable reduction of apoptosis rates to levels of normoxic control cultures (7% +/- 3%; p \textless or = 0.001). In parallel, clustering of administered MNC next to axons and somata of neuronal cells was observed. Furthermore, MNC caused a pronounced increase of chemokines (CCL5; CCL3 and CXCL10).\backslashr\backslashnCONCLUSION\backslashr\backslashnWe established an in vitro model of neuronal hypoxia that affords the possibility to investigate both, apoptotic neuronal cell death and neuroprotective therapies. Here we employed the therapeutic model to study neuroprotective properties of HUCB cells. We hypothesize that the neuroprotective effect of MNC was due to anti-apoptotic mechanisms related to direct cell-cell contacts with injured neuronal cells and distinct changes in neuroprotective, inflammatory cytokines as well as to the upregulation of chemokines within the co-cultures. BACKGROUND One of the most promising options for treatment of stroke using adult stem cells are human umbilical cord blood (HUCB) cells that were already approved for therapeutic efficacy in vivo. However, complexity of animal models has thus far limited the understanding of beneficial cellular mechanisms. To address the influence of HUCB cells on neuronal tissue after stroke we established and employed a human in vitro model of neuronal hypoxia using fully differentiated vulnerable SH-SY5Y cells. These cells were incubated under an oxygen-reduced atmosphere (O2\textless 1%) for 48 hours. Subsequently, HUCB mononuclear cells (MNC) were added to post-hypoxic neuronal cultures. These cultures were characterized regarding to the development of apoptosis and necrosis over three days. Based on this we investigated the therapeutic influence of HUCB MNC on the progression of apoptotic cell death. The impact of HUCB cells and hypoxia on secretion of neuroprotective and inflammatory cytokines, chemokines and expression of adhesion molecules was proved. RESULTS Hypoxic cultivation of neurons initially induced a rate of 26% +/- 13% of apoptosis. Hypoxia also caused an enhanced expression of Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Necrosis was only detected in low amounts. Within the next three days rate of apoptosis in untreated hypoxic cultures cumulated to 85% +/- 11% (p \textless or = 0.001). Specific cytokine (VEGF) patterns also suggest anti-apoptotic strategies of neuronal cells. Remarkably, the administration of MNC showed a noticeable reduction of apoptosis rates to levels of normoxic control cultures (7% +/- 3%; p \textless or = 0.001). In parallel, clustering of administered MNC next to axons and somata of neuronal cells was observed. Furthermore, MNC caused a pronounced increase of chemokines (CCL5; CCL3 and CXCL10). CONCLUSION We established an in vitro model of neuronal hypoxia that affords the possibility to investigate both, apoptotic neuronal cell death and neuroprotective therapies. Here we employed the therapeutic model to study neuroprotective properties of HUCB cells. We hypothesize that the neuroprotective effect of MNC was due to anti-apoptotic mechanisms related to direct cell-cell contacts with injured neuronal cells and distinct changes in neuroprotective, inflammatory cytokines as well as to the upregulation of chemokines within the co-cultures.

Authors: Susann Hau, Doreen M. Reich, Markus Scholz, Wilfried Naumann, Frank Emmrich, Manja Kamprad, Johannes Boltze

Date Published: 2008

Publication Type: Journal article

Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

INTRODUCTION Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of …f large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies. METHODS We successfully genotyped 24 SNPs in a cohort of up to 4,724 BRCA1 and 2,693 BRCA2 female mutation carriers from 15 study groups and assessed whether these variants were associated with risk of breast cancer in BRCA1 and BRCA2 mutation carriers. RESULTS SNPs in five of the 14 candidate genes showed evidence of association with breast cancer risk for BRCA1 or BRCA2 carriers (P \textless 0.05). Notably, the minor alleles of two SNPs (rs7166081 and rs3825977) in high linkage disequilibrium (r^2 = 0.77), located at the SMAD3 locus (15q22), were each associated with increased breast cancer risk for BRCA2 mutation carriers (relative risk = 1.25, 95% confidence interval = 1.07 to 1.45, P(trend) = 0.004; and relative risk = 1.20, 95% confidence interval = 1.03 to 1.40, P(trend) = 0.018). CONCLUSIONS This study provides evidence that the SMAD3 gene, which encodes a key regulatory protein in the transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers. This finding suggests that genes with expression associated with BRCA1 and BRCA2 mutation status are enriched for the presence of common genetic modifiers of breast cancer risk in these populations.

Authors: Logan C. Walker, Zachary S. Fredericksen, Xianshu Wang, Robert Tarrell, Vernon S. Pankratz, Noralane M. Lindor, Jonathan Beesley, Sue Healey, Xiaoqing Chen, Dominique Stoppa-Lyonnet, Carole Tirapo, Sophie Giraud, Sylvie Mazoyer, Danièle Muller, Jean-Pierre Fricker, Capucine Delnatte, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Ines Schönbuchner, Helmut Deissler, Alfons Meindl, Frans B. Hogervorst, Martijn Verheus, Maartje J. Hooning, Ans Mw van den Ouweland, Marcel R. Nelen, Margreet Gem Ausems, Cora M. Aalfs, Christi J. van Asperen, Peter Devilee, Monique M. Gerrits, Quinten Waisfisz, Csilla I. Szabo, Douglas F. Easton, Susan Peock, Margaret Cook, Clare T. Oliver, Debra Frost, Patricia Harrington, D. Gareth Evans, Fiona Lalloo, Ros Eeles, Louise Izatt, Carol Chu, Rosemarie Davidson, Diana Eccles, Kai-Ren Ong, Jackie Cook, Tim Rebbeck, Katherine L. Nathanson, Susan M. Domchek, Christian F. Singer, Daphne Gschwantler-Kaulich, Anne-Catharina Dressler, Georg Pfeiler, Andrew K. Godwin, Tuomas Heikkinen, Heli Nevanlinna, Bjarni A. Agnarsson, Maria Adelaide Caligo, Håkan Olsson, Ulf Kristoffersson, Annelie Liljegren, Brita Arver, Per Karlsson, Beatrice Melin, Olga M. Sinilnikova, Lesley McGuffog, Antonis C. Antoniou, Georgia Chenevix-Trench, Amanda B. Spurdle, Fergus J. Couch

Date Published: 1st Dec 2010

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Excellent outcome of young adults with aggressive non-Hodgkin lymphomas treated with CHOP-like regimens.
GLA - German Lymphoma Alliance

Abstract

Not specified

Authors: K. Hohloch, S. Zeynalova, G. Held, M. Ziepert, M. Loeffler, G. Wulf, N. Schmitz, M. Pfreundschuh, L. Trumper

Date Published: 10th Jul 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Experiences with Current Methods of Integrating Hospital Information Systems
Management of health information systems

Abstract

Not specified

Author: Alfred Winter

Date Published: 1999

Publication Type: InCollection

External ventricular drain infections: risk factors and outcome
SepNet - German Competence Network Sepsis

Abstract (Expand)

External ventricular drainage (EVD) is frequently used in neurosurgery to drain cerebrospinal fluid in patients with raised intracranial pressure. We performed a retrospective single center study in … order to evaluate the incidence of EVD-related infections and to identify underlying risk factors. 246 EVDs were placed in 218 patients over a 30-month period. EVD was continued in median for 7 days (range 1-44). The cumulative incidence of EVD-related infections was 8.3% (95% CI, 5.3-12.7) with a device-associated infection rate of 10.4 per 1000 drainage days (95% CI, 6.2-16.5). The pathogens most commonly identified were coagulase-negative Staphylococcus (62%) followed by Enterococcus spp. (19%). Patients with an EVD-related infection had a significantly longer ICU (11 versus 21 days, P \textless 0.01) and hospital stay (20 versus 28.5 days, P \textless 0.01) than patients without. Median total duration of external drainage was twice as long in patients with EVD-related infection (6 versus 12 days, P \textless 0.01). However, there was no significant difference in the duration between first EVD placement and the occurrence of EVD-related infection and EVD removal in patients without EVD-related infection (6 versus 7 days, P = 0.87), respectively. Interestingly no risk factor for EVD-related infection could be identified in our cohort of patients.

Authors: S. Hagel, T. Bruns, M. W. Pletz, C. Engel, R. Kalff, C. Ewald

Date Published: 2014

Publication Type: Journal article

Human Diseases: disease by infectious agent

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