Chemotherapy and radiotherapy: When to call it quits

Abstract: Background: Patients diagnosed with cancer are often treated with chemotherapy and radiotherapy with curative intent. The transition from curative to palliative intent involves re-evaluation of treatment, and has to take into account the attitudes, beliefs and life aims of the patient. Objective: To discuss the difficulties in determining when to cease chemotherapy and radiotherapy in patients with advanced cancer. Discussion: The concept of treatment evaluation using a ‘burden versus benefit’ paradigm is discussed. Treatment aims must be in concordance with those of the patient, which are often couched in functional terms or linked to future significant life events. Chemotherapy and radiotherapy can offer patients in the palliative phase of cancer illness, benefits in terms of relief of symptoms and meaningful prolongation of life, and should be considered in appropriate circumstances. (author abstract)

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. Patients and setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107730 (95% Cl, $68626-$209881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Codon usage bias and A+T content variation in human papillomavirus genomes

We analyzed the codon usage bias of eight open reading frames (ORFs) across up to 79 human papillomavirus (HPV) genotypes from three distinct phylogenetic groups. All eight ORFs across HPV genotypes show a strong codon usage bias, amongst degenerately encoded amino acids, toward 18 codons mainly with T at the 3rd position. For all 18 degenerately encoded amino acids, codon preferences amongst human and animal PV ORFs are significantly different from those averaged across mammalian genes. Across the HPV types, the L2 ORFs show the highest codon usage bias (73.2 +/- 1.6% and the E4 ORFs the lowest (51.1 +/- 0.5%), reflecting as similar bias in codon 3rd position A + T content (L2: 76.1 +/- 4.2%; E4: 58.6 +/- 4.5%). The E4 ORF, uniquely amongst the HPV ORFs, is G + C rich, while the other ORFs are A + T rich. Codon usage bias correlates positively with A + T content at the codon 3rd position in the E2, E6, L1 and L2 ORFs, but negatively in the E4 ORFs. A general conservation of preferred codon usage across human and non-human PV genotypes whether they originate from a same supergroup or not, together with observed difference between the preferred codon usage for HPV ORFs and for genes of the cells they infect, suggests that specific codon usage bias and A + T content variation may somehow increase the replicational fitness of HPVs in mammalian epithelial cells, and have practical implications for gene therapy of HPV infection. (C) 2003 Elsevier B.V. All rights reserved.

Use of web-based formative assessment to support student learning in metabolism/nutrition unit

In 2002, an integrated basic science course was introduced into the Bachelor of Dental Sciences programme at the University of Queensland, Australia. Learning activities for the Metabolism and Nutrition unit within this integrated course included lectures, problem-based learning tutorials, computer-based self-directed learning exercises and practicals. To support student learning and assist students to develop the skills necessary to become lifelong learners, an extensive bank of formative assessment questions was set up using the commercially available package, WebCT®. Questions included short-answer, multiple-choice and extended matching questions. As significant staff time was involved in setting up the question database, the extent to which students used the formative assessment and their perceptions of its usefulness to their learning were evaluated to determine whether formative assessment should be extended to other units within the course. More than 90% of the class completed formative assessment tasks associated with learning activities scheduled in the first two weeks of the block, but this declined to less than 50% by the fourth and final week of the block. Patterns of usage of the formative assessment were also compared in students who scored in the top 10% for all assessment for the semester with those who scored in the lowest 10%. High-performing students accessed the Web-based formative assessment about twice as often as those who scored in the lowest band. However, marks for the formative assessment tests did not differ significantly between the two groups. In a questionnaire that was administered at the completion of the block, students rated the formative assessment highly, with 80% regarding it as being helpful for their learning. In conclusion, although substantial staff time was required to set up the question database, this appeared to be justified by the positive responses of the students.