Treatment of paediatric pontine glioma with oral trophosphamide and etoposide

To evaluate the overall survival of paediatric patients with pontine gliomas treated with oral trophosphamide and etoposide. Patients between 3 and 17 years of age with either typical diffuse pontine glioma on MRI or histologically proven anaplastic astrocytoma/glioblastoma multiforme located in the pons, were eligible. Treatment consisted of oral trophosphamide 100 mg m−2 day−1 combined with oral etoposide at 25 mg m−2 day−1 starting simultaneously with conventional radiation. Twenty patients were enrolled (median age 6 years, male : female=9 : 11). Surgical procedures included: no surgery: five, open biopsy: three, stereotactic biopsy: six, partial resection: three, and sub-total resection: three. Histological diagnoses included pilocytic astrocytoma: one, astrocytoma with no other specification: three, anaplastic astrocytoma: three, glioblastoma multiforme: eight, no histology: five. The most frequent side effects were haematologic and gastrointestinal. There was no toxic death. The response to combined treatment in 12 evaluable patients was: complete response: 0, partial response: three, stable disease: four, and progressive disease: five. All tumours progressed locally and all patients died. The overall median survival was 8 months. The overall survival rates at 1 and 4 years were: 0.4 and 0.05 respectively. This was not different from a control group of patients documented in the same population. Oral trophosphamide in combination with etoposide did not improve survival of pontine glioma patients. The treatment was well tolerated and should be evaluated for more chemoresponsive paediatric malignancies

Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields

Questionnaire layout and wording influence prevalence and risk estimates of respiratory symptoms in a population cohort

Objective: Results of epidemiological studies are greatly influenced by the chosen methodology. The study aims to investigate how two frequently used questionnaires (Qs), with partly different layout, influence the prevalence of respiratory symptoms. Study Design and Setting: A booklet containing two Qs, the Global Allergy and Asthma European Network Q and the Obstructive Lung Disease in Northern Sweden Q, was mailed to 30 000 subjects aged 16-75 years in West Sweden; 62% responded. Sixteen questions were included in the analysis: seven identical between the Qs, four different in set-up and five with the same layout but different wording. Comparisons were made using differences in proportions, observed agreement and Kappa statistics. Results: Identical questions yielded similar prevalences with high observed agreement and kappa values. Questions with different set-up or differences in wording resulted in significantly different prevalences with lower observed agreement and kappa values. In general, the use of follow-up questions, excluding subjects answering no to the initial question, resulted in 2.9-6.7% units lower prevalence. Conclusion: The question set-up has great influences on epidemiological results, and specifically questions that are set up to be excluded based on a previous no answer leads to lower prevalence compared with detached questions. Therefore, Q layout and exact wording of questions has to be carefully considered when comparing studies.First published online 5 Mars 2012.</p

Respiratory Symptom Relief Related to Reduction in Cigarette Use

INTRODUCTION: Many smokers reduce their cigarette consumption during failed attempts to quit. We report the impact of changes in consumption on smoking-related respiratory symptom severity (SRRSS). METHODS: Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a randomized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation. Cigarette use in the 28 days prior to the interview, and severity of SRRSS using a 7-item respiratory index, were assessed at baseline and at 3-month follow-up. OUTCOME: Baseline minus 3-month assessment difference in SRRSS score. RESULTS: Follow-up of 319 participants (83.3%), mean age 40.4 years, 51.4% male, who smoked 26.4 cigarettes per day, demonstrated a mean reduction of 16.7 cigarettes per day. A reduction in cigarette use was positively and significantly (b=0.29, t=5.16, P<.001) associated with a reduction in smoking-related symptom severity after adjusting for age, gender, race, years of regular smoking, baseline nicotine dependence, and history of treatment for asthma or emphysema. A 1 standard deviation reduction in average daily smoking (about 14.1 cigarettes) was associated with a 0.28 standard deviation decrease in smoking-related symptom severity. CONCLUSION: Reduction in symptom severity increases as absolute reduction in daily smoking increases. This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking