Older age is an adverse prognostic factor in stage I, favorable histology Wilms' tumor treated with vincristine monochemotherapy: a study by the United Kingdom Children's Cancer Study Group, Wilm's Tumor Working Group.

PURPOSE: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms' tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. PATIENTS AND METHODS: During two consecutive trials of the United Kingdom Children's Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms' tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. RESULTS: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P =.001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P =.01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P =.66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). CONCLUSION: Treatment for stage I FH Wilms' tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms' tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.     

Evaluating healthcare education: Issues and methods

This paper analyses the methodological issues inherent in evaluating healthcare education and considers approaches for addressing these.Recent policies have exhorted practitioners to base their practice on evidence; however in healthcare education the evidence base is not extensive. Whilst educational evaluation has advanced in the last decades, standardised designs and toolkits are not available. Each evaluation has different aims and occurs in specific contexts, thus the design has to fit the circumstances, yet meet the challenge of scientific credibility. Indicators of educational processes and outcomes are not scientifically verified; no toolkit of standardised ‘off-the-shelf’ valid, reliable and sensitive measures exists. The evidence base of educational practice is largely derived from small-scale, single case studies; the majority of measures are self-devised, unvalidated tools of unproven reliability, thus meta-synthesis is not appropriate and results are not generalisable. Healthcare educational evaluators need valid and reliable assessments of both knowledge acquisition and its application to practice. The need to establish and explain attribution, i.e. the relationship between educational inputs and outcomes is complex and requires experimental/quasi-experimental design. In addition, educational evaluators face the pragmatic challenge of practice in healthcare contexts, where confounding variables are hard to control and resources are scarce.     

Infusion clearance of subcutaneous iothalamate versus standard renal clearance

 Accurate, timed urine collections for the measurement of glomerular filtration rate (GFR) may be impractical in infants or in patients with urological abnormalities. GFR may be measured without urine collection using a constant subcutaneous infusion of iothalamate. We compare the infusion clearance with conventional renal clearance in 14 children and young adults. The mean clearance ratio (infusion clearance/renal clearance ± 1 SD) was 0.99±0.1 and the mean discrepancy between the two methods was 8.5%±4.7%. The 95% limits of agreement for the ratio of the two methods are 0.83–1.23. These data indicate that subcutaneous infusion of iothalamate is a practical method for measuring GFR in children without a urine collection. Received March 18, 1996; received in revised form February 12, 1997; accepted March 26, 1997     

Augmentation laser for proliferative diabetic retinopathy that fails to respond to initial panretinal photocoagulation.

PURPOSE: A study was performed to determine if diabetic subjects who fail to respond to initial panretinal photocoagulation with regression of retinopathy risk factors do better with supplemental panretinal photocoagulation. METHODS: Thirty-five patients with 3 or more retinopathy risk factors who failed to respond to panretinal photocoagulation with regression to less than 3 retinopathy risk factors by 3 weeks after initial panretinal photocoagulation were prospectively randomized to augmentation laser panretinal photocoagulation (MORE) or to no additional treatment (NOMORE). RESULTS: Six months after initial treatment, the MORE group (n = 16) had regressed a mean of -0.94 retinopathy risk factors (with 95% confidence interval [CI] -1.60 to -0.26), compared with -0.21 retinopathy risk factors (95% CI -0.69 to 0.27) in the NOMORE (n = 19) group (P = 0.055). However, by 1 year, there was no statistically significant difference in the amount of regression of retinopathy risk factors with a mean decrease of -1.12 (95% CI -2.0 to -0.24) versus -1.05 retinopathy risk factors (95% CI -1.80 to -0.28) in the 2 groups, respectively. Similarly, for visual acuity, there was no difference in outcome. For all study patients, the persistence of three or more retinopathy risk factors was associated with a poorer visual result than if there was regression to less than three retinopathy risk factors. CONCLUSION: This study shows that although augmentation panretinal photocoagulation achieved faster regression of retinopathy risk factors, by 1 year, there was no difference in either mean regression of retinopathy risk factors or visual acuity between eyes treated or not treated with augmentation panretinal photocoagulation. In addition, the study shows that the persistence of 3 or more retinopathy risk factors 1 year after treatment was associated with a poorer visual result. Because sample size limited the power of the study to find small differences between groups, and because in proliferative diabetic retinopathy small differences could be important clinically, the authors do not recommend changes in current clinical practice.     

Enhancement of benzo[a]pyrene-induced sister chromatid exchanges in lymphocytes from cigarette smokers occupationally exposed to asbestos

The frequencies of base-line and benzo[a]pyrene [(BP) CAS 50-38-8]-induced sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 22 male asbestos-exposed workers and 10 nonexposed workers of comparable age. A clear association between cigarette smoking and asbestos exposure in the sensitivity of lymphocytes to BP was observed. Among asbestos-exposed workers, lymphocytes from those who smoked cigarettes were significantly more susceptible to the induction of SCE by in vitro exposure to BP (P = .01) than were lymphocytes from nonsmokers. Active smoking elevated the base-line SCE frequency in both asbestos-exposed and nonexposed workers (P = .001), and an interaction between smoking and asbestos in the production of base-line SCE was suggested (P = .07). Asbestos exposure alone was not associated with an enhanced susceptibility to the induction of SCE by BP or with an elevation of base-line SCE. Increased age was associated with an increase in SCE inducibility by BP (P = .01), and a history of smoking was marginally associated with SCE inducibility by BP (P = .07). These findings support the hypothesis that an increased susceptibility of asbestos-exposed individuals to polyaromatic hydrocarbon-induced cancer results from an enhanced sensitivity to the induction of genetic damage rather than to an asbestos-induced differential cellular metabolic capacity.