The bi-cycle concept--relating continuing education directly to patient care.

This excerpted article originally appeared in Stearns NS, Getchell ME, Gold RK. Continuing Medical Education in Community Hospitals: A Manual for Program Development. Boston: Postgraduate Medical Institute, 1971, 88-96; and was published by the Massachusetts Medical Society, as a supplement to The New England Journal of Medicine, Vol. 284; No. 20; May 20, 1971.

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995-2006.

OBJECTIVE: • To examine the use of radiotherapy and radical surgery for bladder urothelial cell carcinoma (UCC) before, during and after national initiatives for reorganization of uro-oncology services. PATIENTS AND METHODS: • Population-based data (1995-2006) from a cancer registry with stable coding practices were analysed. • Bladder UCC was defined using relevant International Classification of Disease site and morphology codes. • Time trends in the use of radiotherapy and radical surgery, and other predictors of their use were examined. RESULTS: • Of 4639 bladder UCC patients aged ≥40 years (76% men), stage information was available for 4303 (93%). • Morphology and stage case mix remained stable during the study period. • Radiotherapy use decreased significantly (from 31% in 1995-1998 to 22% in 2003-2006, P < 0.001) among patients of any stage, whilst radical surgery use increased significantly (from 8 to 13%, P < 0.001), particularly among stage II-IV patients. • The proportion of patients treated by both radiotherapy and surgery also decreased notably (from 4.0 to 1.1%). • Women were significantly more likely to present in stages II-IV [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.06-1.40, P = 0.005], and less likely to be treated with radiotherapy (OR = 0.84, 95% CI: 0.72-0.99, P = 0.036). CONCLUSIONS: • Use of radical surgery in UCC invading bladder muscle increased and use of radiotherapy decreased during the study period, most probably reflecting the increasing availability of specialist surgical management. Sociodemographic variation in treatment was limited to lower use of radiotherapy in women. • Further research should encompass treatment timeliness and other aspects of care quality, as well as exploring potential differences in endoscopic treatments for disease not invading bladder muscle.

Population-based prostate-specific antigen testing in the UK leads to a stage migration of prostate cancer.

OBJECTIVE: To determine, within the UK, the stage and grade of prostate cancers that would be found through population-based prostate specific antigen (PSA) testing and biopsy. SUBJECTS AND METHODS: In the 'Prostate Testing for Cancer and Treatment' trial (ProtecT), men aged 50-69 years were recruited from nine cities in the UK and from randomly selected practices of general practitioners. Those with a PSA level of >3 ng/mL were offered a prostate biopsy. Age, PSA, stage and grade at diagnosis of ProtecT participants with cancer were compared with contemporaneous incident cases aged 50-69 years (age-restricted Cancer Registry cases) registered with the Eastern Cancer Registration and Information Centre (ECRIC). RESULTS: Within ProtecT, 94,427 men agreed to be tested (50% of men contacted), 8807 ( approximately 9%) had a raised PSA level and 2022 (23%) had prostate cancer; 229 ( approximately 12%) had locally advanced (T3 or T4) or metastatic cancers, the rest having clinically localized (T1c or T2) disease. Within ECRIC, 12,661 cancers were recorded over the same period; 3714 were men aged 50-69 years at diagnosis. Men in ProtecT had a lower age distribution and PSA level, and the cancers were of lower stage and grade (P < 0.001 for all comparisons). If population-based PSA testing were introduced in the UK, approximately 2660 men per 100,000 aged 50-69 years would be found to have prostate cancer, compared to current rates of approximately 130 per 100,000. If half of men accepted PSA testing, approximately 160,000 cancers would be found, compared to 30,000 diagnosed each year at present. CONCLUSIONS: Population-based PSA testing resulted in a significant downward stage and grade migration, and most such cancers were of low stage and grade, which could lead to risks of over-treatment for some men.

Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer.

PURPOSE: The prognosis of breast cancer varies considerably among individuals, and inherited genetic factors may help explain this variability. Of particular interest are genes involved in defense against reactive oxygen species (ROS) because ROS are thought to cause DNA damage and contribute to the pathogenesis of cancer. PATIENTS AND METHODS: We examined associations between 54 polymorphisms that tag the known common variants (minor allele frequency > 0.05) in 10 genes involved in oxidative damage repair (CAT, SOD1, SOD2, GPX1, GPX4, GSR, TXN, TXN2, TXNRD1, and TXNRD2) and survival in 4,470 women with breast cancer. RESULTS: Two single nucleotide polymorphisms (SNPs) in GPX4 (rs713041 and rs757229) were associated with all-cause mortality even after adjusting for multiple hypothesis testing (adjusted P = .0041 and P = .0035). These SNPs are correlated with each other (r2 = 0.61). GPX4 rs713041 is located near the selenocysteine insertion sequence element in the GPX4 3' untranslated region, and the rare allele of this SNP is associated with an increased risk of death, with a hazard ratio of 1.27 per rare allele carried (95% CI, 1.13 to 11.43). This effect was not attenuated after adjusting for tumor stage, grade, or estrogen receptor status. We found that the common allele is preferentially expressed in normal lymphocytes, normal breast, and breast tumors compared with the rare allele, but there were no differences in total levels of GPX4 mRNA across genotypes. CONCLUSION: These data provide strong support for the hypothesis that common variation in GPX4 is associated with prognosis after a diagnosis of breast cancer.