Joensuu H.,University of Helsinki |
Eriksson M.,Skåne University Hospital |
Hall K.S.,University of Oslo |
Hartmann J.T.,University of Tübingen |
And 18 more authors.
JAMA - Journal of the American Medical Association | Year: 2012
Context: Adjuvant imatinib administered for 12 months after surgery has improved recurrence-free survival (RFS) of patients with operable gastrointestinal stromal tumor (GIST) compared with placebo. Objective: To investigate the role of imatinib administration duration as adjuvant treatment of patients who have a high estimated risk for GIST recurrence after surgery. Design, Setting, and Patients: Patients with KIT-positive GIST removed at surgery were entered between February 2004 and September 2008 to this randomized, open-label phase 3 study conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of GIST recurrence was estimated using the modified National Institutes of Health Consensus Criteria. Intervention: Imatinib, 400 mg per day, orally for either 12 months or 36 months, started within 12 weeks of surgery. Main Outcome Measures: The primary end point was RFS; the secondary end points included overall survival and treatment safety. Results: Two hundred patients were allocated to each group. The median follow-up time after randomization was 54 months in December 2010. Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to-treat population at a central pathology review. KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%) available for testing. Patients assigned for 36 months of imatinib had longer RFS compared with those assigned for 12 months (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P<.001; 5-year RFS, 65.6% vs 47.9%, respectively) and longer overall survival (HR, 0.45; 95% CI, 0.22-0.89; P=.02; 5-year survival, 92.0% vs 81.7%). Imatinib was generally well tolerated, but 12.6% and 25.8% of patients assigned to the 12- and 36-month groups, respectively, discontinued imatinib for a reason other than GIST recurrence. Conclusion: Compared with 12 months of adjuvant imatinib, 36 months of imatinib improved RFS and overall survival of GIST patients with a high risk of GIST recurrence. ©2012 American Medical Association. All rights reserved.
Boyle R.J.,Imperial College London |
Pedroletti C.,Karolinska Institutet |
Wickman M.,Karolinska Institutet |
Wickman M.,Sachs Childrens Hospital |
And 6 more authors.
Thorax | Year: 2012
Objective: To determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. Setting: Nineteen European asthma clinics. Participants 312 patients aged 7-70 with inadequately controlled persistent atopic asthma. Main outcome measure: Proportion of patients with an increase of ≥0.5 points in asthma quality of life score after 1 year of treatment. Results: TLA devices were successfully installed in the bedrooms of 282 (90%) patients included in the primary efficacy analysis. There was a difference in treatment response rate between active (143 of 189, 76%) and placebo (56 of 92, 61%) groups, difference 14.8% (95% CI 3.1 to 26.5, p=0.02). 3 In patients aged ≥12, on whom the study was powered, the difference in response rate was similar-active 106 of 143 (74%), placebo 42 of 70 (60%), difference 14.1% (0.6 to 27.7, p=0.059). There was a difference between groups in fractional exhaled nitric oxide change of -7.1 ppb (-13.6 to -0.7, p=0.03). Active treatment was associated with less increase in cat-specific IgE than placebo. There was no difference in adverse event rates between treatment groups. Conclusion: Inhalant exposure reduction with TLA improves quality of life, airway inflammation and systemic allergy in patients with persistent atopic asthma. TLA may be a treatment option for patients with inadequately controlled persistent atopic asthma.
Muller-Brandes C.,Hannover Medical School |
Kramer U.,IUF Leibniz Research Institute for Environmental Medicine |
Gappa M.,Hannover Medical School |
Gappa M.,Childrens Hospital and Research Institute |
And 8 more authors.
European Respiratory Journal | Year: 2014
The gold standard for assessing quality of forced expiratory manoeuvres is visual inspection by an expert. American Thoracic Society/European Respiratory Society numerical quality criteria (NQC) include back-extrapolated volume (BEV), repeatability and forced expiratory time (FET). Equipment currently available provides feedback tempting the investigator to use NQC as pass-fail criterion. To investigate whether using NQC instead of visual acceptability is a valid option, we analysed data from a multicentre national reference study in Germany of children aged 4-18 years. Spirometry was performed under field conditions. Receiver operating characteristic analysis was used to assess performance of BEV, repeatability, FET and a combination thereof in relation to visual acceptability. We included data from 3133 healthy Caucasians in the analyses; 72% delivered at least two visually acceptable manoeuvres. Of these, 59% would have been rejected based on combined NQC, mainly because the FET criterion was not feasible. Specificity of the NQC was generally low (BEV 10%, repeatability 30% and FET 50%). Receiver operating characteristic analysis showed that a combination of the three measures could reach at best a sensitivity of 90% and specificity of 56%. We conclude that visual control is mandatory and NQC may help obtain the best possible results, but a fixed cut-off for FET should be abandoned. Copyright © ERS 2014.
Akcam T.M.,Surgery Academy |
Gubisch W.,Marien Hospital |
Unlu H.,Ekol Hospital
Facial Plastic Surgery Clinics of North America | Year: 2012
This article focuses on the surgical treatment of nonmelanoma skin cancers of the head and neck. The risk factors of nonmelanoma skin cancers for recurrence and metastases that are important for choosing the best treatment option are summarized. Surgical treatment options including surgical excision with standard margins, frozen section, staged surgery, and Mohs micrographic surgery are described. Indications, techniques, outcomes, and advantages and disadvantages of each approach are reviewed. Finally, management of incomplete excisions is discussed. © 2012 Elsevier Inc.
Borusiak P.,Sozialpadiatrisches Zentrum |
Biedermann H.,Praxis fur Manualtherapie |
Bosserhoff S.,Marien Hospital |
Opp J.,Sozialpadiatrisches Zentrum
Headache | Year: 2010
Objective.-Clinical trials concerning cervical spine manipulation and mobilization in children and adolescents with cervicogenic headache are lacking. Methods.-We performed a multicenter, prospective, randomized, placebo-controlled, and blinded trial in 52 children and adolescents (21 boys, 31 girls) aged 7-15. After prospective baseline documentation for 2 months patients were either assigned to placebo or true manipulation with another 2-month follow-up. Main outcome measures were defined as: percentage of days with headache, total duration of headache, days with school absence due to headache, consume of analgesics, intensity of headache. Results.-We did not find a significant difference comparing the groups with placebo and true manipulation with respect to the defined main outcome measures. Conclusions.-We were not able to show an efficacy of cervical spine manipulation in 52 children and adolescents. © 2009 American Headache Society.
List A.F.,H. Lee Moffitt Cancer Center and Research Institute |
Bennett J.M.,James lmot Cancer Center |
Sekeres M.A.,Cleveland Clinic |
Skikne B.,Celgene |
And 5 more authors.
Leukemia | Year: 2014
Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression. © 2014 Macmillan Publishers Limited. All rights reserved.
Clinical trial: Controlled, open, randomized multicentre study comparing the effects of treatment on quality of life, safety and efficacy of budesonide or mesalazine enemas in active left-sided ulcerative colitis
Hartmann F.,Marien Hospital |
Hartmann F.,Colitis Crohn Clinical Research Center Rhein Main |
Stein J.,Colitis Crohn Clinical Research Center Rhein Main |
Stein J.,Goethe University Frankfurt
Alimentary Pharmacology and Therapeutics | Year: 2010
Aliment Pharmacol Ther 2010; 32: 368-376 SummaryBackground Therapy for active left-sided ulcerative colitis usually involves topical application of mesalazine (mesalamine) or budesonide. Aim To compare the efficacy and safety of budesonide enema and mesalazine enema in the treatment of active left-sided ulcerative colitis. Methods A total of 237 patients with mild-moderate ulcerative colitis were randomized open 1:1 to receive either budesonide (n = 118) or mesalazine enemas (n = 119) for 8 weeks. Efficacy variables were clinical activity index, endoscopic, histological index and IBDQ scores after 4 and 8 weeks. Results Clinical remission (intention-to-treat analysis) at week 4 was 63.5% for budesonide enemas and 77.2% for mesalazine enemas (P < 0.05). The respective values for the per protocol population (PP) were 59.9% examined in the budesonide group and 77.5% in the mesalazine group (P < 0.02). At the final visit (W8), clinical remission was diagnosed in the ITT analysis for 64.4% of the budesonide group and 77.4% of the mesalazine group (P < 0.05). The respective values for the PP analysis were 59.5% in the budesonide group and 75.3% in the mesalazine group (P < 0.02). Conclusions Compared with budesonide, mesalazine enema was associated with a significantly higher remission rate; this was supported by favourable trends in endoscopic, histological remission rates and the IBDQ score. © 2010 Blackwell Publishing Ltd.
Diederich S.,Marien Hospital
Cancer Imaging | Year: 2011
The poor outcome in symptomatic lung cancer patients and the much better prognosis when lung cancer is diagnosed and treated at early asymptomatic stages call for screening. As lung cancer predominantly affects smokers and individuals exposed to other carcinogens, screening programs need not include the whole population but only these risk groups. Every screening program will tend to better identify the more indolent tumours that grow slowly enough to be detected by screening before symptoms develop, whereas aggressive fast-growing tumours may present as interval cancers despite screening (length-time bias). Some malignant tumours detected with screening may never cause the person's death due to competing causes for death, particularly in heavy smokers, such as cardiovascular disease or other cancers (overdiagnosis bias). If a cancer is still lethal despite detection through screening, the affected individual may live longer with the diagnosis of cancer but not longer altogether (lead-time bias). It is likely that this will have a negative effect on that individual's quality of life. Participation in screening programs may have beneficial as well as adverse effects on smoking habits; in the worst case it may encourage people to continue smoking. Trials assessing chest radiography or sputum microscopy have not demonstrated a reduction in lung cancer mortality through screening, probably because the tests were not sensitive enough. computed tomography promises better sensitivity. Other modern tests such as fibre optic bronchoscopy, analysis of molecular markers or genetic testing in serum, sputum or exhaled air are not yet ready for clinical practice. © 2009 International Cancer Imaging Society.
Diederich S.,Marien Hospital
Cancer Imaging | Year: 2016
In cancer patient during or following oncologic therapies with respiratory symptoms and pulmonary pathology at chest CT the differential diagnosis includes infection, therapy-induced disease and tumour progression. Although CT morphology may be typical or even pathognomonic in some conditions the diagnosis is usually made by a synopsis of imaging, clinical and laboratory features. Close communication with referring colleagues and a good knowledge of potential side effects of therapeutic concepts, their time course and CT morphology is crucial in the differential diagnosis. This review describes a personal approach to the radiological diagnosis of therapy-induced pulmonary abnormalities in cancer patients. © 2016 Diederich.
Giagounidis A.,Marien Hospital
Current Hematologic Malignancy Reports | Year: 2015
Lenalidomide is nowadays an accepted standard treatment for del(5q) MDS. In non-del(5q) disease, its role is more difficult ot define. Studies have shown that about 18 % of patients treated with a standard dose of 10 mg/day on 21 out of 28 days might achieve erythroid transfusion independence rates that last 6 months or longer. The responses to lenalidomide seem to be inversely correlated to the pre-treatment EPO level. The higher the EPO level, the lower the responses. In the absence of other cytogenetic or molecular predictive factors that allow to discern which patient benefit most from treatment, its incorporation into the treatment algorithm is dependent on the available alternatives, including erythropoietic agents, immunosupressive treatments and experimental strategies like thrombopoietin receptor agonists or the antagonists of transforming growth factor beta. Given that 90 % of responses to lenaldiomide occur within four months of treatment, patients not responding within this time frame should discontinue therapy. © 2015, Springer Science+Business Media New York.