Critical assessment of the research outcomes of European birth cohorts: linking environmental factors with non-communicable diseases.

OBJECTIVES: The objective of this review paper was to stimulate collaborative discussions toward the development of a general concept of an open source protocol for a feasible and efficient longitudinal birth cohort study exploring non-communicable diseases (NCDs), their multifactorial etiology and relations between various risk factors. STUDY DESIGN: The present paper systematically reviews the design of existing birth cohorts in Europe containing environmental exposure data, and assesses a quantity and quality of their research outcomes as their potential to be an effective tool for studying non-communicable diseases and their risk factors. METHODS: European birth cohorts with more than 3000 participants have been included in the study. A total number of scientific papers published in the internationally recognized journals and their impact factors and citation records were evaluated for all cohorts as surrogates for their efficiency to contribute to NCDs understanding and thus their prevention. RESULTS: The birth cohorts contributing most significantly to the NCD understanding shared common features: (i) study size between 10,000 and 15,000 mother-child pairs; (ii) repeated assessment of children from prenatal into adulthood; and (iii) availability of biological samples. Smaller cohorts and cohorts with a specific focus generated a lower number of publications; however, these often received considerably a higher number of citations. CONCLUSIONS: General cohort studies with 10,000-15,000 mother-child pairs allow a broader context interpretation, publish a higher number of articles, and often lead to the formation of infrastructures for 'spin-off (nested) studies'.

PET/CT significance for planning radiotherapy of head and neck cancer.

The combination of positron emission tomography and computed tomography (PET/CT) offers metabolic mapping in addition to anatomic information of the primary lesion, nodal and distant metastases in patients with head and neck tumors, and may be therefore beneficial for radiotherapy planning. The aim of our study was to evaluate benefits of combined PET and CT imaging for staging and target volume delineation in this group of patients.Fifty three patients (40 men and 13 women) with confirmed advanced, inoperable or non-radically operated head and neck cancer were assessed based on the results of PET/CT as well as standard diagnostic examinations. All patients were subsequently treated with intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) of 6 MV X-rays. There was an agreement between the standard examinations results and results of PET/CT in 30 cases. In 23 cases there was disagreement either in tumor size, nodal involvement or presence of distant metastases. Results of the tumor size assessment differed significantly in 5 cases. There was no agreement found in nodal involvement in 10 cases. The cancer confirmed by standard examination was not found by PET/CT in 2 cases; 3 PET/CT positive findings were not confirmed by standard examinations. In 3 patients PET-CT revealed new distant metastatic disease. Based on PET/CT assessment we changed treatment strategy and applied potentially curative dose of radiotherapy to previously undiscovered regions in 9 patients. We decided to change the treatment intent in 3 cases and only palliative treatment was applied. Based on our experience and the literature review, PET/CT may be considerable contribution to the standard diagnostic procedures in approximately one third of cases.

[Metastatic renal cell carcinoma treated with everolimus--data from the RENIS Clinical Registry]. / Výsledky terapie metastatického renálního karcinomu lékem everolimus--analýza udaju z klinického registru RENIS.

Everolimus is an oral mTOR kinase inhibitor approved for the treatment of patients with metastatic renal cell carcinoma (mRCC) progressing during or after treatment with vascular endothelial growth factor (VEGF)-targeted agents. Using the national RENIS clinical registry, we have retrospectively analysed outcomes of patients treated for mRCC with everolimus. A total of 78 patients were evaluable. Median progression-free survival from the start of everolimus therapy was 7 months (95% confidence interval 2-12 months). Partial response or stable disease was achieved in 69% of patients. Treatment toxicity was predictable and serious adverse events occurred in only 6% of patients the most common being respiratory toxicity. Everolimus therapy provides significant clinical benefit for heavily pretreated mRCC patients after failure of VEGF-targeted therapy.

[Trabectedin registry]. / Lékový registr--trabectedin.

BACKGROUNDS: The Yondelis (trabectedin) project was initiated in January 2011 with the aim to obtain basic epidemiological information on patients with soft tissue sarcomas, standard treatment procedures, and results of trabectedin therapy in routine clinical practice. Expert patronage is provided by the Czech Society for Oncology, CzMA JEP. The project covers a representative sample of Comprehensive Cancer Care centres established to provide systematic treatment to patients with soft tissue sarcoma. PATIENTS AND METHODS: 45 patients diagnosed with soft tissue sarcoma were retrospectively included in the database. Median age at the initiation of trabectedin therapy was 51 years (23-72 years). Leiomyosarcoma was the most frequent tumour (35.6%), synovial sarcoma occurred in 13.3% of patients; liposarcoma, peripheral nerve sheath tumours and unspecified sarcomas contributed 6.7% each. 62.2% of sarcomas were larger than 5 cm. Trabectedin was administered in a dose of 1.5 mg/m2 once in 3 weeks. 40% of patients received trabectedin as the 2nd line treatment, 35.6% as the 3rd line, and 34.4% as the 4th line. RESULTS: Median number of administered cycles was 4 (1-10 cycles). Neutropenia (28.9% of patients) and elevated liver enzymes (26.7% of patients) were the most frequent adverse affects. 73.8% of patients terminated the therapy due to disease progression. Treatment response was recorded in 6.6% of patients (complete and partial remission), stable disease in 26.7%, and progression in 53.3%. Median overall survival (95% CI) was 11.7 months (9.6; 13.8), median progression-free survival (95% CI) was 3 months (2.4; 3.6). CONCLUSION: Expert cancer societies have recently recommended trabectedin as the 2nd line palliative treatment for soft tissue sarcomas with documented effectiveness, particularly in liposarcomas and leiomyosarcomas, and good safety profile.

[Wet form age-related macular degeneration two years treatment results using anti VEGF drugs]. / Dvouleté výsledky lécby vlhké formy vekem podmínené makulární degenerace s pouzitím léku proti vaskulárnímu endotelovému rustovému faktoru.

AIM: The aim of the study was to establish the efficacy of anti VEGF (Vascular Endothelial Growing Factor) drugs in the treatment of wet form ARMD (Age-Related Macular Degeneration) in everyday clinical practice in the Department of Ophthalmology, Faculty Hospital, Hradec Králové, Czech Republic, E.U., in patients registered in the Czech national registry AMADEUS. MATERIAL AND METHODS: Retrospective study with 24 months follow-up period. In the group were evaluated 143 eyes of 140 patients, out of them were 77 women (65.8 %), of average age 73.09 (71.69 - 74.48) years, and 40 men (34.2 %) of average age 74 (58 - 85) years. All of the patients were completely examined before the beginning of the treatment; during the treatment were, except the standardized eye examination, in patients treated with ranibizumab the color fundus photography and Optical Coherence Tomography (OCT) with measuring of the central retinal thickness performed every three months at least. The patients treated by pegaptanib were examined every six weeks before the drug application. The fluorescence angiography (FA) was performed at the beginning of the treatment to establish the type and extension of the choroidal neovascularization and during the treatment in case of necessity to establish the activity of the choroidal neovascular membrane (CNV). The treatment by ranibizumab was in the regimen PRN (pro re nata), and pegaptanib was applied every six months during the first year with the follow-up evaluation of the findings. The treatment evaluations were performed at 12 and 24 months. RESULTS: During the two years follow - up period, the authors noticed in patients treated with ranibizumab loss of 5.12 letters of ETDRS optotypes in case of mostly classical CNV, in occult CNV loss of 5.45 letters, and in minimally classical CNV loss of 2.83 letters. In three evaluated eyes with classical CNV in patients treated with pegaptanib we noticed after 2 years loss of 6.67 letters, in eleven eyes with occult CNV we established loss of 9.91 letters, and in two eyes with minimally classical CNV the average best-corrected visual acuity (BCVA) remained unchanged. The pegaptanib treatment results may be influenced by small number of evaluated patients. The visual acuity changes during the two years treatment were not statistically significant. We noticed the decrease of average CRT (central retinal thickness) in all types of CNV treated both with ranibizumab and pegaptanib after the two years follow up. To reach these results, an average of 5.51 applications of ranibizumab and 9 applications of pegaptanib during the two years were used. CONCLUSION: In the followed-up group we found, comparing to the natural course of neovascular form of ARMD, retarding of the BCVA decrease during the two years treatment with VEGF inhibitors in everyday clinical practice. Better results were achieved with ranibizumab treatment, however the differences were not statistically significant. Key words: age related macular degeneration, AMADEUS Czech national registry, ranibizumab, pegaptanib.

[Ranibizumab in the ARMD wet form of age-related macular degeneration treatment - two years results obtained from the AMADEuS Registry]. / Ranibizumab v lécbe vlhké formy VPMD - dvouleté výsledky lécby z registru AMADEuS.

AIM: The aim of this study was the retrospective follow up of Age-Related Macular Degeneration (ARMD) wet form patients treated with ranibizumab during 24 months period. The data were recorded into the AMADEuS (Age-related MAcular DEgeneration in patientS in the Czech Republic) Registry and after their evaluation compared with treatment results obtained from other departments of ophthalmology collaborating in the AMADEuS project or results of some foreign studies as well. PATIENTS AND METHODS: The group consisted of patients registered since October 1, 2008 until June 11, 2012, followed up for 24 months period. There were 90 eyes of 89 patients. All patients were completely examined in the Macular ambulance of the Department of Ophthalmology in the Faculty Hospital Brno-Bohunice, Czech Republic, E.U., and consequently the ranibizumab (Lucentis, Novartis) was applied intravitreally in three initials doses one month apart. Thereafter, ranibizumab was applied "on demand". In 43.3 % of eyes the mostly classical, in 27.8 % of eyes occult, and in 28.9 % of eyes the minimally classical choroid neovascular membrane was present. The initial visual acuity was in 3.3 % of eyes in the range 15 - 30 letters of ETDRS optotypes (20/500 - 20/200), in 61.1 % of eyes in the range 31 - 60 letters (20/200 - 20/63), and the visual acuity better than 61 letters of ETDRS optotypes (better than 20/63) was in 35.6 % of eyes. RESULTS: The average initial best-corrected visual acuity (BCVA) in our group of patients was 54.2 letters of EDTRS (SD ± 14.4). At the visit at three months after the start of the treatment the BCVA was 59.6 letters of EDTRS (SD ± 15.0), at the visit after 6 months 57.3 letters of EDTRS (SD ± 14.7), after one year of the study 54.8 letters of EDTRS (SD ± 16), after 18 months of the study 53.4 letters of EDTRS (SD ± 16,8), and after 24 months of the study was the BCVA 51.7 letters of EDTRS (SD ± 16.9). The average CRT (central retinal thickness) value by means of the OCT (optic coherence tomography) examination was at the beginning of the treatment 311.4 µm (SD ± 117.9), after 3 months of treatment 233.5 µm, (SD ± 85.4), after 6 months of treatment 262.2 µm, (SD ± 102,4), after 12 months 261 µm (SD ± 88,4), after 18 months 254.9 µm (SD ± 70.0), and after 24 months 249 µm (SD ± 87.5). The average number of ranibizumab doses during the follow-up period was 5.6. After the 24 months follow-up period, the gain of 15 or more letters of EDTRS was recorded in 11.1 % of patients, the gain of 1 - 14 letters of EDTRS optotypes was recorded in 32.2 % of patients, the decrease of 14 or less letters of EDTRS optotypes was found in 21.2 % of patients, and the decrease of 15 or more letters was found in our group in 22.2 % of patients. CONCLUSION: The ARMD wet form treatment using ranibizumab is up to date the most effective available therapy. The AMADEuS registry is of great importance in the reviewing of the effectiveness of the ARMD wet form treatment.

[Exsudative age-related macular degeneration treatment results in patients registered in the nation-wide AMADEUS register]. / Výsledky lécby vlhké formy vekem podmínené makulární degenerace u pacientu evidovaných v celonárodním registru AMADEUS.

The nation-wide register of patients with the exsudative age-related macular degeneration surveys the appearance and the success rate of the treatment of this disease in the Czech Republic. During the 12 months follow-up period of 38 patients treated with Macugen in monotherapy, receiving at least 7 injections of Macugen during one year period, we found the loss of less than 15 letters of the ETDRS chart in 62.2 % of treated eyes. During the 12 months follow-up period of 205 patients treated with Lucentis in monotherapy, receiving at least 3 injections of Lucentis, we found the loss of less than 15 letters of the EDTRS chart in 82.0 % of treated eyes. During the 12 months follow-up period of patients treated with Visudyne in monotherapy we found the loss of 15 letters of the EDRTS chart in 77.1% of treated eyes.

[Czech Ophthalmologic Society's data collecting system for the monitoring and evaluating of the exsudative age-related macular degeneration treatment--the nation-wide project "AMADEUS"]. / Informacní zázemí Ceské oftalmologické spolecnosti CLS JEP pro monitoring a hodnocení lécby vlhké formy vekem podmínené makulárni degenerace-národní projekt AMADEUS.

The Czech Ophthalmologic Society (member of the Czech Medical Society of Jan Evangelista Purkyne) in collaboration with the Institute of Biostatistics and Analysis of the Masaryk University in Brno established a nation-wide information system for the follow-up of the epidemiology and treatment of the exsudative age-related macular degeneration (ARMD). The project named AMADEUS is a multi-centric, non-invasive, observation prospective study with the aim to improve the patients' treatment and to unify the criteria for the follow-up of the ARMD in the real clinical practice in the Czech Republic. The basic instrument of the whole project is a clinical register collecting parametric data from 9 specialized centers. Especially the project monitors the photodynamic therapy with Verteporfyrine (Visudyne) and treatment by anti-VEGF agents, or Pegaptanib (Macugen) and Ranibizumab (Lucentis). The project's protocol is trying to collect representative data about ARMD diagnosis and treatment; during regularly controls, the efficacy and safety of the treatment are followed-up.The data collecting does not influence the treatment strategy or the availability of chosen treatment for the patient. Since October 2008 until the end of the year 2009, the registry collected complex information about more than 1402 newly treated ARMD patients; out of them, in 582 cases the one-year follow-up period was regularly terminated. The available data shows well-considered indication of drugs indications by the doctors; the treated patients fulfill the indications criteria set by the scientific society. According to the data from the registry, in some treating centers the application schedule is not followed-up in some drugs (especially Pegaptanib); there is the possibility to improve the treatment. All the clinical centers participating in the AMADEUS registry will continue in the data collecting, which after a longer period of time will facilitate further treatment optimization and eliminating of the established imperfections. Further information about the project may be found at the web site: www.amadeus.registry.cz.