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Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8–21.5; P = 5.6 × 10−7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3–4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04–14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07–2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

AIM: In the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures. METHODS: All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0-10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure. RESULTS: 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified. Increased risk of childhood leukaemia was found for maternal exposure to aliphatic (OR 4.3) or aromatic hydrocarbons (OR 3.8) in the preconception period, and for paternal exposure to diesel exhaust (OR 1.4), lead exposure (OR 1.7) and mineral oils (OR 1.4)[corrected]. Risk of NHL appeared to be related to paternal exposure to oxygenated solvents (OR 2.5) and petrol exhaust (OR 2.2). CONCLUSIONS: We found increased risk for childhood leukaemia associated with maternal occupational exposure to aromatic and aliphatic hydrocarbons, particularly in the preconception period; increased risks were also observed for paternal exposure to diesel exhaust fumes, mineral oils and lead. The risk of NHL appeared to be related to paternal exposure to oxygenated solvent and petrol exhausts.

To evaluate the self-reported prevalence of poor adherence to recombinant human growth hormone (rhGH) therapy in a large, representative sample of Italian children and adolescents and to assess treatment and patient level correlates of poor adherence.The study was conducted in 46 pediatric centers throughout Italy. A questionnaire was administered to consecutive children/adolescents treated with rhGH or their parents. Eligible patients were represented by subjects aged between 6 and 16 years, of both sexes, on rhGH treatment for at least 6 months. The questionnaire was administered to the person in charge of preparing the injection. Multivariable logistic regression analysis was performed to identify factors independently associated with adherence.Overall, 1,007 children/adolescents were involved, of whom 24.4% missed 1 or more injections during a typical week and were thus considered as nonadherent. The most frequently reported reasons for missing a dose were being away from home (33.3%), forgetfulness (24.7%), not feeling well (12.9%), and pain (10.3%). Multivariable analysis indicated association between poor adherence and adolescence, low level of parent education, longer duration of treatment, need to convince the child to inject, and low level of awareness of the consequences of not properly following treatment. The likelihood of adherence markedly increased with higher levels of perceived device convenience.Poor adherence is still a major problem in the treatment of growth disorders. Increasing awareness and reassessment of treatment adherence on an annual basis should be part of clinical practice of pediatric endocrinologists involved with rhGH treatment.CI = confidence interval GH = growth hormone rhGH = recombinant human growth hormone.

Background Ototoxicity is a common side effect after platin chemotherapy and existing studies are limited due to small cohorts and a variety of confounding factors [ref:1], [ref:2]. Therefore, studies that enrolled greater numbers of patients will help us to learn more about incidence[for full text, please go to the a.m. URL], 4. Dreiländertagung D-A-CH, 35. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP)

Purpose Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with

Objectives Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. Methods The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998–2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM 2.5 and PM 10 - and gases -NO 2 and O 3 -) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. Results Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM 10 levels were 33.3 (SD=6.3) and 33.4 µg/m 3 (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. Conclusions Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. Design and Methods We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. Results During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women Conclusions Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

Background Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case/control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. Methods The study was carried out in 14 Italian regions (78.3% of Italian population aged 0?10). It included leukaemia, NHL and neuroblastoma cases incident in 0?10 year olds in 1998-2001,registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP)(accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child?s bed (48 hours measurement). Results The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls.ELF-MF long term measurements were obtained for 61.1% of controls and 81.6% of leukaemia cases; 8.8% of controls were exposed at over 0.1 microTesla (μT), 3.5% and 2.1% at respectively over 0.2 and 0.3 μT. 25% of controls? fathers had smoked over 10 cigarettes/day during the year of conception, varying according to education and region. Maternal smoking was less common (71.4% did not smoke in pregnancy). Maternal passive smoking during pregnancy was reported by 31.2% of controls; the child?s passive smoking for 28.6%. Occupational exposure to solvents was estimated in 18.3% of controls? fathers and 7.7% of mothers. Contact with public was more frequent among mothers (36.1%) than fathers (23.4%). Conclusions SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors.

We describe the survival patterns of 10,791 Italian children (age 0-14) diagnosed with cancer during 1989-1998 and who were included in the hospital-based registry of the Italian Association of Paediatric Haematology and Oncology. Five-year cumulative survival percentages were 76% for lymphoproliferative disorders and 68% for solid tumours. Survival rates in 1994-1998 significantly improved for acute lymphocytic leukaemia (ALL), acute non-lymphocytic leukaemia, Hodgkin's lymphoma and Wilms' tumour. Gender and age were determinants of survival for some specific types of cancer. Girls with ALL and neuroblastoma exhibited a significant advantage (hazard ratio HR 0.72, 0.62-0.83) and disadvantage (HR 0.73, 0.59-0.90) over boys, respectively. Children with a Wilms' tumour diagnosed above age 3 had a worse prognosis than younger children (HR 2.3, 1.4-4.1). The persisting gender-related difference in survival rate for ALL requires understanding as to whether it is attributable to delays in the adoption of more recent therapeutic protocols, while the corresponding findings for Wilms' tumour and neuroblastoma deserve further biological interpretation.

Background The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. Design and Methods We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. Results During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women Conclusions Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood. ©2011 Ferrata Storti Foundation.

The number of individuals who have successfully completed treatment for a cancer diagnosed during childhood and are entering adulthood has been increasing. Members of the International Berlin-Frankfurt-Munster Early and Late Toxicity Educational Committee (ELTEC) invited 45 paediatric cancer experts - representing oncologists, psychologists, nurses, epidemiologists, parents, and survivors - from 13 European countries, with five additional experts from North America, to Erice, Sicily, on October 27-29, 2006, to discuss the circumstances in which the word "cure" should be used when speaking about children with cancer, and when and why continuing follow-up and care may be required. The objective of the gathering was to generate from the participants' personal and professional experiences an overview statement of the group's philosophy of cure and care of survivors of childhood cancer. The 10 points reflect what the group considers essential for the survivors' cure and care

Parallelization of VLSI-simulation exploiting model-inherent parallelism is a promising way to accelerate verification processes for whole processor designs. Thereby partitioning of hardware models influences the effciency of following parallel simulations essentially. Based on a formal model of Parallel Cycle Simulation we introduce partition valuation combining communication and load balancing aspects. We choose a 2-level hierarchical partitioning scheme providing a framework for a mixture of experts strategy. Considering a complete model of a PowerPC 604 processor, we demonstrate that Evolutionary Algorithms can be applied successfully to our model partitioning problem on the second hierarchy level, supposing a reduced problem complexity after fast pre-partitioning on the first level. For the first time, we apply superpositions during execution of Evolutionary Algorithms, resulting in a faster decreasing fitness function and an acceleration of population handling.