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Großhansdorf, Germany

Evidence-based guidelines are important for primary prevention of allergic diseases, i.e. atopic dermatitis, allergic rhinoconjunctivitis, and allergic asthma. Scientific publications were searched for the period 2008 - 2013 in the electronic databases and of originally 3,284 hits, 165 studies (15 systematic reviews, 1 meta-analysis, 31 RCTs, 65 cohort-, 12 case-control, and 41 cross sectional studies) were reviewed. The revision of this guideline in 2014 resulted in (1) a conformation of existing recommendations, (2) substantial revisions, and (3) new recommendations. The recommendation on breast feeding over 4 months was confirmed. If breast feeding is not possible, hypoallergenic formulas for babies with a family history of atopic disease is the recommended alternative feeding strategy. Neonates without a family history of atopy can receive a cow's milk formula. Actually there is no scientific evidence for a prolonged introduction of solid food with respect to allergy prevention. Therefore the guideline for allergy prevention suggests introducing solid food with the beginning of the 5th month. The advice to avoid environmental tobacco smoke and the suggestion to vaccinate children according to current recommendations were grossly unchanged, as well as the avoidance of overweight, fish consumption (during pregnancy/ breast feeding and as solid food in the first year), reduction of the exposure to indoor and outdoor air pollutants. The recommendation regarding pet keeping were alleviated and specified: While dogs in a household are not associated with an increased allergy risk, families at risk for atopic disease should not acquire a cat. Newly introduced was the information, that children born via Caesarean section showed up to be at increased risk for the development of asthma later in life. © 2015 Dustri-Verlag Dr. Karl Feistle.

Wedzicha J.A.,Imperial College London | Calverley P.M.,University of Liverpool | Rabe K.F.,University of Kiel | Rabe K.F.,Airway Research Center North
International Journal of COPD | Year: 2016

COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation. COPD is associated with worsening airflow limita- tion over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity. The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depres- sion, and pneumonia. COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode. Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations. Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD. Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis. Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity. Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease. Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. © 2016 Wedzicha et al.

Diel R.,University of Kiel | Diel R.,Airway Research Center North | Hittel N.,Otsuka Novel Products | Schaberg T.,Diaconess Hospital Rotenburg Wumme
Respiratory Medicine | Year: 2015

Objective To assess the cost-effectiveness of adding delamanid (Deltyba™) to a background regimen (BR) for treating multidrug-resistant tuberculosis (MDR-TB) in Germany. Methods The incremental cost-effectiveness of treating a cohort of MDR-TB patients, 38-years old on average, with Deltyba™ plus BR versus a five drug- BR regimen alone was compared in a Markov model over a period of 10 years. Cost per quality-adjusted life year (QALY) and disability-adjusted life years (DALY) were determined from a societal perspective. Recent data from a German cost calculation on MDR-TB were applied to the 24-month outcome results of patients participating in the placebo-controlled, phase II Otsuka's Trial 204. Costs and effectiveness were discounted at a rate of 3% and subjected to deterministic as well as probabilistic sensitivity analysis in a Monte Carlo simulation. Results Based on the current market prices the total discounted cost per patient on BR plus Deltyba™ was €142,732 compared to €150,909 for BR alone. The total discounted QALYs per patient were 8.47 for Deltyba™ versus 6.13 for BR alone. Accordingly, the addition of Deltyba™ proved to be dominant over the BR alone-strategy by simultaneously saving €8177 and gaining 2.34 QALYs. Deltyba™ was cost saving in 73% of probabilistic sensitivity analyses compared to BR alone and 100% cost effective at a willingness-to-pay (WTP) threshold of €10,000. Conclusions Under conditions prevalent in Germany, Deltyba™ added to a five drug BR regimen is likely to be cost-saving compared to BR alone under a wide range of assumptions. Adding delamanid remained cost-effective when costs due to loss of productivity were excluded as the QALYs gained by lower lethality and a higher proportion of successfully treated patients outweighed the delamanid drug costs. These results strongly support the application of Deltyba™ in treating MDR-TB patients. © 2015 The Authors.

Reck M.,Airway Research Center North | Paz-Ares L.,University of Seville
Seminars in Oncology | Year: 2015

Despite the availability of radiotherapy, cytotoxic agents, and targeted agents, a high unmet medical need remains for novel therapies that improve treatment outcomes in patients with lung cancer who are ineligible for surgical resection. Building upon the early promise shown with general immunostimulatory agents, immuno-oncology is at the forefront of research in this field, with several novel agents currently under investigation. In particular, agents targeting immune checkpoints, such as the cytotoxic T-lymphocyte antigen-4 (CTLA-4) receptor and programmed death-1 (PD-1) receptor, have shown in early clinical trials potential for improving tumor responses and survival in patients with non-small cell lung cancer (NSCLC). Here, we examine the rationale for targeting immune checkpoints in lung cancer and review the clinical data from studies with immune checkpoint inhibitors currently in development. The challenges associated with optimizing treatment with these agents in lung cancer also are discussed. © 2015 Elsevier Inc.

Thatcher N.,The Christie Hospital | Hirsch F.R.,Aurora University | Luft A.V.,Leningrad Regional Clinical Hospital | Szczesna A.,Regional Lung Disease Hospital | And 16 more authors.
The Lancet Oncology | Year: 2015

Background: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. Methods: We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m2 administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m2 administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash-a class effect of EGFR antibodies-that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Findings: Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11·5 months [95% CI 10·4-12·6]) vs 9·9 months [8·9-11·1]; stratified hazard ratio 0·84 [95% CI 0·74-0·96; p=0·01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3-4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [<1%]). Including events related to disease progression, adverse events with an outcome of death were reported for 66 (12%) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 (11%) of 541 patients in the gemcitabine and cisplatin group; these were deemed to be related to study drugs in 15 (3%) and ten (2%) patients, respectively. Overall, we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations. Interpretation: Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease. Funding: Eli Lilly and Company. © 2015 Elsevier Ltd.

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