Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.     

Sleep and recovery in physicians on night call: a longitudinal field study

Background  

It is well known that physicians' night-call duty may cause impaired performance and adverse effects on subjective health, but there is limited knowledge about effects on sleep duration and recovery time. In recent years occupational stress and impaired well-being among anaesthesiologists have been frequently reported for in the scientific literature. Given their main focus on handling patients with life-threatening conditions, when on call, one might expect sleep and recovery to be negatively affected by work, especially in this specialist group. The aim of the present study was to examine whether a 16-hour night-call schedule allowed for sufficient recovery in anaesthesiologists compared with other physician specialists handling less life-threatening conditions, when on call.     

Associations between street connectivity and active transportation

Background  

Past studies of associations between measures of the built environment, particularly street connectivity, and active transportation (AT) or leisure walking/bicycling have largely failed to account for spatial autocorrelation of connectivity variables and have seldom examined both the propensity for AT and its duration in a coherent fashion. Such efforts could improve our understanding of the spatial and behavioral aspects of AT. We analyzed spatially identified data from Los Angeles and San Diego Counties collected as part of the 2001 California Health Interview Survey.     

Does chair type influence outcome in the timed “up and go” test in older persons?

Objective  

To test the effects of the use of a collapsible, portable chair (chair B), as opposed to a ‘standard’ chair (chair A), on the outcome of the timed “Up and Go” (TUG) test.     

Exercise and global well-being in community-dwelling adults with fibromyalgia: a systematic review with meta-analysis

Background  

Exercise has been recommended for improving global-well being in adults with fibromyalgia. However, no meta-analysis has determined the effects of exercise on global well-being using a single instrument and when analyzed separately according to intention-to-treat and per-protocol analyses. The purpose of this study was to fill that gap.     

Surviving crack: a qualitative study of the strategies and tactics developed by Brazilian users to deal with the risks associated with the drug

Background  

Due to marginalization, trafficking violence, conflicts with the police and organic and social psychological problems associated with the drug, crack is one of the most devastating drugs currently in use. However, there is evidence that some users manage to stay alive and active while using crack cocaine for many years, despite the numerous adversities and risks involved with this behavior. In this context, the aim of the present study was to identify the strategies and tactics developed by crack users to deal with the risks associated with the culture of use by examining the survival strategies employed by long-term users.