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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.05.547831v1?rss=1 Authors: Berwian, I. M., Troendle, M., de Miquel, C., Ziogas, A., Stefanics, G., Walter, H., Stephan, K. E., Huys, Q. J. Abstract: Background: One in three patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of Major Depressive Disorder (MDD). However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by fMRI has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor. Methods: Patients (n=56) who had remitted from a depressive episode while taking antidepressants underwent EEG recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a six-months follow-up period. 35 healthy controls were also tested. Current source density of the EEG power in the band (8-13Hz) was extracted and alpha-asymmetry was computed by comparing the power across two hemispheres at frontal electrodes (F5 and F6). Outcomes: Sad mood induction was robust across all groups. Reactivity of -asymmetry to sad mood did not distinguish healthy controls from patients with remitted MDD on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in - asymmetry compared to patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy). Interpretation: A simple EEG-based measure of emotional reactivity may have clinical utility in the management of antidepressant discontinuation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.22.521602v1?rss=1 Authors: Audrain, S., Barnett, A. J., McAndrews, M. P. Abstract: Objectives Anterior temporal lobectomy as a treatment for temporal lobe epilepsy is associated with a variable degree of postoperative memory decline, and estimating this decline for individual patients is a critical step of preoperative planning. Presently, predicting memory morbidity relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly understood as a network disorder, and memory a network phenomenon. We aimed to assess the utility of functional network measures to predict postoperative memory changes. Methods Patients with left and right temporal lobe epilepsy (TLE) were recruited from an epilepsy clinic. Patients underwent preoperative resting-state fMRI (rs-fMRI) and pre- and postoperative neuropsychological assessment approximately one year after surgery. We compared functional connectivity throughout the memory network of each patient to a healthy control template based on 19 individuals to identify differences in global organization. A second metric indicated the degree of integration of the to-be-resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical and demographic variables as predictors of memory change after surgery. Results Seventy-two adults with TLE were included in this study (37 left/35 right). Left TLE patients with more abnormal memory networks, and with greater functional integration of the to-be-resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change (F(2,31)=12.01, p=0.0001), outperforming standard clinical and demographic variables. None of the variables examined in this study were associated with visuospatial memory change in patients with right TLE. Conclusion Resting-state connectivity provides valuable information concerning both the integrity of to-be-resected tissue as well as functional reserve across memory-relevant regions outside of the to-be-resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision-making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Neurosurgeon Dr. Kurt Yaeger, from Mt. Sinai Hospital in New York, New York, shares insight to being a healthcare worker on the front lines of the COVID-19 pandemic and provides an overview of his recent publication in World Neurosurgery, Patterns of Health Care Costs Due to External Ventricular Drain Infections.Additional Information about this study can be found below.Background: External ventricular drain (EVD) infections are a significant cause of morbidity among neurosurgical patients and have been correlated with increased length of hospital stay and longer requirements for intensive care. To date, no studies have examined the financial impact of EVD infections.Methods: Patients who underwent EVD placement between December 2010 and January 2016 were included in the study. Clinical records were retrospectively reviewed and health care cost data were obtained from the hospital's finance department. Clinical information included patient demographics, details from the hospital course, and outcomes. Total costs, direct/indirect, and fixed/variable costs were analyzed for every patient.Results: Over the 5-year study period, 246 EVDs were placed in 243 patients with an overall infection rate of 9.9% (N = 24). The median EVD duration for infected versus noninfected patients was 19 and 9 days, respectively (P < 0.0001). Median length of intensive care unit stay also was increased for patients with EVD infection (30 days vs. 13 days, P < 0.0001). Total health care costs were significantly greater for infected patients (US$ 168,692 vs. US$ 83,919, P < 0.0001). This trend was comparable for all other cost subtypes, including fixed-direct costs, fixed-indirect costs, variable direct costs, and variable-indirect costs.Conclusions: EVD infection has a substantial effect on clinical morbidity and healthcare costs. These results demonstrate the imperative need to improve EVD infection prevention, particularly in the setting of a value-based health care system.

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Guest: Anish Patel, DO, FACG Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy Chao Chen, PhD, Abraham G Hartzema, PhD, Hong Xiao, PhD, Yu-Jung Wei, PhD, Naueen Chaudhry, MD, Ofor Ewelukwa, MD, Sarah C Glover, DO, Ellen M Zimmermann, MD BACKGROUND AND AIMS:Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS:Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS:In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% ...

Background: Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤ 4 days, as assessed by Halm's criteria) compared with patients with later positive response [TCS] > 4 days). Methods: Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Results: Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 +/- SD 7.0; median 8.0 days vs. mean 15.6 +/- SD 10.5; median 12.0 days, respectively), lower rate of ICU admission (3.3% vs. 21.3%) and shorter duration of ICU stay (mean 6.2 +/- SD 5.7; median 4.0 days vs. mean 10.4 +/- SD 10.1; median 8.0 days, respectively) compared with later responders. Mortality was low in both groups. Conclusions: Achieving early clinical stabilization in CAP (≤ 4 days) is associated with improved outcomes, lower requirement for initial treatment modification or readmission and lower resource use, compared with a later response.

Background: The objective of this prospectively randomized phase II trial (Trial registration: EUCTR2004-004007-37-DE) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone (LET) or letrozole and zoledronic acid (LET + ZOL). Methods: Patients were randomly assigned to receive either LET 2.5 mg/day (n = 79) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks (n = 89) for 6 months. Primary endpoint was clinical response rate as assessed by mammogram readings. The study was terminated prematurely due to insufficient recruitment. We report here on an exploratory analysis of this data. Results: Central assessment of tumor sizes during the treatment period was available for 131 patients (66 LET, 65 LET + ZOL). Clinical responses (complete or partial) were seen in 54.5% (95% CI: 41.8-66.9) of the patients in the LET arm and 69.2% (95% CI: 56.6-80.1) of those in the LET + ZOL arm (P = 0.106). A multivariate model showed an OR of 1.72 (95% CI: 0.83-3.59) for the experimental arm. Conclusion: No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET. However a trend towards a better reponse in the LET + ZOL arm could be observed. This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy, and it may support the evidence for a direct antitumor action of zoledronic acid.

Background: Acute schistosomiasis constitutes a rare but serious condition in individuals experiencing their first prepatent Schistosoma infection. To circumvent costly and time-consuming diagnostics, an early and rapid diagnosis is required. So far, classic diagnostic tools such as parasite microscopy or serology lack considerable sensitivity at this early stage of Schistosoma infection. To validate the use of a blood based real-time polymerase chain reaction (PCR) test for the detection of Schistosoma DNA in patients with acute schistosomiasis who acquired their infection in various endemic regions we conducted a European-wide prospective study in 11 centres specialized in travel medicine and tropical medicine. Methods: Patients with a history of recent travelling to schistosomiasis endemic regions and freshwater contacts, an episode of fever (body temperature >= 38.5 degrees C) and an absolute or relative eosinophil count of >= 700/mu l or 10%, were eligible for participation. PCR testing with DNA extracted from serum was compared with results from serology and microscopy. Results: Of the 38 patients with acute schistosomiasis included into the study, PCR detected Schistosoma DNA in 35 patients at initial presentation (sensitivity 92%). In contrast, sensitivity of serology (enzyme immunoassay and/or immunofluorescence assay) or parasite microscopy was only 70% and 24%, respectively. Conclusion: For the early diagnosis of acute schistosomiasis, real-time PCR for the detection of schistosoma DNA in serum is more sensitive than classic diagnostic tools such as serology or microscopy, irrespective of the region of infection. Generalization of the results to all Schistosoma species may be difficult as in the study presented here only eggs of S. mansoni were detected by microscopy. A minimum amount of two millilitre of serum is required for sufficient diagnostic accuracy.

Background: Data describing real-life management and treatment of community-acquired pneumonia (CAP) in Europe are limited. REACH (NCT01293435) was a retrospective, observational study collecting data on the management of EU patients hospitalized with CAP. The purpose of this study was to understand patient and disease characteristics in patients hospitalized with CAP and to review current clinical practices and outcomes. Methods: Patients were aged >= 18 years, hospitalized with CAP between March 2010 and February 2011, and requiring in-hospital treatment with intravenous antibiotics. An electronic Case Report Form was used to collect patient, disease and treatment variables, including type of CAP, medical history, treatment setting, antibiotics administered and clinical outcomes. Results: Patients (N = 2,039) were recruited from 128 centres in ten EU countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Turkey, UK). The majority of patients were aged >= 65 years (56.4%) and had CAP only (78.8%). Initial antibiotic treatment modification occurred in 28.9% of patients and was more likely in certain groups (patients with comorbidities; more severely ill patients; patients with healthcare-associated pneumonia, immunosuppression or recurrent episodes of CAP). Streamlining (de-escalation) of therapy occurred in 5.1% of patients. Mean length of hospital stay was 12.6 days and overall mortality was 7.2%. Conclusion: These data provide a current overview of clinical practice in patients with CAP in EU hospitals, revealing high rates of initial antibiotic treatment modification. The findings may precipitate reassessment of optimal management regimens for hospitalized CAP patients.

Background: Coronary artery calcifications (CAC) are markers of coronary atherosclerosis, but do not correlate well with stenosis severity. This study intended to evaluate clinical situations where a combined approach of coronary calcium scoring (CS) and nuclear stress test (SPECT-MPI) is useful for the detection of relevant CAD. Methods: Patients with clinical indication for invasive coronary angiography (ICA) were included into our study during 08/2005- 09/2008. At first all patients underwent CS procedure as part of the study protocol performed by either using a multidetector computed tomography (CT) scanner or a dual-source CT imager. CAC were automatically defined by dedicated software and the Agatston score was semi-automatically calculated. A stress-rest SPECT-MPI study was performed afterwards and scintigraphic images were evaluated quantitatively. Then all patients underwent ICA. Thereby significant CAD was defined as luminal stenosis >= 75% in quantitative coronary analysis (QCA) in >= 1 epicardial vessel. To compare data lacking Gaussian distribution an unpaired Wilcoxon-Test (Mann-Whitney) was used. Otherwise a Students t-test for unpaired samples was applied. Calculations were considered to be significant at a p-value of 0 significant CAD was confirmed by ICA, and excluded in 152/284 (53.5%) patients. Sensitivity for CAD detection by CS alone was calculated as 99.2%, specificity was 30.3%, and negative predictive value was 98.5%. An additional SPECT in patients with CS>0 increased specificity to 80.9% while reducing sensitivity to 87.9%. Diagnostic accuracy was 84.2%. Conclusions: In patients without CS=0 significant CAD can be excluded with a high negative predictive value by CS alone. An additional SPECT-MPI in those patients with CS>0 leads to a high diagnostic accuracy for the detection of CAD while reducing the number of patients needing invasive diagnostic procedure.

Background: An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Methods: Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. Results: HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Conclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic value. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies.

Background: Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient's serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15-3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15-3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods: Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15-3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results: Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15-3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p < 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions: This study found significantly elevated Mucin-1 serum concentrations in ovarian carcinoma patients as compared to those women suffering from benign ovarian diseases. However, it needs to be noted that Mucin-1 concentrations in carcinoma patients showed a rather high variability. Results from immunohistochemistry indicate that Mucin-1 has a prognostic relevance in ovarian carcinomas when evaluating the expression by VU4H5 antibody.

Background: Recent epidemiological studies suggest that chemotherapy has not contributed to a marked improvement of patient outcome during the last decades. In most randomized trials which investigated the efficacy of a 1st-line schedule for metastatic breast cancer (MBC), the median survival ranged between 18 and 24 months. The goal of the present study was to analyse the survival of patients with MBC treated in a single university outpatient clinic. Methods: Patients who had received their complete anti-cancer treatment for MBC in our outpatient clinic between 2000 and 2005 were analyzed for treatment and survival. Results: 232 patients [median age of 53, range 27-87 yrs; ER and/or PgR positive (HR+) n=174 (75%); HER2 over-expression (HER2+) n=79 (34%)] were included in the analysis. Endocrine sensitive patients received 1-2 (58.6%), 3-4 (37.4%) and 5-6 (2.3%) hormonal regimens. Of all patients 53.4% received up to 3 cytostatic agents in palliative intent, 4-6 regimens were applied in 22.1% and 12.9% received more than 6 subsequent regimens during the course of their disease. The median overall survival (OS) from time of diagnosis of metastatic disease was 44 months. Patients with HR positive tumours survived 46 months, whereas the survival of those with HR negative tumours was 34 months (p=0.07). HER2+ patients who received trastuzumab survived for a median of 44 months. Visceral involvement was associated with a shorter survival as compared to non-visceral disease (34 vs. 57 months, p

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age = grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy. Copyright (C) 2011 S. Karger AG, Basel

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly {[}75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia >= grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to non-hematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status. Copyright (C) 2011 S. Karger AG, Basel

Aim: To determine if botulinum toxin type A (BoNT-A) injections can reduce the frequency and severity of migraines. Methods: Patients (n = 127) were randomized to receive placebo or two doses of BoNT-A (Dysport (R)). The primary endpoint was reduction in number of migraine attacks up to week 8 and between weeks 8 and 12 after injection. Patient diaries were used to record secondary endpoints, including frequency, severity and duration of migraine attacks. Results: There was a mean reduction of 0.54 and 0.94 attacks/month with placebo and BoNT-A, respectively, and absolute attack count was less in the verum group (3.6 vs. 4.2 attacks/month), but this was not statistically significant. The patients' global assessment of efficacy was significantly better than placebo in the high-dose group (p = 0.02) but no effects were seen for the other secondary efficacy parameters. Conclusion: Our study showed a trend towards a reduced attack rate with verum but did not show any statistically significant efficacy of BoNT-A in the prophylactic treatment of migraine. Copyright (C) 2009 S. Karger AG, Basel

Objectives: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. Methods: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFa in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. Results: TNFRSF1A sequencing disclosed a novel V173D/ p.Val202Asp substitution encoded by exon 6 in one family, the c.194–14G.A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFa-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. Conclusions: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients.

Background: Concerning surgical management experience with locking plates for proximal humeral fractures has been described with promising results. Though, distinct hardware related complaints after fracture union are reported. Information concerning the outcome after removal of hardware from the proximal humerus is lacking and most studies on hardware removal are focused on the lower extremity. Therefore the aim of this study was to analyze the functional short-term outcome following removal of locking plate fixation of the proximal humerus. Methods: Patients undergoing removal of a locking plate of the proximal humerus were prospectively followed. Patients were subdivided into the following groups: Group HI: symptoms of hardware related subacromial impingement, Group RD: persisting rotation deficit, Group RQ: patients with request for a hardware removal. The clinical (Constant-Murley score) and radiologic (AP and axial view) follow-up took place three and six months after the operation. To evaluate subjective results, the Medical Outcomes Study Short Form-36 (SF-36), was completed. Results: 59 patients were included. The mean length of time with the hardware in place was 15.2 +/- 3.81 months. The mean of the adjusted overall Constant score before hardware removal was 66.2 +/- 25.2% and increased significantly to 73.1 +/- 22.5% after 3 months; and to 84.3 +/- 20.6% after 6 months (p < 0.001). The mean of preoperative pain on the VAS-scale before hardware removal was 5.2 +/- 2.9, after 6 months pain in all groups decreased significantly (p < 0.001). The SF-36 physical component score revealed a significant overall improvement in both genders (p < 0.001) at six months. Conclusion: A significant improvement of clinical outcome following removal was found. However, a general recommendation for hardware removal is not justified, as the risk of an anew surgical and anesthetic procedure with all possible complications has to be carefully taken into account. However, for patients with distinct symptoms it might be justified.

Background: In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid ( 5-ALA) increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy. Methods: Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas. Results: Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes ( moderate dysplasia) which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80-270 min prior to fluorescence bronchoscopy, with an optimum at 160 min. Conclusion: According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio.

Background: An erythema migrans (EM) remaining smaller than 5 cm in diameter, called mini EM by us, has not been addressed in detail. Objective: To study the significance of the mini EM as a sign of Lyme borreliosis. Methods: Patients with suspected mini EM were retrospectively selected out of 257 consecutive patients with EM. The diagnosis of mini EM rested on the cultivation of Borrelia burgdorferi. Species and subtype analysis of culture isolates was performed using outer surface protein A (OspA) polymerase chain reaction followed by restriction fragment length polymorphism and sequencing of the OspA gene. Results: There was one patient with definite (0.4%) and another patient with a questionable mini EM. Borrelia garinii OspA type 6 was identified in the patient with the definite and B. burgdorferi sensu lato in the patient with the questionable mini EM. Conclusion: The mini EM represents an important and apparently uncommon sign of early Lyme borreliosis.

Background and Aim: It has been recommended to monitor the success of H. pylori eradication therapy with the 13C-urea breath test (UBT). However, the UBT is expensive and requires the visit of the fasting patient. Stool tests for detection of H. pylori antigen overcome these problems, but the HpSA® based on polyclonal antibodies has a lower accuracy due to lot-to-lot variability. We evaluated a novel monoclonal stool antigen test in adults referred for upper endoscopy to a private practice. Methods: Patients with a rapid urease test (RUT) were recruited if they denied acid suppressive drugs or antibiotics during the last 4 weeks. H. pylori infection was confirmed by either a positive culture and/or positive histology. Prior to and 4-6 weeks after triple therapy UBT and the monoclonal stool antigen test (RIDASCREEN FemtoLab H.pylori, R-Biopharm AG, Germany) were performed. Results: Of 51 H. pylori infected patients (23f, 28m, age 26-79 years) the UBT was positive in 49 and the stool antigen test in 48 (sensitivity: 96% and 94% respectively), while both tests revealed negative results in 3 patients with a positive RUT only. After eradication therapy, there was 100% concordance between UBT and stool test results (40 negative, 10 positive, 1 lost to follow up). Conclusions: In the setting of a private office this monoclonal stool antigen test is as reliable, but less costly (20 vs. 43 Euro) and more convenient than the UBT for detection of H. pylori infection prior to and 4-6 weeks after eradication therapy.

Background: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. Patients and Methods: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test (TM)). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received >= 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (>= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). Conclusions: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression.

ABSTRACT Backgroud: The World Health Organization Disability Assessment Schedule II (WHODAS II) is a new measure of functioning and disability that is conceptually compatible with the International Classification of Functioning, Disability, and Health (ICF). In contrast to other measures of health status, the WHODAS II is based on an international classification system, it is designed to be applicable across different cultures, and it treats all disorders at parity when determining the level of functioning. Objective: The general objective of this study is to investigate whether the WHODAS II – German version – is a useful instrument for measuring functioning and disability in patients with musculoskeletal conditions, cardiovascular and general internal conditions, stroke, breast cancer and depressive disorder. Specific objectives are to assess its psychometric properties reliability (internal consistency, Cronbach's Alpha), validity (factor analysis of dimensionality, convergent validity, discriminant validity), and sensitivity to change (effect size and standardized response mean), to determine to what extent the WHODAS II correlates with a traditional generic instrument for measuring Health Related Quality of Life, the SF-36, and to define its sensitivity to change after a rehabilitative intervention in relation to that other instrument. Methods: Patients with musculoskeletal conditions, cardiovascular and general internal conditions, stroke, breast cancer and depressive disorder participated. The patients completed the questionnaires WHODAS II and SF-36. After a rehabilitation treatment the same patients completed these questionnaires again in order to assess sensitivity to change. Analyses of measurement properties were conducted. Sensitivity to change was calculated by the effect size (ES) and standardized response mean (SRM). Results: Mean score on the WHODAS II is 21.98 (SD 14.32) for musculoskeletal conditions, 18.47 (SD 15.32) for internal conditions, 38.72 (SD 24.79) for stroke, 23.84 (SD 16.61) for breast cancer, and 44.56 (SD 18.95) for depressive disorder. High reliability is obtained. For the most part, the results of the scale replication confirm the determined six domains of the questionnaire. For the domain Activities, a clear distinction between work und household activities is apparent in both musculoskeletal and internal conditions. The correlations found in comparison to the SF-36 indicated that the WHODAS II (German version) measured indeed the expected constructs. The effect sizes of the WHODAS II Total Score range from 0.163 to 0.687 depending on the subgroup; effect sizes of the SF-36 summary scores from 0.025 to 1.395, respectively. In terms of patients reporting an improvement of general health status, effect sizes are accordingly higher (0.220 to 0.915 for the WHODAS II; 0.083 to 2.023 for the SF-36). Conclusion: The WHODAS II (German version) is a useful instrument for measuring functioning and disability in patients with musculoskeletal diseases, internal diseases, stroke, breast cancer and depressive disorder. It is reliable and valid and shows similar sensitivity to change scores as the SF-36 in the accordingly subscales.

Background: Traumatic experiences associated with cardiac surgery (CS) can result in traumatic memories and posttraumatic stress disorder (PTSD). Because it is known that subjects who develop PTSD often show sustained reductions in circulating cortisol concentrations, we performed a prospective, randomized study to examine whether exogenously administered stress doses of hydrocortisone during the perioperative period of CS reduces the long-term incidence of chronic stress and PTSD symptoms. Methods: Patients (n=91) were prospectively randomized to receive either stress doses of hydrocortisone or standard treatment during the perioperative period of CS. Of 48 available patients at 6 months after CS, 26 had received stress doses of hydrocortisone and 22 standard treatment. Traumatic memories and PTSD symptoms were diagnosed with previously validated questionnaires. Results: As compared with patients after standard therapy, patients from the hydrocortisone group had significantly lower chronic stress symptom scores (p

108 of 421 patients undergoing radiotherapy for malignancies of abdominal and/or pelvic origin participated in this study about quality of life and its changes over time. METHODS: Patients were asked to answer a battery of questionnaires which included the FACT-G, SDS, SSS, FKV, FBK and FLZ combined with questions about their living situation, radiotherapy side effects and need for additional support. Points in time were the first week of radiation therapy (T1), the end of therapy (T2), six weeks (T3) and six months (T4) after radiation. RESULTS: Participants are younger, less depressed, have a better overall performance status and require less additional support than patients refusing or dropping out of the study. Significant changes show in some scores and subscores as there are the physical and overall qol and the relationship with the doctors (FACT-G), physical, social and overall distress (FBK), active coping-style (FKV) and satisfaction with health status (FLZ). Patients prefer asking for information and speaking with their doctors. One third tends to deny to profit from psychotherapeutic interventions. Factor analysis shows six main domains influencing quality of life : social support, physical and social distress, emotional distress, financial satisfaction, social satisfaction and denying coping strategies. DISCUSSION: Participants belong to a well selectioned group with good physical and psychosocial resources. They require nevertheless additional support and admit in most of the cases to profit of talks with psychologists. It has to be supposed that non-participating patients are even more in need of such help. Cluster analysis supposes that desire for psychological support is specific for distressed and dissatisfied patients. Further evaluation of the economic benefits of individual psycho-oncologic prevention is needed. A short scoring questionnaire using six main items of qol should help physicians to prevue the patients need and aptity for psycho-oncologic interventions as for example individual psychotherapy, group therapy and support of the family and medical staff.

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years.

Background: A prospective observational study was undertaken in 2,481 patients undergoing elective colon resection in 114 German centers to identify optimal drug and dosing modalities and risk factors for postoperative infection. Methods: Patients were pair matched using six risk factors and divided into 672 pairs (ceftriaxone vs, other cephalosporins, group A) and 400 pairs (ceftriaxone vs. penicillins, group B). End points were local and systemic postoperative infection and cost effectiveness. Results: Local infection rates were 6.0 versus 6.5% (group A) and 4.0 versus 10.5% (group B); systemic infection rates in groups A and B were 4.9 versus 6.3% and 3.3 versus 10.5%, respectively. Ceftriaxone was more effective than penicillins overall (6.8 vs. 17.8%, p < 0.001). Length of postoperative hospital stay was 16.2 versus 16.9 days (group A) and 15.8 versus 17.6 days (group B). Of the six risk factors, age and concomitant disease were significant for systemic infection, and blood loss, rectum resection and immunosuppressive therapy were significant for local infection. Penicillin was a risk factor compared to ceftriaxone (p < 0.0001). Ceftriaxone saved Q160.7 versus other cephalosporins and O416.2 versus penicillins. Conclusion: Clinical and microbiological efficacy are responsible for the cost effectiveness of ceftriaxone for perioperative prophylaxis in colorectal surgery. Copyright (C) 2000 S. Karger AG, Basel.