Gerta Rücker

Universitätsklinikum Freiburg, Freiburg an der Elbe, Lower Saxony, Germany

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Publications (88)338.9 Total impact

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    ABSTRACT: Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.
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    ABSTRACT: We performed a systematic review of the currently available evidence on whether psychological treatments are effective for treating depressed primary care patients in comparison with usual care or placebo, taking the type of therapy and its delivery mode into account. Randomized controlled trials comparing a psychological treatment with a usual care or a placebo control in adult, depressed, primary care patients were identified by searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013. At least 2 reviewers extracted information from included studies and assessed the risk of bias. Random effects meta-analyses were performed using posttreatment depression scores as outcome. A total of 30 studies with 5,159 patients met the inclusion criteria. Compared with control, the effect (standardized mean difference) at completion of treatment was -0.30 (95% CI, -0.48 to -0.13) for face-to-face cognitive behavioral therapy (CBT), -0.14 (-0.40 to 0.12) for face-to-face problem-solving therapy, -0.24 (-0.47 to -0.02) for face-to-face interpersonal psychotherapy, -0.28 (-0.44 to -0.12) for other face-to-face psychological interventions, -0.43 (-0.62 to -0.24) for remote therapist-led CBT, -0.56 (-1.57 to 0.45) for remote therapist-led problem-solving therapy, -0.40 (-0.69 to -0.11) for guided self-help CBT, and -0.27 (-0.44 to -0.10) for no or minimal contact CBT. There is evidence that psychological treatments are effective in depressed primary care patients. For CBT approaches, substantial evidence suggests that interventions that are less resource intensive might have effects similar to more intense treatments. © 2015 Annals of Family Medicine, Inc.
    The Annals of Family Medicine 01/2015; 13(1):56-68. DOI:10.1370/afm.1719 · 4.57 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate whether antidepressants are more effective than placebo in the primary care setting, and whether there are differences between substance classes regarding efficacy and acceptability. We conducted literature searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013. Randomized trials in depressed adults treated by primary care physicians were included in the review. We performed both conventional pairwise meta-analysis and network meta-analysis combining direct and indirect evidence. Main outcome measures were response and study discontinuation due to adverse effects. A total of 66 studies with 15,161 patients met the inclusion criteria. In network meta-analysis, tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine), a low-dose serotonin antagonist and reuptake inhibitor (SARI; trazodone) and hypericum extracts were found to be significantly superior to placebo, with estimated odds ratios between 1.69 and 2.03. There were no statistically significant differences between these drug classes. Reversible inhibitors of monoaminoxidase A (rMAO-As) and hypericum extracts were associated with significantly fewer dropouts because of adverse effects compared with TCAs, SSRIs, the SNRI, a noradrenaline reuptake inhibitor (NRI), and noradrenergic and specific serotonergic antidepressant agents (NaSSAs). Compared with other drugs, TCAs and SSRIs have the most solid evidence base for being effective in the primary care setting, but the effect size compared with placebo is relatively small. Further agents (hypericum, rMAO-As, SNRI, NRI, NaSSAs, SARI) showed some positive results, but limitations of the currently available evidence makes a clear recommendation on their place in clinical practice difficult. © 2015 Annals of Family Medicine, Inc.
    The Annals of Family Medicine 01/2015; 13(1):69-79. DOI:10.1370/afm.1687 · 4.57 Impact Factor
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    Gerta Rücker, Guido Schwarzer
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    ABSTRACT: Statisticians investigate new methods in simulations to evaluate their properties for future real data applications. Results are often presented in a number of figures, e.g., Trellis plots. We had conducted a simulation study on six statistical methods for estimating the treatment effect in binary outcome meta-analyses, where selection bias (e.g., publication bias) was suspected because of apparent funnel plot asymmetry. We varied five simulation parameters: true treatment effect, extent of selection, event proportion in control group, heterogeneity parameter, and number of studies in meta-analysis. In combination, this yielded a total number of 768 scenarios. To present all results using Trellis plots, 12 figures were needed. Methods: Choosing bias as criterion of interest, we present a 'nested loop plot', a diagram type that aims to have all simulation results in one plot. The idea was to bring all scenarios into a lexicographical order and arrange them consecutively on the horizontal axis of a plot, whereas the treatment effect estimate is presented on the vertical axis. Results: The plot illustrates how parameters simultaneously influenced the estimate. It can be combined with a Trellis plot in a so-called hybrid plot. Nested loop plots may also be applied to other criteria such as the variance of estimation. Conclusion: The nested loop plot, similar to a time series graph, summarizes all information about the results of a simulation study with respect to a chosen criterion in one picture and provides a suitable alternative or an addition to Trellis plots.
    BMC Medical Research Methodology 12/2014; 14(1):129. DOI:10.1186/1471-2288-14-129 · 2.17 Impact Factor
  • Gerta Rücker, Guido Schwarzer
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    ABSTRACT: Network meta-analysis is a statistical method combining information from randomised trials that compare two or more treatments for a given medical condition. Consistent treatment effects are estimated for all possible treatment comparisons. For estimation, weighted least squares regression that in a natural way generalises standard pairwise meta-analysis can be used. Typically, as part of the network, multi-arm studies are found. In a multi-arm study, observed pairwise comparisons are correlated, which must be accounted for. To this aim, two methods have been proposed, a standard regression approach and a new approach coming from graph theory and based on contrast-based data (Rücker 2012). In the standard approach, the dimension of the design matrix is appropriately reduced until it is invertible ('reduce dimension'). In the alternative approach, the weights of comparisons coming from multi-arm studies are appropriately reduced ('reduce weights'). As it was unclear, to date, how these approaches are related to each other, we give a mathematical proof that both approaches lead to identical estimates. The 'reduce weights' approach can be interpreted as the construction of a network of independent two-arm studies, which is basically equivalent to the given network with multi-arm studies. Thus, a simple random-effects model is obtained, with one additional parameter for a common heterogeneity variance. This is applied to a systematic review in depression. Copyright © 2014 John Wiley & Sons, Ltd.
    Statistics in Medicine 11/2014; 33(25). DOI:10.1002/sim.6236 · 2.04 Impact Factor
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    ABSTRACT: Background Neuroborreliosis is a tick-borne infectious disease of the nervous system caused by Borrelia burgdorferi. Common clinical manifestations of neuroborreliosis are cranial nerve dysfunctions, polyradiculoneuritis, and meningitis. Diagnosis is usually based on clinical presentation, serologic testing, and analysis of cerebrospinal fluid. Many aspects of pharmacological treatment, such as choice of drug, dosage, and duration are subject of intense debate, leading to uncertainties in patients and healthcare providers alike. To approach the questions regarding pharmacological treatment of neuroborreliosis, we will perform a systematic review. Methods We will perform a comprehensive systematic literature search for potentially eligible studies that report outcomes after pharmacological interventions. To adequately consider the wealth of research that has been conducted so far, this review will evaluate randomized controlled trials (RCTs) and non-randomized studies on treatment of neuroborreliosis. We will assess potential risk of bias for each RCT meeting our selection criteria using the Cochrane risk of bias tool for RCTs. For non-randomized studies, we will use the Newcastle-Ottawa Scale and the recently piloted Cochrane risk of bias tool for non-randomized studies. Our primary outcome of interest will be neurological symptoms and the secondary outcomes will be disability, patient-reported outcomes (quality of life, and, if reported separately from other neurological symptoms, pain, fatigue, depression, cognition, and sleep), adverse events, and cerebrospinal fluid pleocytosis. Pooling of data and meta-analysis will only be deemed justified between studies with similar design (e.g., RCTs are only combined with other RCTs), characteristics (e.g., similar populations), and of acceptable heterogeneity (I2 < 80%). Pooled estimates will be calculated using RevMan software. Prespecified subgroup analyses will evaluate groups of antibiotics, length of antibiotic treatment, and different doses of doxycycline. We will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion This systematic review will summarize the available evidence from RCTs and non-randomized studies regarding pharmacological treatment of neuroborreliosis. The available evidence will be summarized and discussed to provide a basis for decision-making for patients and healthcare professionals. Systematic review registration PROSPERO registration number: CRD42014008839
    10/2014; 3(1):117. DOI:10.1186/2046-4053-3-117
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    ABSTRACT: Informal carers of people with dementia can suffer from depressive symptoms, emotional distress and other physiological, social and financial consequences.
    Cochrane database of systematic reviews (Online) 09/2014; 9:CD009126. DOI:10.1002/14651858.CD009126.pub2 · 5.70 Impact Factor
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    ABSTRACT: Non-steroidal antiandrogens and castration are the main therapy options for advanced stages of prostate cancer. However, debate regarding the value of these treatment options continues.
    Cochrane database of systematic reviews (Online) 06/2014; 6(6):CD009266. DOI:10.1002/14651858.CD009266.pub2 · 5.70 Impact Factor
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    ABSTRACT: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification. A total of 44 international interdisciplinary observers each defined a [(18)F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were "experts" (E; n = 3), "experienced interdisciplinary pairs" (EP; 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), "single field specialists" (SFS; n = 13), and "students" (S; n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated. E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35). The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field.
    Strahlentherapie und Onkologie 03/2014; 190(6). DOI:10.1007/s00066-014-0644-y · 2.73 Impact Factor
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    ABSTRACT: The 1964 U.S. Surgeon General's report on smoking and health included substantial use of a meta-analysis by statistician William G. Cochran that was far ahead of its time. A reconstruction of that meta-analysis includes a forest plot of the crucial results.
    New England Journal of Medicine 01/2014; 370(2):186-188. DOI:10.1056/NEJMc1315315 · 54.42 Impact Factor
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    ABSTRACT: Neoadjuvant chemotherapy (NC) is an established therapy in breast cancer, able to downstage positive axillary lymph nodes, but might hamper their detectibility. Even if clinical observations suggest lower lymph node yield (LNY) after NC, data are inconclusive and it is unclear whether NC dependent parameters influence detection rates by axillary lymph node dissection (ALND). We analyzed retrospectively the LNY in 182 patients with ALND after NC and 351 patients with primary ALND. Impact of surgery or pathological examination and specific histomorphological alterations were evaluated. Outcome analyses regarding recurrence rates, disease free (DFS) and overall survival (OS) were performed. Axillary LNY was significantly lower in the NC in comparison to the primary surgery group (median 13 vs. 16; p < 0.0001). The likelihood of incomplete axillary staging was four times higher in the NC group (14.8% vs. 3.4%, p < 0.0001). Multivariate analyses excluded any influence by surgeon or pathologist. However, the chemotherapy dependent histological feature lymphoid depletion was an independent predictive factor for a lower LNY. Outcome analyses revealed no significant impact of the LNY on local and regional recurrence rates as well as DFS and OS, respectively. NC significantly reduces the LNY by ALND and has profound effects on the histomorphological appearance of lymph nodes. The current recommendations for a minimum removal of 10 lymph nodes by ALND are clearly compromised by the clinically already established concept of NC. The LNY of less than 10 by ALND after NC might not be indicative for an insufficient axillary staging.
    BMC Cancer 01/2014; 14(1):4. DOI:10.1186/1471-2407-14-4 · 3.32 Impact Factor
  • Gerta Rücker, Martin Schumacher
    The Lancet Infectious Diseases 12/2013; 13(12):1012-1013. DOI:10.1016/S1473-3099(13)70303-7 · 19.45 Impact Factor
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    ABSTRACT: The aim of this study was to determine the prevalence of respiratory viruses and to prospectively evaluate the performance of the fast-track diagnostics (FTD) respiratory pathogens multiplex PCR assay shortly after the 2009/10 influenza pandemic. Highly sensitive monoplex real-time PCR assays served as references. Discrepant results were further analyzed by the xTAG RVP Fast assay. A total of 369 respiratory samples from children and adults were collected prospectively in Germany from December 2009 until June 2010. The sensitivity and specificity of the FTD assay after resolution of discrepant results was 92.2 % and 99.5 %, respectively. Lowest specificity of the FTD assay was observed for human bocavirus. Multiple detections were recorded in 33/369 (8.9 %) of the samples by monoplex PCR and in 43/369 (11.7 %) using the FTD assay. The most prevalent viruses were respiratory syncytial virus and human metapneumovirus. Only pandemic influenza virus A/H1N1 (2009), and not seasonal influenza virus, was detected. Viruses other than influenza virus accounted for the majority of acute respiratory infections. The FTD assay can be easily implemented in general diagnostic laboratories and facilitate the optimization of patient-management schemes.
    Archives of Virology 10/2013; 159(4). DOI:10.1007/s00705-013-1876-3 · 2.28 Impact Factor
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    ABSTRACT: IMPORTANCE When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications for the interpretation of placebo-controlled trials, the knowledge base on the subject is weak. OBJECTIVE To investigate whether different types of placebo treatments are associated with different responses using the studies of migraine prophylaxis for this analysis. DESIGN, SETTING, AND PARTICIPANTS We searched relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects estimates according to the type of placebo for the proportions of treatment response. We performed meta-regression analyses to identify sources of heterogeneity. In a network meta-analysis, direct and indirect comparisons within and across trials were combined. Additional analyses were performed for continuous outcomes. EXPOSURE Active migraine treatment and the placebo control conditions. MAIN OUTCOMES AND MEASURES Proportion of treatment responders, defined as having an attack frequency reduction of at least 50%. Other available outcomes in order of preference included a reduction of 50% or greater in migraine days, the number of headache days, or headache score or a significant improvement as assessed by the patients or their physicians. RESULTS Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI, 0.30-0.47]) and sham surgery (0.58 [0.37-0.77]) were associated with a more pronounced reduction of migraine frequency than oral pharmacological placebos (0.22 [0.17-0.28]) and were the only significant predictors of response in placebo groups in multivariable analyses (P = .005 and P = .001, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]). Corresponding analyses for continuous outcomes showed similar findings. CONCLUSIONS AND RELEVANCE Sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ between treatment modalities.
    JAMA Internal Medicine 10/2013; 173(21):1941-1951. DOI:10.1001/jamainternmed.2013.10391 · 13.25 Impact Factor
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    ABSTRACT: For some patients with recurrent, unresectable, and previously irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT) may be a curative option. Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management. This retrospective single-institutional study investigates feasibility, toxicity, and outcome of reirradiation (re-RT) combined with EGFR blockade for these patients.Between June 2008 and June 2012, 23 patients with inoperable and previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients.One patient died of anaphylactic shock during the first cetuximab administration; two discontinued treatment on their own request. In all, 20 patients completed re-RT (50.4–66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35 %), dysphagia (30 %), acneiform rash (30 %), and mucositis (15 %). The 1-year overall survival rate was 34.8 %. Median overall and progression-free survival times were 9 and 4.3 months, respectively. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95 % confidence interval [CI] 0.0383–0.6111), while a period from first radiation to re-RT longer than 120 months negatively (HR 0.1633, 95 % CI 0.0305–0.8734) influenced patient with concurrent cetuximab was feasible. Compared to platinum-based chemotherapy with fluorouracil and cetuximab, this therapeutic approach did not demonstrate survival benefit. Prolonged intervals from first treatment to re-RT seem to be unfavorable.
    Strahlentherapie und Onkologie 10/2013; 189(10). DOI:10.1007/s00066-013-0402-6 · 2.73 Impact Factor
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    Daniela Vetter, Gerta Rücker, Ilse Storch
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    ABSTRACT: Meta-analysis is a powerful research summarization technique. In the medical field, for example, meta-analysis is an indispensable tool as part of systematic reviews for healthcare decision making. The advantages of meta-analysis have also been recognized in the fields of ecology and conservation biology with the method becoming increasingly popular since the 1990s. ‘‘Meta-analysis’’, however, is not well-defined in these fields, but is regularly confused with other summary analysis techniques, such as multiple regression methods, vote-counting or other quantitative analyses. We argue that this vague and inconsistent utilization of the term is problematic, because a meta-analysis typically provides scientifically rigorous results. We therefore advocate a consistent and well-defined usage of the term in our disciplines, based on the standardized definition applied in the medical sciences. We searched the Web of Knowledge for meta-analyses in the subject area ‘‘biodiversity conservation’’ and evaluated the usage of the term ‘‘meta-analysis’’. Based on meta-analysis literature from the medical sciences, we determined steps that in our opinion are mandatory when performing meta-analysis and rated articles according to these steps. In the first round of rating, we assessed the usage of four ‘‘technical’’ steps that are normally applied in meta-analytical software. In the second round, we only evaluated the highly rated articles from the first round. We considered three steps regarding more qualitative aspects of interpretation and results presentation. Of the 133 evaluated articles in the first round, only 45% fulfilled all technical requirements for a meta-analysis, while 25% did not fulfill any of the requisite steps. In the second round, only one article of 83 fulfilled all requisite steps, while 22% did not fulfill any requirement. Our findings highlight the ambiguous and vague usage of the term ‘‘meta-analysis’’ in ecology and conservation biology and underline the importance of a consistent and clear definition. We conclude with recommendations on how the term should be applied in the future.
    Ecosphere 06/2013; 4(6):74. DOI:10.1890/ES13-00062.1 · 2.60 Impact Factor
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    ABSTRACT: Background There is currently no consensus regarding the optimal timing for androgen suppression therapy in patients with prostate cancer that have undergone local therapy with curative intent but are proven to have node-positive disease without signs of distant metastases at the time of local therapy. The objective of this systematic review was to determine the benefits and harms of early (at the time of local therapy) versus deferred (at the time of clinical disease progression) androgen suppression therapy for patients with node-positive prostate cancer after local therapy. Methods The protocol was registered prospectively (CRD42011001221; We searched the MEDLINE, EMBASE, and CENTRAL databases, as well as reference lists, the abstracts of three major conferences, and three trial registers, to identify randomized controlled trials (search update 04/08/2012). Two authors independently screened the identified articles, assessed trial quality, and extracted data. Results Four studies including 398 patients were identified for inclusion. Early androgen suppression therapy lead to a significant decrease in overall mortality (HR 0.62, 95% CI 0.46-0.84), cancer-specific mortality (HR 0.34, 95% CI 0.18-0.64), and clinical progression at 3 or 9 years (RR 0.29, 95% CI 0.16-0.52 at 3 years and RR 0.49, 95% CI 0.36-0.67 at 9 years). One study showed an increase of adverse effects with early androgen suppression therapy. All trials had substantial methodological limitations. Conclusions The data available suggest an improvement in survival and delayed disease progression but increased adverse events for patients with node-positive prostate cancer after local therapy treated with early androgen suppression therapy versus deferred androgen suppression therapy. However, quality of data is low. Randomized controlled trials with blinding of outcome assessment, planned to determine the timing of androgen suppression therapy in node-positive prostate cancer using modern diagnostic imaging modalities, biochemical testing, and standardized follow-up schedules should be conducted to confirm these findings.
    BMC Cancer 03/2013; 13(1):131. DOI:10.1186/1471-2407-13-131 · 3.32 Impact Factor
  • Gerta Rücker, Gerd Antes
    Restorative neurology and neuroscience 01/2013; 31(3). DOI:10.3233/RNN-120275 · 4.18 Impact Factor
  • Gerta Rücker
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    ABSTRACT: Network meta-analysis is an active field of research in clinical biostatistics. It aims to combine information from all randomized comparisons among a set of treatments for a given medical condition. We show how graph-theoretical methods can be applied to network meta-analysis. A meta-analytic graph consists of vertices (treatments) and edges (randomized comparisons). We illustrate the correspondence between meta-analytic networks and electrical networks, where variance corresponds to resistance, treatment effects to voltage, and weighted treatment effects to current flows. Based thereon, we then show that graph-theoretical methods that have been routinely applied to electrical networks also work well in network meta-analysis. In more detail, the resulting consistent treatment effects induced in the edges can be estimated via the Moore–Penrose pseudoinverse of the Laplacian matrix. Moreover, the variances of the treatment effects are estimated in analogy to electrical effective resistances. It is shown that this method, being computationally simple, leads to the usual fixed effect model estimate when applied to pairwise meta-analysis and is consistent with published results when applied to network meta-analysis examples from the literature. Moreover, problems of heterogeneity and inconsistency, random effects modeling and including multi-armed trials are addressed. Copyright © 2012 John Wiley & Sons, Ltd.
    12/2012; 3(4). DOI:10.1002/jrsm.1058
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    ABSTRACT: Background: In medical imaging used for planning of radiation therapy, observers delineate contours of a treatment volume in a series of images of uniform slice thickness. Objective: To summarize agreement in contouring between an arbitrary number of observers by a single number, we generalized the kappa index proposed by Zijdenbos et al. (1994). Methods: Observers characterized voxels by allocating them to one of two categories, inside or outside the contoured region. Fleiss' kappa was used to measure association between n indistinguishable observers. Given the number Vi of voxels contoured by exactly i observers (i = 1, ..., n), the resulting overall kappa is representable as a ratio of weighted sums of the Vi. Results: Overall kappa was applied to analyze inter-center variations in a multicenter trial on radiotherapy planning in patients with locally advanced lung cancer. A contouring dummy run was performed within the quality assurance program. Contouring was done twice, once before and once after a training program. Observer agreement was enhanced from 0.59 (with a 95% confidence interval (CI) of 0.51-0.67) to 0.69 (95% CI 0.59-0.78). Conclusion: By contrast to average pairwise indices, overall kappa measures observer agreement for more than two observers using the full information about overlapping volumes, while not distinguishing between observers. It is particularly adequate for measuring observer agreement when identification of observers is not possible or desirable and when there is no gold standard.
    Methods of Information in Medicine 11/2012; 51(6):489-494. DOI:10.3414/ME12-01-0005 · 1.08 Impact Factor

Publication Stats

2k Citations
338.90 Total Impact Points


  • 2008–2015
    • Universitätsklinikum Freiburg
      • Institute of Medical Biometry and Statistics
      Freiburg an der Elbe, Lower Saxony, Germany
  • 1991–2014
    • University of Freiburg
      • • Institute of Medical Biometry and Medical Informatics
      • • Institute of Organic Chemistry and Biochemistry (Organic Chemistry)
      Freiburg, Baden-Württemberg, Germany
  • 2002
    • University of Bayreuth
      Bayreuth, Bavaria, Germany