Specification of the Dose to Organs at Risk in External Beam Radiotherapy

Reporting of the clinical relevant dose to organs at risk (OR) and other normal tissues is crucial in trials and protocols where the aim is to assess late complications and to increase the therapeutic ratio for external beam radiotherapy. The dose distribution in normal tissues and ORs are, however, most often heterogeneous, at least when more than two opposing beams are applied. To decide the most clinical relevant dose with respect to late occurring complications is therefore not a straight forward problem. In this work we discuss what parameters characterise the dose-volume-histogram (DVH) best by calculating normal tissue complication probabilities (NTCPs) by using the Lyman model and various sets of statistical parameters drawn out from the DVHs. These NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of parameters are evaluated. Our calculations indicate that the NTCP based on the Lyman model is best correlated to the D_max value, for serially organised tissues such as the spinal cord. For organs, described largely as tissues organised in parallel, the D_median or D_mean of the DVH may be applied. Our calculations reveal that D_mean is the parameter of choice when D_meclian is quite small, but when the two parameters approach each other, D_mediarl will be a better choice, using a unity volume fraction. For ORs characterised by a mixed serial and parallel functional structure, as the heart, neither D_max, D_median, nor D_mi,_an may predict the actual NTCP.     

Trends in physical activity behaviours and attitudes among South Australian youth between 1985 and 2004

Rising youth obesity is a serious public health concern. There is a widespread view that declining physical activity is contributing to this trend. A total of 929 young South Australians (age = 9–15 years) were surveyed in 1985 and 2004 on usual physical activity in several contexts, including attitudes to physical activity. Eight of 10 South Australian schools participating in the 1985 Schools Health and Fitness Survey were revisited in 2004. Comparisons were made on: organised sport, active transport, physical education (PE), playground activity, vigorous physical activity (VPA), total leisure-time physical activity (LTPA), and attitudes to PE and school sport. The questionnaire and method of administration were identical in both surveys. There were no differences between surveys in club and school sport participation, walking to school, and reported enjoyment of PE and school sport. In 2004 fewer children rode to school, but PE classes were more frequent. The percentage of children who ‘sit and talk’ during school breaks had increased, with a decreased percentage of older girls who ‘run around’ during school breaks. There was a significantly higher LTPA in MET.min in 2004 for boys, which was particularly evident at higher percentiles. There were no changes in mean or distribution of LTPA for the whole sample or girls. The percentage of respondents reporting ≥3 bouts of VPA in the previous week rose from 51% (1985) to 76% (2004). There is no consistent evidence of declining physical activity among South Australian youth. It is apparent that physical activity in some contexts has declined, while in other contexts levels are the same or higher than in 1985. This underscores the complex nature of physical activity and the influences on this behaviour.     

Effect of TRFK-5 on airway responsiveness in ovalbumin-treated guinea pigs exposed to tobacco smoke.

Tobacco smoke (TS) exposure can induce airway hyperresponsiveness, especially in asthma. A feature of asthma is eosinophilia. We hypothesized that tobacco smoke exposure enhances eosinophil responsiveness in sensitized guinea pigs. Tobacco smoke-exposed, ovalbumin (OA)-sensitized guinea pigs were treated with TRFK-5 (1.0 mg/kg, intraperitoneal), an anti-interleukin (IL)-5 agent, or its vehicle. Guinea pigs were challenged with aerosols of OA, capsaicin, histamine, and methacholine. TRFK-5 attenuated airway responsiveness to OA but not to capsaicin, histamine, or methacholine. Bronchial alveolar lavage fluid analysis confirmed TRFK-5 attenuated airway eosinophilia in OA-treated guinea pigs. Therefore, airway responsiveness to OA is enhanced by eosinophils or IL-5 itself.     

Induction of HSP72 in Rat Liver by Chronic Ethanol Consumption Combined with Exercise: Association with the Prevention of Ethanol-Induced Fatty Liver by Exercise

Ethanol-induced fatty liver in rats was attenuated by repeated running exercise, and the protective effect of exercise was associated with the synergistic expression of heat shock proteins (HSP72). Rats were placed in four groups of six. The two ethanol-fed groups of rats received a liquid diet (Lieber-DeCarli formulation) in which 36% of the calories were derived from ethanol. One group remained sedentary (S/E), whereas the other was trained to run on a rodent treadmill at a speed of 27 m/min, 1 hr/day, 5 days/week, for 7 weeks (R/E). Two other groups–one exercised as previously mentioned (R/C) and one sedentary (S/C)–received control-liquid diets in which the ethanol was isocalorically substituted with a dextran/maltose mixture. The degree of fatty infiltration in liver sections stained with hematoxylin and eosin was graded on a 0–4 scale and the data analyzed by ANOVA on ranks. Ethanol significantly induced fatty infiltration in the S/E group, whereas fatty infiltration in the livers of the R/E group was not different from the S/C group. Electrophoresis and Western blotting of liver homogenates demonstrated that HSP72 was not expressed in either the S/C or S/E groups and was only slightly expressed in the R/C group. The combination of exercise and ethanol, however, resulted in an elevated expression of HSP72 in the R/E group. The content of HSP73 was unaffected by any treatment.     

A Pharmacoeconomic Model to Evaluate Antibiotic Costs

Study Objectives . To characterize patient sociodemographics and health, describe vancomycin treatment parameters and clinician-rated outcomes, and determine costs associated with treatment including preparation and administration, adverse events, and toxicity. Design . A prospective study to develop a model for costs associated with antibiotic treatment (vancomycin). Setting . A community hospital. Patients . One hundred adults with active infections. Interventions . Mean duration of therapy was 10 days, and most patients received 2000 mg/day. Serum concentrations were monitored in two of three patients. Detailed cost analyses were completed on a subset of 26 patients selected at random from the overall sample. Measurements and Main Results . Sepsis and skin and skin structure infections were the most common indications for vancomycin therapy. Treatment was effective in 81 patients, failed in 9, and was not evaluable in 10. Thirty-eight percent of patients experienced adverse events attributable to the drug. Phlebitis was common, and red man syndrome, nephrotoxicity, and ototoxicity were infrequent. Conclusions . Total cost of vancomycin treatment for 100 patients was $30,251: $23,855 for preparation and administration, $1710 for monitoring serum concentrations, and $4686 for treating adverse reactions. Drug costs accounted for only 55% of the total cost. Vancomycin is safe and effective, but phlebitis is underreported and significantly affects cost.